Small Vessel Disease and Associations with Cerebrospinal Fluid Amyloid, Tau, and Neurodegeneration (ATN) Biomarkers and Cognition in Young Onset Dementia.

Abstract

Small vessel disease (SVD) and Alzheimer's disease (AD) frequently coexist; however, it remains unclear how they collectively affect cognition. We investigated associations between SVD and AD biomarkers, namely amyloid, tau, and neurodegeneration (ATN) in young onset dementia (YOD) and explored how SVD and ATN interact to affect cognition. 80 YOD individuals were recruited from a memory clinic. SVD burden (SVD+) was operationalized as a score >1 on the Staals scale and ATN was measured using cerebrospinal fluid (CSF). SVD+ was associated with lower CSF Aβ1-42 (B = -0.20, 95% CI: -0.32 to -0.08) and greater neurodegeneration, indexed as hippocampal atrophy (B = -0.24, 95% CI: -0.40 to -0.04). SVD+ was not associated with tau. Cognitive impairment was associated with CSF Aβ1-42 (B = -0.35, 95% CI: -0.55 to -0.18) but not SVD. Rather, SVD was indirectly associated with cognition via reduced CSF Aβ1-42, specifically with global cognition (B = -0.03, 95% CI: -0.09 to -0.01) and memory (B = 0.08, 95% CI: -.01 to .21). SVD was indirectly associated with cognition via increased neurodegeneration in grey matter (Global cognition: B = -0.06, 95% CI: -0.17 to -0.03; Memory: B = 0.05, 95% CI: 0.01 to 0.18) and the hippocampus (Global cognition: B = -0.05, 95% CI: -0.11 to -0.01; Memory: B = 0.06, 95% CI: 0.01 to 0.17). In YOD, SVD burden was associated with AD pathology, namely CSF Aβ1-42. SVD indirectly contributed to cognitive impairment via reducing CSF Aβ1-42 and increasing neurodegeneration.