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White Matter Hyperintensities Impact Biomarker Prediction of Cognitive Decline

Bachmann, D.; Gericke, C.; Wybitul, M.; Saake, A.; Studer, S.; Rauen, K.; Gruber, E.; Buchmann, A.; Hullner, M.; Blennow, K.; Zetterberg, H.; Nitsch, R. M.; Hock, C.; Treyer, V.; Gietl, A.

2025-08-12 neurology
10.1101/2025.08.09.25333299 medRxiv
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IntroductionAccounting for common co-pathologies such as white matter hyperintensities (WMH) of presumed vascular origin may improve the prognostic performance of imaging and blood-based biomarkers for cognitive decline in Alzheimers disease (AD). MethodsWe analyzed longitudinal cognitive data from 216 (median age: 67.2 years; median follow up: 5.3 years) community-dwelling older adults who underwent MRI, A{beta} PET, and plasma p-tau217, neurofilament light chain, and glial fibrillary acidic protein assessment. ResultsWMHs predicted declines in executive function, processing speed, and global cognition, and amplified the effects of imaging and plasma biomarkers, especially on episodic memory. The interaction between A{beta}-PET and WMH volume was the primary interaction associated with faster memory decline. DiscussionCoexisting AD pathology and WMHs shorten the preclinical stage of AD. Consideration of A{beta}-PET and blood-based biomarkers in the context of an individuals WMH burden may improve the prognostic value of these biomarkers.

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