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

Abstract

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.

Vulnerability to Hypertension Is a Major Determinant of Racial Disparities in Alzheimer’s Disease Risk

“…The contributions of other diseases considered in this study were much weaker, even when combined. Given that hypertension is a manageable and potentially preventable 5 , 6 condition, mitigating the effects of this disease in engendering higher AD incidence in Black Americans should be a prominent public health concern. Furthermore, interventions focused on Black American communities, especially with high numbers of 75+ individuals, are urgently needed.…”

“…The onset of AD was the primary outcome of interest. Ten diseases were selected based on the results of a literature review of probable AD disease-related risk factors and the presence of race-related differences in the epidemiology of these conditions: hypertension, 5 , 6 , 18 cerebrovascular disease, 9 several other diseases of the circulatory system 1 , 10 (including ischemic heart disease, atherosclerotic cardiovascular disease, and heart failure), diabetes mellitus, 4 renal disease, 7 traumatic brain injury, 11 and depression. 8 …”

“… 1–3 The effects of such differences go beyond their direct impact on AD, affecting the onset of other diseases, including those associated with higher AD risk. Indeed, many diseases known to be associated with increased risk of AD onset such as diabetes mellitus, 4 hypertension, 5 , 6 renal disease, 7 depression, 8 cerebrovascular disease, 9 cardiovascular diseases, 1 , 10 and traumatic brain injury 11 have notable race-related differences 12–15 and can contribute to disparities in AD risk.…”