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.

Background Hypertension is an important risk factor for all‐cause dementia and Alzheimer’s disease (AD). Reports about the relation between mid‐life hypertension and AD‐related neuropathology are sparse and inconsistent. We conducted a systematic review to collate and synthesize the literature on the relation between hypertension and AD neuropathology. Methods Search terms included dementia, Alzheimer’s disease, hypertension, autopsy, obduction and neuropathology. The main outcome was AD‐related neuropathological changes at autopsy (including amyloid plaques and neurofibrillary tangles) with hypertension as exposure, either collected retrospectively from medical records or prospectively measured at clinical evaluation(s). We included prospective and retrospective cohort studies with individuals from general and selected (e.g. memory clinic) populations. We excluded case‐control studies. Results We found 10 studies (total N = 3054, median 231 participants, range 50‐1288) that were very heterogeneous concerning populations, methodological approach and statistical analysis. Most studies reported no association between midlife hypertension and AD‐changes at autopsy. Two studies (total n = 1531) reported an association between hypertension and elevated numbers of neurofibrillary tangles and neuritic plaques. Of those studies, one reported that both a low and a high BP in late‐life was associated with an increased burden of amyloid plaques and tangles (U‐shape). Conclusions Our study shows no consistent association between blood pressure and AD‐neuropathology. However, based on our results, we speculate that the association between hypertension and AD‐neuropathology is age‐dependent, and that U‐shaped relations may have been obscured in linear analyses. Future studies could take this phenomenon into account when investigating the relation between hypertension and AD neuropathology.