Chapter 9

Transcending Entrenched Tensions

The world is indeed complex; so too should be our representations and analyses of it. Yet science has traditionally sought to reduce the “booming, buzzing, confusion” to simple, universal, and timeless underlying laws.

—Sandra D. Mitchell, Unsimple Truths¹

Competing Ideas about Causality

The preceding chapters have made clear that the interrelated tensions highlighted in the opening Orientations revolve to a greater or lesser degree around matters relating to ideas about AD causation. Is Alzheimer’s best modeled as though this condition is purely a “material” matter? In other words, does AD take hold and evolve entirely in the brain as a fully localized phenomenon? If yes, then efforts to treat this condition should be focused on the presumed molecular pathologies associated with the final common pathway(s) that result from the amyloid cascade hypothesis, or some modified version of it. This localized approach is by definition reductionistic, a product of a consciously parsimonious approach, and is oriented primarily to the development of effective drugs. The shift in emphasis toward prevention based on detection of AD biomarkers does not dislodge this reductionism; it means only that if effective drugs are discovered, then they will be administered before the behavioral changes associated with AD can be discerned by means of cognitive testing.

In practice, reductionism is being further embedded it seems because, as a result of the shift to prevention, Alzheimer-associated neuropathology has for the first time been formally bifurcated from clinical symptomatology in the new diagnostic guidelines—thus sundering mind and body. An intermediate stage between normality and dementia is explicitly recognized, in which biomarker changes can be detected but individuals show no signs of behavioral changes (see chapter 4). A good number of people with amyloid biomarkers will develop AD-like behavioral symptoms several years after the biomarkers are first observed, but others will not. Those individuals who test biomarker positive, but who remain cognitively normal until death, are presumed by most researchers to be repositories of the disease that would have eventually become manifest had death not intervened.

Versions of this dominant model of AD grounded in localization theory have held sway for many years. Even so, adherents do not deny that many factors external to the body may well predispose individuals to, and increase susceptibility for, dementia; although the majority make no attempt to research variables other than those internal to the brain. The result has been that serious ruptures have long pervaded the AD world because everything extraneous to the body has been pushed to one side by the majority of experts and given short shrift. It is probably safe to assume that dementia is universally distributed though time and space,² but contemporary research, including the emerging work on epigenetics, has made it clear that it is not equally distributed within or among families, communities, or populations, strongly supporting the position that environments—sociopolitical and ecological—influence the development and functioning of the brain. But findings such as these do not captivate molecular researchers working to cure neuropathologies, except those few who have moved in the direction of epigenetic investigations.

A small number of experts over the past 100 years have never been enamored by arguments about plaques and tangles. These individuals have often stressed the significance of the social and environmental milieus in which aging takes place, and range from the work of the psychiatrist David Rothschild writing in the 1940s,³ to the contemporary writings of the recently deceased psychologist Tom Kitwood and his followers in Great Britain whose motto is “the person comes first.”⁴ Research in cross-cultural epidemiology has also highlighted the significance of environmental milieus,⁵ as does the work of Carol Brayne and colleagues based in the United Kingdom, and now evolving research on epigenetics raises numerous questions for further investigation into developmental and life course experiences and susceptibility to dementia. A concerted effort to reduce obesity and diabetes worldwide would without doubt lower the incidence of mixed dementias. But, in effect, this will only amount to an extended application of localization theory to other bodily systems and their effects on brain functioning, unless the social and political dimensions that account for the prevalence of these diseases—above all, poverty, inequalities, and the promotion and marketing of fast food—are systematically tackled—something that is beginning to take place in certain towns and cities, such as the restrictions in size of soda bottles suggested by Michael Bloomberg, the current mayor of New York City.

Contextualizing the Brain

The move to biomarker-based diagnostic criteria for prodromal dementia will cement a bifurcation of mind and body. But the very fact that biomarker signifiers are based on probabilities involving estimates of risk and susceptibility leaves the door open for a critical discourse, one that asks why some people get sick and others do not,⁶ thus forcing a move upstream to consider possible contributions made by mind, individuals, families, and environments as either protective, neutralizing, or causative agents.

Certain readers may have wondered as they perused the preceding chapters why “mind” simply does not appear in discussions. After all, is not the mind of an individual a mediator between stimuli external and internal to the human body? But this position is not accepted by many vocal philosophers of the day. Patricia Churchland, for example, believes that it is “the brain rather than some non-physical stuff, that feels, thinks, decides.”⁷ And by far the majority of neurologists and cognitive psychologists assume that when they test patients using the Mini-Mental State Examination, MoCA, and so on, they are measuring mental activities that take place fully inside the brain, and are, in effect, a direct reflection of brain structure and function. However, in his book Out of Our Heads, the philosopher Alva Noë argues persuasively, “[Y]ou are not your brain.” Noë concedes that prominent philosophers of neuroscience counter such a position, but in turn he responds that at present, we simply have no evidence as to how a vast assembly of nerve cells and their associated molecules might give rise to consciousness.

For Noë and philosophers who share his view, to have a mind is to be conscious, whereas to have a brain is to have a certain kind of bodily organ or part. The brain is only one key element in the achievement of consciousness—consciousness is a phenomenon that requires the “joint operations of brain, body, and world. Indeed consciousness is an achievement of the whole animal in its environmental context. I deny, in short, that you are your brain. But I don’t deny that you have a brain. And I certainly don’t deny that you have a mind.”⁸ Explicitly following the philosopher Susan Hurley, Noë argues that the bony skull is not a “magical membrane” that delimits trafficking, and mental processes do not have to be explained entirely in terms of internal processes. Hence, he argues, we would do well to understand the phenomena of mind, and therefore of consciousness and experience, as one of “boundary crossing.” Noë reminds readers about the plasticity of the human brain, evident by its long-term evolutionary adaptations, as well as environmental adaptations over shorter durations, and also over the life course of individuals—a never-ending relay of responses to stimuli, external and internal to the body, that takes place over a vast time dimension.

Noë comments that establishment neuroscience is committed to the Cartesian doctrine: “[A] thing within us that thinks and feels. Where the neuroscientific establishment breaks with Descartes is in supposing that the thinking thing is the brain.” Neuroscience and certain philosophers have, in effect, obliterated the ghost in the machine, and Descartes’s dualism is collapsed into a monism, but this move has left us with a piece of meat—the brain—that simply cannot account for consciousness and subjective human experience in all its variety. Noë conceptualizes mind, as did Hurley, as horizontally modular architecture not bounded by the confines of the human body. He concludes that neuroscience must come to terms with the way in which we are “dynamically coupled with the world.”⁹ And his position is not unlike that of the biologist Scott Gilbert, who argues that new insights about individual biological development suggest that “self” is permeable and that “[w]e are each a complex community, indeed, a collection of ecosystems.”¹⁰

Noë has nothing to say about dementia, but his writing clearly suggests that he would reject localization theory as, at best, a partial account of dementia-like phenomenon and other neuropathological conditions (see the book Dementia: Mind, Meaning, and the Person for a full explication of this position).¹¹ Of course, mind, in its popular understanding as confined fully in the brain and operating as the seat of brain-bounded self and subjectivity, cannot cause the terrible neurological devastation of AD—there is nothing psychosomatic about AD, although psychiatric disorder may be a contributor at times. But mind as consciousness and as part of everyday lived experience that involves not only shared social life, education, access to adequate nutrition, and so on, but also, at times, enormous trauma, can undoubtedly make an indirect contribution to neuropathology. By definition, this boundary-traversing mind is a concept that mediates between external and internal environments and stimuli. And this mind permits us to ask why some people become demented and others remain cognitively “normal” even when “neuropathology” is detected. The chain of AD causality is partially shifted from proximate to more distal causes, to use Ernst Mayr’s terminology.¹²

Deeply held assumptions in the neurological world that account for the tenacity of localization theory ensured that AD became understood as a condition confined to the brain, in terms of both cause and effect. This facilitated the recognition of AD as a bona fide disease to which moral recriminations should not be attached. But, by reducing causal explanations for AD to molecular changes alone, medicalization sidelined socioeconomic, political, and public health arguments in connection with risk for AD. One matter that would be brought to the fore by shifting an explanatory model for AD causation to spheres more expansive than neuropathology is the question of allocation of responsibility for Alzheimer’s. I will return to this point in the closing paragraphs.

Is Alzheimer Disease on a Continuum with Normal Aging?

Turning to the second tension, that of AD as normal or pathological aging, Wang and colleagues argue that it is appropriate to think of every individual as being “predisposed” to developing Alzheimer disease. And the biologist of aging Tom Kirkwood points out that “aging is a continuum, affecting all of us all the time.”¹³ His position is that aging is inextricably entangled with conditions that become manifest in later life, including dementia. Using epidemiological methods, Carol Brayne and colleagues concluded that factors other than the simple presence of Alzheimer neuropathology must determine the clinical expression of dementia, notably in those 75 years of age and older. Their argument (see also chapter 1) states, “[C]ognitive dysfunction in later life is a life-span issue and is affected by genetic, developmental, and lifestyle factors, accumulated neural insults, innate and acquired cerebral reserve and compensatory mechanisms, and age-related decline.”¹⁴ Moreover, decades of accumulated autopsy evidence have demonstrated that amyloid plaques, tangles, and other assumed signifiers of Alzheimer’s can be found to varying degrees in all aging brains.

In a 2007 article Brayne reminds readers that age itself is, by a long way, the greatest risk factor for dementia, and individuals aged 90 and older have more than 25 times the risk of developing dementia than those aged 65 to 69.¹⁵ She is critical of research attempts to isolate and study “pure” Alzheimer’s, because in such studies individuals with age-related pathologies such as vascular disease have been so often excluded as research subjects, although in recent years this has changed somewhat. Brayne points out that if, for example, one were to exclude people with hypertension, then about 30% of many older populations could not be subjects for dementia research, thus introducing a major bias, and raising an important epistemological question also raised explicitly by David Bennett and Howard Chertkow: what is “normal” in an elderly population? Alzheimer researchers have a perennial problem notes Brayne, “deciding where normal aging stops and dementia starts,” and such decisions depend in large part on expectations about aging that are profoundly influenced by culture and politics.¹⁶

In common with a good number of researchers today, Brayne believes that Alzheimer’s is not a single disease but a syndrome, with at least two and possibly several subtypes, each of which is closely associated with the aging process. Such heterogeneity should not be standardized into oblivion, Brayne argues, but on the contrary, acknowledged and researched with care. Carol Brayne is the principal investigator in a research program that commenced in 1985 that focuses on longitudinal population-based studies of people aged 65 and older. When I talked with her in 2010, she had this to say:

The great bulk of people with dementia are 75 and up and most of them are labeled as AD … and I actually think that for these older groups going right back and thinking about senile dementia, but obviously trying to find a new, more acceptable label for this overarching condition, would be better for them; and more honest, in a way. … I think we need to look at a person and see where they are on a cognitive spectrum and how they manage in daily life—this makes Alzheimer’s a spectrum condition—it’s like saying it’s a disability, and you have to assess what is a person’s level of capacity for day to day functions—this approach is much more patient oriented than most, and pays attention to comorbidities, including heart conditions and diabetes and so on, not just to Alzheimer’s. This is where domicile visits and old age psychiatrists are crucial. The phrase I use these days is “capacity to benefit.”

Brayne’s position is strongly influenced by the previous findings of her group noted in earlier chapters in which, among a sample of over 450 individuals, a very high proportion of older people exhibit so-called neuropathology in their brains at death but, even so, do not show signs of dementia while alive. Brayne agrees that early-onset, dominantly inherited Alzheimer disease conforms closely to gold standard plaque and tangle pathology, and she concedes that this may also be the case for late-onset cases of AD diagnosed in individuals in their 60s and perhaps early 70s. But for the majority of people clinically diagnosed with AD, those who are 75 and older, she argues that something different is at work—that the plaques and tangles in the brains of such individuals are almost without exception present together with a heterogeneous mix of other signs of neuropathology. She has two difficulties with this situation: first that the majority of the research carried out in connection with AD has been done with people in their 60s and 70s, individuals whose symptoms resemble something closer to so-called pure Alzheimer disease. Brayne argues that the findings from such research may well not apply to the majority of diagnosed cases who are among older age groups. Second, it is necessary to account for why so many older people whose brains are “littered” with “pathology” do not exhibit dementia in daily life. With this in mind, Brayne and her team undertook a remarkable study in which they examined closely the oft-repeated claim that education has a potentially protective role against dementia.

Large population-based cohort studies, involving over 870 individuals in all, were tracked in this project, from either 1985 or 1991.¹⁷ The number of years of education completed by these people was recorded at the outset, and they were interviewed repeatedly over the years until death, at which time dementia-related pathologies were systematically assessed at autopsy. At death, 56% of these individuals had been clinically diagnosed with dementia. The findings showed that longer years of education were associated with lower rates of dementia, and with greater brain weight, but no relationship was found between dementia and either neurodegenerative pathologies or vascular pathologies. Furthermore, the “dose” of education was significant, in that more education reduced dementia risk independently of the severity of pathology.

These researchers emphasize that further research is called for, and they agree that the relationship among education, neuropathology, and dementia remains unclear, but suggest that their sample provides “sufficient power” to begin to tackle three questions effectively: Does education protect against the accumulation of pathologies in the brain? Does education appear to compensate in some way for the usual cognitive impairment associated with pathology? And, third, does such compensation vary with pathological severity? Their conclusion is that “the number of years of education has no protective effect against the accumulation of neurodegenerative or vascular pathologies in the brain at death.” However, education militates against “an association of pathological burden and cognitive decline” even when, for the majority, there had been intervals of more than 70 years between years in school and death. Furthermore, it appears that those individuals who had experienced more education early in life were better protected.

This research supports a “brain reserve” or “cognitive reserve” hypothesis; however, the researchers are cautious about the significance of the findings, and note the shortcomings of previous research in connection with this concept, most often due to sampling bias. They are alert to the strong possibility that education may well be a proxy for socioeconomic status, exposure to toxins, and/or poor diet. Their findings make clear that greater brain weight is associated with more education—but acknowledge that this finding could be either cause or effect. They also recognize that education, and not simply number of years in school, no doubt has an effect over the entire life span. Brayne and colleagues conclude, “Those with more education do appear to have heavier brains and maintain cognition in the face of a burden of neuropathology compared to those with less education. Education attenuates dementia risk but does not mitigate it altogether,” as the notable case of the philosopher and novelist, Iris Murdoch, made evident. The group recognizes that considerable individual variation exists, despite population-based findings, demanding further investigation.

Anthropologists are likely to suggest that some fine-grained research is in order among populations where little or no formal education is the norm and literacy rates are low. Research, fairly sparse though it is, suggests that such populations do not appear to have high rates of dementia, although it is by no means absent. These findings raise interesting questions about the care of demented persons and the possibility that the actions of families and communities may slow down or ameliorate the cognitive changes associated with dementia.¹⁸

The epistemological question of the relationship of aging and dementia remains unanswered, of course, and is unlikely to be settled any time soon. M. Marsel Mesulam, a Chicago-based neurologist, trained also in psychiatry, argued more than two decades ago against a unifying theory of Alzheimer causation. He pointed out that the idea of “neuroplasticity,” a concept that refers, as he put it, “to processes of vital importance for the structural upkeep of the brain and for the functional adaptation of the organism to the environment,” decreases with age, and this explains why age is the single most important and universal risk factor for AD. According to this formulation, Mesulam argued, Alzheimer’s associated with old age may not be a disease at all, but simply the inevitable manifestations of a failure to keep up with the “increasingly burdensome work of plasticity.”¹⁹ His position is that an aging brain is normal, but certain variables—genetics, environment, and lifestyles (figure 9.1)—may result in perturbations that accelerate the aging process (or, alternatively, as the work of Brayne and colleagues and other researchers suggests, protect against the ravages of aging). Mesulam concluded,

[I]mportant insights related to the pathophysiology and prevention of AD may come from the fields of developmental biology. One of the most important goals will be to understand the processes that influence plasticity in the adult human brain and to determine whether their vulnerability to aging and to the other AD-causing factors can be modified.²⁰

Mesulam’s argument is not one of a radical discontinuity between aging and dementia, and he implies that dementia may well be best understood as a “normal” endpoint in very elderly people. The position taken by Martin Roth (see chapter 1), that of a marked discontinuity between aging and dementia once a crucial threshold has been passed, is not entirely at odds with that of Mesulam. Roth’s argument may be appropriate for Alzheimer’s diagnosed among younger people, and particularly in cases of dominantly inherited AD. When Roth stated “AD cannot be accounted for in terms of a continuous and predictable extension of normal mental aging,” he based his opinion on research findings obtained primarily from samples of people aged largely 70 and younger, and at a time when PIB scanning was not available. The research of Brayne’s group and others, also in line with that of Mesulam, strongly suggests that such a statement does not apply to the burgeoning numbers of older people.²¹

Roth acknowledged that genetics and environment no doubt play a role, and account for why some individuals are apparently more vulnerable to AD than are others. However, his assumption, and that of most other researchers, including those searching for effective drugs, has been, and continues to be, that plaques are irrefutable evidence of Alzheimer’s in the making, and, with very few exceptions indeed, tangles are the clinching pathological signs of the disease, at whatever age it strikes individuals. Such a diagnosis is decontextualized from everyday life and rests on the belief that localization theory will provide the final answers. But the reality is that new findings are regularly made about both amyloid and tau. The picture becomes ever more complex as technologies enable deeper probing, causing a growing number of researchers to question whether amyloid is indeed driving the neural dysfunction associated with AD. Furthermore, emerging biomarker research is showing that the progression of prodromal dementia does not necessarily take place in the orderly manner set out by the researchers who proposed the move to prevention of AD (see chapter 4); brain structure changes have been shown to take place as early as or even earlier than the commencement of amyloid deposition in some cases.²²

A great deal remains to be explained, and if drug failures continue to plague the field, then the amyloid hypothesis must be severely modified or dropped entirely, as even those researchers who are the most committed to a molecular approach now concede.²³ A move under way to pay closer attention to cell loss, the significance of which has always been thought of as secondary due to the attention given to plaques and tangles, may rather rapidly bring about some modification of the cascade hypothesis. Paradoxically, biomarker findings has been a major reason for deeper investigation into the onset and significance of cell loss, including the finding that some individuals can apparently adapt to such a loss better than others.

Figure 9.1.

The Tunbridge Wells Rambler’s Association, Kent, UK. Annual Bluebell Walk led by the author’s father at age 90. Photograph in possession of Margaret Lock; photographer unknown.

Not only is there still a very long way to go in pinning down the molecularized universe of AD-like dementias, but, furthermore, half the story continues to be barely recognized and researched. The question of what it is that protects so many individuals from dementia even at a great age, including many of those who are assumed to be at risk due to their genetic heritage, has rarely been examined systematically, although work such as that of Brayne and colleagues is an exception. This issue, noted in passing by so many researchers when talking with me, foregrounds the manner in which the biology of aging itself is embedded in social, political, and economic matters. The politics of AD research has been, above all else, to emphasize the horror of dementia, and its unwanted repercussions on the economy, in order first and foremost to raise money for research to cure the disease. Although healthy lifestyles are promoted by AD societies and other organizations dealing with the elderly, the vital question about what it is that raises the odds of having a dementia-free old age is nevertheless marginalized.

In order to assess why and how so many individuals remain healthy and active even in old age, a move must be made away from AD causation conceptualized as in the brain alone, to the boundary-traversing mind, to persons, and to social and political milieus. Of course, a localized approach to the AD conundrum and medicalization of AD will nevertheless continue.

Embedded Bodies

The epigenetic findings by Wang and his colleagues referred to in the previous chapter appear to support and advance the ideas put forward much earlier by Mesulam. And comments by Evelyn Fox Keller, the philosopher of science, cited earlier are also relevant, as we turn to a consideration of the third tension in the AD world. For Fox Keller separation of the terms nature and nurture—the insertion of an “and” in the phrase—is to make these concepts into a false dichotomy. She argues, “From its very beginning, development depends on the complex orchestration of multiple courses of action that involve interactions among many different kinds of elements.” This “entanglement between genes and environment” results from “an immensely complex web of interactions between environmental stimuli (both internal and external to the cell) and the structure, conformation, and nucleotide sequence of the DNA molecule.”²⁴ Such a position grounds the science of epigenetics and is applicable throughout individual life spans, Fox Keller insists, and not merely during early development.

Fox Keller limits her argument to what she describes as environmental stimuli, but both epidemiological and emerging epigenetic findings in connection with Alzheimer’s suggest that researchers would do well to go further and examine social and political factors. This would include variables mediated by the boundary-traversing mind, such as education, traumatic social and familial events, social isolation, deprivation, and so on, and, in addition, variables that affect neurodevelopment directly, including exposure to toxins, prions, other disease-causing entities, inadequate diet, and others. Clearly, this is a very tall order that would almost certainly entail sophisticated longitudinal studies demanding cooperation across disciplinary boundaries. It is apparent that this will not be easy, particularly because it would require specialists in various disciplines who normally compete for a finite amount of research money to cooperate with one another. But perhaps the disruption in normal science that the AD world is undergoing will result in the kind of “fruitful tension” noted by Fleck, out of which new congeries and novel approaches may arise.

At a conference on epigenetics held in 2011 at McGill University, one of the presenters titled his PowerPoint presentation “DNA Methylation: A Molecular Link between Nature and Nurture.” In his talk, Moshe Szyf, a leading figure in environmental epigenetics in North America, presented a discussion of research findings made by his team involving 25 subjects who had been abused as children, and later committed suicide. The families had agreed to donate the brains of their relatives for research. Upon examination, these brains showed a significantly different pattern of DNA methylation than did those of individuals who had committed suicide where no known abuse had taken place, and also with a control group.²⁵ Szyf cautions, “Although epidemiological data provides evidence that there is an interaction between nature (genetics) and social and physical environments (nurture) in human development; the main open question remains the mechanism.”²⁶ But he is also the first to admit that obtaining large enough samples to carry out this type of research to great effect is extraordinarily difficult. And a recent review article of epigenetics makes it very clear how provisional are many epigenetic findings to date.²⁷

The anthropologist Jörg Niewöhner cautions us about an inappropriate direction in which epigenetics may be moving. He argues that aspects of the social world are liable to be reduced in this type of research to a “quasi-natural experimental system” in which “the molecularization of biography and milieu” may result in standardized models of social change that travel between labs and from thence out into the wider public discourse.²⁸ Unless such findings can be contextualized in the larger arenas of culture, political economy, and family life, including family intergenerational histories, highly truncated accounts about suicide causation are likely to result, in which parental behavior thought to be wanting may well be interpreted as causal of defective methylation processes that then contribute to suicidal behavior.

Niewöhner has made a preliminary attempt to set out how variables external to the body may be systematically incorporated into lab-created epigenetic findings. He focused on the heterogeneous subfield known as “environmental epigenetics” in which macro-environments are beginning to be given due attention by molecular biologists.²⁹ Niewöhner argues that environmental epigenetic interactions result in “embedded bodies.” Such a body, he writes, is “heavily impregnated by its own past and by the social and material environment within which it dwells. It is a body that is imprinted by evolutionary and trans-generational time, by ‘early-life,’ and a body that is highly susceptible to changes in its social and material environment.”³⁰ Niewöhner calls for a “molecularization of biography” in which events of significance in people’s lives are researched and documented, to a limited extent standardized, and then systematically examined for associations with bodily epigenetic changes.³¹ He emphasizes that environmental epigenetics is not, as yet, a well-established discipline, and that there is a long way to go before, for example, the public health implications of its findings could be put to work, but, Niewöhner insists, a serious effort should nevertheless be made to include social and political variables that appear to be implicated in epigenetic effects. The concept of “local biologies” put forward by Lock in the early 1990s represents an earlier effort to come to grips with the crucial importance of extrasomatic variables as key contributors to embedded bodies.³²

The discussions in previous chapters about Alzheimer genetics, particularly the variation among and across each of the APOE polymorphisms, and about the distribution of plaque in human brains and its less than reliable association with the behavioral changes of dementia, are graphic examples that substantiate a concept of embedded bodies. Such evidence suggests that if improved insights into AD causality with the objective of bringing about its prevention are desired, to simply focus on prodromal AD established by the presence of standardized biomarkers will serve to push the story back to an earlier stage of proximate causation, but no more. A move such as this will not engage with “ultimate” causation—that is, with the numerous extrasomatic factors that are clearly implicated in aging and dementia. Nor will it succeed in creating risk estimates that can predict with accuracy who among us are going to become demented—increasing recognition that the world of biology is, at best, only “law-like,” supports this contention. As clinicians repeated to me time and again, family history continues to predict risk for AD far more reliably than does any other variable, and it seems that biomarker usage may not change this situation. The number of times the word “uncertainty” has been used in this book by so many researchers whom I interviewed, is remarkable.

Readers may recall what was cited earlier by one of the leading researchers in the AD enterprise: “The array of challenges for the mission to prevent AD within a decade are no less daunting than those faced by similar national endeavors such as the Apollo space program, the Manhattan Project, or the Human Genome Project.”³³ If the AD “epidemic” is to be confronted, a public health approach orchestrated at global and local levels is called for, one that targets variables than can readily be manipulated without resort to expensive technologies, high-powered facilities, and highly trained personnel.³⁴ This, surely, is the most humanitarian and effective way to approach the problem, one that does not, of course, rule out support of a well-funded research program designed to tackle the molecular puzzles that are so challenging.

Ultimately, however, in addition to further researching molecular changes in the brain and rigorously detecting statistical differences in AD incidence among populations and groups, another level of inquiry is called for. Appreciation of the inextricable entanglement of individual biology with evolutionary, historical, environmental, social, cultural, and political variables, a never-ending process that can usefully be thought of as “biosocial differentiation,” demands attention.³⁵ Only thus can the extent of the variation of AD incidence, and the reasons that contribute to its complexity, begin to be understood. Without the painstaking collection of such knowledge a shift to prevention is liable to run aground. One aspect of this research involves investigation into neuroprotection, but to do this effectively, the brain must first be decentered. Fascinating findings about centenarians and their genetics,³⁶ and about environments and social arrangements that appear to support long, healthy lives,³⁷ are steps in the right direction.

Although those who work to increase funding for AD wish to sustain a frightening image of the global future ravaged by an unstoppable AD epidemic, the reality is that there will be no silver bullet for Alzheimer disease—the heterogeneity of the condition that so many researchers surely recognize, ensures that this will be so. The challenge presented by an aging brain exceeds that posed by all other organs of body. Even so, perhaps it will be expedient to retain an overarching AD category for political purposes—the AD label would be used as a heuristic device, a good-enough category, designed to keep societies and governments focused on the enormity of the problem. If and when AD is systematically broken down into subtypes, knowledge about this fine-tuning will filter out into the public domain without necessarily reducing the symbolic power of AD as a tragedy that must be countered by every possible means, including concerted research efforts, outstanding clinical care, and improved family support.

The hype associated with the current “shake-up” in the AD world may lead people in wealthy countries to believe that at last we are on track for a cure. But every indication is that we should not hold our breath in light of the persistent failure of drug trials. The work of Thomas McKeown discussed briefly in the introductory pages of this book showed that during the long interim in which scientists were struggling to develop antibiotics in the early part of the 20th century, improved nutrition and hygiene brought about a major increase in longevity due to a substantial drop in infectious diseases, long before drugs were available. We would do well to keep this in mind—breakthroughs in big science take time, and with a “pandemic” of aging fast approaching, as we are led to believe, a great deal can be done relatively simply to alleviate the situation through improved care of and social support for the elderly, particularly when individuals become dependent and frail.

The positive contribution that so many older people make to society goes consistently unnoticed and demands attention. A recent study in the United Kingdom, for example, showed that far from being a burden on the economy, older people are net contributors, if one includes tax payments, spending power, caring responsibilities, and the volunteering effort of people aged 65 and older. In the study, it was calculated that this cohort contributes almost £40 billion (approximately $65 billon) more to the U.K. economy than it receives in state pensions, welfare, and health services. This research also suggests that this benefit to the economy will increase in coming years as the “baby boomer” cohort enters retirement. By 2030, it is projected that the net contribution of older people will be worth some £75 billion.³⁸

The current move to prevention in the AD world by means of surveillance of biomarkers is presently for research purposes alone, in the hope of eventually bringing drugs to market. In the unlikely event that these technologies are approved for clinical use, drugs developed, and their prescription routinized, most elderly people in the world will not have access to them unless enormous social and political changes first take place—a highly unlikely scenario. And facilities will most certainly not be available for the majority of individuals, regardless of where they live, to have AD biomarkers regularly monitored from middle age on. As the memories and minds of these individuals decline with age, a large number may well continue to be thought of merely as mad, senile, or simply old and faded. Their burden on meager health care systems and local economies will not be that great, although families will indeed be burdened, with the result that large numbers of elderly may well be subjected to neglect and even starvation. Such lives may count for little, except possibly to boost global statistics designed to normalize the approaching pandemic of aging, and very occasionally these individuals will be of use as research subjects.³⁹

To improve the lot of this vast majority, therefore, a globally orchestrated political shift to the implementation of public health programs is urgently needed, one that is not ultimately driven by a molecularized approach to AD. This approach would be designed to engage with the reality of aging while attempting to reduce dementia prevalence, or at least slow its progression, no doubt largely through the agency of family and communities that receive governmental support. Such a move would also reduce the stigma that continues to be associated with dementia in so many places. But a public health approach such as this, essential though it is, can have only a limited effect. It is clear that, equally important, the contribution to AD incidence of contemporary global politics must be explicitly acknowledged and, if at all possible, acted upon. Alleviation of poverty and chronic inequalities and universal access to good nutrition, sanitation, and education have long been recognized as crucial to human health; the situation today is somewhat improved in some parts of the world, but for millions this is not the case. The forcible removal of hundreds of people from arable land and their relocation, ever-increasing polluted environments, and numerous other harmful stresses exerted on huge swaths of the world’s population due to the demands of endless capital accumulation are increasingly toxic. While these conditions persist and increase, Alzheimer incidence will not be reduced. Nor will the incidence of many other illnesses, several of which, including diabetes and obesity, contribute directly to dementia.

In closing, one further reality must be kept in mind: no amount of preventive measures and no drug will defeat aging (even though certain maverick scientists are attempting just this), nor can dementia be “wiped out” as though it is an infectious disease—aging and dementia cannot be disentangled; all we can strive for is to find ways to stave off or halt the progression of AD at whatever age it strikes.