Vascular risk and physical activity as modulators of cognitive and neurodegenerative trajectories: Independent and interactive effects with beta‐amyloid: Novel insights into the role of vascular risk factors in the development of Alzheimer's disease and neurodegeneration. (7th December 2020)

• Record Type: Journal Article
• Authors: Chhatwal, Jasmeer P; Rabin, Jennifer S; Yang, Hyun‐Sik; Klein, Hannah; Scott, Matthew R; Kirn, Dylan; Pruzin, Jeremy J; Yau, Wai‐Ying; Schultz, Aaron P; Johnson, Keith A; Sperling, Reisa A
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 10
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.044145
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Understanding the extent to which vascular and lifestyle factors operate independently and synergistically with Alzheimer's disease pathology is critical to designing optimized clinical trials and to assessing the efficacy of interventions to delay cognitive impairment. We examined this question by leveraging data from a longitudinal cohort study with detailed cognitive and multi‐modal imaging data (the Harvard Aging Brain Study; HABS). Method: We used cross‐sectional and longitudinal data from HABS (n = 223; mean age at entry: 72y; mean follow‐up of 5.9y), including 11C‐Pittsburgh‐Compound‐B (PiB) amyloid PET, 18F‐Flortaucipir (FTP) tau PET, MRI, pedometer‐measured physical activity data, cognitive testing (Preclinical Alzheimer Cognitive Composite; PACC), and the Framingham Heart Study Cardiovascular Disease Risk Score (FHS‐CVD). Using linear mixed effects models, we examined the interplay of vascular risk factors, imaging measures of cerebrovascular injury, and physical activity with PET measures of b‐amyloid burden as they relate to longitudinal cognitive performance, neurodegeneration, and tau pathology. Result: We observed that higher FHS‐CVD at study entry was predictive of poorer longitudinal cognitive performance on the PACC, alone and interactively with PiB‐PET (both p<0.001). Greater baseline physical activity (mean steps) was predictive of better longitudinal cognitive performance when interacted with PiB‐PET (p <0.001). Lower FHS‐CVD and greater physical activity were both predictive of less neurodegeneration (longitudinal MRI measures of hippocampal and gray matter volumes) when interacted with PiB‐PET (all p < 0.01). In the subset of participants with available tau PET, FHS‐CVD but not physical activity interacted with PiB‐PET to significantly predict cross‐sectional and longitudinal tau accumulation (p < 0.05). Diffusion but not FLAIR measures of white matter disruption added to FHS‐CVD in predicting cognitive decline. Conclusion: Together with many prior studies, these data indicate strong additive and/or synergistic effects of vascular risk and physical activity with b‐amyloid in prediction of longitudinal cognition, neurodegeneration, and tau accumulation. These results suggest interventions targeting physical activity and vascular risk in order to delay cognitive decline may be particularly effective in people with elevated β‐amyloid burden. Similarly, consideration of vascular and lifestyle factors may improve our understanding of the potential clinical effectiveness of anti‐amyloid and tau therapies currently in testing.