Page numbers in italics refer to figures and tables
ADNI. See Alzheimer’s Disease Neuroimaging Initiative
ADRDA. See Alzheimer’s Disease and Related Disorders Association
African Americans, 150, 164, 182
aging: as biggest risk factor for Alzheimer’s disease, 196, 233, 235; as a continuum, 49–50, 232–38; entanglement with Alzheimer’s disease (see aging, entanglement with Alzheimer’s disease); global demographics, 15–16, 247n2; global responses to, 15–17; historical perspectives on, 27–28, 30–32; medicalization of, 37–38; modern rise of longevity, 17–18; and Nun study, 44–45; poor correlation between behavioral and neuropathological changes (see cognitive function, normal); societal attitudes toward, 38. See also elderly people
aging, entanglement with Alzheimer’s disease, 3, 5, 9–10, 24, 27, 105–6, 208, 226–27; and Alzheimer’s disease as diffuse clinical syndrome, 47–49; and decreasing neuroplasticity, 235–36; and diagnosis issues, 61–63, 82; and difficulty of risk assessment, 9; and mild cognitive impairment, 80, 82; and politicization of Alzheimer’s disease, 41; problems with isolating “pure” AD cases, 57, 233; question of what is “normal” in an elderly population, 27, 37, 233
Aisen, Paul, 96
aluminum, 196
AlzGene database, 159
Alzheimer, Alois, 26, 28–30, 33–34, 36
Alzheimer’s Association, 13, 100, 106–8, 147, 181
Alzheimer’s Association International Conference, 98
Alzheimer’s Disease and Related Disorders Association (ADRDA), 40, 54
Alzheimer’s Disease Genetics Consortium, 166
Alzheimer’s Disease International, 13, 14
Alzheimer’s Disease Neuroimaging Initiative (ADNI), 124–27
Alzheimer’s disease: early-onset AD and late-onset AD as same or different processes, 74, 134, 140, 144–45, 152, 210; economic and social repercussions, 12–13, 215; as the epidemic of the 21st century, 1–4; and loss of self, 91, 127–28; medicalization and destigmatization, 14–15, 232; name origin, 35; ontological status, 2, 6–8, 22–23, 54, 64, 134–35; politicization of, 12–14, 38–42, 71, 237, 241; prodromal phase, 10, 73–74, 93–99, 107, 108, 186, 230; sources of information on, 204–6; statistics on prevalence, 12; subtaxa of, 7, 209, 233; uncertain etiology, 3, 110; and worldwide “call to arms,” 213–15. See also aging, entanglement with Alzheimer’s disease; causes and associations of Alzheimer’s disease; diagnosis of Alzheimer’s disease; dominantly inherited Alzheimer’s disease; late-onset Alzheimer’s disease; media reporting on Alzheimer’s disease; prevention of Alzheimer’s disease; research on Alzheimer’s disease; risk assessment
Alzheimer Society of Canada (ASC), 204–6
Alzheimer’s Prevention Initiative (API), 136
Alzheimer’s Society UK, 181
Amos, Amanda, 177
Amouyel, Phillippe, 160
amyloid cascade hypothesis, 10–11; and Colombia clinical trial, 141; critiques of, 67–68, 209; defined/described, 65–70; and diagnosis of Alzheimer’s disease, 52; as dominant AD paradigm, 10–11, 40, 65–70, 129; and dominantly inherited Alzheimer’s disease, 133; and drug development (see anti-amyloid therapeutics under following heading); and early diagnosis, 11, 74; persistence of, in spite of shortcomings, 155, 216, 236–37
amyloid plaque, 33, 46; age of onset of accumulation, 141; amyloid-β trigger scenario, 154; anti-amyloid therapeutics, 10–11, 27, 66, 70–72, 101, 209, 210–11, 215–17, 236 (see also clinical trials); and APOEε4 gene, 121, 145, 151–55; detection of, in vivo (see PET imaging); and differences between early- and late-onset AD, 217; differences in amyloid present from birth, 209, 215; and epigenetics, 226; and failure of clinical trials, 10, 27, 66, 71–72, 101; and history of Alzheimer’s disease, 32–36; and inflammation, 163; lack of, in mice, 104; neurodegeneration prior to plaque deposition, 217, 236; and NIA–Alzheimer’s Association diagnosis criteria, 107; nonconcordance between amyloid deposition and neurodegeneration, 116; plaques present in cognitively normal people, 7, 10, 27, 37, 44–46, 66, 116, 120–24, 211; plaques present in many/most aging brains, 10, 37, 46, 57, 116, 123, 233–34; positive functions, 66, 68, 70, 120, 152–53
API. See Alzheimer’s Prevention Initiative
APOEε4 gene, 23, 143–55, 158, 264n49; and amyloid plaques, 121, 145, 151–55; and neurodegeneration, 150–55, 265n63; risk of AD in homozygous individuals, 182; as susceptibility gene, 143–48, 181
APOE gene, 143, 146, 148, 150, 152, 181–83; activity of, 265n63; ε2 allele, 143, 146, 150, 153, 264n49; ε3 allele, 143, 146, 148–52, 264n49; ε4 allele (see APOEε4 gene); ε5 allele, 149; evolution of, 148–50; gene-gene interactions, 164; genetic testing for, 180–83; and genome-wide association studies, 158; and grandmothering hypothesis, 148, 152; heterozygous vs. homozygous subjects, 263n38; prevalence and penetrance of, 167; questions about significance of APOE alleles to AD incidence, 146–47; REVEAL trials on responses to genetic testing and disclosure, 181–83; worldwide distribution of alleles, 143, 149
Arboleda, Joseph, 136
arteriosclerosis, 37
ASC. See Alzheimer Society of Canada
As You Like It (Shakespeare), 27–28
Asians, 164
autopsies: and cognitively normal subjects, 30, 39, 42, 46, 99; correlation between postmortem neuropathology and clinical diagnosis of dementia, 46, 52–53, 57; debate over relationship between normal and abnormal biological states, 42–43; discovery of plaques and tangles, 32–34; high cost of, 53; and Nun study, 44–45; results compared to PET scans, 118–19
Bagic, Nikola, 140
Banner Alzheimer’s Institute, 136, 138
Barad, Karen, 6
Barnes, Barry, 220
Basque families. See Colombia, familial Alzheimer’s disease in
Beck, Ulrich, 12
Berrios, German, 35
biomarker testing, 8–9, 73–74; critique of proposed guidelines, 101–6; and debate over interpretation of apparent neuropathology in cognitively normal individuals, 120–24; and duress of research subjects, 125, 139; and early diagnosis, 229; endophenotypes, 219; list of tests, 131; recruitment of research subjects, 118, 125, 182, 214; and risk assessment, 77; and shift to molecular prevention of AD, 216–17; uncertainties, 109 (see also under specific biomarkers); unintended consequences, 9, 96; and worldwide “call to arms,” 213–15. See also genetic testing; lumbar puncture/cerebrospinal fluid analysis; MRI scans; neuroimaging; PET imaging
Bohr, Niels, 6
brain: boundary-transversing mind, 24, 231–32, 238; brain trauma, 3, 7, 55; brain weight and education level, 235; cerebral reserve hypothesis, 44 (see also cognitive reserve); debate over relationship between normal and abnormal biological states, 42–47; neuroplasticity, 235–36; sociopolitical and ecological influences on, 230, 238. See also amyloid plaque; autopsies; cognitive function, impaired; cognitive function, normal; cognitive reserve; localization theory of dementia; MRI scans; neurofibrillary tangles; neuroimaging; neuropathology; PET imaging
Brayne, Carol, 47, 48, 61, 62, 128, 230, 232–34, 236
BRCA gene, 179
breast cancer, 179
Breitner, John, 61
Brisbane, Arthur, 94
Bristol-Myers Squibb (pharmaceutical company), 71, 96
Brooks, David, 114
Broussais, François-Joseph-Victor, 42–43
Buchanan, Anne, 222
Buee, Luc, 116
Cambrosio, Alberto, 48–49, 249n49
Canada, 13, 53, 55. See also Alzheimer Society of Canada
Canguilhem, Georges, 43
CAP. See Consortium for Alzheimer’s Prevention
Carbo, Rosa Maria, 149
caregiving, 25, 40, 172, 199–200, 203
Carome, Michael, 119
Cartesian dualism, 231
causes and associations of Alzheimer’s disease, 3, 4, 6, 7; age as biggest risk factor, 196, 233, 235; competing ideas about, 229–30; and embedded bodies concept, 239–40; lay beliefs about, 196–201; marginalization of extrasomatic factors, 230–32, 237. See also amyloid cascade hypothesis; genes; immune system; inflammation; localization theory of dementia; obesity; oxidative stress; risk assessment; social conditions; toxins
cell loss, 10, 69, 237. See also neurofibrillary tangles
The Century of the Gene (Fox Keller), 219
cerebral arteriosclerosis, 37
cerebral reserve hypothesis, 44. See also cognitive reserve
cerebrospinal fluid analysis. See lumbar puncture/cerebrospinal fluid analysis
Chertkow, Howard, 82, 123, 233
cholinergic hypothesis, 71, 72
cholinesterase inhibitors, 71
chromatin, 227
Churchland, Patricia, 231
Clinical Dementia Rating Scale, 78–79
clinical trials, 48–49; benefit to local populations, 140–42; and CAP session at Vancouver meeting of 2012, 210–11; dropout rates, 128; ethics of, 140–41; failure of clinical trials designed to target removal of amyloid plaques, 27, 66, 71–72, 101, 215–17, 241; and familial, early-onset Alzheimer’s disease in Colombian families, 136–42, 216–17; and media reporting, 96; “offshoring” of, 140; problems with, 165; and subtypes of Alzheimer’s disease, 209. See also research subjects
CLU (clusterin gene), 160, 162
Coalition Against Major Diseases, 72
cognitive function, impaired. See Alzheimer’s disease; dementia; dominantly inherited Alzheimer’s disease; memory loss; mild cognitive impairment; neuropathology
cognitive function, normal: amyloid deposition detected through PET scans, 115–16, 260–61n47; and APOE alleles and cerebral Aβ deposition, 153–54; and autopsies, 30, 39, 42, 46, 99; debate over interpretation of apparent neuropathology in cognitively normal individuals, 120–24, 229–30, 260–61n47; debate over relationship between normal and abnormal biological states, 42–47; and education level, 234–36; neuropathology in cognitively normal people, 3, 5, 7, 10, 27, 37, 44–46, 66, 99, 116, 120–24, 211, 234–35; plaques present in many/most aging brains, 10, 37, 46, 57, 116, 123, 233–34; “protected” minds, 27 (see also cognitive reserve); question of what is “normal” in an elderly population, 27, 37, 233
cognitive reserve, 7, 41–42, 44, 69, 116, 123, 235
Cohen, Lawrence, 15
Cohn, Simon, 127
Colombia, familial Alzheimer’s disease in, 135–42, 206, 211; preliminary findings of study, 216–17
consciousness, 5, 231–32. See also brain; mind
Consortium for Alzheimer’s Prevention (CAP), 210
The Constant Gardner (Le Carré), 49
Cox, S., 176
CRI (complement receptor I gene), 160
Cunnignham-Burley, Sarah, 177
cure for Alzheimer’s disease. See clinical trials; prevention of Alzheimer’s disease
deCode Genetics, 208
de Leon, Mony J., 97
dementia: conditions causing, 55; entanglement theory of, 5, 9–10 (see also aging, entanglement with Alzheimer’s disease); historical perspectives on aging and dementia, 27–28, 30–32; lack of, in some subjects with AD neuropathology (see cognitive function, normal); lack of diagnosis for the majority of people, 172; Lewy body dementia, 47, 56; mixed, 47, 55, 60, 64; presymptomatic, 8, 9 (see also prodromal phase of Alzheimer’s disease); screening tests, 54–55, 78–79, 83–84, 231, 254n13, 258n35; vascular dementia, 47, 55, 150. See also diagnosis of Alzheimer’s disease; history of Alzheimer’s disease; localization theory of dementia
depression, 62, 128, 190–91, 196–97, 201
diabetes, 57, 121, 123, 149, 230, 242
diagnosis of Alzheimer’s disease, 3, 51–75, 106; Alzheimer’s as a diagnosis of exclusion, 55–57, 64; and amyloid cascade hypothesis as prevailing paradigm, 65–70; and biomarkers (see biomarker testing); confounding factors, 53, 55; dangers of premature diagnosis, 81, 101; “The Diagnosis of Dementia Due to Alzheimer Disease” report, 108–11; diagnosis of “pure” AD as artifact of attempts at standardization, 61–62; difficulty of diagnosing presymptomatic AD, 10; discrepancies between clinical and neuropathological diagnosis, 22, 38, 44–45, 106–8; discrepancies between memory clinics and general family practice settings, 22; DSM criteria, 61; early diagnosis and hopes for prevention, 73–75 (see also prodromal phase of Alzheimer’s disease); and entanglement of aging and Alzheimer’s (see aging, entanglement with Alzheimer’s disease); inconsistencies in clinical diagnosis, 52–60; inconsistencies in neuropathological diagnosis, 60–65; media reporting on early diagnosis, 93–99; mild cognitive impairment diagnosis, 22 (see also mild cognitive impairment); NIA–Alzheimer’s Association criteria, 106–8, 113, 147; NINCDS-ADRDA criteria, 54; revising the definition of Alzheimer’s disease, 98–131 (see also biomarker testing); ruling out false positives through neuroimaging, 117; screening tests, 54–55, 78–79, 83–84, 254n13, 258n35. See also autopsies; biomarker testing; mild cognitive impairment
DIAN. See Dominantly Inherited Alzheimer Network
discrimination. See social conditions
divination, 23, 174–206. See also risk assessment
DNA, 218–21. See also genes; genetic testing
Dominantly Inherited Alzheimer Network (DIAN), 210–11, 216
dominantly inherited Alzheimer’s disease, 23, 65, 133–43; age of onset, 134, 141; and APOE alleles, 167; and Colombian families of Basque origin, 135–38, 206, 216–17; and disclosure/nondisclosure of genetic test results to research subjects, 142; early-onset AD and late-onset AD as same or different processes, 74, 134, 140, 144–45, 152, 210; genes for, 133–43; and genome-wide association studies, 167; neuropathological features, 134–35; possible negative consequences of genetic testing, 138; and Volga German families, 133–34
Doreiswamy, P. Murali, 96
Douglas, Mary, 76
Down syndrome, 65
drug development, 70–72. See also clinical trials
DSM criteria, 61
early-onset Alzheimer’s disease. See dominantly inherited Alzheimer’s disease
education level, 3, 7, 69, 234–36, 242
Elan (pharmaceutical company), 71
elderly people: contributions to society, 241; discrimination against, 38, 39; global demographics, 15–16, 247n2; and global responses to aging, 15–17; need for improved care and social support for, 241. See also aging; cognitive function, impaired; cognitive function, normal; research subjects
Eli Lilly (pharmaceutical company), 71–72, 216
embedded bodies concept, 24, 239–40
entanglement theory of dementia, 5, 20. See also aging, entanglement with Alzheimer’s disease
epigenetics, 5–7, 24, 218–21, 230, 238–39; developmental systems theory, 220; epigenetic inheritance, 175; and lay understandings of gene-environment interactions, 223–25; and life experience of individuals, 225–28, 238, 239; methylation, 226, 227, 238–39; term origin, 247n6
ethics: and entanglement of aging and Alzheimer’s, 9; and genome-wide association studies, 169; and informing research subjects of their test results, 97, 212 (see also REVEAL trials on responses to genetic testing and disclosure); and research on familial AD in Colombian families, 137, 140–41
ethnicity, 143, 148–50, 163, 164, 182
eugenics, 257n11
Ewald, François, 76
familial Alzheimer’s disease. See dominantly inherited Alzheimer’s disease
Finch, Caleb, 148
florbetapir, 118
folic acid deficiency, 55
Fox Keller, Evelyn, 170, 218, 219, 238
Franklin, Sarah, 176
Freud, Sigmund, 35
funding for Alzheimer’s disease research, 4, 50, 129; compared to funding for other major diseases, 207–8; focus of, 8, 50, 155; and genome-wide association studies, 172; lack of funding for caregiving, 40; and politicization of Alzheimer’s risk, 13–14, 40–41, 237, 241
Genentech (pharmaceutical company), 138, 140
genes, 23–24, 132–55, 163; ADAM10 gene, 170–71; AlzGene database, 159; CLU (clusterin) gene, 160, 162; common disease/common variation hypothesis, 157, 167, 266n4; and complexity of organisms, 221–23; contextual effects ignored, 220; CRI (complement receptor I gene), 160; discovery of additional genes associated with AD, 227; and disease taxonomies, 7; and dominantly inherited Alzheimer’s disease, 133–43; endophenotypes, 219; evolution of APOE gene, 148–50; gene-environment interactions, 218–20, 223–25, 238 (see also epigenetics); gene-gene interactions, 164, 168–69, 171; genetic homogeneity over the lifecycle, 220–21; genetic testing (see genetic testing); genome-wide association studies (see genome-wide association studies); and grandmothering hypothesis, 148, 152; lay understandings of genetics, 176, 193–96, 203–4, 223–25; and “missing” heritability, 168–69, 171, 267n21; penetrance of, 134, 167, 170, 177; polymorphisms, defined, 266n2; prevalence of, 167; protective genes, 208, 209; rare variants with large effect sizes, 169, 171; single gene disorders, 23–24, 176–80; single nucleotide polymorphisms (SNPs), 157, 266n3; SORL1 gene, 171; TOMM40 gene, 171; TREM2 gene, 227; worldwide distribution of alleles, 149. See also APOEε4 gene; APOE gene; APP gene; epigenetics; presenilin-1 gene; presenilin-2 gene
genetic testing, 201–4; and APOE alleles, 180–83; and “biosociality,” 179–80; disclosure/nondisclosure of test results to study participants, 4, 142, 181, 206 (see also REVEAL trials under this heading); discouraged by physicians, 202, 205; and dominantly inherited Alzheimer’s disease, 142–43; and family history, 193–96; and family planning, 143, 176, 177; and “genetic citizenship,” 206; genetic counseling, 192–93; and Huntington disease, 177–78; interviews with subjects of unknown genotype, 201–4; issues faced by subjects following testing, 177; and lay understandings of genetics, 176, 193–96; low number of at-risk individuals choosing genetic testing for single gene disorders, 177; people’s responses to test results, 177–79, 181–206; position of AD societies, 181, 185, 202; possible negative consequences of, 138, 177, 192, 257n11; private company testing, 181; REVEAL trials, 181–206; and uncertainty, 2, 9, 178–81, 185–86, 199
genome-wide association studies (GWAS), 23, 156–73; AlzGene database, 159; discovery of additional genes associated with AD, 160, 166, 170–71; and ethics, 169; limitations of, 161, 165–66; and “missing” heritability, 168–69, 171; questions triggered by, 162–66; single nucleotide polymorphisms (SNPs), 157, 170
Ghana, 247n2
Gilbert, Scott, 232
Global Deterioration Scale, 78–79
Goldstein, David, 169
Golgi, Camillo, 32
Green, Robert, 183, 185, 186, 212
Griesinger, Wilhelm, 30
Griffiths, Paul, 220
Grundke-Iqbal, 209
GWAS. See genome-wide association studies
Hallowell, Nina, 179
Hardy, John, 41, 65, 66, 72, 74, 135, 145, 152, 209, 215
Hendrie, Hugh, 150
Hepatitis C, 51
hippocampus, 69
Hispanics, 164
history of Alzheimer’s disease, 26–50; Alzheimer’s disease as diffuse clinical syndrome, 47–49; August D. case, 31–34, 36; and debate over relationship between normal and abnormal biological states, 42–47; discovery of Alzheimer’s disease, 29–30, 33–36; historical perspectives on aging and dementia, 27–28, 30–32; Johann F. case, 34, 36; and medicalization of aging, 37–38; and naming of disease, 35; partial eclipse of AD in the early and mid 20th century, 36–37; and plaques and tangles, 32–36, 33; politicization of Alzheimer’s disease, 38–42; and psychiatry, 29–30; recognition in the 1970s, 15, 39–42; stigma against mental illness, 29
HIV, 51
Holstein, Martha, 37
Hughes, Charles, 30
Human Genome Project, 218
Huntington disease, 55, 176–77
Hurley, Susan, 231
Hyman, Bradley, 26–27, 50, 134–35
hypothyroidism, 55
Hyslop, Peter, 14, 152, 165–66, 171
ICAD. See International Conference on Alzheimer’s Disease
Iceland, 208
IGAP. See International Genomics of Alzheimer’s Project
immunoglobulin, 209
inequality. See social conditions
infarcts. See stroke
inflammation, 7, 68, 105, 112, 162–63, 171
International Conference on Alzheimer’s Disease (ICAD), 98, 100
International Genomics of Alzheimer’s Project (IGAP), 210
International Psychogeriatric Association, 80
Iqbal, 209
Jack, Clifford, 117
Katz, Russell, 96
Katzman, Robert, 39
Kerr, Anne, 177
Khachaturian, Zaven, 54, 62, 128, 132, 213
King Lear (Shakespeare), 230n3
Kitwood, Tom, 230
Kolata, Gina, 93–99, 105, 126, 162, 208
Kral, Voijtech Adalbert, 78
Kuhn, Thomas, 3, 10, 19, 107–8, 155
Langreth, Robert, 71
late-onset Alzheimer’s disease: and APOEε4 gene (see APOEε4 gene); early-onset AD and late-onset AD as same or different processes, 74, 134, 140, 144–45, 152, 210; as extreme form of normal aging, 226–27; and rare variants of APP, PSEN1, and PSEN2 gene, 171. See also Alzheimer’s disease
Lectures on Senile and Chronic Diseases (Charcot), 37
Lewontin, Richard, 132, 221–23
lifestyle, 3, 4, 7, 105, 223–25, 235, 238, 242
Lill, Christina, 169
Lippman, Abby, 176
Lishman, William, 41
localization theory of dementia, 5, 9–10, 30, 33–35, 42, 45, 47, 61, 214–15, 230, 232, 236. See also amyloid cascade hypothesis; neuropathology
The Longevity Revolution (Butler), 1
Lopera, Francisco, 135–37, 141
Lou Gehrig’s disease (ALS), 61
Lovestone, Simon, 74
lumbar puncture/cerebrospinal fluid analysis, 9, 39, 73–74, 94–95, 101, 112–14, 126
Mapping Fate (Wexler), 177
Maury, C.P.J., 68
MCI. See mild cognitive impairment
McKellin, W., 176
media reporting on Alzheimer’s disease, 13; and ADNI study, 126; and Colombia clinical trial, 141; and early diagnosis, 93–98; and genetics, 162, 205; impact of “Dear Abby” column, 40; and PET scans, 116; and recognition of Alzheimer’s disease in the 1970s, 39–40
memory clinics, 57–58, 82–93, 258n33
memory loss: and acetylcholine, 71, 72; benign senescent forgetfulness, 78; and discovery of Alzheimer’s disease, 31; and mild cognitive impairment, 77–93; recall as focus of AD clinical testing, 72; and repression, 38
mental activity, 58, 121, 196, 198. See also education level
mild cognitive impairment (MCI), 22, 74, 77–93, 258n27; and continuum of Alzheimer’s disease, 108; and dangers of premature diagnosis of Alzheimer’s disease, 81; different viewpoints on, 80–82; and language problems, 88–89; list of evaluation methods, 130; and memory clinics, 82–93; origin of diagnosis category, 79–82; patients’ fears about, 89–90; patients’ lack of knowledge about, 89; and REVEAL trials, 206, 212; and revised diagnosis guidelines, 109, 111; screening tests, 78–79, 83–84, 258n35
mind: AD neuropathology present in many cognitively normal people (see cognitive function, normal); boundary-transversing mind, 24, 231–32, 238; and Cartesian dualism, 231; and localization vs. entanglement theories of dementia, 5 (see also aging, entanglement with Alzheimer’s disease; localization theory of dementia); loss of self, 91, 127–28; reductionism and bifurcation of mind and body, 228–30
Mini-Mental State Examination (MMSE), 54–55, 254n13, 258n35
Mintun, Mark, 120–22, 260–61n47
The Mirage of a Space Between Nature and Nurture (Keller), 170
mitochondria, 68
MMSE. See Mini-Mental State Examination
Montréal Cognitive Assessment instrument (MoCA), 82, 83, 258n35
Morris, John, 47, 61, 92–93, 111, 120, 125, 142, 153, 211, 216
multiple sclerosis, 51
Murdoch, Iris, 235
The Myth of Alzheimer’s: What You Aren’t Being Told about Today’s Most Dreaded Diagnosis (Whitehouse), 62–64, 104–5
Nascher, Ignatz, 37
National Alzheimer Project Act, 172, 208
National Institute on Aging (NIA), 40, 100, 106–8, 147
National Institute of Neurological and Communicative Disorders and Stroke (NINCDS), 54
National Institutes of Health (NIH), 138. See also REVEAL trials on responses to genetic testing and disclosure
Nature after the Genome (Parry and Dupré), 220
Neel, James, 149
neurofibrillary tangles, 46, 65, 236; and history of Alzheimer’s disease, 32–36; and NIA–Alzheimer’s Association diagnosis criteria, 107; present in cognitively normal people, 44–45 (see also cognitive function, normal); tau-related pathology, 67, 112–13
neuroimaging, 9, 10; ADNI study, 124–27; and critique of proposed guidelines, 101; and detection of neurodegeneration, 116–17, 117; and media reporting, 93–94, 97. See also MRI scans; PET imaging
neuropathology, 46; APOEε4 gene and neurodegeneration, 150–55; cell loss, 10, 69, 237 (see also neurofibrillary tangles); in cognitively normal individuals (see cognitive function, normal); and cognitive reserve (see cognitive reserve); debate over relationship between normal and abnormal biological states, 42–47; and dominantly inherited Alzheimer’s disease, 134–35, 141–42; and education level, 235; mismatch between clinical and neuropathological diagnosis, 38, 44–45, 120; neurodegeneration prior to plaque deposition, 217, 236; and NIA–Alzheimer’s Association diagnosis criteria, 106–8. See also amyloid cascade hypothesis; amyloid plaque; neurofibrillary tangles; tau protein
Newton, R. D., 39
NIA. See National Institute on Aging
Niewöhner, Jörg, 239
Nigeria, 150
NINCDS. See National Institute of Neurological and Communicative Disorders and Stroke
Nobel Prize, 32
normality. See cognitive function, normal
Obama, Barack, 138, 172, 207–8
Out of Our Heads (Noë), 231
Padolsky, Miriam, 204
paintings of William Utermohlen, 243–46
paisa mutation of presenilin-1 gene, 135–38. See also Colombia, familial Alzheimer’s disease in
Palladino, Paolo, 49
paradigm shift, 3, 10, 107–8, 128–29, 216
Parkinson’s disease, 55
Parry, Sarah, 220
PET imaging, 73–74, 101, 114–17; and ADNI study, 124–27; critiques of, 119–20; and debate over interpretation of apparent neuropathology in cognitively normal individuals, 120–24, 260–61n47; and detection of amyloid in vivo, 114–17; and detection of neurodegeneration, 116–17, 117; and research directions, 118–19; and revised definition of Alzheimer’s disease, 112; and schizophrenia, 119
Pfizer (pharmaceutical company), 71, 215
pharmaceutical companies, 8, 10–11, 47, 71, 105, 106, 129. See also clinical trials; specific companies
PIB tracer molecule, 114–17, 120–23, 125, 153–54, 261n47
PICALM gene, 160
Pick, Arnold, 35
Pinel, Philippe, 30
plaques. See amyloid plaque
politicization of Alzheimer’s disease, 12–14, 38–42, 71, 237, 241
Potamkin Prize, 116
poverty, 4, 7, 15, 140, 230, 242
prediction of Alzheimer’s disease. See risk assessment
presenilin-1 gene, 133–38, 164, 171
presenilin-2 gene, 133–34, 163, 171
prevention of Alzheimer’s disease, 4, 7–11, 76–99; and early diagnosis, 73–75, 77–93, 229; lay beliefs about, 196–97, 223–25; marginalization of extrasomatic factors, 230–32, 237; and media reporting, 93–99; need for focus on extrasomatic factors, 239–42 (see also epigenetics); shift to molecular prevention, 212, 216–17 (see also biomarker testing); and styles of thought, 19; and uncertainty in risk assessment, 9–10. See also diet; education level; exercise; lifestyle; mental activity; public health; social conditions
prodromal phase of Alzheimer’s disease, 10, 73–74, 93–99, 107, 108, 186, 230
psychiatry, and history of Alzheimer’s disease, 29–30
public health, 4, 24, 240, 242
Purisini, Gaetano, 35
racism. See social conditions
Ramon y Cajal, Santiago, 32
Reagan, Ronald, 97
Reiman, Eric, 136–37, 140, 211, 216
research on Alzheimer’s disease: Alzheimer Disease Neuroimaging (ADNI) study, 124–27; assumptions of researchers, 20; Canadian Study of Health and Aging, 55; and familial AD in Colombian families, 136–42, 216–17; focus on amyloid cascade hypothesis, 65–68 (see also clinical trials); global networking among researchers, 18–20, 249n49; MIRAGE study, 183–86; and “partial connections,” 21; and PET scans, 118–19; politics of, 237; problems with isolating “pure” AD cases, 57, 233; recent results (Vancouver conference 2013), 207–13; research subjects (see research subjects); and styles of thought, 18–21; tensions between types of researchers, 48
research subjects: and biomarker testing, 125, 127–28, 139; disclosure/nondisclosure of test results to, 4, 85, 87, 91–92, 139 (see also REVEAL trials on responses to genetic testing and disclosure); and familial AD in Colombian families, 136–42, 216–17; as “hybrid bioclinical entities” (research subjects and patients), 80, 85; impact of uncertainties on, 110, 128; recruitment of, 118, 125, 182, 207, 214
responsibility for ill health, 175, 225, 232, 257n11
REVEAL trials on responses to genetic testing and disclosure, 181–206; conceptualization of, 183–86; imparting risk estimates, 192–93, 270n40; and lifetime risk curves, 184, 185; and MCI subjects, 206, 212; and participants’ beliefs about causes/prevention of AD, 196–201; participants’ family and caregiving concerns, 189–90, 199–200; recall of genotypes, 186–92; risk perceptions of trial participants, 186–92; and trial participants’ lay knowledge, 187, 193–96
Richards, Marcus, 48
Richards, Martin, 194
risk assessment, 9–10, 23, 174–206; and APOE alleles, 180–83; and continued uncertainty following testing, 178–83, 185–86; difficulty of, 2, 9–10, 180–81 (see also genetic testing); and family history, 193–96, 203–4, 240; lifetime risk curves, 184, 185; philosophy of risk, 76–77; and probability theory, 11–12; and single gene disorders, 176–78, 180. See also biomarker testing; REVEAL trials on responses to genetic testing and disclosure
Ronald and Nancy Reagan Research Institute, 112
Sapolsky, Robert, 148
Saunders, Ann, 147
Scacchi, Renato, 149
Schellenberg, Gerard, 163–65, 210, 219–20
schizophrenia, 119
Schneider, Julie, 128
screening tests, 54–55, 78–79, 83–84, 231, 254n13, 258n35
Sebelius, Kathleen, 207
Segelken, Roger, 39
Selkoe, Dennis, 66
Shakespeare, William, 27–28, 230n3
Skovronsky, Daniel, 93
Smith, Mark, 66, 67–69, 71, 105
social burden of Alzheimer’s disease, 25; and funding, 40; and patients’ fears about the future, 89–91, 189–90, 199–200; projected Medicare costs, 109. See also caregiving
social conditions, 7, 15, 172, 230, 235, 238, 242
solanezumab, 216
SORL1 gene, 171
spinal taps. See lumbar puncture/cerebrospinal fluid analysis
sports, 7
Stefansson, Kari, 208
Stix, Gary, 208
Strathern, Marilyn, 21
Strohman, R., 221
suicide, 239
Sydenham, Thomas, 5
syphilis, 33
The Taming of Chance (Hacking), 11
tangles. See neurofibrillary tangles
Tanzi, Rudolph, 69–70, 152–53, 158–59, 166–71
Templeton, Alan, 146
Thies, William, 63–65, 92, 125, 129
“thought collectives” (Fleck’s conception), 19–21
TOMM40 gene, 171
traumatic experiences, 238, 239
TREM2 gene, 227
Trojanowski, John, 126
Turner, Victor, 91
United Kingdom, 14, 40. See also Alzheimer’s Society UK
United States, 172, 208, 215. See also Alzheimer’s Association; Alzheimer’s Disease and Related Disorders Association; Alzheimer’s Disease Neuroimaging Initiative; Coalition Against Major Diseases; International Psychogeriatric Association; National Institute on Aging; National Institute of Neurological and Communicative Disorders and Stroke
vascular dementia, 47, 55, 150
vitamin B12 deficiency, 55
Volga German families, 133–34, 163
Waddington, C. H., 247n6
Wang, Sun-Chong, 226, 227, 232, 238
Weber, L. W., 34
Weisgraber, K. H., 265n63
Wexler, Nancy, 177
Whitehouse, Peter, 32, 40, 62–64, 71, 80–81, 104–6, 186
Williams, Julie, 159–60, 162–63
Wolfe, Sidney, 119
World Alzheimer’s Day, 14
Wundt, Wilhelm, 35
Yoxen, Edward, 175