Resting-state connectivity modifies the effects of amyloid on cognitive and physical function: evidence for network-based cognitive reserve

Laurienti, P. J.; Kritchevsky, S. B.; Lyday, R. G.; Miller, M. E.; Lockhart, S. N.; Rundle, M. M.; Hugenschmidt, C. E.; Burdette, J. H.; Shappell, H. M.; Chen, H.; Baker, L. D.; Neyland, B. R.; Holtzer, R.

doi:10.1101/2024.11.07.622257

bioRxiv · 10.1101/2024.11.07.622257

Resting-state connectivity modifies the effects of amyloid on cognitive and physical function: evidence for network-based cognitive reserve

Laurienti, P. J.·Kritchevsky, S. B.·Lyday, R. G.·Miller, M. E.·Lockhart, S. N.·Rundle, M. M.·Hugenschmidt, C. E.·Burdette, J. H.·Shappell, H. M.·Chen, H.·Baker, L. D.·Neyland, B. R.·Holtzer, R.

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Abstract

Cognitive and physical function are interrelated in aging co-occurring impairments in both domains can be debilitating and lead to increased risk of developing dementia. Amyloid beta (A{beta}) deposition in the brain is linked to cognitive decline and is also associated with poorer physical function in older adults. However, significant inter-individual variability exists with respect to the influence of increased brain A{beta} concentrations on cognitive and physical outcomes. Identifying factors that explain inter-individual variability in associations between A{beta} and clinical outcomes could inform interventions designed to delay declines in both cognitive and physical function. Cognitive reserve (CR) is considered a buffer that allows for cognitive performance that is better than expected for a given level of brain injury or pathology. Although the neural mechanisms underlying CR remain unknown, there is growing evidence that resting-state brain networks may serve as a neural surrogate for CR. The currently study evaluated whether functional brain networks modified associations between brain A{beta} and cognitive and physical function in community-dwelling older adults from the Brain Networks and Mobility (B-NET) study. We found that the integrity of the central executive and basal ganglia networks modified associations of A{beta} with cognitive and physical performance. Associations between brain A{beta} and cognitive and physical function were less pronounced when brain network integrity was high. The current study introduces novel evidence for brain networks underlying CR as a buffer against the influence of A{beta} accumulation on cognitive and physical function. Significance StatementThere is a growing number of medications targeting beta amyloid for the treatment of Alzheimers disease. The treatments effectively lower brain amyloid but do not have as robust of an effect on clinical outcomes. The current study introduces novel evidence for brain networks as a buffer against the influence of A{beta} accumulation on cognitive and physical function in older adults with normal cognition. Future studies should examine if brain network integrity underlies the variability in treatment response to amyloid-lowering drugs in patients with cognitive decline.

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Laurienti, P. J., Kritchevsky, S. B., Lyday, R. G., Miller, M. E., Lockhart, S. N., Rundle, M. M., Hugenschmidt, C. E., Burdette, J. H., Shappell, H. M., Chen, H., Baker, L. D., Neyland, B. R., Holtzer, R.. 2024-11-07. Resting-state connectivity modifies the effects of amyloid on cognitive and physical function: evidence for network-based cognitive reserve. https://doi.org/10.1101/2024.11.07.622257

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