Neurofibrillary Tangles and Conversion to Mild Cognitive Impairment with Certain Antihypertensives

J Alzheimers Dis. 2019;70(1):153-161. doi: 10.3233/JAD-190011.


Background: Individuals taking renin angiotensin system (RAS) acting antihypertensives exhibit slower cognitive decline and are less likely to progress from mild cognitive impairment (MCI) to Alzheimer's disease (AD), but the mechanism remains unclear.

Objective: We tested the hypothesis that individuals taking RAS acting antihypertensives exhibit less AD-related neuropathology and slower disease progression than individuals taking non-RAS acting antihypertensives.

Method: Participants included 83 individuals with MCI who were taking an antihypertensive at baseline, had at least two follow-up visits, and had postmortem neuropathological data. Participants were old (M = 83.1 years), 32% male, well educated (M = 15.7 years), and 9.2% Black.

Results: RAS medication users (N = 38) were less likely to progress to AD than non-RAS users (N = 45). RAS users exhibited fewer neurofibrillary tangles than non-RAS users in the hippocampal CA1 region (p < 0.01), entorhinal cortex (p = 0.03), and the angular gyrus, inferior temporal, mid-frontal cortex, and superior frontal (p = 0.01).

Conclusion: Prevention or clearance of neurofibrillary tangles represents a mechanism by which RAS medications may slow disease progression.

Keywords: Alzheimer’s disease; blood pressure; hypertension; mild cognitive impairment; neuropathology; prevention; renin angiotensin system; tau.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Brain / pathology*
  • Cognition / physiology*
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / psychology
  • Disease Progression
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / pathology
  • Hypertension / psychology
  • Male
  • Neurofibrillary Tangles / pathology*
  • Renin-Angiotensin System / drug effects


  • Antihypertensive Agents