Lorenza Scotti1, Lisette Bassi2, Davide Soranna3, Federico Verde4, Vincenzo Silani4, Antonio Torsello5, Gianfranco Parati6, Antonella Zambon7. 1. Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. Electronic address: lorenza.scotti@uniupo.it. 2. Syneos Health Inc., Milan, Italy. 3. Biostatistic Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy. 4. Department of Neurology - Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milano, Milan, Italy. 5. School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy. 6. School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; Department of Cardiovascular Neural and Metabolic Sciences, IRCCS Istituto Auxologico Italiano, S. Luca Hospital, Milan, Italy. 7. Biostatistic Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy.
Abstract
OBJECTIVE: To evaluate the association of all RAAS inhibitors, ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on dementia onset (any dementia, Alzheimer's disease and vascular dementia) using a meta-analytic approach. METHODS: A systematic MEDLINE search was carried out to identify all observational studies published up to the 30th September 2020 evaluating the association between RAAS inhibitors and risk of dementia. Studies were included if original investigations considering incident dementia cases, with ACEIs and/or ARBs as exposure and other antihypertensives (AHs) use as reference, and if reporting association estimates and relative variability measures. Random effect pooled relative risks (pRR) and the corresponding 95% confidence intervals (95%CI) were calculated according to DerSimonian and Laird's (DL) or to Hartung Knapp Sidik Jonkman (HKSJ) method depending on the number of studies and between-studies heterogeneity. A linear mixed meta-regression model (MM) was applied to take into account correlation among association estimates from the same study. RESULTS: 15 studies were included in the meta-analysis. ARBs but not ACEIs' use led to a significant reduction of the risk of any dementia (pRR 0.78, 95%CIMM 0.70-0.87) and Alzheimer's disease (pRR 0.73, 95%CIMM 0.60-0.90). Moreover, when compared to ACEIs, ARBs reduced of 14% the risk of any dementia (pRR 0.86, 95%CIDL 0.79-0.94). CONCLUSIONS: ARBs but not ACEIs led to a reduction in the risk of any dementia. The difference between ARBs and ACEIs in terms of preventive effectiveness could be due to distinct profiles of antagonism towards independent receptor pathways or to differential influences on amyloid metabolism.
OBJECTIVE: To evaluate the association of all RAAS inhibitors, ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on dementia onset (any dementia, Alzheimer's disease and vascular dementia) using a meta-analytic approach. METHODS: A systematic MEDLINE search was carried out to identify all observational studies published up to the 30th September 2020 evaluating the association between RAAS inhibitors and risk of dementia. Studies were included if original investigations considering incident dementia cases, with ACEIs and/or ARBs as exposure and other antihypertensives (AHs) use as reference, and if reporting association estimates and relative variability measures. Random effect pooled relative risks (pRR) and the corresponding 95% confidence intervals (95%CI) were calculated according to DerSimonian and Laird's (DL) or to Hartung Knapp Sidik Jonkman (HKSJ) method depending on the number of studies and between-studies heterogeneity. A linear mixed meta-regression model (MM) was applied to take into account correlation among association estimates from the same study. RESULTS: 15 studies were included in the meta-analysis. ARBs but not ACEIs' use led to a significant reduction of the risk of any dementia (pRR 0.78, 95%CIMM 0.70-0.87) and Alzheimer's disease (pRR 0.73, 95%CIMM 0.60-0.90). Moreover, when compared to ACEIs, ARBs reduced of 14% the risk of any dementia (pRR 0.86, 95%CIDL 0.79-0.94). CONCLUSIONS: ARBs but not ACEIs led to a reduction in the risk of any dementia. The difference between ARBs and ACEIs in terms of preventive effectiveness could be due to distinct profiles of antagonism towards independent receptor pathways or to differential influences on amyloid metabolism.
Authors: Caglar Cosarderelioglu; Lolita S Nidadavolu; Claudene J George; Ruth Marx-Rattner; Laura Powell; Qian-Li Xue; Jing Tian; Esther S Oh; Luigi Ferrucci; Pervin Dincer; David A Bennett; Jeremy D Walston; Peter M Abadir Journal: Geroscience Date: 2022-08-15 Impact factor: 7.581
Authors: Xi Pan; Donglan Zhang; Ji Haeng Heo; Chanhyun Park; Gang Li; Christine M Dengler-Crish; Yan Li; Yian Gu; Henry N Young; Devin L Lavender; Lu Shi Journal: Drugs Aging Date: 2022-10-17 Impact factor: 4.271