Wasserman, B. A. | Search bioRxiv

bioRxiv2026

Spatial Patterns of White Matter Hyperintensities and Cognitive Function in Older Adults: A Community-Based Study

Abstract Objectives White matter hyperintensities (WMH) are associated with cognitive decline in older adults. We examined whether anatomically defined spatial WMH patterns are associated with cognitive performance and subsequent decline in a large community-based cohort with approximately six years of follow-up. Methods We analyzed 1,667 participants (mean age 76 years) from the Atherosclerosis Risk in Communities Neurocognitive Study. WMH were segmented from FLAIR images and mapped to 112 white matter regions using deep-learning-based parcellation. Principal component analysis identified dominant WMH distribution patterns; candidate components were selected by Horn's parallel analysis and retained if stable across resampled split samples. Linear mixed-effects models examined associations between WMH patterns and cognitive performance at baseline and follow-up, adjusting for demographic, genomic, and vascular risk factors. Robustness was assessed using analyses accounting for total WMH burden, study center, and selective attrition. Results Of 14 candidate principal components (PCs) identified by parallel analysis, eight met the resampling stability criterion and were retained, together explaining 42% of the variance. Three components were associated with cross-sectional or future cognition. PC3, characterized by deep white matter burden in the corpus callosum and anterior corona radiata with relative preservation of superficial white matter, showed no cross-sectional association at baseline but was associated with accelerated decline across multiple domains. Interpretation A deep spatial pattern of WMH loading on the corpus callosum and anterior corona radiata was associated with subsequent cognitive decline in the absence of a cross-sectional association at baseline, independent of total lesion burden.

neuroscience↗

bioRxiv2020

Using seasonal genomic changes to understand historical adaptation: parallel selection on stickleback in highly-variable estuaries

Parallel evolution is considered strong evidence for natural selection. However, few studies have investigated the process of parallel selection as it plays out in real time. The common approach is to study historical signatures of selection in populations already well adapted to different environments. Here, to document selection in action under natural conditions, we study six populations of threespine stickleback (Gasterosteus aculeatus) inhabiting bar-built estuaries that undergo seasonal cycles of environmental changes. Estuaries are periodically isolated from the ocean due to sandbar formation during dry summer months, with concurrent environmental shifts that resemble the long-term changes associated with postglacial colonization of freshwater habitats by marine populations. We used pooled whole-genome sequencing (Pool-WGS) to track seasonal allele frequency changes in these populations and search for signatures of natural selection. We found consistent changes in allele frequency across estuaries, suggesting a potential role for parallel selection. Functional enrichment among candidate genes included transmembrane ion transport and calcium binding, which are important for osmoregulation and ion balance. The genomic changes that occur in threespine stickleback from bar-built estuaries could provide a glimpse into the early stages of adaptation that have occurred in many historical marine to freshwater transitions.

genomics↗