Cardiovascular Disease and Alzheimer's Disease: The Heart-Brain Axis

Abstract

Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in aging adults across the United States. Prior studies indicate that the presence of atherosclerosis, the pathogenic basis of CVD, is linked with dementias. Alzheimer's disease (AD) and AD-related dementias are a major public health challenge in the United States. Recent studies indicate that ≈3.7 million Americans ≥65 years of age had clinical AD in 2017, with projected increases to 9.3 million by 2060. Treatment options for AD remain limited. Development of disease-modifying therapies are challenging due, in part, to the long preclinical window of AD. The preclinical incubation period of AD starts in midlife, providing a critical window for identification and optimization of AD risk factors. Studies link AD with CVD risk factors such as hypertension, inflammation, and dyslipidemia. Both AD and CVD are progressive diseases with decades-long development periods. CVD can clinically manifest several years earlier than AD, making CVD and its risk factors a potential predictor of future AD. The current review focuses on the state of literature on molecular and metabolic pathways modulating the heart-brain axis underlying the potential association of midlife CVD risk factors and their effect on AD and related dementias. Further, we explore potential CVD/dementia preventive strategies during the window of opportunity in midlife and the future of research in the field in the multiomics and novel biomarker use era.

Keywords: Alzheimer's disease; atherosclerosis; brain biomarkers; cardiac risk factors; cardiovascular disease; cerebrovascular disease; dementia.

Figure 1. Amyloid beta and associated disease states.

Pathophysiological mechanisms underlying elevated amyloid beta levels and associated disease states.

Figure 2. Alzheimer's disease and cardiovascular disease: risk factors and mechanisms.

Shared risk factors between Alzheimer's disease pathology and cardiovascular diseases including myocardial infarction, stroke, and cardiac death. APOE4 indicates apolipoprotein E4.

Figure 3. The Heart–Brain clinic.

Proposed midlife evaluation of patients at risk of cardiovascular and neurocognitive diseases in the heart–brain clinic. APOE4 indicates apolipoprotein E4; CVD, cardiovascular disease; and FDG‐PET, ¹⁸F‐fluorodeoxyglucose‐positron emission tomography.