Jodi D Edwards1,2,3, Joel Ramirez1,2,3, Brandy L Callahan1,2, Sheldon W Tobe4, Paul Oh5, Courtney Berezuk1,2,3, Krista Lanctôt2,6,7, Walter Swardfager1,2,3,7, Sean Nestor1, Alexander Kiss8, Stephen Strother9,10, Sandra E Black1,2,3,11. 1. LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Canada. 2. Hurvitz Brain Sciences Program, Sunnybrook Research Institute>, University of Toronto, Toronto, Canada. 3. Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Site, Toronto, Canada. 4. Nephrology, University of Toronto, Toronto, Canada. 5. Toronto Rehabilitation Institute, Toronto, Canada. 6. Geriatric Psychiatry, University of Toronto, Toronto, Canada. 7. Pharmacology and Toxicology, University of Toronto, Toronto, Canada. 8. Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, Toronto, Canada. 9. Medical Biophysics, University of Toronto, Toronto, Canada. 10. Rotman Research Institute, Toronto, Canada. 11. Department of Medicine (Neurology), Sunnybrook Health Sciences and University of Toronto, Toronto, Canada.
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.
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 ADpatients 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.
Authors: Jessica Alber; Suvarna Alladi; Hee-Joon Bae; David A Barton; Laurel A Beckett; Joanne M Bell; Sara E Berman; Geert Jan Biessels; Sandra E Black; Isabelle Bos; Gene L Bowman; Emanuele Brai; Adam M Brickman; Brandy L Callahan; Roderick A Corriveau; Silvia Fossati; Rebecca F Gottesman; Deborah R Gustafson; Vladimir Hachinski; Kathleen M Hayden; Alex M Helman; Timothy M Hughes; Jeremy D Isaacs; Angela L Jefferson; Sterling C Johnson; Alifiya Kapasi; Silke Kern; Jay C Kwon; Juraj Kukolja; Athene Lee; Samuel N Lockhart; Anne Murray; Katie E Osborn; Melinda C Power; Brittani R Price; Hanneke F M Rhodius-Meester; Jacqueline A Rondeau; Allyson C Rosen; Douglas L Rosene; Julie A Schneider; Henrieta Scholtzova; C Elizabeth Shaaban; Narlon C B S Silva; Heather M Snyder; Walter Swardfager; Aron M Troen; Susanne J van Veluw; Prashanthi Vemuri; Anders Wallin; Cheryl Wellington; Donna M Wilcock; Sharon Xiangwen Xie; Atticus H Hainsworth Journal: Alzheimers Dement (N Y) Date: 2019-04-09
Authors: Brian Houle; Thomas Gaziano; Meagan Farrell; F Xavier Gómez-Olivé; Lindsay C Kobayashi; Nigel J Crowther; Alisha N Wade; Livia Montana; Ryan G Wagner; Lisa Berkman; Stephen M Tollman Journal: BMC Public Health Date: 2019-11-27 Impact factor: 3.295
Authors: Michael Ouk; Che-Yuan Wu; Jennifer S Rabin; Aaron Jackson; Jodi D Edwards; Joel Ramirez; Mario Masellis; Richard H Swartz; Nathan Herrmann; Krista L Lanctôt; Sandra E Black; Walter Swardfager Journal: Alzheimers Res Ther Date: 2021-02-11 Impact factor: 6.982
Authors: Liu Shi; Colin R Buchanan; Simon R Cox; Robert F Hillary; Riccardo E Marioni; Archie Campbell; Caroline Hayward; Aleks Stolicyn; Heather C Whalley; Mathew A Harris; Jennifer Waymont; Gordon Waiter; Ellen Backhouse; Joanna M Wardlaw; Douglas Steele; Andrew Mcintosh; Simon Lovestone; Noel J Buckley; Alejo J Nevado-Holgado Journal: Alzheimers Dement (Amst) Date: 2021-09-27