RESUMEN
BACKGROUND: Small vessel disease (SVD) and Alzheimer's disease (AD) frequently coexist; however, it remains unclear how they collectively affect cognition. OBJECTIVE: 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. METHODS: 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). RESULTS: SVD+ was associated with lower CSF Aß1-42 (Bâ=â-0.20, 95% CI: -0.32 to -0.08) and greater neurodegeneration, indexed as hippocampal atrophy (Bâ=â-0.24, 95% CI: -0.40 to -0.04). SVD+ was not associated with tau. Cognitive impairment was associated with CSF Aß1-42 (Bâ=â-0.35, 95% CI: -0.55 to -0.18) but not SVD. Rather, SVD was indirectly associated with cognition via reduced CSF Aß1-42, specifically with global cognition (Bâ=â-0.03, 95% CI: -0.09 to -0.01) and memory (Bâ=â0.08, 95% CI: -.01 to .21). SVD was indirectly associated with cognition via increased neurodegeneration in grey matter (Global cognition: Bâ=â-0.06, 95% CI: -0.17 to -0.03; Memory: Bâ=â0.05, 95% CI: 0.01 to 0.18) and the hippocampus (Global cognition: Bâ=â-0.05, 95% CI: -0.11 to -0.01; Memory: Bâ=â0.06, 95% CI: 0.01 to 0.17). CONCLUSION: In YOD, SVD burden was associated with AD pathology, namely CSF Aß1-42. SVD indirectly contributed to cognitive impairment via reducing CSF Aß1-42 and increasing neurodegeneration.