Over the last century, Alzheimer’s disease has proven a highly malleable concept. Initially an obscure diagnosis pertaining to rare cases of young onset dementia, by the latter half of the 20th century the label had replaced “senility” as the global shorthand for age-related memory loss—a discreet end-of-life disease amenable to cure (Whitehouse and George 2008). However, failures to develop effective therapies in the 21st century have, as McKeown, Malhi, and Singh (2021) write, engendered another paradigmatic shift away from late-stage treatments and toward a pre-symptomatic model aimed at identifying the condition upstream using biomarkers/genes and interceding with “personalized” treatments. New socially-constructed “pre-disease” categories such as Mild Cognitive Impairment (MCI), Subjective Cognitive Decline (SCD), and preclinical Alzheimer’s have emerged to promote treatment of milder-and-milder forms of memory loss—the latter construct representing a situation wherein Alzheimer’s-associated biomarkers are present in the absence of clinical signs and symptoms.
This early intervention paradigm is fraught with practical, philosophical, and ethical challenges. At the core sits an inconvenient truth: that what we have singularly called “Alzheimer’s disease” for the last half-century is defined by its heterogeneous, age-related, and multi-factorial nature, and thus more appropriately regarded as a syndrome, i.e., “Alzheimer’s diseases”. Consequently, for a condition where pathology is not destiny (to the point where AD is difficult to diagnose at autopsy given use of variable criteria and methods) (Hyman et al. 2012), it is daunting to imagine a future where early-stage biomarkers assume predictive power. Invariably, as McKeown et al. (2021) write, pursuit of early diagnostics will be burdened with potential for false positives/negatives until proven adequately reliable, specific, sensitive, and valid. So too does the conceptual move upstream to earlier “diagnostic” labeling risk excess medicalization, especially when some degree of memory loss and accumulation of neuropathology associated with so-called “Alzheimer’s disease” is the statistical norm for aging brains beyond sixty-five years. Do we wish to extend one of society’s most feared and stigmatizing labels to people, especially when present treatments are so limited and a “cure” non-existent and even unlikely given complexities with heterogeneity/overlap with aging? Ultimately, it is sentient human beings with fragile, finite lives and relational bonds who must bear the consequences of medical labels, and we must approach telling people they are “at-risk” for dementia (or becoming caregivers) with requisite caution, sensitivity, and humanity (George 2010).
There are also valid concerns about industry’s influence within the “upstream” paradigm. Early intervention tests (e.g., amyloid-imaging) can be lucrative for commercial providers even as their use offers unclear diagnostic accuracy and creates anxiety, ambiguity, and uncertainty for patients and families. Moreover, it is possible that “pre-disease” categories will augment off-label use of current FDA-approved (but rather ineffective) Alzheimer’s drugs. Professional organizations and big pharma have funded expert panels that have established diagnostic parameters for MCI and preclinical Alzheimer’s, frequently producing biased articles reifying the categories that justify therapeutic trials for patients with pre-disease labels. As this “diagnostic creep” occurs, there are inevitably increasing opportunities for companies offering treatment/diagnostics to enlarge market share, and any engagement with the ethics of early intervention must grapple with the conflicts of interest baked into the very premise of the upstream research model itself.
Speaking of markets, it is also the case that the shifting biomedical paradigm has permeated the broader culture beyond clinical/research settings. A multi-billion dollar “marketplace of memory” encompassing nootropics/supplements, digital brain-fitness games, and other personalized products has emerged in the past decade. Upstream logic is manifest in these products, many of which are marketed as early interventions for anxiety-addled Baby Boomers hoping to reduce risk for dementia via rituals of self-care. These products are largely decoupled from biomarkers, with perceived “risk” implicit in the consumer’s engagement with the product and generated by ambient cultural fear of cognitive aging rather than a discrete biologic risk factor. Conceptually, products are predicated on notions of neuroplasticity (the brain’s capacity to rewire itself throughout life), cognitive reserve (the brain’s resilience to age-related pathological changes), and a belief that early intervention will be efficacious in protecting/enhancing memory, recall, and executive function. Increasingly, such products are being marketed to younger generations, offering to prevent age-related cognitive loss, but also give individuals living in hyper-competitive Western capitalist societies an edge in productivity, cognitive processing, and ultimately meritocratic achievement (George and Whitehouse 2021). Despite the excesses of marketing departments, which US regulatory bodies have begun cracking down on, data on the efficacy of products in meaningfully improving cognition or preventing dementia is generally insufficient, and task-specific benefits do not appear to generalize to global cognition, everyday tasks, or quality of life. Moreover, as with biomarker diagnostics, products of the marketplace of memory are generally individuated, tending to eschew any sense of collective community needs, shared risk-factors, and societal interdependence.
However, recent research demonstrating a surprising decline in rates of dementia over the past several decades may potentially help refigure the early intervention paradigm around more collective goals and values. In recent years, studies from the US, Canada, the United Kingdom, France, Sweden, and the Netherlands have shown that, while overall numbers of those affected by dementia continue rising, there has been a general reduction in dementia prevalence and incidence over the past four decades (Livingston et al. 2020; Wolters et al. 2020). This phenomenon appears to be intertwined, not with pharmaceutical/biotech advancements, but rather with the political-economic organization and public health efforts of Western democracies in the mid-20th century.
Specifically, after the global crisis of the 1930s and World War II, governments largely adopted Keynesian economic practices to more tightly manage capitalism and use taxation/redistribution in building strong national welfare states. With respect to dementia risk, generations of elders who have entered their retirement years in recent decades were lifelong biopsychosocial beneficiaries of state investments unique to this historical moment. One clear systemic contributor identified in the data (Livingston et al. 2020) are national healthcare systems, which, by addressing hyperlipidemia, hypertension, diabetes, and other vascular risk-factors, have reduced downstream incidence of cerebrovascular and heart disease, contributing to population-level improvements in brain health. So too did the increased provision of socialized systems like public education (e.g., the G.I. Bill in the US) ensure a major uptick in citizens receiving high school and college educations that helped build cognitive reserve at the population-level (i.e., “population-reserve”). There is further evidence that state-led public health interventions such as removal of lead from gasoline (e.g., the US Clean Air Act of the 1970s, which substantially lowered national blood-lead levels and effective smoking-cessation campaigns have also contributed to dementia rate reductions (Fuller-Thomson and Jopling 2017).
Such revelatory findings challenge us to think even more rigorously about what “ethical early intervention” might mean, how we might once again “treat populations” in service of brain health, and what societal priorities ought to be over the next decade. For instance, what if “risk” was not paradigmatically treated as a personalized phenomenon (e.g., biomarkers), but rather a collective one in the sense that all citizens are aging, at-risk for dementia, and bonded by shared susceptibility to external determinants of brain aging across the life-course? Such a reframing moves us beyond individual, market-based prevention strategies characteristic of our current “neoliberal” era, to thinking once again about how public policies and environmental investments that reduce poverty, improve material wellbeing, eliminate exposure to toxins, and enhance community support might potentiate the brain health of entire populations in the 21st century (Bambra and Schrecker 2015). Embracing such collective investments in confronting one of our most feared illnesses might also help foster a greater sense of unity, interconnection, solidarity, and shared destiny at a time of great fragmentation, fractiousness, and runaway inequality in Western democracies. In this way, the universal fear of Alzheimer’s might actually be a gateway to tackling larger questions about the organization of our society, how we are governed, and what we owe to one another.
Ultimately, the pursuit of a healthier society remains the best tool we have for improving brain health and care of the vulnerable (George and Whitehouse 2021). The 19th-century aphorism often attributed to Rudolf Virchow, father of social medicine, still rings true today: “Politics is nothing else but medicine on a large scale.” From our vantage point in the early 21st century, appropriate state investments in collective wellbeing and public health might not only potentially reduce dementia once again for generations hence, but also synergistically help address complex interrelated issues like the climate crisis, future pandemics, social injustice, and income/wealth inequality. Moving forward, neuroethicists/bioethicists must strongly critique institutions and individuals claiming medical progress on Alzheimer’s, challenging the very notion of “progress” in neoliberal societies. There is danger in identifying problems but accepting solutions too superficially, as such a process may produce actions that render the original problem and others related to it worse. We live in an era burdened by so-called “wicked” problems that demand large-scale, integrated solutions; thus, we must bring both collective wisdom from the past and life-affirming values and visions for the future to bear in thinking (and acting) our way out of the many crises we face.
Both authors have contributed significantly to the manuscript and consent to their names on the manuscript.
No potential conflict of interest was reported by the author(s).
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