Orientations
1. Robert Butler, The Longevity Revolution: The Benefits and Challenges of Living a Long Life (New York: Public Affairs, 2008), 121.
2. In developing countries, such as Ghana, the proportion of people aged 60 and older is rising but for the moment remains at less than 10%; however, because the absolute numbers are large, this transformation is characterized as an “aging epidemic.” See http://www.modernghana.com/news2/137880/1/ageing-epidemic-looms-in-ghana.html. In China, with an economy that is at once developed and developing, the aging of society is even more dramatic. The Chinese themselves describe the situation as one of “growing old before getting rich.” See Hong Zhang, “Vignette 2: China,” in Sharon Kaufman, Julie Livingston, Hong Zhang, and Margaret Lock, “Transforming the Concepts of Aging: Three Case Studies from Anthropology,” in Oxford Textbook of Old Age Psychiatry, ed. Tom Dening and Alan Thomas (Oxford: Oxford University Press, 2013); see also Richard Jackson, Keisuke Nakashima, and Neil Howe, China’s Long March to Retirement Reform: The Graying of the Middle Kingdom Revisited (Washington, D.C.: Center for Strategic & International Studies, 2009), http://csis.org/files/media/csis/pubs/090422_gai_chinareport_en.pdf.
3. Paul M. V. Martin and Estelle Martin-Granel, “2,500-Year Evolution of the Term Epidemic,” Emerging Infectious Diseases 12, no. 6 (2006): 976–80.
4. See http://www.google.ca/#hl=en&source=hp&biw=1471&bih=1009&q=Alzheimer%27s+epidemic&aq=f&aqi=g1g-m1g-v2&aql=&oq=&fp=484a924e15169ff5 (accessed March 10, 2011).
5. Meredith Wadman and Nature Magazine, “U.S. Government Sets Out Alzheimer’s Plan,” Scientific American, May 23, 2012, http://www.scientificamerican.com/article.cfm?id=us-government-sets-alzheimers-plan.
6. The term “epigenetics” was created by C. H. Waddington in 1942. When Waddington coined the term the physical nature of genes and their role in heredity were not known; he used it as a conceptual model of how genes might interact with their surroundings to produce a phenotype. The contemporary meaning in scientific discourse is more narrow, referring to heritable traits (over rounds of cell division and sometimes trans-generationally) that do not involve changes to the underlying DNA sequence. See http://en.wikipedia.org/wiki/Epigenetics.
7. Peter J. Whitehouse and Daniel George, The Myth of Alzheimer’s: What You Aren’t Being Told about Today’s Most Dreaded Diagnosis (New York: St. Martin’s, 2008).
8. Postgenomic research is research carried out since the mapping of the human genome in which emphasis is given to the function of genes in context.
9. Karen Barad, Meeting the Universe Halfway: Quantum Physics and the Entanglement of Matter and Meaning (Durham, N.C.: Duke University Press, 2007), 56.
10. Ibid., 33.
11. In addition to ibid., see Lorraine Daston and Peter Galison, Objectivity (New York: Zone Books, 2007), and Margaret M. Lock and Vinh-Kim Nguyen, An Anthropology of Biomedicine (Oxford: Wiley-Blackwell, 2010).
12. Ian Hacking, “Making up People,” in Reconstructing Individualism: Autonomy, Individuality, and the Self in Western Thought, ed. T. C. Heller, M. Sosna, and D. E. Wellberry (Stanford: Stanford University Press, 1986), 222–36, http://www.icesi.edu.co/blogs/antro_conocimiento/files/2012/02/Hacking_making-up-people.pdf; Donna J. Haraway, Simians, Cyborgs, and Women: The Reinvention of Nature (New York: Routledge, 1991); Bruno Latour, Pandora’s Hope: Essays on the Reality of Science Studies (Cambridge, Mass.: Harvard University Press, 1999); Hans-Jörg Rheinberger, “Beyond Nature and Culture: Modes of Reasoning in the Age of Molecular Biology and Medicine,” in Living and Working with the New Medical Technologies: Intersections of Inquiry, ed. Margaret Lock, Allan Young, and Alberto Cambrosio (Cambridge: Cambridge University Press, 2000), 19–30.
13. Lock and Nguyen, Anthropology of Biomedicine, 94.
14. Ludwik Fleck, Genesis and Development of a Scientific Fact (Chicago: University of Chicago Press, 1979). See also Charles E. Rosenberg, “What Is Disease? In Memory of Owsei Temkin,” Bulletin of the History of Medicine 77, no. 3 (2003): 491–505.
15. Warwick Anderson, The Collectors of Lost Souls: Turning Kuru Scientists into White Men (Baltimore: Johns Hopkins University Press, 2008); Lock and Nguyen, Anthropology of Biomedicine, 103–7; Jacques Pepin, The Origin of AIDS (Cambridge: Cambridge University Press, 2011).
16. Bruno Latour, The Pasteurization of France (Cambridge, Mass.: Harvard University Press, 1988).
17. Alan Cassels, “Drug Bust,” Common Ground, November 2010, http://www.commonground.ca/iss/232/cg232_cassels.shtml.
18. See, for example, Michael Lambek, Knowledge and Practice in Mayotte: Local Discourses of Islam, Sorcery and Spirit Possession (Toronto: Toronto University Press, 1993); Susan Reynolds Whyte, Questioning Misfortune: The Pragmatics of Uncertainty in Eastern Uganda (Cambridge: Cambridge University Press, 1997).
19. For an elaboration of this approach, see, for example, Felicia A. Huppert, Carol Brayne, and Daniel W. O’Conner, eds., Dementia and Normal Aging (Cambridge: Cambridge University Press, 1994); and Marcus Richards and Carol Brayne, “What Do We Mean by Alzheimer Disease?,” British Medical Journal 341 (2010): 865–67.
20. Ian Hacking, The Taming of Chance (Cambridge: Cambridge University Press, 1990), 2.
21. Lorraine Daston, Classical Probability in the Enlightenment (Princeton: Princeton University Press, 1988).
22. Hacking, Taming of Chance, 2.
23. Ulrich Beck, World at Risk (Cambridge: Polity Press, 2007), 5.
24. Ibid., 5.
25. Ibid., 216.
26. Ibid., 8.
27. Ibid., 9.
28. Alzheimer’s Disease International, World Alzheimer Report 2009: Executive Summary (2009), 1, http://www.alz.co.uk/research/files/WorldAlzheimerReport-ExecutiveSummary.pdf.
29. Ibid., 11.
30. “Leading Edge: How Much Is Dementia Care Worth?,” The Lancet Neurology 9, no. 11 (2010): 1037.
31. “Over the Mountain to Alzheimer’s,” Maclean’s, January 4, 2010, http://www2.macleans.ca/2010/01/04/over-the-mountain-to-alzheimers/.
32. “2008 Alzheimer’s Disease Facts and Figures,” Alzheimer’s & Dementia 4, no. 2 (2008): 110–33.
33. Carolyn Abraham, “Dementia Researchers Feel Blocked by Ottawa, Big Pharma, Medical Dogma,” Globe and Mail, September 17, 2010, http://www.theglobeandmail.com/life/health-and-fitness/dementia-researchers-feel-blocked-by-ottawa-big-pharma-medical-dogma/article4389415/.
34. “Northern Ireland Dementia Total More Than Estimated,” BBC News, February 3, 2010, http://news.bbc.co.uk/2/hi/uk_news/northern_ireland/8494975.stm.
35. Although anthropological research has shown repeatedly that even though many people everywhere accept biomedical accounts of proximate disease causation—that is, accounts about what has gone wrong inside the body—nevertheless a large number of individuals continue to pose the question of “why me” and seek out explanations for what it is in their past behavior and everyday life that accounts for the problem having arisen in the first place. See, for example, Mark Nichter, Global Health: Why Cultural Perceptions, Social Representations, and Biopolitics Matter (Tucson: University of Arizona Press, 2008).
36. Lawrence Cohen, No Aging in India: Alzheimer’s, the Bad Family, and Other Modern Things (Berkeley: University of California Press, 1998), 184.
37. Margaret Lock, “Centering the Household: The Remaking of Female Maturity in Japan,” in Re-Imagining Japanese Women, ed. Anne Imamura (Berkeley: University of California Press, 1996), 73–103; Milton Ezrati, “Japan’s Aging Economics,” Foreign Affairs, May/June 1997, http://www.foreignaffairs.com/articles/53050/milton-ezrati/japans-aging-economics.
38. Jennifer Robertson, “Robo Sapiens Japanicus: Humanoid Robots and the Posthuman Family,” Critical Asian Studies 39, no. 3 (2007): 369–98.
39. United Nations Department of Economic and Social Affairs, Population Division, World Population Ageing: 1950–2050 (2002), http://www.un.org/esa/population/publications/worldageing19502050/.
40. Yogesh Shah, “Gray Tsunami: Challenges and Solutions of Global Aging,” DMU Magazine, Summer 2011, http://www.dmu.edu/magazine/summer-2011/my-turn-summer-2011/gray-tsunami-challenges-and-solutions-of-global-aging/.
41. Richard Jackson and Neil Howe, The Graying of the Middle Kingdom: The Demographics and Economics of Retirement Policy in China (Washington, D.C.: Center for Strategic & International Studies, 2004), http://csis.org/files/media/csis/pubs/grayingkingdom.pdf.
42. David Barboza, “China, in a Shift, Takes on Its Alzheimer’s Problem,” New York Times, January 12, 2011.
43. Hong Zhang, “Who Will Care for Our Parents? Changing Boundaries of Family and Public Roles in Providing Care for the Aged in China,” Journal of Long-Term Home Health Care 25 (2007): 39–46; see also Kaufman et al., “Transforming the Concepts of Aging.”
44. See the section by Hong Zhang in Kaufman et al., “Transforming the Concepts of Aging.”
45. David L. Kertzer and Peter Laslett, Aging in the Past: Demography, Society and Old Age (Berkeley: University of California Press, 1995).
46. Ed Yong, “Life Begins at 100: Secrets of the Centenarians,” Mind Power News, 2009, http://www.mindpowernews.com/LifeBeginsAt100.htm.
47. Butler, Longevity Revolution, 13. See also Thomas McKeown, The Modern Rise of Population (New York: Academic Press, 1976).
48. United Nations Department of Economic and Social Affairs, Population Division, World Population Ageing.
49. This discussion about global networking among researchers working on Alzheimer disease has much in common with the concept of “biomedical platforms” set out by Peter Keating and Alberto Cambrosio, Biomedical Platforms: Realigning the Normal and the Pathological in Late-Twentieth-Century Medicine (Cambridge, Mass.: MIT Press, 2003). Keating and Cambrosio argue that this concept “sheds new light on the articulation and the regulation of the practices focused on the normal and the pathological that characterize contemporary biomedicine” (22). Their purpose is to demonstrate that biomedical platforms are “neither science nor technology but a way of articulating the two” (326). Above all, this hybrid space that has emerged since the end of World War II today defines the standards according to which biomedical actions are evaluated.
50. For development of this theme, see Alexander Peine, “Challenging Incommensurability: What We Can Learn from Ludwik Fleck and the Analysis of Configurational Innovation,” Minerva 49 (2011): 489–508, 493.
51. See also Susan Leigh Star, “Cooperation without Consensus in Scientific Problem Solving: Dynamics of Closure in Open Systems,” in CSCW: Cooperation or Conflict?, ed. Steve Easterbrook (London: Springer, 1993), 93–106; Peter Galison and David Stump, eds., The Disunity of Science—Boundaries, Contexts, and Power (Stanford: Stanford University Press, 1996).
52. See, for example, Cohen, No Aging in India; E. Herskovits, “Struggling over Subjectivity: Debates about the ‘Self’ and Alzheimer Disease,” Medical Anthropology Quarterly 9 (1996): 146–64; Charlotte Ikels, “The Experience of Dementia in China,” Culture, Medicine, and Psychiatry 22 (1998): 257–83; Annette Leibing and Lawrence Cohen, eds., Thinking about Dementia: Culture, Loss, and the Anthropology of Senility (New Brunswick, N.J.: Rutgers University Press, 2006); Daniel R. George, “Overcoming the Social Death of Dementia through Language,” Lancet 376 (2010): 586–87; Judith Levine, “Managing Dad,” in Treating Dementia: Do We Have a Pill for It?, ed. Jesse F. Ballenger, Peter Whitehouse, Constantine G. Lykestsos, Peter V. Rabins, and Jason H. T. Karlawish (Baltimore: Johns Hopkins University Press, 2009), 116–24; John W. Traphagan, Taming Oblivion: Aging Bodies and the Fear of Senility in Japan (Albany: State University of New York Press, 2000).
Chapter 1
Making and Remaking Alzheimer Disease
1. Jonathan Franzen, “My Father’s Brain,” The New Yorker, September 10, 2001, 85.
2. Richard M. Torack, The Pathologic Physiology of Dementia, with Indications for Diagnosis and Treatment (Berlin: Springer-Verlag, 1978).
3. King Lear of course is not a comedy. He is often described by literary critics as demented, but Lear’s extreme behavioral changes, including powerful hallucinations and complete derangement followed by an apparent return to normal, should be understood as literary device on the part of Shakespeare and not interpreted via our medicalized minds in a search for truth. The statement by Jacques, on the other hand, does represent the dominant idea of the day that persisted well into the 19th century about the ages of man or the wheel of life. See M. Lock, Encounters with Aging: Mythologies of Menopause in Japan and North America (Berkeley: University of California Press, 1993), 305–6, http://www.ucpress.edu/book.php?isbn=9780520201620.
4. Torack, Pathologic Physiology, 1.
5. Eric Engstrom, “Researching Dementia in Imperial Germany: Alois Alzheimer and the Economies of Psychiatric Practice,” Culture, Medicine, and Psychiatry 31, no. 3 (2007): 405–13.
6. H. Braak and E. Braak, “Neuropathological Stageing of Alzheimer-Related Changes,” Journal of Neuropathology & Experimental Neurology 59 (2000): 733–48.
7. Konrad Maurer and Ulrike Maurer, Alzheimer: The Life of a Physician and the Career of a Disease (New York: Columbia University Press, 1986), 41.
8. Ibid., ix.
9. Theodore M. Brown, “Mental Diseases,” in Companion Encyclopedia of the History of Medicine, vol. 1, ed. W. F. Bynum and Roy Porter (London: Routledge, 1993), 442.
10. Ibid., 444.
11. Michel Foucault, The Birth of the Clinic: An Archaeology of Medical Perception, trans. A. M. Sheridan Smith (New York: Vintage Books, 1973), 131.
12. Charles Hughes, “Insanity Defined on the Basis of Disease,” The Alienist and Neurologist 20 (1887): 170–74, 173.
13. G. E. Berrios, “Alzheimer Disease: A Conceptual History,” International Journal of Geriatric Psychiatry 5 (1990): 355–65, 356.
14. Cohen, No Aging in India, 63.
15. Maurer and Maurer, Alzheimer, 2, 4.
16. Ibid., 151–52.
17. Berrios, “Alzheimer Disease.”
18. Atwood Gaines and Peter Whitehouse, “Building a Mystery: Alzheimer Disease, Mild Cognitive Impairment, and Beyond,” Philosophy, Psychiatry, & Psychology 13 (2006): 61–74, 63.
19. Braak and Braak, “Neuropathological Stageing.”
20. Cathy Gere, “ ‘Nature’s Experiment’: Epilepsy, Localization of Brain Function and the Emergence of the Cerebral Subject,” in Neurocultures: Glimpses into an Expanding Universe, ed. Francisco Ortega and Fernando Vidal (Frankfurt: Peter Lang, 2011), 235–47. Gere’s essay tracks the use of epileptics as research subjects in neurology in the early 20th century, culminating in the experiments carried out by Wilder Penfield at the Montréal Neurological Institute in the 1950s with over 1,100 individuals with epilepsy whose brains were experimented upon using local anesthesia.
21. Berrios, “Alzheimer Disease,” 358.
22. Maurer and Maurer, Alzheimer, 163.
23. Ibid., 142.
24. Hans-Jurgen Möller and Manuel B. Graeber, “Johann F.: The Historical Relevance of the Case for the Concept of Alzheimer Disease,” in Concepts of Alzheimer Disease: Biological, Clinical, and Cultural Perspectives, ed. Peter J. Whitehouse, Konrad Maurer, and Jesse F. Ballenger (Baltimore: Johns Hopkins University Press, 2000), 30–46.
25. Maurer and Maurer, Alzheimer, 217.
26. Berrios, “Alzheimer Disease,” 360.
27. I am indebted to Jesse Ballenger for this thought.
28. Berrios, “Alzheimer Disease,” 362.
29. Wolfgang Jilek, “Emil Kraepelin and Comparative Sociocultural Psychiatry,” European Archives of Psychiatry and Clinical Neuroscience 245 (1995): 231–38.
30. David J. Libon, Catherine C. Price, Kenneth M. Heilman, and Murray Grossman, “Alzheimer’s ‘Other Dementia,’ ” Cognitive and Behavioral Neurology 19, no. 2 (2006): 112–16; Torack, Pathologic Physiology.
31. Konrad Maurer, Stephan Volk, and Hector Gerbaldo, “Auguste D: The History of Alois Alzheimer’s First Case,” in Whitehouse, Maurer, and Ballenger, Concepts of Alzheimer Disease, 20–29, 20.
32. Berrios, “Alzheimer Disease.”
33. T. Simchowicz, “Histologische Studien über die senile Demenz,” in Histologische und histopathologische Arbeiten, vol. 4, ed. F. Nissl and A. Alzheimer (Jena: Fischer, 1913), 267–444.
34. N. Gellerstedt reported this finding in 1933; see W. A. Lishman, “The History of Research into Dementia and Its Relationship to Current Concepts,” in Huppert, Brayne, and O’Conner, Dementia and Normal Aging, 41–56.
35. Ibid., 44.
36. Thomas G. Beach, “The History of Alzheimer Disease: Three Debates,” Journal of the History of Medicine 42 (1987): 327–42.
37. Ibid.
38. M. Leale, “The Senile Degenerations, Their Symptom-Complex and Treatment,” International Clinics 4 (1911): 37–47.
39. C. Mercier, Sanity and Insanity (London: Walter Scott, 1895).
40. Martha Holstein, “Alzheimer Disease and Senile Dementia, 1885–1920: An Interpretive History of Disease Negotiation,” Journal of Aging Studies 11 (1997): 1–13, 7; see also T. Cole, The Journey of Life: A Cultural History of Aging in America. Cambridge: Cambridge University Press, 1991.
41. Ignatz Nascher, “Senile Mentality,” International Clinics 4 (1911): 48–59.
42. Jesse F. Ballenger, Self, Senility, and Alzheimer’s Disease in Modern America: A History (Baltimore: Johns Hopkins University Press, 2006), 30.
43. Ibid., 119.
44. Cited in ibid., 48.
45. See ibid., 56–80.
46. Martin Roth, Bernard E. Thomlinson, and Gary Blessed, “Correlation between Scores for Dementia and Counts of Senile Plaques in Cerebral Grey Matter of Elderly Subjects,” Nature 209 (1966): 109–10, 109.
47. Ballenger, Self, Senility, and Alzheimer’s Disease, 91.
48. Alex Comfort, A Good Age (New York: Simon & Schuster, 1976), 47.
49. Robert Katzman, “The Prevalence and Malignancy of Alzheimer Disease: A Major Killer,” Archives of Neurology 33 (1976): 217–18.
50. Konrad Dillman, “Epistemological Lessons from History,” in Whitehouse, Maurer, and Ballenger, Concepts of Alzheimer Disease, 129–57, 141.
51. Robert Katzman and Katherine L. Bick, “The Rediscovery of Alzheimer Disease in the 1960s and 1970s,” in Whitehouse, Maurer, and Ballenger, Concepts of Alzheimer Disease, 104–14.
52. Ballenger, Self, Senility, and Alzheimer’s Disease, 98.
53. Roger H. Segelken, “Alzheimer Activist,” New York Times, September 24, 2008.
54. Patrick Fox, “From Senility to Alzheimer Disease: The Rise of the Alzheimer Disease Movement,” Milbank Quarterly 67 (1989): 58–102.
55. R. Binstock and S. G. Post, eds., Too Old for Health Care? Controversies in Medicine, Law, Economics, and Ethics (Baltimore: Johns Hopkins University Press, 1991).
56. Whitehouse, Maurer, and Ballenger, Concepts of Alzheimer Disease, 206–7.
57. Medical Research Council, Senile and Presenile Dementias: A Report of the MRC Subcommittee, Compiled by W. A. Lishman (London: Medical Research Council, 1977).
58. Patrick Fox, “The Role of the Concept of Alzheimer Disease,” in Whitehouse, Maurer, and Ballenger, Concepts of Alzheimer Disease, 209–33.
59. M. J. Delvecchio Good, B. J. Good, C. Schaffer, and S. E. Lind, “American Oncology and the Discourse on Hope,” Culture, Medicine, and Psychiatry 14, no. 1 (1990): 59–79.
60. Fox, “From Senility to Alzheimer Disease”; Claudia Chaufan, Brooke Hollister, Jennifer Nazareno, and Patrick Fox, “Medical Ideology as a Double-Edged Sword: The Politics of Cure and Care in the Making of Alzheimer’s Disease,” Social Science & Medicine 74 (2012): 788–95.
61. Chaufan et al., “Medical Ideology.”
62. Lishman, “History of Research,” 50.
63. Ibid., 50–51.
64. As my colleague Allan Young puts it.
65. Lishman, “History of Research,” 52.
66. Martin Roth, “Dementia and Normal Aging of the Brain,” in Huppert, Brayne, and O’Conner, Dementia and Normal Aging, 57–76, 65.
67. Foucault, Birth of the Clinic.
68. See ibid., chap. 8.
69. Hacking, Taming of Chance. See also Georges Canguilhem, The Normal and the Pathological (New York: Zone Books, 1991).
70. Lock, Encounters with Aging.
71. Hacking, Taming of Chance, 164.
72. Canguilhem, Normal and the Pathological, 228.
73. David Snowdon, Aging with Grace: What the Nun Study Teaches Us about Leading Longer, Healthier and More Meaningful Lives (New York: Bantam Books, 2001).
74. R. H. Swartz, S. E. Black, and P. St George-Hyslop, “Apolipoprotein E and Alzheimer’s Disease: A Genetic, Molecular and Neuroimaging Review,” Canadian Journal of Neurological Sciences 26, no. 2 (1999): 77–88.
75. David Snowdon, “Aging and Alzheimer Disease: Lessons from the Nun Study,” The Gerontologist 35 (1997): 150–56, 150.
76. George M. Savva, Stephen B. Wharton, Paul G. Ince, Gillian Forster, Fiona E. Matthews, and Carol Brayne, “Age, Neuropathology, and Dementia,” New England Journal of Medicine 360, no. 22 (2009): 2302–9, 2306.
77. Ibid., 2308.
78. Carol Brayne and Paul Calloway, “Normal Ageing, Impaired Cognitive Function, and Senile Dementia of the Alzheimer’s Type: A Continuum?,” The Lancet 331 (1988): 1265–67.
79. Julie A. Schneider, Zoe Arvanitakis, Sue E. Leurgans, and David A. Bennett, “The Neuropathology of Probable Alzheimer Disease and Mild Cognitive Impairment,” Annals of Neurology 66, no. 2 (2009): 200–208; Eric E. Smith and Steven M. Greenberg, “Beta-Amyloid, Blood Vessels and Brain Function,” Stroke 40, no. 7 (2009): 2601–6; Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study, “Pathological Correlates of Late-Onset Dementia in a Multicentre, Community-Based Population in England and Wales,” The Lancet 357 (2001): 169–75.
80. Howard A. Crystal, Dennis Dickson, Peter Davies, David Masur, Ellen Grober, and Richard B. Lipton, “The Relative Frequency of ‘Dementia of Unknown Etiology’ Increases with Age and Is Nearly 50% in Nonagenarians,” Archives of Neurology 57, no. 5 (2000): 713–19.
81. Carol F. Lippa and John C. Morris, “Alzheimer Neuropathology in Nondemented Aging Keeping Mind over Matter,” Neurology 66, no. 12 (2006): 1801–2.
82. Richards and Brayne, “What Do We Mean?”
83. Ibid., 865.
84. Ibid., 866.
85. Robert N. Butler, Richard A. Miller, Daniel Perry, Bruce A. Carnes, T. Franklin Williams, Christine Cassel, Jacob Brody, et al., “New Model of Health Promotion and Disease Prevention for the 21st Century,” British Medical Journal 337 (2008): a399.
86. Tiago Moreira and Paolo Palladino, “Ageing between Gerontology and Biomedicine,” BioSocieties 4, no. 4 (2009): 349–65, 351–52.
87. House of Lords, Science and Technology Committee: 6th Report (London: Parliament, 2006), http://www.publications.parliament.uk/pa/ld200506/ldselect/ldsctech/146/14603.htm.
88. Moreira and Palladino, “Ageing between Gerontology and Biomedicine,” 351–52.
89. Tom Kirkwood, Time of Our Lives: The Science of Human Aging (Oxford: Oxford University Press, 1999), cited in House of Lords, Science and Technology Committee; see also Moreira and Palladino, “Ageing between Gerontology and Biomedicine,” 363.
Chapter 2
Striving to Standardize Alzheimer Disease
1. Zaven Khachaturian, “Plundered Memories,” The Sciences 37, no. 4 (1997): 20–23.
2. Charles E. Rosenberg, “The Tyranny of Diagnosis: Specific Entities and Individual Experience,” Milbank Quarterly 80, no. 2 (2002): 237–60, 237.
3. Ibid., 240.
4. See also Marc Berg, Rationalizing Medical Work: Decision-Support Techniques and Medical Practices (Cambridge, Mass.: MIT Press, 1997); N. A. Christakis, “The Ellipsis of Prognosis in Modern Medical Thought,” Social Science & Medicine 44, no. 3 (1997): 301–15; Lock and Nguyen, Anthropology of Biomedicine; Harry M. Marks, The Progress of Experiment: Science and Therapeutic Reform in the United States, 1900–1990 (Cambridge: Cambridge University Press, 1997).
5. Aimee Pasqua Borazanci, Meghan K. Harris, Robert N. Schwendimann, Eduardo Gonzalez-Toledo, Amir H. Maghzi, Masoud Etemadifar, Nadejda Alekseeva, James Pinkston, Roger E. Kelley, and Alireza Minagar, “Multiple Sclerosis: Clinical Features, Pathophysiology, Neuroimaging and Future Therapies,” Future Neurology 4, no. 2 (2009): 229–46.
6. In medicine the concept of sensitivity measures the percentage of sick people correctly identified as having the condition in question, whereas specificity measures the proportion of negatives correctly identified, that is, the percentage of healthy people who are correctly identified as not having the condition.
7. The neuropathologist in charge of the brain bank located at one of the teaching hospitals of McGill University informed me that this is the case in Montréal.
8. See also Siddhartha Mukherjee, The Emperor of All Maladies: A Biography of Cancer (New York: Scribner, 2010).
9. Canadian Study of Health and Aging Working Group, “The Incidence of Dementia in Canada,” Neurology 55, no. 1 (2000): 66–73.
10. Kathleen M. Hayden, Peter P. Zandi, Constantine G. Lyketsos, Ara S. Khachaturian, Lori A. Bastian, Gene Charoonruk, JoAnn T. Tschanz, et al., “Vascular Risk Factors for Incident Alzheimer Disease and Vascular Dementia: The Cache County Study,” Alzheimer Disease & Associated Disorders 20, no. 2 (2006): 93–100; David A. Bennett, Philip L. De Jager, Sue E. Leurgans, and Julie A. Schneider, “Neuropathologic Intermediate Phenotypes Enhance Association to Alzheimer Susceptibility Alleles,” Neurology 72, no. 17 (2009): 1495–1503; Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study, “Pathological Correlates.”
11. See Carol Brayne, “Research and Alzheimer’s Disease: An Epidemiological Perspective,” Psychological Medicine 23, no. 2 (1993): 287–96 and Carol Brayne and Daniel Davis, “Making Alzheimer’s and Dementia Research Fit for Populations,” The Lancet 380 (2012): 1441–43.
12. Zaven S. Khachaturian, “Diagnosis of Alzheimer’s Disease,” Archives of Neurology 42, no. 11 (1985): 1097–1105.
13. The Mini-Mental State Examination is the most widely used standardized instrument in the world designed to screen for what is known as “cognitive impairment.” It was created in 1975 and has been translated into ten languages. It is described as “mini” because it was reduced in size from earlier tests and is not designed to assess mood or psychological states. The test, which is rarely administered in its full form and usually takes about ten minutes or so to complete, has been criticized by some as too long and others as too brief. An updated and revised version was made available in 2010. Psychological Assessment Resources has a copyright on the test, which can be bought today as an Android phone application. It is recommended not only for use by general practitioners, psychiatrists, and neurologists, but also for personal and home use. See, M. F. Folstein, S. E. Folstein, and P. R. McHugh, “ ‘Mini-mental State’: A Practical Method for Grading the Cognitive State of Patients for the Clinician,” Journal of Psychiatric Research 12, no. 3 (1975): 189–98; E. L. Teng and H. C. Chui, “The Modified Mini-Mental State (3MS) Examination,” Journal of Clinical Psychiatry 48, no. 8 (1987): 314–18.
14. T. Erkinjuntti, T. Ostbye, R. Steenhuis, and V. Hachinski, “The Effect of Different Diagnostic Criteria on the Prevalence of Dementia,” New England Journal of Medicine 337, no. 23 (1997): 1667–74.
15. Janice E. Graham, Kenneth Rockwood, B. Lynn Beattie, Ian McDowell, Robin Eastwood, and Serge Gauthier, “Standardization of the Diagnosis of Dementia in the Canadian Study of Health and Aging,” Neuroepidemiology 15, no. 5 (1996): 246–56; Z. Nagy, M. M. Esiri, K. A. Jobst, et al., “The Effects of Additional Pathology on the Cognitive Deficit in Alzheimer Disease,” Journal of Neuropathology & Experimental Neurology 56 (1997): 163–70; K. Ritchie, D. Leibovici, B. Lessert, and J. Touchon, “A Typology of Sub-clinical Senescent Cognitive Disorder.” British Journal of Psychiatry 168 (1966): 470–76; Gustavo C. Román and Donald R. Royall, “Executive Control Function: A Rational Basis for the Diagnosis of Vascular Dementia,” Alzheimer Disease & Associated Disorders 13 (1999): S4–S8.
16. Graham et al., “Standardization of the Diagnosis.”
17. See Danny George and Peter Whitehouse, “The Classification of Alzheimer Disease and Mild Cognitive Impairment,” in Ballenger et al., Treating Dementia, 5–24.
18. Fadi Massoud, Gayatri Devi, Yaakov Stern, Arlene Lawton, James E. Goldman, Yan Liu, Steven S. Chin, and Richard Mayeux, “A Clinicopathological Comparison of Community-Based and Clinic-Based Cohorts of Patients with Dementia,” Archives of Neurology 56, no. 11 (1999): 1368–73.
19. C. Duyckaerts, P. Delaère, J.-J. Hauw, A. L. Abbamondi-Pinto, S. Sorbi, I. Allen, J. P. Brion, et al., “Rating of the Lesions in Senile Dementia of the Alzheimer Type: Concordance between Laboratories. A European Multicenter Study under the Auspices of EURAGE,” Journal of the Neurological Sciences 97, nos. 2–3 (1990): 295–323.
20. John V. Bowler, David G. Munoz, Harold Merskey, and Vladimir Hachinski, “Fallacies in the Pathological Confirmation of the Diagnosis of Alzheimer’s Disease,” Journal of Neurology, Neurosurgery & Psychiatry 64, no. 1 (1998): 18–24.
21. C. J. Gilleard, “Is Alzheimer’s Disease Preventable? A Review of Two Decades of Epidemiological Research,” Aging and Mental Health 4 (2000): 101–18, 102.
22. Ibid., 102; see also S. S. Erlich and R. L. Davis, “Alzheimer’s Disease in the Very Aged,” Journal of Neuropathology & Experimental Neurology 39, no. 3 (1980): 352–54; H. M. Wisniewski, A. Rabe, W. Silverman, and W. Zigman, “Neuropathological Diagnosis of Alzheimer Disease: A Survey of Current Practices,” Alzheimer Disease & Associated Disorders 2, no. 4 (1988): 396–414.
23. John C. Morris, “The Relationship of Plaques and Tangles to Alzheimer Disease Phenotype,” in Pathobiology of Alzheimer’s Disease, ed. Alison M. Goate and Frank Ashall (London: Academic Press, 1995), 193–218.
24. John C. S. Breitner, “Dementia—Epidemiological Considerations, Nomenclature, and a Tacit Consensus Definition,” Journal of Geriatric Psychiatry and Neurology 19, no. 3 (2006): 129–36, 136.
25. Jesse F. Ballenger, “DSM-V: Continuing the Confusion about Aging, Alzheimer’s and Dementia,” H-madness: History of Psychiatry, March 19, 2010, http://historypsychiatry.com/2010/03/19/dsm-v-continuing-the-confusion-about-aging-alzheimer%e2%80%99s-and-dementia/.
26. Carol Brayne, “The Elephant in the Room—Healthy Brains in Later Life, Epidemiology and Public Health,” Nature Reviews Neuroscience 8, no. 3 (2007): 233–39.
27. Catalina Amador-Ortiz, Wen-Lang Lin, Zeshan Ahmed, David Personett, Peter Davies, Ranjan Duara, Neill R. Graff-Radford, Michael L. Hutton, and Dennis W. Dickson, “TDP-43 Immunoreactivity in Hippocampal Sclerosis and Alzheimer’s Disease,” Annals of Neurology 61, no. 5 (2007): 435–45.
28. Khachaturian, “Plundered Memories,” 21.
29. Brayne and Davis, “Making Alzheimer’s and Dementia Research Fit,” 1441.
30. Whitehouse and George, Myth of Alzheimer’s.
31. John A. Hardy and Gerald A. Higgins, “Alzheimer’s Disease: The Amyloid Cascade Hypothesis,” Science 256 (1992): 184–85.
32. Ibid., 184.
33. Ibid., 184, emphasis added.
34. Ballenger et al., Treating Dementia; see also Whitehouse and George, Myth of Alzheimer’s, esp. chap. 5, “Waiting for Godot.”
35. George Perry, Akihiko Nunomura, Arun K. Raina, and Mark A. Smith, “Amyloid-β Junkies,” The Lancet 355 (2000): 757.
36. John A. Hardy and Dennis J. Selkoe, “The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics,” Science 297 (2002): 353–56.
37. See, for example, Stephanie J. Soscia, James E. Kirby, Kevin J. Washicosky, Stephanie M. Tucker, Martin Ingelsson, Bradley Hyman, Mark A. Burton, et al., “The Alzheimer’s Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide,” PLoS ONE 5, no. 3 (2010): e9505.
38. Amritpal Mudher and Simon Lovestone, “Alzheimer’s Disease—Do Tauists and Baptists Finally Shake Hands?,” Trends in Neurosciences 25, no. 1 (2002): 22–26.
39. Ibid.
40. Ibid., 25.
41. Virginia M.-Y. Lee, “Tauists and Baptists United—Well Almost!,” Science 293 (2001): 1446–47.
42. Benjamin Yang, “A United Disease Theory Brings Two Groups of Alzheimer’s Disease Researchers Together,” Discovery Medicine, May 10, 2009, http://www.discoverymedicine.com/Benjamin-Yang/2009/05/10/a-united-disease-theory-brings-two-groups-of-alzheimer-researchers-together/.
43. The Editors, “Alzheimer Disease,” Nature Medicine 12, no. 7 (2006): 746–84.
44. Apoorva Mandavilli, “The Amyloid Code,” Nature Medicine 12, no. 7 (2006): 747–51.
45. Ibid., 747.
46. Edith G. McGeer and Pat L. McGeer, “Neuroinflammation: Alzheimer Disease, and Other Aging Disorders,” in Pharmacological Mechanisms in Alzheimer’s Therapeutics, ed. A. C. Cuello (New York: Springer, 2007), 149–66.
47. C.P.J. Maury, “The Emerging Concept of Functional Amyloid,” Journal of Internal Medicine 265, no. 3 (2009): 329–34.
48. Rudy J. Castellani, Hyoung-gon Lee, Sandra L. Siedlak, Akihiko Nunomura, Takaaki Hayashi, Masao Nakamura, Xiongwei Zhu, George Perry, and Mark A. Smith, “Reexamining Alzheimer’s Disease: Evidence for a Protective Role for Amyloid-β Protein Precursor and Amyloid-β,” Journal of Alzheimer’s Disease 18, no. 2 (2009): 447–52.
49. Jesse F. Ballenger, “Necessary Interventions: Antidementia Drugs and Heightened Expectations for Aging in Modern American Cultures and Society,” in Ballenger et al., Treating Dementia, 189–209, 199.
50. Ibid., 201.
51. Tiago Moreira, “Truth and Hope in Drug Development and Evaluation in Alzheimer Disease,” in Ballenger et al., Treating Dementia, 210–30.
52. See, for example, Elaine K. Perry, Peter H. Gibson, Garry Blessed, Robert H. Perry, and Bernard E. Tomlinson, “Neurotransmitter Enzyme Abnormalities in Senile Dementia. Choline Acetyltransferase and Glutamic Acid Decarboxylase Activities in Necropsy Brain Tissue,” Journal of the Neurological Sciences 34, no. 2 (1977): 247–65; Elaine K. Perry, Robert H. Perry, Peter H. Gibson, Garry Blessed, and Bernard E. Tomlinson, “A Cholinergic Connection between Normal Aging and Senile Dementia in the Human Hippocampus,” Neuroscience Letters 6, no. 1 (1977): 85–89.
53. Peter J. Whitehouse, Donald L. Price, Arthur W. Clark, Joseph T. Coyle, and Mahlon R. DeLong, “Alzheimer Disease: Evidence for Selective Loss of Cholinergic Neurons in the Nucleus Basalis,” Annals of Neurology 10, no. 2 (1981): 122–26.
54. Ballenger, “Necessary Interventions”; Moreira, “Truth and Hope”; Peter J. Whitehouse, “Can We Fix This with a Pill? Qualities of Life and the Aging Brain,” in Ballenger et al., Treating Dementia, 168–82.
55. Alison Abbott, “The Plaque Plan,” Nature 456 (2008): 161–64.
56. Robert Langreth, “Eli Lilly Alzheimer’s Disease Failure Bolsters Amyloid Theory Skeptics—Forbes,” Forbes, August 17, 2010, http://www.forbes.com/sites/robertlangreth/2010/08/17/eli-lilly-alzheimers-failure-bolsters-skeptics-on-amyloid-theory/.
57. Clive Holmes, Delphine Boche, David Wilkinson, Ghasem Yadegarfar, Vivienne Hopkins, Anthony Bayer, Roy W. Jones, et al., “Long-Term Effects of Aβ42 Immunisation in Alzheimer’s Disease: Follow-Up of a Randomised, Placebo-Controlled Phase I Trial,” The Lancet 372 (2008): 216–23, 222.
58. Ballenger, Self, Senility, and Alzheimer’s Disease, 99.
59. See, for example, I. J. Bennett, E. J. Golob, E. S. Parker, and A. Starr, “Memory Evaluation in Mild Cognitive Impairment Using Recall and Recognition Tests,” Journal of Clinical and Experimental Neuropsychology 28, no. 8 (2006): 1408–22.
60. Bruno Dubois, Howard H. Feldman, Claudia Jacova, Steven T. DeKosky, Pascale Barberger-Gateau, Jeffrey Cummings, André Delacourte, et al., “Research Criteria for the Diagnosis of Alzheimer’s Disease: Revising the NINCDS-ADRDA Criteria,” The Lancet Neurology 6, no. 8 (2007): 734–46.
61. Ibid., 734.
62. Ibid., 743.
63. Abbott, “The Plaque Plan.”
64. Ibid., 163.
65. Ibid., 164.
66. John A. Hardy, “The Amyloid Cascade Hypothesis Has Misled the Pharmaceutical Industry,” Biochemical Society Transactions 39, no. 4 (2011): 920–23.
Chapter 3
Paths to Alzheimer Prevention
1. John Bayley, Iris: A Memoir of Iris Murdoch (London: Abacus, 2002), 216–17.
2. Patricia Jasen, “Breast Cancer and the Language of Risk, 1750–1950,” Social History of Medicine 15, no. 1 (2002): 17–43.
3. François Ewald, “Insurance and Risk,” in The Foucault Effect: Studies in Governmentality, edited by Graham Burchell, Colin Gordon, and Peter Miller (Hemel Hempstead: Harvester Wheatsheaf, 1991), 197–210, see 208.
4. Ibid., 208.
5. Mary Douglas, “Risk as a Forensic Resource,” Daedalus 119, no. 4 (1990): 1–16.
6. Michel Foucault, The History of Sexuality, vol. 1 (New York: Vintage Books, 1980).
7. Robert Castel, “From Dangerousness to Risk,” in Burchell, Gordon, and Miller, The Foucault Effect, 281–98, see 289.
8. It is my understanding that the terms “corporeal” and “embodied” risk were first coined by Anne M. Kavanagh and Dorothy H. Broom, “Embodied Risk: My Body, Myself?,” Social Science & Medicine 46, no. 3 (1998): 437–44.
9. Mark Schiffman, Nicolas Wentzensen, Sholom Wacholder, Walter Kinney, Julia C. Gage, and Philip E. Castle, “Human Papillomavirus Testing in the Prevention of Cervical Cancer,” Journal of the National Cancer Institute 103, no. 5 (2011): 368–83; Marc B. Garnick, “The Great Prostate Cancer Debate,” Scientific American 306, no. 2 (2012): 38–43.
10. See http://medical-dictionary.thefreedictionary.com/biomarker.
11. Of course, in connection with reproduction, insurance companies may seek to assign responsibility to individuals for passing on their so-called “defective” genes, and in the days when eugenics was practiced genes were loaded with moral valence. As we will see, especially in chapter 6, the more that is uncovered about gene structure and function in the postgenomic era, the more it becomes difficult to associate genes and human responsibility.
12. Pseudonyms were given to all interviewed patients and family members.
13. Also known as the Verdun Protestant Hospital, the Protestant Insane Asylum initially was a philanthropic institution set in farmland, which the patients tended. Today known as the Douglas Mental Health University Institute or, more informally, the Douglas, patients assist with hospital administration and care of its beautiful grounds.
14. Jeremia Heinik, “V. A. Kral and the Origins of Benign Senescent Forgetfulness and Mild Cognitive Impairment,” International Psychogeriatrics 22, no. 3 (2010): 395–402, 398.
15. James Golomb, Alan Kluger, and Steven H. Ferris, “Mild Cognitive Impairment: Historical Development and Summary of Research,” Dialogues in Clinical Neuroscience 6, no. 4 (2004): 351–67, 352.
16. Glenn E. Smith, Ronald C. Petersen, Joseph E. Parisi, Robert J. Ivnik, Emre Kokmen, Eric G. Tangalos, and Stephen Waring, “Definition, Course, and Outcome of Mild Cognitive Impairment,” Aging, Neuropsychiatry and Cognition 3 (1996): 141–47.
17. Ronald C. Petersen, Rachelle Doody, Alexander Kurz, Richard C. Mohs, John C. Morris, Peter V. Rabins, Karen Ritchie, Martin Rossor, Leon Thal, and Bengt Winblad, “Current Concepts in Mild Cognitive Impairment,” Archives of Neurology 58, no. 12 (2001): 1985–92, 1991.
18. Cited in Tiago Moreira, Carl May, and John Bond, “Regulatory Objectivity in Action Mild Cognitive Impairment and the Collective Production of Uncertainty,” Social Studies of Science 39, no. 5 (2009): 665–90, 205 of the FDA report, www.fda.gov/ohrms/dockets/AC/01/transcripts/3724t1.pdf.
19. Moreira, May, and Bond, “Regulatory Objectivity,” 684.
20. Ronald C. Petersen, ed., Mild Cognitive Impairment: Aging to Alzheimer’s Disease (Oxford: Oxford University Press, 2003), 12.
21. Moreira, May, and Bond, “Regulatory Objectivity,” 685.
22. Ibid., 672.
23. B. Winblad, K. Palmer, M. Kivipelto, V. Jelic, L. Fratiglioni, L.-O. Wahlund, A. Nordberg, et al., “Mild Cognitive Impairment—Beyond Controversies, towards a Consensus: Report of the International Working Group on Mild Cognitive Impairment,” Journal of Internal Medicine 256, no. 3 (2004): 240–46.
24. Moreira, May, and Bond, “Regulatory Objectivity,” 666. Here Moreira and colleagues follow the lead of Keating and Cambrosio, Biomedical Platforms.
25. Serge Gauthier, Barry Reisberg, Michael Zaudig, Ronald C. Petersen, Karen Ritchie, Karl Broich, Sylvie Belleville, et al., “Mild Cognitive Impairment,” Lancet 367 (2006): 1262–70.
26. Ibid., 1268.
27. “Amnestic” means a partial or total loss of memory. Amnestic cognitive impairment is today the most commonly diagnosed form of MCI.
28. Ronald C. Petersen, “The Current Status of Mild Cognitive Impairment—What Do We Tell Our Patients?,” Nature Clinical Practice Neurology 3, no. 2 (2007): 60–61, 60.
29. Ibid., 61.
30. Ronald C. Petersen, “Mild Cognitive Impairment Is Relevant,” Philosophy, Psychiatry, & Psychology 13, no. 1 (2006): 45–49.
31. Peter J. Whitehouse, “Mild Cognitive Impairment—A Confused Concept?,” Nature Clinical Practice Neurology 3, no. 2 (2007): 62–63, 63.
32. Ziad S. Nasreddine, Natalie A. Phillips, Valérie Bédirian, Simon Charbonneau, Victor Whitehead, Isabelle Collin, Jeffrey L. Cummings, and Howard Chertkow, “The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool for Mild Cognitive Impairment,” Journal of the American Geriatric Society 53, no. 4 (2005): 695–99.
33. Memory clinics are springing up in the United Kingdom, even though the specialty of old age psychiatry takes primary responsibility for most cases of early-onset dementia there. In France there are as many as 150 memory clinics staffed by psychiatrists. Approaches to MCI and the early stages of dementia vary considerably among countries depending in large part on which clinical specialty, neurology or psychiatry, takes primary responsibility.
34. This research underwent an ethics clearance at McGill University and was supported by the director of the memory clinic where the interviews were conducted. All interviewed patients signed an informed consent form before the interview commenced and were at liberty to terminate the interview at any time. As noted above, pseudonyms are used throughout when citing interviews.
35. It has been argued that MoCA is superior to the MMSE in testing for the “intermediate category” known as MCI, and that there are no other screening tools that reliably and quickly distinguish those with MCI from “normal control research subjects”; see Nasreddine et al., “Montreal Cognitive Assessment.”
36. Erin Andersen, “Isolated by Affliction, Isolated by Language,” Globe and Mail, December 18, 2010.
37. Gina Kolata, “Finding Suggests New Target for Alzheimer’s Drugs,” New York Times, September 1, 2010.
38. Gina Kolata, “New Scan May Spot Alzheimer’s,” New York Times, July 13, 2010.
39. Gina Kolata, “In Spinal-Fluid Test, an Early Warning on Alzheimer’s,” New York Times, August 9, 2010.
40. Arthur Brisbane, “The Trouble with Absolutes,” New York Times, July 13, 2010, Public Editor’s Journal sec., http://publiceditor.blogs.nytimes.com/2010/08/24/the-trouble-with-absolutes/.
41. Alliance for Human Research Protection, “NY Times Corrects Gina Kolata Re: Alzheimer’s,” September 16, 2010, http://www.ahrp.org/cms/content/view/726/1/. See also Health News Review, http://www.healthnewsreview.org/2012/06/historian-writes-on-medical-journalism-in-the-war-on-alzheimers, and Science Journalism Tracker, http://ksj.mit.edu/tracker/2011/01/ny-times-strangely-quiet-alzheimers-test.
42. Gina Kolata, “Guidelines Seek Early Detection of Alzheimer’s,” New York Times, July 14, 2010, http://query.nytimes.com/gst/fullpage.html.
43. Ibid.
44. Gina Kolata, “Drug Trials Test Bold Plan to Slow Alzheimer’s,” New York Times, July 16, 2010.
45. Gina Kolata, “Insights Give New Hope for New Attack on Alzheimer’s,” New York Times, December 13, 2010.
46. Quoted in Gina Kolata, “Early Tests for Alzheimer’s Pose Diagnosis Dilemma,” New York Times, December 17, 2010.
47. Gina Kolata, “F.D.A. Sees Promise in Alzheimer’s Imaging Drug,” New York Times, January 20, 2011.
48. Bruno Dubois, Howard H. Feldman, Claudia Jacova, Jeffrey L. Cummings, Steven T. Dekosky, Pascale Barberger-Gateau, André Delacourte, et al., “Revising the Definition of Alzheimer’s Disease: A New Lexicon,” The Lancet Neurology 9, no. 11 (2010): 1118–27, 1118.
49. Ibid., 1118.
50. Ibid., 1124–25.
51. Ibid., 1125.
Chapter 4
Embodied Risk Made Visible
1. John Berger, Ways of Seeing (London: Penguin, 1972), 7.
2. Sanjay W. Pimplikar, “Alzheimer’s Isn’t Up to the Tests,” New York Times, July 19, 2010, Opinion sec., http://www.nytimes.com/2010/07/20/opinion/20pimplikar.html.
3. Garnick, “Great Prostate Cancer Debate.”
4. Whitehouse and George, Myth of Alzheimer’s, 4.
5. Bradley T. Hyman, Creighton H. Phelps, Thomas G. Beach, Eileen H. Bigio, Nigel J. Cairns, Maria C. Carrillo, Dennis W. Dickson, et al., “National Institute on Aging–Alzheimer’s Association Guidelines for the Neuropathologic Assessment of Alzheimer’s Disease,” Alzheimer’s & Dementia 8, no. 1 (2012): 1–13.
6. See Clifford R. Jack, Jr., Marilyn S. Albert, David S. Knopman, Guy M. McKhann, Reisa A. Sperling, Maria C. Carrillo, Bill Thies, and Creighton H. Phelps, “Introduction to the Recommendations from the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease,” Alzheimer’s & Dementia 7, no. 3 (2011): 257–62, 258.
7. See ibid., 259.
8. For the guidelines in connection with the new neuropathologic assessment of Alzheimer disease, see Hyman et al., “National Institute on Aging.”
9. See Jack et al., “Introduction to the Recommendations.”
10. See ibid.
11. Harald Hampel, Simone Lista, and Zaven S. Khachaturian, “Development of Biomarkers to Chart All Alzheimer’s Disease Stages: The Royal Road to Cutting the Therapeutic Gordian Knot,” Alzheimer’s & Dementia 8, no. 4 (2012): 312–36.
12. Thomas Kuhn, The Structure of Scientific Revolutions (Chicago: University of Chicago Press, 1962).
13. Ibid. See 50th Anniversary ed. (Chicago: University of Chicago Press, 2012), 91.
14. Ian Hacking, “Introduction,” in Kuhn, The Structure of Scientific Revolutions, 50th Anniversary ed., vii–xxxvii.
15. Reisa A. Sperling, Paul S. Aisen, Laurel A. Beckett, David A. Bennett, Suzanne Craft, Anne M. Fagan, Takeshi Iwatsubo, et al., “Toward Defining the Preclinical Stages of Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease,” Alzheimer’s & Dementia 7, no. 3 (2011): 280–92, 282.
16. Ibid., 282.
17. Ibid., 282.
18. Ibid., 283.
19. Ibid., 284.
20. Ibid., 287.
21. John C. Morris, “Revised Criteria for Mild Cognitive Impairment May Compromise the Diagnosis of Alzheimer Disease Dementia,” Archives of Neurology 69, no. 6 (2012): 700–708, 700.
22. Ibid., 700.
23. Ibid., 705.
24. Ibid., 706.
25. Leonard F. M. Scinto and Kirk R. Daffner, eds., The Early Diagnosis of Alzheimer’s Disease (Totowa, N.J.: Humana Press, 2000).
26. A. Zara Herskovits and John H. Growdon, “Sharpen That Needle,” Archives of Neurology 67, no. 8 (2010): 918–20, 918.
27. Geert De Meyer, Fred Shapiro, Hugo Vanderstichele, Eugeen Vanmechelen, Sebastiaan Engelborghs, Peter Paul De Deyn, Els Coart, et al., “Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People,” Archives of Neurology 67, no. 8 (2010): 949–56, 949.
28. Ibid., 954, emphasis added.
29. Haiqun Lin, Charles E. McCulloch, Bruce W. Turnbull, Elizabeth H. Slate, and Larry C. Clark, “A Latent Class Mixed Model for Analysing Biomarker Trajectories with Irregularly Scheduled Observations,” Statistics in Medicine 19, no. 10 (2000): 1303–18.
30. William E. Klunk, Henry Engler, Agneta Nordberg, Yanming Wang, Gunnar Blomqvist, Daniel P. Holt, Mats Bergström, et al., “Imaging Brain Amyloid in Alzheimer’s Disease with Pittsburgh Compound-B,” Annals of Neurology 55, no. 3 (2004): 306–19, 317.
31. G. G. Glenner, “Alzheimer’s Disease: The Commonest Form of Amyloidosis,” Archives of Pathology & Laboratory Medicine 107, no. 6 (1983): 281–82.
32. Kerryn E. Pike, Greg Savage, Victor L. Villemagne, Steven Ng, Simon A. Moss, Paul Maruff, Chester A. Mathis, William E. Klunk, Colin L. Masters, and Christopher C. Rowe, “Β-amyloid Imaging and Memory in Non-demented Individuals: Evidence for Preclinical Alzheimer’s Disease,” Brain 130, no. 11 (2007): 2837–44.
33. Howard Jay Aizenstein, Robert D. Nebes, Judith A. Saxton, Julie C. Price, Chester A. Mathis, Nicholas D. Tsopelas, Scott K. Ziolko, et al., “Frequent Amyloid Deposition without Significant Cognitive Impairment among the Elderly,” Archives of Neurology 65, no. 11 (2008): 1509–17.
34. Kerim Munir, Suzanne Coulter, John H. Growdon, Ann MacDonald, Patrick J. Skerrett, and Jane A. Leopold, “How to Solve Three Puzzles,” Newsweek 151, no. 3 (January 21, 2008): 64–66, 65.
35. M. A. Mintun, G. N. Larossa, Y. I. Sheline, C. S. Dence, S. Y. Lee, R. H. Mach, W. E. Klunk, C. A. Mathis, S. T. DeKosky, and J. C. Morris, “[11C]PIB in a Nondemented Population: Potential Antecedent Marker of Alzheimer Disease,” Neurology 67, no. 3 (2006): 446–52; Clifford R. Jack, Val J. Lowe, Stephen D. Weigand, Heather J. Wiste, Matthew L. Senjem, David S. Knopman, Maria M. Shiung, et al., “Serial PIB and MRI in Normal, Mild Cognitive Impairment and Alzheimer’s Disease: Implications for Sequence of Pathological Events in Alzheimer’s Disease,” Brain 132, no. 5 (2009): 1355–65, 1363.
36. Sperling, “Toward Defining the Preclinical Stages of Alzheimer’s Disease,” 282.
37. Jack et al., “Serial PIB and MRI,” 1363.
38. Ibid., 1363.
39. C. M. Clark and J. A. Schneider, “Use of Florbetapir-PET for Imaging Β-amyloid Pathology,” Journal of the American Medical Association 305, no. 3 (2011): 275–83.
40. Ibid., 280.
41. Monique Breteler, “Mapping Out Biomarkers for Alzheimer Disease,” Journal of the American Medical Association 305, no. 3 (2011): 304–5, 304.
42. Ibid., 305.
43. Ibid., 305.
44. Michael Carome and Sidney Wolfe, “Florbetapir-PET Imaging and Postmortem Β-amyloid Pathology,” Journal of the American Medical Association 305, no. 18 (2011): 1857–58.
45. Joseph Dumit, “Critically Producing Brain Images of Mind,” in Critical Neuroscience: A Handbook of the Social and Cultural Contexts of Neuroscience, ed. Suparna Choudhury and Jan Slaby (Chichester, UK: Wiley-Blackwell, 2012), 195–226, 222.
46. W. J. Jagust, S. M. Landau, L. M. Shaw, J. Q. Trojanowski, R. A. Koeppe, E. M. Reiman, N. L. Foster, et al., “Relationships between Biomarkers in Aging and Dementia,” Neurology 73, no. 15 (2009): 1193–99.
47. Mark Mintun stated, “[M]ultiple papers now exist that show that subjects who appear cognitively normal but are shown to have amyloid in their brain by PET scanning, have statistically decreased cognitive or memory function compared to subjects who do have amyloid.” However, he added, these studies are cross-sectional and do not predict the future. Mintun regarded a paper by Storandt et al., in which it was noted that the PIB-positive group had been going downward on certain longitudinal cognitive measures, as highly relevant. The only caveat, Mintun added, “was that most of the longitudinal data was done prior to the PET PIB amyloid scan (as part of these subject’s long-term commitment to the longitudinal research studies). And so it is not a real prospective study.” See Martha Storandt, Mark A. Mintun, Denise Head, and John C. Morris, “Cognitive Decline and Brain Volume Loss Are Signatures of Cerebral Aβ Deposition Identified with PIB,” Archives of Neurology 66, no. 12 (2009): 1476–81. A second source noted by Mintun is by Morris et al., in which it was shown that cognitively normal elderly individuals do “advance” to dementia at a higher rate if they are positive on PET PIB amyloid scans. However, the caveat with this study, Mintun stated, “is that the follow-up was very short and the number of people who actually became cognitively impaired was very small.” See John C. Morris, Catherine M. Roe, Elizabeth A. Grant, Denise Head, Martha Storandt, Alison M. Goate, Anne M. Fagan, David M. Holtzman, and Mark A. Mintun, “Pittsburgh Compound B Imaging and Prediction of Progression from Cognitive Normality to Symptomatic Alzheimer Disease,” Archives of Neurology 66, no. 12 (2009): 1469–75.
48. F. C. Redlich, “The Concept of Health in Psychiatry,” in Explorations in Social Psychiatry, ed. Alexander H. Leighton, J. N. Clausen, and R. N. Wilson (New York: Basic Books, 1957), 138–64.
49. Zaven Khachaturian, “Perspective on the Alzheimer’s Disease Neuroimaging Initiative: Progress Report and Future Plans,” Alzheimer’s & Dementia 6, no. 3 (2010): 199–201, 201.
50. Zaven S. Khachaturian and Ara S. Khachaturian, “Prevent Alzheimer’s Disease by 2020: A National Strategic Goal,” Alzheimer’s & Dementia 5, no. 2 (2009): 81–84, 82.
51. Ibid., 84.
52. Michael W. Weiner, Paul S. Aisen, Clifford R. Jack Jr., William J. Jagust, John Q. Trojanowski, Leslie Shaw, Andrew J. Saykin, et al., “The Alzheimer’s Disease Neuroimaging Initiative: Progress Report and Future Plans,” Alzheimer’s & Dementia 6, no. 3 (2010): 202–11.
53. Ibid., 204.
54. Ibid., 204.
55. Ibid., 209.
56. Gina Kolata, “Rare Sharing of Data Led to Results on Alzheimer’s,” New York Times, August 12, 2010, Health/Research sec., http://www.nytimes.com/2010/08/13/health/research/13alzheimer.html.
57. Weiner et al., “Alzheimer’s Disease Neuroimaging Initiative,” 209.
58. Nikolas Rose, The Politics of Life Itself: Biomedicine, Power, and Subjectivity in the Twenty-First Century (Princeton: Princeton University Press, 2006), 192.
59. Simon Cohn, “Disrupting Images: Neuroscientific Representations in the Lives of Psychiatric Patients,” in Choudhury and Slaby, Critical Neuroscience, 179–94.
60. Julie A. Schneider, Zoe Arvanitakis, Woojeong Bang, and David A. Bennett, “Mixed Brain Pathologies Account for Most Dementia Cases in Community-Dwelling Older Persons,” Neurology 69, no. 24 (2007): 2197–2204; Carol Brayne, Blossom C. M. Stephan, and Fiona E. Matthews, “A European Perspective on Population Studies of Dementia,” Alzheimer’s & Dementia 7, no. 1 (2011): 3–9; Savva et al., “Age, Neuropathology, and Dementia.”
61. Khachaturian, “Plundered Memories,” 22.
62. Stephen Lunn, “End of Alzheimer’s Curse ‘a Decade Away,’ ” The Australian, September 19, 2001.
Chapter 5
Alzheimer Genes: Biomarkers of Prediction and Prevention
1. Michael Ignatieff, Scar Tissue (London: Chatto & Windus, 1993), 50.
2. Khachaturian, “Plundered Memories,” 21.
3. An autosomal dominant mutation inherited from one parent alone is sufficient to cause the condition in question. If one parent carries the mutation, there is, therefore, a 50 percent chance that the offspring will inherit the mutation.
4. A. Goate, M. C. Chartier-Harlin, M. Mullan, J. Brown, F. Crawford, L. Fidani, L. Giuffra, A. Haynes, N. Irving, and L. James, “Segregation of a Missense Mutation in the Amyloid Precursor Protein Gene with Familial Alzheimer’s Disease,” Nature 349 (1991): 704–6.
5. “Alzheimer’s Disease: Amyloid Precursor Protein—Good, Bad or Both?,” ScienceDaily, December 29, 2009, http://www.sciencedaily.com/releases/2009/10/091018171806.htm.
6. Andrea Tedde, Benedetta Nacmias, Monica Ciantelli, Paolo Forleo, Elena Cellini, Silvia Bagnoli, Carolina Piccini, Paolo Caffarra, Enrico Ghidoni, Marco Paganini, Laura Bracco, and Sandro Sorbi, “Identification of New Presenilin Gene Mutations in Early-Onset Familial Alzheimer Disease,” Archives of Neurology 60, no. 11 (2003): 1541–44.
7. L. Tilley, K. Morgan, and N. Kalsheker, “Genetic Risk Factors in Alzheimer’s Disease,” Molecular Pathology 51, no. 6 (1998): 293–304; I. Raiha, J. Kaprio, M. Koskenvuo, T. Rajala, and L. Sourander, “Alzheimer’s Disease in Finnish Twins,” Lancet 347 (1996): 573–78; L. E. Nee, R. Eldridge, T. Sunderland, C. B. Thomas, D. Katz, K. E. Thompson, H. Weingartner, H. Weiss, C. Julian, and R. Cohen, “Dementia of the Alzheimer Type: Clinical and Family Study of 22 Twin Pairs,” Neurology 37, no. 3 (1987): 359–63.
8. Carlos Cruchaga, Sumitra Chakraverty, Kevin Mayo, Francesco L. M. Vallania, Robi D. Mitra, Kelley Faber, Jennifer Williamson, Tom Bird, Ramon Diaz-Arrastia, Tatiana M. Foroud, Bradley F. Boeve, Neill R. Graff-Radford, Pamela St. Jean, Michael Lawson, Margaret G. Ehm, Richard Mayeux, and Alison M. Goate, “Rare Variants in APP, PSEN1 and PSEN2 Increase Risk for AD in Late-Onset Alzheimer’s Disease Families,” PLoS ONE 7, no. 2 (2012): e31039.
9. Bradley T. Hyman, “Alzheimer’s Disease or Alzheimer’s Diseases? Clues from Molecular Epidemiology,” Annals of Neurology 40, no. 2 (1996): 135–36.
10. Ibid., 136.
11. Gabriel García Márquez, One Hundred Years of Solitude (New York: HarperPerennial, 1991), 47.
12. “The Colombian Alzheimer’s Family Testing Possible Cures,” BBC News, May 19, 2011, Latin America & Caribbean sec., http://www.bbc.co.uk/news/world-latin-america-13428265.
13. Pam Belluck, “Alzheimer’s Stalks a Columbian Family,” New York Times, June 1, 2010, Health sec., http://www.nytimes.com/2010/06/02/health/02alzheimers.html.
14. “Colombian Alzheimer’s Family Testing.”
15. Belluck, “Alzheimer’s Stalks”; see also Pam Belluck and Salvador Rodriguez, “Hoping to Crack Alzheimer’s, Together as a Family,” New York Times, October 3, 2011, Health sec., http://www.nytimes.com/2011/10/04/health/04alzheimers.html.
16. Michele G. Sullivan, “Studies Take Aim at Groups at High Risk for Alzheimer’s,” WorldCare Clinical, March 21, 2011.
17. Julie Steenhuysen, “Roche Alzheimer’s Drug Picked for Major Test,” Reuters, May 15, 2012, http://www.reuters.com/article/2012/05/15/us-alzheimers-genentech-idUSBRE84E0UJ20120515.
18. Ibid.
19. Pam Belluck, “New Drug Trial Seeks to Stop Alzheimer’s Before It Starts,” New York Times, May 15, 2012, Health/Research sec., http://www.nytimes.com/2012/05/16/health/research/prevention-is-goal-of-alzheimers-drug-trial.html.
20. Office of Public Affairs, University of California, Santa Barbara, “Clinical Trials for Alzheimer’s Disease Preventative Drug to Begin Early 2013,” news release, May 21, 2012, http://www.ia.ucsb.edu/pa/display.aspx?pkey=2734.
21. Steenhuysen, “Roche Alzheimer’s Drug.”
22. Alex John London and Jonathan Kimmelman, “Justice in Translation: From Bench to Bedside in the Developing World,” The Lancet 372 (2008): 82–85.
23. Margaret Lock, “Interrogating the Human Genome Diversity Project,” Social Science & Medicine 39, no. 5 (1994): 603–6; Margaret Lock, “The Alienation of Body Tissue and the Biopolitics of Immortalized Cell Lines,” Body & Society 7, nos. 2–3 (2001): 63–91; Adriana Petryna, “Clinical Trials Offshored: On Private Sector Science and Public Health,” BioSocieties 2, no. 1 (March 2007): 21–40; Philip Mirowski and Robert Van Horn, “The Contract Research Organization and the Commercialization of Scientific Research,” Social Studies of Science 35, no. 4 (2005): 503–48; Prasanna Kumar Patra and Margaret Sleeboom-Faulkner, “Bionetworking: Experimental Stem Cell Therapy and Patient Recruitment in India,” Anthropology & Medicine 16, no. 2 (2009): 147–63.
24. Natalia Acosta-Baena, Diego Sepulveda-Falla, Carlos Mario Lopera-Gómez, Mario César Jaramillo-Elorza, Sonia Moreno, Daniel Camilo Aguirre-Acevedo, Amanda Saldarriaga, and Francisco Lopera, “Pre-dementia Clinical Stages in Presenilin 1 E280A Familial Early-Onset Alzheimer’s Disease: A Retrospective Cohort Study,” The Lancet Neurology 10, no. 3 (2011): 213–20.
25. John J. Mitchell, Annie Capua, Carol Clow, and Charles R. Scriver, “Twenty-Year Outcome Analysis of Genetic Screening Programs for Tay-Sachs and Beta-Thalassemia Disease Carriers in High Schools,” American Journal of Human Genetics 59, no. 4 (1996): 793–98; Stefan Beck and Jörg Niewöhner, “Translating Genetic Testing and Screening in Cyprus and Germany: Contingencies, Continuities, Ordering Effects and Bio-Cultural Intimacy,” in The Handbook of Genetics & Society: Mapping the New Genomic Era, ed. Paul Atkinson, Peter Glasner, and Margaret Lock (New York: Routledge, 2009), 76–93; Barbara Prainsack and Gil Siegal, “The Rise of Genetic Couplehood? A Comparative View of Premarital Genetic Testing,” BioSocieties 1, no. 1 (2006): 17–36; J. Ekstein and H. Katzenstein, “The Dor Yeshorim Story: Community-Based Carrier Screening for Tay-Sachs Disease,” Advances in Genetics 44 (2001): 297–310.
26. W. J. Strittmatter, D. Y. Huang, R. Bhasin, A. D. Roses, and D. Goldgaber, “Avid Binding of Beta A Amyloid Peptide to Its Own Precursor,” Experimental Neurology 122, no. 2 (1993): 327–34; E. H. Corder, A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell, G. W. Small, A. D. Roses, J. L. Haines, and M. A. Pericak-Vance, “Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer’s Disease in Late Onset Families,” Science 261 (1993): 921–23; A. M. Saunders, W. J. Strittmatter, D. Schmechel, P. H. George-Hyslop, M. A. Pericak-Vance, S. H. Joo, B. L. Rosi, J. F. Gusella, D. R. Crapper-MacLachlan, and M. J. Alberts, “Association of Apolipoprotein E Allele Epsilon 4 with Late-Onset Familial and Sporadic Alzheimer’s Disease,” Neurology 43, no. 8 (1993): 1467–72.
27. Allen D. Roses, “Apolipoprotein E and Alzheimer’s Disease: A Rapidly Expanding Field with Medical and Epidemiological Consequences,” Annals of the New York Academy of Sciences 802, no. 1 (1996): 50–57; Ronald C. Petersen, Stephen C. Waring, Glenn E. Smith, Eric G. Tangalos, and Stephen N. Thibodeau, “Predictive Value of APOE Genotyping in Incipient Alzheimer’s Disease,” Annals of the New York Academy of Sciences 802, no. 1 (1996): 58–69.
28. R. M. Corbo and R. Scacchi, “Apolipoprotein E (APOE) Allele Distribution in the World: Is APOEε4 a ‘Thrifty’ Allele?” Annals of Human Genetics 63 (1999): 301–10.
29. Dennis J. Selkoe, “The Pathophysiology of Alzheimer’s Disease,” in Scinto and Daffner, The Early Diagnosis of Alzheimer’s Disease, 83–104.
30. Corder et al., “Gene Dose of Apolipoprotein E Type 4.”
31. Tilley, Morgan, and Kalsheker, “Genetic Risk Factors.”
32. John A. Hardy, “ApoE, Amyloid, and Alzheimer’s Disease,” Science 263 (1994): 454–55.”
33. M. I. Kamboh, “Apolipoprotein E Polymorphism and Susceptibility to Alzheimer’s Disease,” Human Biology 67, no. 2 (1995): 195–215.
34. Lars Bertram and Rudolph E. Tanzi, “Alzheimer’s Disease: One Disorder, Too Many Genes?,” Human Molecular Genetics 13, no. 90001 (January 13, 2004): R135–R141, R135.
35. Ibid., R137.
36. Graham et al., “Standardization of the Diagnosis.”
37. M. B. Liddell, S. Lovestone, and M. J. Owen, “Genetic Risk of Alzheimer Disease: Advising Relatives,” British Journal of Psychiatry 178 (2001): 7–11; K. Ritchie and A. M. Dupuy, “The Current Status of APOε4 as a Risk Factor for Alzheimer’s Disease: An Epidemiological Perspective,” International Journal of Geriatric Psychiatry 14, no. 9 (1999): 695–700.
38. The term “heterozygous” refers to the case where a person carries only one APOE ε4 allele (along with either an APOE ε2 or 3). Someone who is homozygous for APOE ε4 has two of these alleles.
39. Martin R. Farlow, “Alzheimer’s Disease: Clinical Implications of the Apolipoprotein E Genotype,” Neurology 48, no. 5, suppl. 6 (1997): S30–S34.
40. Clive Holmes, “The Genetics of Alzheimer’s Disease,” Menopause International 8, no. 1 (2002): 20–23; Farlow, “Alzheimer’s Disease.”
41. Holmes, “Genetics of Alzheimer’s Disease”; Swartz, Black, and St George-Hyslop, “Apolipoprotein E and Alzheimer’s Disease.”
42. Holmes, “Genetics of Alzheimer’s Disease.”
43. Deborah Blacker and Rudolph E. Tanzi, “Genetic Testing in the Early Diagnosis of Alzheimer Disease,” in Scinto and Daffner, The Early Diagnosis of Alzheimer’s Disease, 105–26.
44. See John H. Growdon, “Apolipoprotein E and Alzheimer Disease,” Archives of Neurology 55, no. 8 (1998): 1053–54, for a summary of these early findings.
45. Alan R. Templeton, “The Complexity of the Genotype-Phenotype Relationship and the Limitations of Using Genetic ‘Markers’ at the Individual Level,” Science in Context 11, nos. 3–4 (1998): 373–89, 376.
46. G. W. Small, S. Komo, A. La Rue, S. Saxena, M. E. Phelps, J. C. Mazziotta, A. M. Saunders, J. L. Haines, M. A. Pericak-Vance, and A. D. Roses, “Early Detection of Alzheimer’s Disease by Combining Apolipoprotein E and Neuroimaging,” Annals of the New York Academy of Sciences 802 (1996): 70–78, 76.
47. Roses, “Apolipoprotein E and Alzheimer’s Disease: A Rapidly Expanding Field.”
48. Allen D. Roses, “Apolipoprotein E and Alzheimer’s Disease: The Tip of the Susceptibility Iceberg,” Annals of the New York Academy of Sciences 855, no. 1 (1998): 738–43.
49. The ε2 allele has a cystine at positions 112 and 158 in the receptor-binding region of APOE. The ε3 allele is cystine-112 and argenine-158. The APOEε4 allele has argenine at both positions. See Nader Ghebranious, Lynn Ivacic, Jamie Mallum, and Charles Dokken, “Detection of ApoE E2, E3 and E4 Alleles Using MALDI-TOF Mass Spectrometry and the Homogeneous Mass-Extend Technology,” Nucleic Acids Research 33, no. 17 (2005): e149.
50. Daniel Glass and Steven E. Arnold, “Some Evolutionary Perspectives on Alzheimer’s Disease Pathogenesis and Pathology,” Alzheimer’s and Dementia 8, no. 4 (2012): 343–50.
51. C. E. Finch and R. M. Sapolsky, “The Evolution of Alzheimer Disease, the Reproductive Schedule, and apoE Isoforms,” Neurobiology of Aging 20, no. 4 (1999): 407–28.
52. Ibid.
53. M. Gearing, G. W. Rebeck, B. T. Hyman, J. Tigges, and S. S. Mirra, “Neuropathology and Apolipoprotein E Profile of Aged Chimpanzees: Implications for Alzheimer Disease,” Neurobiology, Proceedings of the National Academy of Sciences of the United States of America 91, no. 20 (1994): 9382–86. Dementia in mammals other than humans is exceptionally hard to investigate in the wild, especially given that most animals die before reaching old age.
54. R. W. Mahley, “Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology,” Science 240 (1988): 622–30.
55. Matthew C. Keller and Geoffrey Miller, “Resolving the Paradox of Common, Harmful, Heritable Mental Disorders: Which Evolutionary Genetic Models Work Best?,” Behavioral Brain Science 29, no. 4 (2006): 385–452.
56. Yin C. Paradies, Michael J. Montoya, and Stephanie M. Fullerton, “Racialized Genetics and the Study of Complex Diseases: The Thrifty Genotype Revisited,” Perspectives in Biology and Medicine 50, no. 2 (2007): 203–27.
57. Corbo and Scacchi, “Apolipoprotein E (APOE) Allele Distribution.”
58. Stephanie M. Fullerton, Andrew G. Clark, Kenneth M. Weiss, Deborah A. Nickerson, Scott L. Taylor, Jari H. Stengård, Veikko Salomaa, Erkki Vartiainen, Markus Perola, Eric Boerwinkle, and Charles F. Sing, “Apolipoprotein E Variation at the Sequence Haplotype Level: Implications for the Origin and Maintenance of a Major Human Polymorphism,” American Journal of Human Genetics 67, no. 4 (2000): 881–900.
59. Hugh Hendrie, “Diagnosis of Dementia and Alzheimer’s Disease in Indianapolis and Ibadan: Challenges in Cross-Cultural Studies of Aging and Dementia,” Alzheimer’s & Dementia 5, no. 4 (2009): P122; Oye Gureje, Adesola Ogunniyi, and Lola Kola, “The Profile and Impact of Probable Dementia in a Sub-Saharan African Community: Results from the Ibadan Study of Aging,” Journal of Psychosomatic Research 61, no. 3 (2006): 327–33. See also L. A. Farrer, “Familial Risk for Alzheimer Disease in Ethnic Minorities: Nondiscriminating Genes,” Archives of Neurology 57, no. 1 (2000): 28–29.
60. Neill R. Graff-Radford, Robert C. Green, Rodney C. P. Go, Michael L. Hutton, Timi Edeki, David Bachman, Jennifer L. Adamson, et al., “Association between Apolipoprotein E Genotype and Alzheimer Disease in African American Subjects,” Archives of Neurology 59, no. 4 (2002): 594–600
61. L. A. Farrer, “Intercontinental Epidemiology of Alzheimer Disease: A Global Approach to Bad Gene Hunting,” Journal of the American Medical Association 285, no. 6 (2001): 796–98.
62. The default network is a network of brain regions that are active when the individual is not focused on the outside world and the brain is at wakeful rest. See also Michael D. Greicius, Gaurav Srivastava, Allan L. Reiss, and Vinod Menon, “Default-Mode Network Activity Distinguishes Alzheimer’s Disease from Healthy Aging: Evidence from Functional MRI,” Proceedings of the National Academy of Sciences of the United States of America 101, no. 13 (2004): 4637–42.
63. R. W. Mahley, K. H. Weisgraber, and Y. Huang, “Apolipoprotein E4: A Causative Factor and Therapeutic Target in Neuropathology, Including Alzheimer Disease,” Proceedings of the National Academy of Sciences 103, no. 15 (2006): 5644–51. The abstract of this article is as follows:
The premise of this review is that apolipoprotein (apo) E4 is much more than a contributing factor to neurodegeneration. ApoE has critical functions in redistributing lipids among CNS cells for normal lipid homeostasis, repairing injured neurons, maintaining synapto-dendritic connections, and scavenging toxins. In multiple pathways affecting neuropathology, including Alzheimer disease, APOE acts directly or in concert with age, head injury, oxidative stress, ischemia, inflammation, and excess amyloid beta peptide production to cause neurological disorders, accelerating progression, altering prognosis, or lowering age of onset. We envision that unique structural features of APOE4 are responsible for APOE4-associated neuropathology. Although the structures of APOE2, APOE3, and APOE4 are in dynamic equilibrium, APOE4, which is detrimental in a variety of neurological disorders, is more likely to assume a pathological conformation. Importantly, APOE4 displays domain interaction (an interaction between the N- and C-terminal domains of the protein that results in a compact structure) and molten globule formation (the formation of stable, reactive intermediates with potentially pathological activities). In response to CNS stress or injury, neurons can synthesize APOE. APOE4 uniquely undergoes neuron-specific proteolysis, resulting in bioactive toxic fragments that enter the cytosol, alter the cytoskeleton, disrupt mitochondrial energy balance, and cause cell death. Our findings suggest potential therapeutic strategies, including the use of “structure correctors” to convert APOE4 to an “APOE3-like” molecule, protease inhibitors to prevent the generation of toxic APOE4 fragments, and “mitochondrial protectors” to prevent cellular energy disruption.
64. John C. Morris, Catherine M. Roe, Chengjie Xiong, Anne M. Fagan, Alison M. Goate, David M. Holtzman, and Mark A. Mintun, “APOE Predicts Aβ but Not Tau Alzheimer’s Pathology in Cognitively Normal Aging,” Annals of Neurology 67, no. 1 (2010): 122–31, 127.
65. Joseph L. Price, Daniel W. McKeel Jr., Virginia D. Buckles, Catherine M. Roe, Chengjie Xiong, Michael Grundman, Lawrence A. Hansen, et al., “Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease,” Neurobiology of Aging 30, no. 7 (2009): 1026–36.
66. Morris et al., “APOE Predicts,” 127.
67. Ibid., 128.
68. Eric Karran, Marc Mercken, and Bart De Strooper, “The Amyloid Cascade Hypothesis for Alzheimer’s Disease: An Appraisal for the Development of Therapeutics,” Nature Reviews Drug Discovery 10, no. 9 (2011): 698–712, 701, 705.
69. Ibid., 710.
Chapter 6
Genome-Wide Association Studies: Back to the Future
1. Anne V. Buchanan, Samuel Sholtis, Joan Richtsmeier, and Kenneth M. Weiss, “What Are Genes ‘for’ or Where Are Traits ‘from’? What Is the Question?,” BioEssays 31, no. 2 (2009): 198–208.
2. A polymorphism is a discrete genetic trait that exists in a population in at least two forms. That is, more than one allele exists at a gene locus in any given population. By convention, the frequency of the rarest of the alleles must be no less than 1 percent. The most common type of polymorphism exists as variation at a single base pair. Polymorphisms can also be much larger in size and involve long stretches of DNA. Natural selection, genetic drift, and/or gene flow—that is, human migration—account for allelic frequencies in populations. Mutations are rare and cannot account by themselves directly for changes in allele frequencies.
3. See http://learn.genetics.utah.edu/content/health/pharma/snips/ for further, readily comprehensible details about SNPs. SNPs are the most simple form and most common source of genetic polymorphism in the human genome, approximately 90 percent of all human DNA polymorphisms.
4. There is some argument among experts about the common disease/common variation hypothesis, but the AD geneticists to whom I spoke adhere to it as set out above, and their publications corroborate this position. This hypothesis has been very lucrative in snaring large amounts of money for GWAS research.
5. Lars Bertram and Rudolph E. Tanzi, “Genome-wide Association Studies in Alzheimer’s Disease,” Human Molecular Genetics 18, no. R2 (2009): 270–81.
6. Ibid.
7. Hui Shi, Christopher Medway, James Bullock, Kristelle Brown, Noor Kalsheker, and Kevin Morgan, “Analysis of Genome-Wide Association Study (GWAS) Data Looking for Replicating Signals in Alzheimer’s Disease (AD),” International Journal of Molecular Epidemiology and Genetics 1, no. 1 (2009): 53–66, 53.
8. Gabrielle Strobel, “Paper Alert: GWAS Hits Clusterin, CR1, PICALM Formally Published,” Alzheimer Research Forum, September 7, 2009, http://www.alzforum.org/new/detail.asp?id=2233.
9. Julie Williams, 2009, comment in Strobel, “Paper Alert.”
10. http://www.news-medical.net/news/20090907/CLU-and-PICALM-genes-associated-with-Alzheimers-disease.aspx.
11. Adam C. Naj, Gyungah Jun, Gary W. Beecham, Li-San Wang, Badri Narayan Vardarajan, Jacqueline Buros, Paul J. Gallins, et al., “Common Variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 Are Associated with Late-Onset Alzheimer’s Disease,” Nature Genetics 43, no. 5 (2011): 436–41, 436.
12. Ibid., 443.
13. Walter Gilbert, “A Vision of the Grail,” in The Code of Codes: Scientific and Social Issues in the Human Genome Project, ed. Daniel Kevles and Leroy Hood (Cambridge, Mass.: Harvard University Press, 1992), 83–97.
14. Gina Kolata, “Vast Gene Study Yields Insights on Alzheimer’s,” New York Times, April 3, 2011.
15. Unfortunately I did not ask Schellenberg what he thought about the research being planned for Colombian subjects discussed in chapter 5.
16. For an explanation of the statistical concept of p value, see http://en.wikipedia.org/wiki/P-value.
17. The odds ratio is a measure of effect size, describing the strength of association or nonindependence between two binary data values. It is used as a descriptive statistic and plays an important role in logistic regression. Unlike other measures of association for paired binary data such as the relative risk, the odds ratio treats the two variables being compared symmetrically and can be estimated using some types of nonrandom samples. See http://en.wikipedia.org/wiki/Odds_ratio.
18. “New Alzheimer’s Genes Identified,” CBC News—Health, April 3, 2011, http://www.cbc.ca/news/health/story/2011/04/01/alzheimer-genes-identified.html, emphasis added.
19. See http://www.youtube.com/watch?v=WKCa5Cv_fDg&feature=relmfu.
20. Meredith Wadman, “Fleshing Out the US Alzheimer’s Strategy,” Nature News, January 19, 2012, http://www.nature.com/news/fleshing-out-the-us-alzheimer-s-strategy-1.9856.
21. The heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment, and random chance can all contribute to the variation between individuals in their phenotypic characteristics, and heritability analyzes the relative contributions of differences in genetic and nongenetic factors to the total phenotypic variance in a population. The term “missing heritability” is used when researchers are unable to demonstrate the assumed genetic contribution to a condition.
22. Teri A. Manolio, Francis S. Collins, Nancy J. Cox, David B. Goldstein, Lucia A. Hindorff, David J. Hunter, Mark I. McCarthy, et al., “Finding the Missing Heritability of Complex Diseases,” Nature 461 (2009): 747–53, 747.
23. Ibid., 751; see also Wei Zheng, Jirong Long, Yu-Tang Gao, Chun Li, Ying Zheng, Yong-Bin Xiang, Wanqing Wen, et al., “Genome-wide Association Study Identifies a New Breast Cancer Susceptibility Locus at 6q25.1,” Nature Genetics 41, no. 3 (2009): 324–28.
24. Samuel P. Dickson, Kai Wang, Ian Krantz, Hakon Hakonarson, and David B. Goldstein, “Rare Variants Create Synthetic Genome-Wide Associations,” PLoS Biology 8, no. 1 (2010): e1000294.
25. Or Zuk, Eliana Hechter, Shamil R. Sunyaev, and Eric S. Lander, “The Mystery of Missing Heritability: Genetic Interactions Create Phantom Heritability,” Proceedings of the National Academy of Sciences, December 5, 2011, http://www.pnas.org/content/early/2012/01/04/1119675109.
26. Lars Bertram, Christina M. Lill, and Rudolph E. Tanzi, “The Genetics of Alzheimer Disease: Back to the Future,” Neuron 68, no. 2 (2010): 270–81.
27. I am indebted to Ken Weiss for this comment.
28. Cruchaga et al., “Rare Variants,” emphasis original.
29. Khachaturian, “Plundered Memories,” 21.
30. Alzheimer’s Association, William Thies, and Laura Bleiler, “2011 Alzheimer’s Disease Facts and Figures,” Alzheimer’s & Dementia 7, no. 2 (2011): 208–44, 235.
Chapter 7
Living with Embodied Omens
1. E. E. Evans-Pritchard, Witchcraft, Oracles and Magic among the Azande (Oxford: Clarendon, 1937).
2. Nadia C. Serematakis, The Last Word: Women, Death, and Divination in Inner Mani (Chicago: University of Chicago Press, 1991).
3. Epigenomics, meaning literally over and above the genome, will be discussed in the following chapter.
4. Rose, Politics of Life Itself.
5. Edward J. Yoxen, “Constructing Genetic Diseases,” in The Problem of Medical Knowledge: Examining the Social Construction of Medicine, ed. P. Wright and A. Treacher (Edinburgh: University of Edinburgh, 1982), 144–61, see 144.
6. See, for example, Whyte, Questioning Misfortune.
7. Yoxen, “Constructing Genetic Diseases.”
8. Abby Lippman, “Led (Astray) by Genetic Maps: The Cartography of the Human Genome and Human Care,” Social Science & Medicine 35, no. 12 (1992): 1469–96, 1470.
9. See, for example, Troy Duster, Backdoor to Eugenics (New York: Routledge, 1990); Troy Duster, “Buried Alive: The Concept of Race in Science,” in Goodman, Heath, and Lindee, Genetic Nature/Culture: Anthropology and Science beyond the Two Culture Divide, ed. Alan H. Goodman, Deborah Heath, and M. Susan Lindee (Berkeley: University of California Press, 2003), 258–77; Keith Wailoo and Stephen Pemberton, The Troubled Dream of Genetic Medicine: Ethnicity and Innovation in Tay-Sachs, Cystic Fibrosis, and Sickle Cell Disease (Baltimore: Johns Hopkins University Press, 2006).
10. Rose, Politics of Life Itself, 125.
11. Sarah Franklin, “Life,” in The Encyclopedia of Bioethics, ed. Warren T. Reich (New York: Simon & Schuster, 1995), 456–62.
12. Nina Hallowell, “Doing the Right Thing: Genetic Risk and Responsibility,” Sociology of Health & Illness 21, no. 5 (1999): 597–621; Anne Kerr, Sarah Cunningham-Burley, and Amanda Amos, “The New Genetics and Health: Mobilizing Lay Expertise,” Public Understanding of Science 7, no. 1 (1998): 41–60; Susan Michie, Harriet Drake, Theresa Marteau, and Martin Bobrow, “A Comparison of Public and Professionals’ Attitudes towards Genetic Developments,” Public Understanding of Science 4, no. 3 (1995): 243–53; Carlos Novas and Nikolas Rose, “Genetic Risk and the Birth of the Somatic Individual,” Economy and Society 29, no. 4 (2000): 485–513.
13. Deborah Heath and Karen-Sue Taussig, “Genetic Citizenship,” in A Companion to the Anthropology of Politics, ed. D. Nguyent and J. Vincent (London: Blackwell, 2004), 152–67; Rayna Rapp, “Cell Life and Death, Child Life and Death: Genomic Horizons, Genetic Diseases, Family Stories,” in Remaking Life and Death: Toward an Anthropology of the Biosciences, ed. Sarah Franklin and Margaret Lock (Santa Fe, N.Mex.: School of American Research Press, 2004), 23–60.
14. C. M. Condit, “How the Public Understands Genetics: Non-Deterministic and Non-Discriminatory Interpretations of the ‘Blueprint’ Metaphor,” Public Understanding of Science 8, no. 3 (1999): 169–80; Margaret Lock, Stephanie Lloyd, and Janalyn Prest, “Genetic Susceptibility and Alzheimer Disease: The Penetrance and Uptake of Genetic Knowledge,” in Cohen and Leibing, Thinking about Dementia, 123–54.
15. S. Cox and W. McKellin, “ ‘There’s This Thing in Our Family’: Predictive Testing and the Construction of Risk for Huntington Disease,” in Sociological Perspectives on the New Genetics, ed. P. Conrad and J. Gabe (London: Blackwell, 1999), 121–48, 140.
16. Kerr, Cunningham-Burley, and Amos, “New Genetics and Health.”
17. Diagnosing Huntington Disease, http://www.nhs.uk/Conditions/Huntingtons-disease/Pages/Diagnosis.aspx; Diane Beeson and Theresa Doksum, “Family Values and Resistance to Genetic Testing,” in Bioethics in Social Context, ed. Barry Hoffmaster (Philadelphia: Temple University Press, 2001), 153–79; Kimberley A. Quaid and Michael Morris, “Reluctance to Undergo Predictive Testing: The Case of Huntington Disease,” American Journal of Medical Genetics 45, no. 1 (1993): 41–45.
18. Shirley Hill, Managing Sickle Cell Disease in Low-Income Families (Philadelphia: Temple University Press, 1994); Rayna Rapp, Testing Women, Testing the Fetus: The Social Impact of Amniocentesis (New York: Routledge, 1999).
19. Kira A. Apse, Barbara B. Biesecker, Francis M. Giardiello, Barbara P. Fuller, and Barbara A. Bernhardt, “Perceptions of Genetic Discrimination among At-Risk Relatives of Colorectal Cancer Patients,” Genetics in Medicine 6, no. 6 (2004): 510–16.
20. Monica Konrad, Narrating the New Predictive Genetics: Ethics, Ethnography, and Science (Cambridge: Cambridge University Press, 2005).
21. Alice Wexler, Mapping Fate: A Memoir of Family Risk and Genetic Research (Berkeley: University of California Press, 1995), 224.
22. Ibid., 238.
23. Hallowell, “Doing the Right Thing.”
24. Ian Hacking, “The Looping Effects of Human Kinds,” in Causal Cognition: A Multidisciplinary Approach, ed. D. Sperber, D. Premack, and A. J. Premack (Oxford: Oxford Medical Publications, 1995), 351–83.
25. Paul Rabinow, “Artificiality and Enlightenment: From Sociobiology to Biosociality,” in Essays on the Anthropology of Reason (Princeton: Princeton University Press, 1996), 91–111.
26. Paul Rabinow, “Afterword: Concept Work,” in Biosocialities, Genetics and the Social Sciences: Making Biologies and Identities, ed. Sarah Gibbon and Carlos Novas (London: Routledge, 2007), 188–92; see also Gibbon and Novas, Biosocialities, Genetics and the Social Sciences; Lock and Nguyen, Anthropology of Biomedicine.
27. Duana Fullwiley, The Enculturated Gene: Sickle Cell Health Politics and Biological Difference in West Africa (Princeton: Princeton University Press, 2012).
28. Jill Waalen and Ernest Beutler, “Genetic Screening for Low-Penetrance Variants in Protein-Coding Genes,” Annual Review of Genomics and Human Genetics 10 (2009): 431–50.
29. C. R. Scriver and P. J. Waters, “Monogenic Traits Are Not Simple: Lessons from Phenylketonuria,” Trends in Genetics 15, no. 7 (1999): 267–72.
30. S. G. Post, P. J. Whitehouse, R. H. Binstock, T. D. Bird, S. K. Eckert, L. A. Farrer, L. M. Fleck, et al., “The Clinical Introduction of Genetic Testing for Alzheimer Disease: An Ethical Perspective,” Journal of the American Medical Association 277, no. 10 (1997): 832–36; Norman R. Relkin, “Apolipoprotein E Genotyping in Alzheimer’s Disease,” The Lancet 347 (1996): 1091–95; Norman R. Relkin, Younga J. Kwon, Julia Tsai, and Samuel Gandy, “The National Institute on Aging/Alzheimer’s Association Recommendations on the Application of Apolipoprotein E Genotyping to Alzheimer’s Disease,” Annals of the New York Academy of Sciences 802, no. 1 (1996): 149–76;
31. http://www.alz.org/national/documents/topicsheet_genetictesting.pdf; http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=434; http://www.alzheimer.ca/~/media/Files/national/brochures-tough-issues/Tough_Issues_Genetics_2007_e.ashx; http://www.francealzheimer.org.
32. See, for example, Hyman Schipper, who believes that knowledge about their APOE status will encourage individuals to pay more attention to their dietary intake: Hyman M. Schipper, “Presymptomatic Apolipoprotein E Genotyping for Alzheimer’s Disease Risk Assessment and Prevention,” Alzheimer’s & Dementia 7, no. 4 (2011): e118–e123.
33. Personal communication with Robert Green, January 2012.
34. Frederick J. Kier and Victor Molinari, “ ‘Do-It-Yourself’ Dementia Testing: Issues Regarding an Alzheimer’s Home Screening Test,” The Gerontologist 43, no. 3 (2003): 295–301.
35. The REVEAL Study is funded by the ELSI Branch of the National Human Genome Research Institute (RO1 HG/AGO2213). Additional support was provided by an NIA Mentoring Award to Dr. Green (K24 AG027841) and by the Boston University General Clinical Research Center (GCRC; MO1 RR00533).
36. Ashida Sato, Laura M. Koehly, J. Scott Roberts, Clara A. Chen, Susan Hiraki, and Robert C. Green, “Disclosing the Disclosure: Factors Associated with Communicating the Results of Genetic Susceptibility Testing for Alzheimer’s Disease,” Journal of Health Communication 14, no. 8 (2009): 768–84.
37. L. Adrienne Cupples, Lindsay A. Farrer, A. Dessa Sadovnick, Norman Relkin, Peter Whitehouse, and Robert C. Green, “Estimating Risk Curves for First-degree Relatives of Patients with Alzheimer’s Disease: The REVEAL Study,” Genetics in Medicine 6, no. 4 (2004): 192–96.
38. Robert C. Green, V. C. Clarke, N. J. Thompson, J. L. Woodard, and R. Letz, “Early Detection of Alzheimer Disease: Methods, Markers, and Misgivings,” Alzheimer Disease & Associated Disorders 11, suppl. 5 (1997): S1–S5, discussion S37–S39.
39. L. A. Farrer, L. A. Cupples, J. L. Haines, B. Hyman, W. A. Kukull, R. Mayeux, R. H. Myers, M. A. Pericak-Vance, N. Risch, and C. M. van Duijn, “Effects of Age, Sex, and Ethnicity on the Association between Apolipoprotein E Genotype and Alzheimer Disease. A Meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium,” Journal of the American Medical Association 278, no. 16 (1997): 1349–56.
40. In REVEAL 2 some individuals were given an abbreviated disclosure session by the involved clinicians, rather than genetic counselors. The purpose was to find out if a briefer form of disclosure would be as satisfactory as the original longer form with the idea that such disclosure sessions would become part of general practice.
41. Susan Larusse, J. Scott Roberts, Theresa M. Marteau, Heather Katsen, Erin L. Linnenbringer, Melissa Barber, Peter Whitehouse, Kimberly Quaid, Tamsen Brown, Robert C. Green, and Norman R. Relkin, “Genetic Susceptibility Testing versus Family History-Based Risk Assessment: Impact on Perceived Risk of Alzheimer’s Disease,” Genetic Medicine 7 (2005): 48–53; J. S. Roberts, K. D. Christensen, and R. C. Green, “Using Alzheimer’s Disease as a Model for Genetic Risk Disclosure: Implications for Personal Genomics,” Clinical Genetics 80, no. 5 (2011): 407–14.
42. Cupples et al., “Estimating Risk Curves”; see also L. A. Farrer, L. A. Cupples, J. L. Haines, B. Hyman, W. A. Kukull, R. Mayeux, R. H. Myers, M. A. Pericak-Vance, N. Risch, and C. M. van Duijn, “Effects of Age, Sex, and Ethnicity on the Association between Apolipoprotein E Genotype and Alzheimer Disease. A Meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium,” Journal of the American Medical Association 278, no. 16 (1997): 1349–56.
43. Margaret Lock, Julia Freeman, Gillian Chilibeck, Briony Beveridge, and Miriam Padolsky, “Susceptibility Genes and the Question of Embodied Identity,” Medical Anthropology Quarterly 21, no. 3 (2007): 256–76.
44. Jill S. Goldman, Susan E. Hahn, Jennifer Williamson Catania, Susan LaRusse-Eckert, Melissa Barber Butson, Malia Rumbaugh, Michelle N. Strecker, et al., “Genetic Counseling and Testing for Alzheimer Disease: Joint Practice Guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors,” Genetics in Medicine 13, no. 6 (2011): 597–605.
45. Sato et al., “Disclosing the Disclosure.”
46. Robert C. Green, J. Scott Roberts, L. Adrienne Cupples, Norman R. Relkin, Peter J. Whitehouse, Tamsen Brown, Susan LaRusse Eckert, et al., “Disclosure of APOE Genotype for Risk of Alzheimer’s Disease,” New England Journal of Medicine 361, no. 3 (2009): 245–54.
47. I am indebted to Gillian Chilibeck for the phrase “familiarization of Alzheimer’s risk.”
48. Martin Richards, “Lay and Professional Knowledge of Genetics and Inheritance,” Public Understanding of Science 5, no. 3 (1996): 217–30.
49. J. Turney, “The Public Understanding of Science—Where Next?.” European Journal of Genetics in Society 1, no. 2 (1995): 5–22, 12.
50. Katie Featherstone, Paul Atkinson, Aditva Bharadwai, and Angus Clarke, Risky Relations: Family, Kinship and the New Genetics (Oxford: Berg, 2006); C. Emslie, K. Hunt, and G. Watt, “A Chip Off the Old Block? Lay Understandings of Inheritance amongst Men and Women in Mid-life,” Public Understanding of Science 12, no. 1 (2003): 47–65; Richards, “Lay and Professional Knowledge.”
51. Barbara Duden and Silja Samerki, “ ‘Pop Genes’: An Investigation of ‘the Gene’ in Popular Parlance,” in Biomedicine as Culture: Instrumental Practices, Technoscientific Knowledge, and New Modes of Life, ed. R. V. Burri and J. Dumit (New York: Routledge, 2007), 167–90, 167.
52. Goldman et al., “Genetic Counseling and Testing”; Roberts, Christensen, and Green, “Using Alzheimer’s Disease.”
53. Martyn Pickersgill, Sarah Cunningham-Burley, and Paul Martin, “Constituting Neurologic Subjects: Neuroscience, Subjectivity and the Mundane Significance of the Brain,” Subjectivity 4 (2011): 346–65, 361.
54. Joseph Dumit, Picturing Personhood: Brain Scans and Biomedical Identity (Princeton: Princeton University Press, 2004); Ortega and Vidal, Neurocultures; Jan Slaby, “Steps towards a Critical Neuroscience,” Phenomenology and the Cognitive Sciences 9, no. 3 (2010): 397–416, see “Hermeneutics of Subjectification,” 403.
55. Lock et al., “Susceptibility Genes and the Question of Embodied Identity.”
56. Roberts, Christensen, and Green, “Using Alzheimer’s Disease.”
57. Padolsky conducted participant observation research in 2005 at the Alzheimer Society of Ottawa office, at ASO classes and workshops, and at several ASO special events over the course of twelve months. She interviewed nine ASO staff members, including most of the Family Support and Education team, the director of Family Support and Education, the executive director of ASO, and a sample of administrative staff. In addition, ASC and ASO publications were compared to the materials put out by the U.K. and U.S. Alzheimer societies.
58. Alzheimer Society of Canada, Alzheimer Care: Ethical Guidelines; Genetic Testing (2006), http://www.alzheimer.ca/english/care/ethics-genetictest.htm.
59. Lock et al., “Susceptibility Genes and the Question of Embodied Identity.”
60. Ten of the newspapers with articles on AD are published in either Canada, the United States, the United Kingdom, or Australia, and the seven magazines are published in either Canada or the United States.
61. Margaret Lock, Julia Freeman, Rosemary Sharples, and Stephanie Lloyd, “When It Runs in the Family: Putting Susceptibility Genes in Perspective,” Public Understanding of Science 15, no. 3 (2006): 277–300; Lock et al., “Susceptibility Genes and the Question of Embodied Identity”; Briony Beveridge was responsible for the comprehensive analysis of newspaper reporting on AD.
62. Rayna Rapp, Deborah Heath, and Karen-Sue Taussig, “Genealogical Disease: Where Hereditary Abnormality, Biomedical Explanation, and Family Responsibility Meet,” in Relative Matters: New Directions in the Study of Kinship, ed. Sarah Franklin and Susan MacKinnon (Durham, N.C.: Duke University Press, 2001), 384–412; Rapp, “Cell Life and Death.”
63. Michel Callon and Vololona Rabeharisoa, “Gino’s Lesson on Humanity: Genetics, Mutual Entanglements and the Sociologist’s Role,” Economy and Society 33, no. 1 (2004): 1–27; Heath and Taussig, “Genetic Citizenship”; Rapp, “Cell Life and Death”; Karen-Sue Taussig, Rayna Rapp, and Deborah Heath, “Flexible Eugenics: Technologies of the Self in the Age of Genetics,” in Goodman, Heath, and Lindee, Genetic Nature/Culture, 58–76.
Chapter 8
Chance Untamed and the Return of Fate
1. René Dubos, Mirage of Health (London: Harper and Row, 1959), 1–2.
2. National Institutes of Health, Alzheimer Disease Research Summit 2012: Path to Treatment and Prevention (Bethesda, Md.: National Institutes of Health, 2012), http://www.nia.nih.gov/about/events/2012/alzheimers-disease-research-summit-2012-path-treatment-and-prevention.
3. Even so, certain governments remain strikingly resistant to recognition of the undeniable increase in diagnosed cases of AD, Canada being one intransigent example.
4. See, for example, Howard Gleckman, “The Obama Administration’s War on Alzheimer’s,” Forbes, January 11, 2012, http://www.forbes.com/sites/howardgleckman/2012/01/11/the-obama-administrations-war-on-alzheimers/.
5. Gary Stix, “Obama’s War on Alzheimer’s: Will We Be Able to Treat the Disease by 2025?,” Scientific American, January 31, 2012, http://blogs.scientificamerican.com/observations/2012/01/31/obamas-war-on-alzheimers-will-we-be-able-to-treat-the-disease-by-2025/.
6. Gina Kolata, “In Preventing Alzheimer’s, Mutation May Aid Drug Quest,” New York Times, July 11, 2012.
7. Thorlakur Jonsson, Jasvinder K. Atwal, Stacy Steinberg, Jon Snaedal, Palmi V. Jonsson, Sigurbjorn Bjornsson, Hreinn Stefansson, et al., “A Mutation in APP Protects Against Alzheimer’s Disease and Age-Related Cognitive Decline,” Nature 488 (2012): 96–99, 96.
8. Ibid, 98.
9. Kolata, “In Preventing Alzheimer’s.”
10. Lauren Gravitz, “Drugs: A Tangled Web of Targets,” Nature 475 (2011): S9–S11.
11. Randall Bateman and John Morris, “The Dominantly Inherited Alzheimer’s Network Trials: An Opportunity to Prevent Alzheimer’s Disease,” Alzheimer’s & Dementia 8, no. 4 (2012): 427.
12. Eric Reiman, Francisco Lopera, Jessica Langbaum, Adam Fleisher, Naparkamon Ayutyanont, Yakeel Quiros, Laura Jakimovitch, Carolyn Langlois, and Pierre Tariot, “The Alzheimer’s Prevention Initiative,” Alzheimer’s & Dementia 8, no. 4 (2012): 427.
13. William Jagust, “Aging, Amyloid and Neural Activity,” Alzheimer’s & Dementia 8, no. 4 (2012): 427.
14. Glass and Arnold, “Some Evolutionary Perspectives.”
15. Robert Green, Scott Roberts, Jason Karlawish, Thomas Obisesan, L. Adrienne Cupples, Denise Lautenbach, Margaret Bradbury, et al., “Disclosure of APOE Genotype to Persons with Mild Cognitive Impairment (MCI),” Alzheimer’s & Dementia 8, no. 4 (2012): 423.
16. Reisa A. Sperling and Scott Roberts, “Disclosure of Amyloid Status in Secondary Prevention Trials for Alzheimer’s Disease,” Alzheimer’s & Dementia 8, no. 4 (2012): 423.
17. Jason Karlawish, “Disclosing Amyloid Imaging Results,” Alzheimer’s & Dementia 8, no. 4 (2012): 423.
18. Hampel, Lista, and Khachaturian, “Development of Biomarkers,” 332.
19. Ibid., 313.
20. Ara S. Khachaturian, Michelle M. Mielke, and Zaven S. Khachaturian, “Biomarker Development: A Population-Level Perspective,” Alzheimer’s & Dementia 8, no. 4 (2012): 247–49.
21. Alzheimer’s Association International Conference, “Sleep Duration, Sleep Disorders, and Circadian Patterns Are Risk Factors and Indicators of Cognitive Decline” (press release, 2012), http://www.prnewswire.com/news-releases/sleep-duration-sleep-disorders-and-circadian-patterns-are-risk-factors-and-indicators-of-cognitive-decline-162589416.html.
22. Andrew Pollack, “Alzheimer’s Drug Fails Its First Big Clinical Trial,” New York Times, July 23, 2012.
23. Tom Murphy, “Alzheimer’s Drug Fails Study but Flashes Potential,” Associated Press, August 24, 2012.
24. Michael C. Purdy, “Investigational Drugs Chosen for Major Alzheimer’s Prevention Method (Washington University in St. Louis, 2012), http://www.wustel.edu.
25. Eric Reiman, Yakeel T. Quiroz, Adam S. Fleisher, Kewei Chen, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio, Anne M. Fagan, Aarti R. Shah, Sergio Alvarez, Andrés Arbelaez, Margarita Giraldo, Natalia Acosta-Baena, Reisa A. Sperling, Brad Dickerson, Chantal E. Stern, Victoria Tirado, Claudia Munoz, Rebecca A. Reiman, Matthew J. Huentelman, Gene E. Alexander, Jessica B. S. Langbaum, Kenneth S. Kosik, Pierre N. Tariot, and Francisco Lopera, “Brain Imaging and Fluid Biomarker Analysis in Young Adults at Genetic Risk for Autosomal Dominant Alzheimer’s Disease in the Presenilin 1 E280A Kindred: A Case-Control Study,” The Lancet Neurology 11 (2012): 1048–56; Adam S. Fleisher, Kewei Chen, Yakeel T. Quiroz, Laura J. Jakimovich, Madelyn Gutierrez Gomez, Carolyn M. Langois, Jessica B. S. Langbaum, Napatkamon Ayutyanont, Auttawut Roontiva, Pradeep Thiyyagura, Wendy Lee, Hua Mo, Liliana Lopez, Sonia Moreno, Natalia Acosta-Baena, Margarita Giraldo, Gloria Garcia, Rebecca A. Reiman, Matthew J. Huentelman, Kenneth S. Kosik, Pierre N. Tariot, Francisco Lopera, and Eric M. Reiman, “Florbetapir PET Analysis of Amyloid-β Deposition in the Presenilin 1 E280A Autosomal Dominant Alzheimer’s Disease Kindred: A Cross-Sectional Study,” The Lancet Neurology 11 (2012): 1057–65; Nick Fox, “When, Where, and How Does Alzheimer’s Disease Start?,” The Lancet Neurology 11 (2012): 1017–18; William Jagust, “Tracking Brain Amyloid-β in Presymptomatic Alzheimer’s Disease,” The Lancet Neurology 11 (2012): 1018–20.
26. Mo Costandi, “Disrupted Sleep Might Signal Early Stages of Alzheimer’s,” Scientific American, October 18, 2012, http://www.scientificamerican.com/article.cfm?id=disrupted-sleep-might-signal-early-stages-of-alzheimers.
27. Karola Stotz, Adam Bostanci, and Paul Griffiths, “Tracking the Shift to ‘Postgenomics,’ ” Community Genetics 9, no. 3 (2006): 190–96.
28. Evelyn Fox Keller, The Century of the Gene (Cambridge, Mass.: Harvard University Press, 2000), 277.
29. S. R. Eddy, “Non-coding RNA Genes and the Modern RNA World,” Nature Reviews Genetics 2, no. 12 (2001): 919–29; John S. Mattick, “Challenging the Dogma: The Hidden Layer of Non-Protein-Coding RNAs in Complex Organisms,” BioEssays 25, no. 10 (2003): 930–39; John S. Mattick, “The Hidden Genetic Program of Complex Organisms,” Scientific American 291, no. 4 (2004): 60–67.
30. Mattick, “Challenging the Dogma.”
31. A. Petronis, “Human Morbid Genetics Revisited: Relevance of Epigenetics,” Trends in Genetics 17, no. 3 (2001): 142–46.
32. Pleiotropy means the diverse effects of a single gene or gene pair on several organ systems and function.
33. I. I. Gottesman, “Schizophrenia Epigenesis: Past, Present, and Future,” Acta Psychiatrica Scandinavica. Supplementum 384 (1994): 26–33.
34. Keller, Century of the Gene, 147.
35. Kenneth M. Weiss and Anne V. Buchanan, The Mermaid’s Tale: Four Billion Years of Cooperation in the Making of Living Things (Cambridge, Mass.: Harvard University Press, 2009), 89.
36. Paul E. Griffiths, “Developmental Systems Theory,” in Nature Encyclopedia of the Life Sciences (London: John Wiley, 2001), 1; see also Susan Oyama, Paul E. Griffiths, and Russel D. Gray, Cycles of Contingency: Developmental Systems and Evolution, Life and Mind. Cambridge, Mass.: MIT Press, 2001.
37. Eva Jablonka and Marion J. Lamb, Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life (Cambridge, Mass.: MIT Press, 2005), 82.
38. Barry Barnes and John Dupré, Genomes: And What to Make of Them (Chicago: University of Chicago Press, 2008), 50.
39. Sarah Parry and John Dupré, “Introducing Nature After the Genome,” in Nature After the Genome, ed. Sarah Parry and John Dupré (Oxford: Blackwell, 2010), 3–16.
40. John Dupré, “The Polygenomic Organism,” in Nature After the Genome, ed. Sarah Parry and John Dupré (Oxford: Blackwell, 2010), 19–31, 25.
41. R. Strohman, “A New Paradigm for Life: Beyond Genetic Determinism,” California Monthly 111 (2001): 4–27, 8.
42. Eva M. Neumann-Held and Christopher Rehmann-Sutter, Genes in Development: Rereading the Molecular Paradigm (Durham, N.C.: Duke University Press, 2006), 2.
43. Evan T. Powers, Richard I. Morimoto, Andrew Dillin, Jeffery W. Kelly, and William E. Balch, “Biological and Chemical Approaches to Diseases of Proteostasis Deficiency,” Annual Review of Biochemistry 78 (2009): 959–91.
44. Richard C. Lewontin, “Science and Simplicity,” New York Review of Books 50 (2003): 39–42, 39.
45. Jonathan Weiner, The Beak of the Finch (New York: Vintage Books, 1994).
46. Alec Wilkinson, “The Lobsterman,” The New Yorker, July 31, 2006, 56–65.
47. Kenneth M. Weiss and Anne V. Buchanan, “Is Life Law-Like?” Genetics 188, no. 4 (2011): 761–71, 761; see also P. K. Stanford, Exceeding Our Grasp: Science, History and the Problem of Unconceived Alternatives (New York: Oxford University Press, 2006); C. K. Waters, “Causes That Make a Difference,” Journal of Philosophy 104 (2007): 551–79.
48. Weiss and Buchanan, “Is Life Law-Like?,” 761.
49. David Runciman, “Will We Be All Right in the End?,” London Review of Books 34, no. 1 (2012): 3–5.
50. Gillian Chilibeck, Margaret Lock, and Megha Sehdev, “Postgenomics, Uncertain Futures, and the Familiarization of Susceptibility Genes,” Social Science & Medicine 72, no. 11 (2011): 1768–75, see 1773–74.
51. Mary Midgley, Science and Poetry (London: Routledge, 2001), 120.
52. Nima Mosammaparast and Yang Shi, “Reversal of Histone Methylation: Biochemical and Molecular Mechanisms of Histone Demethylases,” Annual Review of Biochemistry 79 (2010): 155–79.
53. Patrick O. McGowan, Aya Sasaki, Ana C. D’Alessio, Sergiy Dymov, Benoit Labonté, Moshe Szyf, Gustavo Turecki, and Michael J. Meaney, “Epigenetic Regulation of the Glucocorticoid Receptor in Human Brain Associates with Childhood Abuse,” Nature Neuroscience 12, no. 3 (2009): 342–48; Patrick O. McGowan and Moshe Szyf, “The Epigenetics of Social Adversity in Early Life: Implications for Mental Health Outcomes,” Neurobiology of Disease 39, no. 1 (2010): 66–72; L. H. Lumey, “Decreased Birthweights in Infants after Maternal in Utero Exposure to the Dutch Famine of 1944–1945,” Paediatric and Perinatal Epidemiology 6, no. 2 (1992): 240–53; J. E. Harding, “The Nutritional Basis of the Fetal Origins of Adult Disease,” International Journal of Epidemiology 30, no. 1 (2001): 15–23.
54. Moshe Szyf, Patrick McGowan, and Michael J. Meaney, “The Social Environment and the Epigenome,” Environmental and Molecular Mutagenesis 49, no. 1 (2008): 46–60; Lucia Daxinger and Emma Whitelaw, “Understanding Transgenerational Epigenetic Inheritance via the Gametes in Mammals,” Nature Reviews Genetics 13, no. 3 (2012): 153–62. See also Margaret Lock, “The Lure of the Epigenome,” The Lancet 381 (2013) 1986–1897.
55. Ji-Song Guan, Stephen J. Haggarty, Emanuela Giacometti, Jan-Hermen Dannenberg, Nadine Joseph, Jun Gao, Thomas J. F. Nieland, et al., “HDAC2 Negatively Regulates Memory Formation and Synaptic Plasticity,” Nature 459 (2009): 55–60.
56. Sun-Chong Wang, Beatrice Oelze, and Axel Schumacher, “Age-Specific Epigenetic Drift in Late-Onset Alzheimer’s Disease,” PLoS ONE 3, no. 7 (2008): e2698, citing Dana C. Dolinoy, Radhika Das, Jennifer R. Weidman, and Randy L. Jirtle, “Metastable Epialleles, Imprinting, and the Fetal Origins of Adult Diseases,” Pediatric Research 61, no. 5, pt. 2 (2007): 30R–37R.
57. Wang, Oelze, and Schumacher, “Age-Specific Epigenetic Drift.”
58. Diego Mastroeni, Ann McKee, Andrew Grover, Joseph Rogers, and Paul D. Coleman, “Epigenetic Differences in Cortical Neurons from a Pair of Monozygotic Twins Discordant for Alzheimer’s Disease,” PLoS ONE 4, no. 8 (2009), http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719870/.
59. Wang, Oelze, and Schumacher, “Age-Specific Epigenetic Drift.”
60. Jablonka and Lamb, Evolution in Four Dimensions, 128.
61. See, for example, Estelle Sontag, Christa Hladik, Lisa Montgomery, Ampa Luangpirom, Ingrid Mudrak, Egon Ogris, and Charles L. White III, “Downregulation of Protein Phosphatase 2A Carboxyl Methylation and Methyltransferase May Contribute to Alzheimer Disease Pathogenesis,” Journal of Neuropathology & Experimental Neurology 63, no. 10 (2004): 1080–91; Kimberly D. Siegmund, Caroline M. Connor, Mihaela Campan, Tiffany I. Long, Daniel J. Weisenberger, Detlev Biniszkiewicz, Rudolf Jaenisch, Peter W. Laird, and Schahram Akbarian, “DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated Neurons,” PLoS ONE 2, no. 9 (2007), http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964879/; Diego Mastroeni, Andrew Grover, Elaine Delvaux, Charisse Whiteside, Paul D. Coleman, and Joseph Rogers, “Epigenetic Mechanisms in Alzheimer’s Disease,” Neurobiology of Aging 32, no. 7 (2011): 1161–80.
62. Marc Winnefeld and Frank Lyko, “The Aging Epigenome: DNA Methylation from the Cradle to the Grave,” Genome Biology 13, no. 7 (2012): 165–68.
63. Rita Guerreiro, Aleksandra Wojtas, Jose Bras, Minerva Carrasquillo, Ekaterina Rogaeva, Elisa Majounie, Carlos Cruchaga, Celeste Sassi, John S. K. Kauwe, Steven Younkin, Lilinaz Hazrati, John Collinge, Jennifer Pocock, Tammaryn Lashley, Julie Williams, Jean-Charles Lambert, Philippe Amouyel, Alison Goate, Rosa Rademakers, Kevin Morgan, John Powell, Peter St George-Hyslop, Andrew Singleton, and John Hardy, “Trem2 Variants in Alzheimer’s Disease,” New England Journal of Medicine 368 (November 14, 2012): 117–27; Thorlakur Jonsson, Hreinn Stefansson, Stacy Steinberg, Ingileif Jonsdottir, Palmi V. Jonsson, Jon Snaedal, Sigurbjorn Bjornsson, Johanna Huttenlocher, Allan I. Levey, James J. Lah, Dan Rujescu, Harald Hampel, Ina Giegling, Ole A. Andreassen, Knut Engedal, Ingun Ulstein, Srdjan Djurovic, Carla Ibrahim-Verbaa, Albert Hofman, M. Arfan Ikram, Cornelia M. van Duijn, Unnur Thorsteinsdottir, Augustine Kong, and Kari Stefansson, “Variant of TREM2 Associated with the Risk of Alzheimer’s Disease,” New England Journal of Medicine 368 (November 14, 2012): 107–16, doi:10.1056/NEJMoa1211103.
64. Gina Kolata, “Alzheimer’s Tied to Mutation Harming Immune Response,” New York Times, November 14, 2012.
Chapter 9
Transcending Entrenched Tensions
1. Sandra D. Mitchell, Unsimple Truths: Science, Complexity and Policy (Chicago: University of Chicago Press, 2009), 11.
2. Martin Prince, Renata Bryce, Emiliano Albanese, Anders Wimo, Wagner Ribeiro, Cleusa P. Ferri, “The Global Prevalence of Dementia: A Systematic Review and Metaanalysis,” Alzheimer’s and Dementia 9 (2013): 63–75.
3. David Rothschild, “The Practical Value of Research in the Psychoses of Later Life,” Diseases of the Nervous System 8, no. 4 (1947): 123–28.
4. Tom Kitwood, Dementia Reconsidered: The Person Comes First (Maidenhead: Open University Press, 1997).
5. Farrer, “Familial Risk for Alzheimer Disease”; Hugh Hendrie, “Diagnosis of Dementia,” 122.
6. J. C. Heyman, M. L. Barer Hertzman, and R. G. Evans, eds., Healthier Societies: From Analysis to Action (Oxford: Oxford University Press, 2006).
7. Patricia Churchland, Brain-Wise: Studies in Neurophilosophy (Cambridge, Mass.: MIT Press, 2002), 1.
8. Alva Noë, Out of Our Heads: Why You Are Not Your Brain and Other Lessons from the Biology of Consciousness (New York: Farrar, Straus and Giroux, 2009), 10.
9. Ibid., 181.
10. Scott F. Gilbert, “The Genome in Its Ecological Context: Philosophical Perspectives on Interspecies Epigenesis,” Annals of the New York Academy of Sciences 981 (2002): 202–18, 213.
11. Julian C. Hughes, Stephen J. Louw, and Steven R. Sabat, Dementia: Mind, Meaning, and the Person (Oxford: Oxford University Press, 2006).
12. Ernst Mayr, “Cause and Effect in Biology,” Science 134 (1961): 1501–6.
13. Kirkwood, Time of Our Lives, cited in House of Lords, Science and Technology Committee; see also Moreira and Palladino, “Ageing between Gerontology and Biomedicine,” 363.
14. Savva et al., “Age, Neuropathology, and Dementia,” 2308.
15. Agustin G. Yip, Carol Brayne, and Fiona E. Matthews, “Risk Factors for Incident Dementia in England and Wales: The Medical Research Council Cognitive Function and Ageing Study. A Population-Based Nested Case-Control Study,” Age and Ageing 35, no. 2 (2006): 154–60.
16. See also Sharon Kaufman, … And a Time to Die: How American Hospitals Shape the End of Life (New York: Scribner, 2005); D. D. Von Dras and H. T. Blumenthal, “Dementia of the Aged: Disease or Atypical-Accelerated Aging? Biopathological and Psychological Perspectives,” Journal of the American Geriatrics Society 40, no. 3 (1992): 285–94.
17. Carol Brayne, Paul G. Ince, Hannah A. D. Keage, Ian G. McKeith, Fiona E. Matthews, Tuomo Polvikoski, and Raimo Sulkava, “Education, the Brain and Dementia: Neuroprotection or Compensation? EClipSE Collaborative Members,” Brain 133, no. 8 (2010): 2210–16.
18. Martin Prince, Daisy Acosta, Helen Chiu, Marcia Scazufca, and Mathew Varghese, “Dementia Diagnosis in Developing Countries: A Cross-Cultural Validation Study,” Lancet 361 (2003): 909–17.
19. M. Marsel Mesulam, “Neuroplasticity Failure in Alzheimer’s Disease: Bridging the Gap between Plaques and Tangles,” Neuron 24, no. 3 (1999): 521–29, 526.
20. Ibid., 529.
21. Roth, “Dementia and Normal Aging,” 65.
22. Hampel, Lista, and Khachaturian, “Development of Biomarkers,” 315.
23. Ibid., 315.
24. Evelyn Fox Keller, The Mirage of a Space between Nature and Nurture (Durham, N.C.: Duke University Press, 2010), 7.
25. McGowan and Szyf, “Epigenetics of Social Adversity,” emphasis added.
26. Moshe Szyf, “The Early Life Social Environment and DNA Methylation: DNA Methylation Mediating the Long-Term Impact of Social Environments Early in Life,” Epigenetics 8 (2011): 971–78, 971.
27. Daxinger and Whitelaw, “Understanding Transgenerational Epigenetic Inheritance.”
28. Jörg Niewöhner, “Epigenetics: Embedded Bodies and the Molecularization of Biography and Milieu,” BioSocieties 6 (2011): 279–98, 291.
29. Ibid.
30. Jörg Niewöhner, Martin Döring, Michalis Kontopodis, Jeannette Madarász, and Christoph Heintze, “Cardiovascular Disease and Obesity Prevention in Germany: An Investigation into a Heterogeneous Engineering Project,” Science, Technology & Human Values 36, no. 5 (2011): 723–51.
31. Niewöhner, “Epigenetics,” 290–92.
32. Lock, Encounters with Aging.
33. Zaven S. Khachaturian and Ara S. Khachaturian, “Prevent Alzheimer’s Disease by 2020,” 84.
34. See also Danny George, Peter Whitehouse, Simon d’Alton, and Jesse Ballinger, “Through the Amyloid Gateway,” The Lancet 380 (2012): 1986–87.
35. Lock and Nguyen, Anthropology of Biomedicine, 1.
36. Robin McKie, “Discovery of ‘Methuselah Gene’ Unlocks Secret of Long Life,” The Observer, February 3, 2002; Lorna M. Lopez, Sarah E. Harris, Michelle Luciano, Dave Liewald, Gail Davies, Alan J. Gow, Albert Tenesa, et al., “Evolutionary Conserved Longevity Genes and Human Cognitive Abilities in Elderly Cohorts,” European Journal of Human Genetics 20, no. 3 (2012): 341–47.
37. S. Miyagi, N. Iwama, T. Kawabata, and K. Hasegawa, “Longevity and Diet in Okinawa, Japan: The Past, Present and Future,” Asia-Pacific Journal of Public Health 15, suppl. (2003): S3–S9.
38. David Brindle, “Older People Are an Asset, Not a Drain,” Guardian, March 2, 2011.
39. See Didier Fassin, “Another Politics of Life Is Possible,” Theory, Culture & Society 26, no. 5 (2009): 44–60 for a “politics of life” and the differential value placed on lives.
Afterword
Portraits from the Mind
1. Sebastian J. Crutch, Ron Isaacs, and Martin N. Rossor, “Some Workmen Can Blame Their Tools: Artistic Change in an Individual with Alzheimer’s Disease,” The Lancet 357 (2001): 2129–33.
2. Alzheimer’s Association, Portraits From the Mind: The Works of William Utermohlen 1955–2000: A Retrospective of the Artist’s Work Before and After His Diagnosis with Alzheimer’s Disease (Salt Lake City, Utah: Myriad Pharmaceuticals, 2008), 22. One of the authors of The Lancet article cited above, Ron Isaacs, was William Utermohlen’s nurse.
3. Crutch, Isaacs, and Rossor, “Some Workmen Can Blame Their Tools,” 2130.
4. Galerie Beckel-Odille-Boïcos, William Utermohlen: Paintings and Drawings 1955–1997 (Paris, 2000), extract from exhibition notes.
5. Crutch, Isaacs, and Rossor, “Some Workmen Can Blame Their Tools,” 2132.
6. Ibid., 2133.