Antihypertensive Treatment is associated with MRI-Derived Markers of Neurodegeneration and Impaired Cognition: A Propensity-Weighted Cohort Study

Article type: Research Article

Authors: Edwards, Jodi D.^{a; b; c; 1; *} | Ramirez, Joel^{a; b; c; 1} | Callahan, Brandy L.^{a; b} | Tobe, Sheldon W.^d | Oh, Paul^e | Berezuk, Courtney^{a; b; c} | Lanctôt, Krista^{b; f; g} | Swardfager, Walter^{a; b; c; g} | Nestor, Sean^a | Kiss, Alexander^h | Strother, Stephen^{i; j} | Black, Sandra E.^{a; b; c; k} | for the Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Canada | [b] Hurvitz Brain Sciences Program, Sunnybrook Research Institute>, University of Toronto, Toronto, Canada | [c] Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Site, Toronto, Canada | [d] Nephrology, University of Toronto, Toronto, Canada | [e] Toronto Rehabilitation Institute, Toronto, Canada | [f] Geriatric Psychiatry, University of Toronto, Toronto, Canada | [g] Pharmacology and Toxicology, University of Toronto, Toronto, Canada | [h] Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, Toronto, Canada | [i] Medical Biophysics, University of Toronto, Toronto, Canada | [j] Rotman Research Institute, Toronto, Canada | [k] Department of Medicine (Neurology), Sunnybrook Health Sciences and University of Toronto, Toronto, Canada

Correspondence: [*] Correspondence to: Jodi D. Edwards, PhD, Sunnybrook Research Institute, Room A421- 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. Tel.: +1 416 480 6100 x85420; Fax: +1 416 480 6199; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background:Hypertension is an important risk factor for Alzheimer’s disease (AD) and cerebral small vessel disease. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are common anti-hypertensive treatments, but have differential effects on cortical amyloid. Objective:The objective of this study was to evaluate associations between anti-hypertensive treatment, brain volume, and cognition, using a propensity-weighted analysis to account for confounding by indication. Methods:We identified a cohort of normal elderly adults and individuals with mild cognitive impairment (MCI) or AD (N = 886; mean age = 75.0) from the Alzheimer’s Disease Neuroimaging Initiative. Primary outcomes were brain parenchymal fraction, total hippocampal volume, and white matter hyperintensity (WMH) volume. Secondary outcomes were standardized scores on neuropsychological tests. Propensity-weighted adjusted multivariate linear regression was used to estimate associations between anti-hypertensive treatment class and MRI volumes and cognition. Results:Individuals treated with ARBs showed larger hippocampal volumes (R2 = 0.83, p = 0.05) and brain parenchymal fraction (R2 = 0.83, p = 0.01) than those treated with ACEIs. When stratified by diagnosis, this effect remained only in normal elderly adults and MCI patients, and a significant association between ARBs and lower WMH volume (R2 = 0.83, p = 0.03) emerged for AD patients only. ARBs were also associated with significantly better performance on tests of episodic and verbal memory, language, and executive function (all p < 0.05). Conclusions:Findings are consistent with evidence for a neuroprotective effect of treatment with ARBs for brain structure and cognition. This study has potential implications for the treatment of hypertension, particularly in elderly adults at risk of cognitive decline and AD.

Keywords: Alzheimer’s disease, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, hypertension, white matter hyperintensities

DOI: 10.3233/JAD-170238

Journal: Journal of Alzheimer's Disease, vol. 59, no. 3, pp. 1113-1122, 2017