Hypertension and Alzheimer's disease pathology at autopsy: A systematic review

Hypertension is an important risk factor for Alzheimer's disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be associated with AD neuropathological changes (ADNC), but reports are sparse and inconsistent. This systematic review included 15 autopsy studies (n = 5879) from observational cohorts. Studies were highly heterogeneous regarding populations, follow-up duration, hypertension operationalization, neuropathological methods, and statistical analyses. Hypertension seems associated with higher plaque and tangle burden, but results are inconsistent. Four studies (n = 3993/5879; 68%), reported clear associations between hypertension and ADNC. Another four suggested that antihypertensive medication may protect against ADNC. Larger studies with longer follow-up reported the strongest relationships. Our findings suggest a positive association between hypertension and ADNC, but effects may be modest, and possibly attenuate with higher hypertension age and antihypertensive medication use. Investigating interactions among plaques, tangles, cerebrovascular pathology, and dementia may be key in better understanding hypertension's role in dementia development.