Baker, L. D. | 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↗

bioRxiv2022

Physical resilience in the brain: The effect of white matter disease on brain networks in cognitively normal older adults

BACKGROUNDPhysical resilience with age is considered a key feature of healthy aging, but current understanding of the neural contributions to resilience is limited. Additionally, few methods exist to identify physical resilience and observe the mechanisms through which resilience manifests. METHODSTo address these gaps, we used data from 189 participants from the Brain Networks and Mobility (B-NET) study who completed the short physical performance battery (SPPB) as well as its expanded version (eSPPB), magnetic resonance imaging (MRI), and functional MRI (fMRI). Functional brain networks were generated using graph theory methods. We grouped participants based on SPPB scores (<10=unhealthy & 10-12=healthy) and median splits of white matter hyperintensity volumes: Expected Healthy (EH: low WMH, healthy SPPB, n=81), Expected Impaired (EI: high WMH, unhealthy SPPB, n=42), Unexpected Healthy (UH: high WMH, healthy SPPB, n=53), and Unexpected Impaired (UI: low WMH, unhealthy SPPB, n=13). UH is considered the "resilient" group due to their maintained function despite elevated WMH burden. Continuous analyses assessed the relationships between network properties, mobility, and cognition. RESULTSHigher SPPB scores were associated (p<0.01) with greater sensorimotor cortex community structure (SMN-CS) consistency. While no main effect of the resilience interaction term (SPPB*WMH) was found on SMN-CS, UH showed higher numbers of second-order connections between the SMN and anterior cingulate cortex (ACC) than EI (p<0.01). CONCLUSIONSIncreased connectivity between SMN and ACC may be a marker of physical resilience within the brain.

neuroscience↗