Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons

Abstract

Objective: To test the hypothesis that use of antihypertensive medication is associated with lower Alzheimer disease (AD) neuropathology.

Methods: This was a postmortem study of 291 brains limited to those with normal neuropathology or with uncomplicated AD neuropathology (i.e., without other dementia-associated neuropathology) in persons with or without hypertension (HTN) who were and were not treated with antihypertensive medications. Neuritic plaque (NP) and neurofibrillary tangle (NFT) densities, quantified in selected brain regions according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathologic criteria, with additional cortical NP counts, yielded 24 neuropathologic regional measures or summaries. Medicated hypertension (HTN-med; n = 77), nonmedicated HTN (HTN-nomed; n = 42), and non-HTN (no-HTN; n = 172) groups were compared by analyses of variance.

Results: The HTN-med group had significantly less neuropathology than the no-HTN group. The no-HTN group averaged over 50% higher mean NP and NFT ratings, and double the mean NP count, of the HTN-med group. The HTN-nomed group had significantly more neuropathology than the HTN-med group, but not significantly less than the no-HTN group.

Conclusions: There was substantially less Alzheimer disease (AD) neuropathology in the medicated hypertension group than the nonhypertensive group, which may reflect a salutary effect of antihypertensive medication against AD-associated neuropathology.

Figure Means and standard errors of means for three groups based on hypertension (HTN) and medication status *p < 0.05 for analysis of variance comparing the three groups after Holm correction for multiple tests of significance. (A) Alzheimer disease (AD) neuritic plaque (NP) density scores. Left axis: Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) rating scores reflecting NP density (with and without cores) for specific brain regions: hippocampus (Hipp), amygdala (Amyg), entorhinal cortex (EC), mid frontal cortex (MF), superior middle temporal cortex (SMT), inferior parietal cortex (IP), and occipital primary visual cortex (OC). Right axis: Sum of CERAD rating scores: NP1 sums MF, SMT, IP, and OC; NP2 sums Hipp, Amyg, EC, MF, SMT, IP, and OC. (B) AD neurofibrillary density scores. Left axis: CERAD rating scores reflecting neurofibrillary tangle density in various brain regions (Hipp, Amyg, EC, MF, SMT, IP, and OC). All except NFT in Hipp EC and OV were significant (p < 0.021 to p < 0.0005). Right axis: Sum of CERAD rating scores: NFT1 sums MF, SMT, IP, and OC; NFT2 sums Hipp, Amyg, EC, MF, SMT, IP, and OC. (C) Mean plaque density per mm²: total NP counts (with and without cores) in CERAD-defined neocortical brain regions: middle frontal gyrus (MFG), orbital frontal cortex (OFG), SMT, inferior parietal lobule (IPL), OC, and their mean. (D) Neuropathologic average of standardized NP and NFT density measurements. HTN-med vs no-HTN, p < 0.0005.