Physical reserve and its underpinning functional neural networks moderate the relationship between white matter hyperintensity and postural balance in older adults with subcortical ischemic vascular cognitive impairment.

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one's capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional networks associated with PR, and examining the relationship between PR, WMH, and postural balance. PR was defined in 22 community-dwelling older adults with SIVCI. Functional networks of PR were computed using general linear model. Subsequent analyses examined whether PR and relevant networks moderated the relationship between WMH and postural balance under two conditions-eyes open while standing on foam (EOF) or on floor (EONF). We found that PR and the relevant networks-frontoparietal network (FPN) and default mode network (DMN)-significantly moderated the association between WMH and postural balance. For individuals with high PR, postural balance remained stable regardless of the extent of WMH load; whereas for those with low PR, postural balance worsened as WMH load increased. These results suggest the attenuated effects of WMH on postural stability due to PR may be underpinned by functional neural network reorganization in the FPN and DMN as a part of compensatory processes.

Exploring the Contribution of Myelin Content in Normal Appearing White Matter to Cognitive Outcomes in Cerebral Small Vessel Disease.

BACKGROUND: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood. OBJECTIVE: The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD. METHODS: This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05. RESULTS: After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (ß â€Š= -0.29, p = 0.037) and poorer working memory (ß= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132). CONCLUSION: Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function.

Cerebral Amyloid-ß Deposition Is Associated with Impaired Gait Speed and Lower Extremity Function.

BACKGROUND: Impaired physical function (i.e., slowing of gait, muscle weakness, and poor mobility) is common in older adults with cognitive impairment and dementia. Evidence suggests that cerebral small vessel disease, specifically white matter lesions (WMLs), is associated with impaired physical function, but little research has been conducted to understand the specific role of Alzheimer's disease pathology in physical outcomes. OBJECTIVE: The objective of this study was to examine the association between cerebral amyloid-ß (Aß) deposition and physical function in people with cognitive impairment. METHODS: Thirty participants completed an 11C Pittsburgh compound B (PIB) position emission tomography (PET) scan to quantify global Aß deposition using standardized uptake value ratio (SUVR). We assessed usual gait speed, muscle strength of the lower extremities, balance, and functional mobility using the Short Physical Performance Battery (SPPB) and the Timed Up and Go Test (TUGT). Multiple linear regression analyses examined the association between Aß and each measure of physical function, adjusting for age, body mass index, and WML load. RESULTS: Global PIB SUVR was significantly associated with usual gait speed (ß= -0.52, p = 0.01) and SPPB performance (ß= -0.47, p = 0.02), such that increased Aß deposition was associated with reduced performance on both measures. Global PIB SUVR was not significantly associated with TUGT performance (ß= 0.32, p = 0.08). CONCLUSIONS: Cerebral Aß deposition is associated with reduced gait speed, muscle strength, and balance in older adults with cognitive impairment independent of WML load. However, Aß deposition was not associated with functional mobility.