Small Vessel Disease and Associations with Cerebrospinal Fluid Amyloid, Tau, and Neurodegeneration (ATN) Biomarkers and Cognition in Young Onset Dementia
Affiliations: [a] Department of Neurology, National Neuroscience Institute, Singapore, Singapore
| [b]
Duke-NUS Medical School, Singapore, Singapore
| [c]
Lee Kong Chian School of Medicine, Singapore
Correspondence:
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Correspondence to: A/Prof Nagaendran Kandiah, FRCP, Level 3, Clinical Staff Office, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. Tel.: +65 6357 7171; Fax: +65 6357 7137; E-mail: [email protected].
Abstract: 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 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). Conclusion: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.
