Rundle, M. M. | bioRxiv Science

bioRxiv2024

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

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.

neuroscience↗

bioRxiv2020

Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer's Disease

Normal aging and Alzheimers Disease (AD) are accompanied by large-scale alterations in brain organization that undermine brain function. Although hemispheric asymmetry is a global organizing feature of cortex thought to promote brain efficiency, current descriptions of cortical thinning in aging and AD have largely overlooked cortical asymmetry. Consequently, the foundational question of whether and where the cerebral hemispheres change at different rates in aging and AD remains open. First, applying vertex-wise data-driven clustering in a longitudinal discovery sample (aged 20-89; 2577 observations; 1851 longitudinal) we identified cortical regions exhibiting similar age-trajectories of asymmetry across the adult lifespan. Next, we sought replication in 4 independent longitudinal aging cohorts. We show that higher-order regions of cortex that exhibit pronounced asymmetry at age ~20 also show asymmetry change in aging. Results revealed that both leftward and rightward asymmetry is progressively lost on a similar time-scale across adult life. Hence, faster thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This simple organizational principle showed high consistency across multiple aging cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating samples. Finally, we show that regions exhibiting gradual asymmetry-loss over healthy adult life exhibit faster asymmetry-change in AD. Overall, our results suggest a system-wide breakdown in the adaptive asymmetric organization of cortex across adult life which is further accelerated in AD, and may implicate thickness asymmetry as a viable marker for declining hemispheric specialization in aging and AD. SignificanceThe brain becomes progressively disorganized with age, and brain alterations accelerated in Alzheimers disease may occur gradually over the lifespan. Although hemispheric asymmetry aids efficient network organization, efforts to identify structural markers of age-related decline have largely overlooked cortical asymmetry. Here we show the hemisphere that is thicker when younger, thins faster. This leads to progressive system-wide loss of regional thickness asymmetry across life. In multiple aging cohorts, asymmetry-loss showed high reproducibility topologically across cortex and similar timing-of-change in aging. Asymmetry-change was further accelerated in AD. Our findings uncover a new principle of brain aging - thicker homotopic cortex thins faster - and suggest we may have unveiled a structural marker for a widely-hypothesized decline in hemispheric specialization in aging and AD.

neuroscience↗