Repositioning Drugs to Reduce the Disparate Burden of Alzheimer’s Disease

Douglas Barthold & Julie Zissimopoulos

AD imposes a large, multifaceted, and disparate burden on individuals, families and society

The burden of Alzheimer’s Disease (AD) on afflicted individuals and the health system as a whole is substantial. The Alzheimer’s Association estimates that in 2016, 5.4 million people in the United States are living with AD.¹ By 2050, the number of Americans with AD is estimated to reach 9.1 million.² The health care expenditures associated with AD are projected to grow from $181 billion in 2010 to $1,140 billion in 2050 and to consume an ever larger portion of total US health expenditures.² Additionally, caregiving by family consumes time and money, and may affect the health of caregivers.³

It is not necessary to completely prevent AD in order to reduce its burden. Zissimopoulos et al. (2015) found that delaying onset for just one year now will result in 20% lower prevalence of AD in 2050, declining from a projected 9.1 million to 7.8 million Americans with AD. This delay offers substantial cost reductions as well, saving $160 billion in health care costs and approximately 300 million hours of care by family members in the year 2050, for a total value of $223 billion in medical costs and informal caregiving cost savings. Innovations that delay onset of AD by 5 years can save over $600 billion in AD total costs in 2050.²

AD affects some populations more than others. The incidence rates for blacks and Hispanics are about twice as high as for whites (4.2%, 3.8%, and 1.9%, respectively).⁴ These groups are also disproportionately affected by other chronic conditions, including diabetes, hypertension, and hyperlipidemia.^5-7 The socio‐environmental, behavioral, and biological factors that contribute to racial and ethnic disparities in AD may be exacerbated by disparities in access to health care services and in quality of care. There is concern that minorities receive care that falls short on several dimensions of quality, including safety, timeliness, effectiveness, efficiency, patient-centeredness, and equity.⁸ Racial and ethnic minority families consequently shoulder a high burden of Alzheimer’s disease.⁹

Identifying approved medications that affect risk of AD may reduce disparate burden of disease

Pharmaceutical therapies can help suppress symptoms of AD, but currently none can prevent or delay its onset and progression, and only a limited number of novel therapeutics are advancing through the development pipeline. With few prospective treatments targeting AD, identifying therapeutics for other conditions that have potential to prevent or treat AD is a promising approach for reducing risk of the disease and racial and ethnic disparities in risk. Multiple therapies for high-prevalence conditions such as diabetes, hypertension, hyperlipidemia, gastroesophageal reflux disease (GERD), and insomnia have been associated with AD risk. While the association of approved medication for non-AD conditions with AD varies across class of drugs, and lacks consensus across studies, there are some classes that show promise. For diabetes, glucagon-like peptides and amylin agonists both show protective associations with AD.^10-12 Among hypertension drugs, beta-blockers and ACE inhibitors show protective associations.^13-15 For insomnia, endocrine-metabolic agents and atypical antipsychotics appear to be protective.^16-19 Two classes of GERD drugs, on the other hand, have shown evidence as risk factors for AD.^20-22 Statins, used to treat hyperlipidemia, have shown mixed associations with AD.^23,24

Some of these drugs are already widely prescribed and used by the elderly population, and could delay the onset of AD, but the evidence is incomplete. The work on statins is an example; many of the randomized controlled trials (RCTs) had short follow-up times, and disqualified patients with hyperlipidemia, who are the most likely to benefit from statins.²⁵ Additionally, studies on statins and AD included insufficient samples of racial and ethnic minorities. The homogeneity of the study populations is especially problematic. Not only is race associated with variations in incidence of chronic disease and medication adherence, but the pharmacokinetic processes of drugs may also differ across racial and ethnic groups.^5,8,26 Thus, even within classes of drugs, the treatment effectiveness of specific molecules is likely to vary across racial and ethnic groups. Identifying drugs that are prescribed for chronic conditions and impact AD, and analyzing differences in effectiveness across racial and ethnic groups, may aid in in reducing racial and ethnic disparities in AD.

A data-driven approach to reducing racial and ethnic disparities in Alzheimer’s disease

The prevailing paradigm in academic-based therapeutic development stands on the approach in which a discovery at the bench is followed by a search for a potential disease application. The poor reproducibility of preclinical discovery research and translational validity of animal models are two factors frequently cited for the high failure rate of AD drugs during Phase II and III clinical trials. A promising approach combines data from surveys, health records, medical claims records, and genetic data with statistical methods to identify and analyze current treatments for non-AD conditions that may delay or prevent Alzheimer’s disease. For example, pharmaceutical drugs and health care claims data from millions of Medicare beneficiaries provide insight into the diagnosed health conditions, prescribed drugs, diagnostic services, health care services, and treatments of older Americans. Studies based on these data benefit from large samples of racial and ethnic minorities, unlike studies based on data from small clinical trials. Studies that combine multiple rich data sources and rigorous methods can inform ways to reduce AD’s multifaceted burden and reduce racial and ethnic disparities in the disease.

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