Background: Subcortical ischemic vascular cognitive impairment (SIVCI) is highly prevalent in older individuals. White matter hyperintensities (WMH) are a defining feature of SIVCI. There are sex differences in SIVCI, with females having higher volume and faster WMH progression than males. Resistance exercise training (RT) can slow WMH progression in cognitively unimpaired individuals; however, evidence in SIVCI is scarce. It is also unknown if biological sex influences WMH response to exercise. We investigated whether RT mitigated WMH in older individuals living with SIVCI and assessed whether biological sex moderated intervention effects.
Methods: This was a 12-month single-blind, randomized controlled trial. Participants were randomized to RT (n = 45, females = 32) or a balance and tone (BAT) control group (n = 46, females = 29). Study eligibility included: 1) age 55 years and older; 2) magnetic resonance imaging (MRI) evidence of cerebral small vessel disease; 3) mild cognitive impairment; and 4) absence of dementia. We measured WMH using a seed-based pipeline incorporating T2- and PD-weighted MRI scans. We extracted volumes for whole-brain and lobe-specific regions-of-interest. Differences between groups from baseline to 12 months were assessed via analysis of covariance adjusting for baseline WMH volume, estimated intracranial volume, and sex. We assessed sex-specific effects via group-by-sex interaction terms.
Results: Seventy-four participants (aged 74.3 [SD = 5.6], 65% females) completed follow-up assessment and were included in the analysis. At 12 months, no main effect of intervention was observed for whole-brain WMH volume (estimated mean difference [asinh-transformed cm]: -0.045, 95% CI: -0.124 to 0.034, p = 0.264). Biological sex significantly moderated intervention effects on whole-brain WMH volume (p = 0.019), whereby RT reduced WMH volume (vs BAT controls) in females (-0.113, 95% CI: -0.208 to -0.018, p = 0.021) but not males (0.081, 95% CI: -0.048 to 0.211, p = 0.216). Lobe-specific analysis revealed that RT reduced WMH volume (vs BAT controls) in the parietal (-0.074, 95% CI: -0.148 to -0.0004, p = 0.049) and temporal (-0.069, 95%CI: -0.138 to -0.00003, p = 0.049) lobes. Group-by-sex interaction effects approached significance for parietal WMH volume (p = 0.052), suggesting an overall sex-dependent effect of training.
Conclusion: RT may be an effective strategy to mitigate WMH progression in older individuals with SIVCI and females likely reap greater benefits than males.
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http://dx.doi.org/10.1002/alz.092848 | DOI Listing |
Background: In recent efforts to improve early identification, staging, and prediction of risk of persons at risk for vascular contributions to cognitive impairment and dementia (VCID) in relation with small vessel disease (SVD), the MarkVCID consortium has worked to identify and validate fluid- and imaging-based biomarkers for SVD associated with VCID. Free water (FW) measured derived from diffusion tensor imaging and one of the selected neuroimaging biomarker "kits", has been demonstrated to have excellent instrumental validity and to be a sensitive biomarker of cognitive performances. We sought to further examine FW clinical relevance by investigating whether FW predicts cognitive worsening over time.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
Background: To aid development of prevention strategies, we investigated whether a composite measure of late-midlife lifestyle health was associated with (1) change in brain tau burden, vascular burden and neurodegeneration and (2) cognitive trajectories when accounting for these brain changes.
Method: We included 324 individuals from the Wisconsin Registry for Alzheimer's Prevention. Late-midlife lifestyle was assessed using the Lifestyle for Brain Health (LIBRA) score, encompassing 12 risk-and protective factors for cognitive decline and dementia.
Alzheimers Dement
December 2024
Neuroimage Analytics Laboratory and Glenn Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX, USA.
Background: The location of proposed brain MRI markers of small vessel disease (SVD) might reflect their pathogenesis and may translate into differential associations with cognition. We derived regional MRI markers of SVD and studied: (i) associations with cognitive performance, (ii) patterns most likely to reflect underlying SVD, (iii) mediating effects on the relationships of age and cardiovascular disease (CVD) risk with cognition.
Method: In 891 participants from The Multi-Ethnic Study of Atherosclerosis, we segmented enlarged perivascular spaces (ePVS), white matter hyperintensities (WMH) and microbleeds (MBs) using deep learning-based algorithms, and calculated white matter (WM) microstructural integrity measures of fractional anisotropy (FA), trace (TR) and free water (FW) using automated DTI-processing pipelines.
Alzheimers Dement
December 2024
Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Background: Autosomal dominant Alzheimer disease (ADAD) is characterized by genetic mutations affecting the beta-amyloid (Aβ) pathway. However, vascular and immune factors play important roles which are not completely understood. Understanding the function of the neurovascular unit (NVU) comprised of neurons, glial cells, and vasculature, at different disease stages appears ideal to developing and evaluating therapeutics.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Background: White matter hyperintensities (WMH) were reported to contribute to the thinning of regional cortex connected to WMH in cerebral small vessel disease. However, the relationship between WMH and regional changes in WMH-connected cortex in Alzheimer's disease (AD) remains unclear. The objective of this study is to investigate the association between WMH and regional cortical thickness, amyloid and tau deposition, and synaptic density changes in the WMH-connected cortex.
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