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Contributions of amyloid beta and cerebral small vessel disease in clinical decline.

Moonen, J.E.F., Haan, R., Bos, I., Teunissen, C., Giessen, E. van de, Tomassen, J., Braber, A. den, Landen, S.M. van der, Geus, E.J.C. de, Legdeur, N., Harten, A.C. van, Trieu, C., Boer, C. de, Kroeze, L., Barkhof, F., Visser, P.J., Flier, W.M. van der. Contributions of amyloid beta and cerebral small vessel disease in clinical decline. Alzheimers & Dementia: 2023
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Introduction
We assessed whether co-morbid small vessel disease (SVD) has clinical predictive value in preclinical or prodromal Alzheimer's disease.

Methods
In 1090 non-demented participants (65.4 ± 10.7 years) SVD was assessed with magnetic resonance imaging and amyloid beta (Aβ) with lumbar puncture and/or positron emission tomography scan (mean follow-up for cognitive function 3.1 ± 2.4 years).

Results
Thirty-nine percent had neither Aβ nor SVD (A-V-), 21% had SVD only (A-V+), 23% Aβ only (A+V-), and 17% had both (A+V+). Pooled cohort linear mixed model analyses demonstrated that compared to A-V- (reference), A+V- had a faster rate of cognitive decline. Co-morbid SVD (A+V+) did not further increase rate of decline. Cox regression showed that dementia risk was modestly increased in A-V+ (hazard ratio [95% confidence interval: 1.8 [1.0-3.2]) and most strongly in A+ groups. Also, mortality risk was increased in A+ groups.

Discussion
In non-demented persons Aβ was predictive of cognitive decline, dementia, and mortality. SVD modestly predicts dementia in A-, but did not increase deleterious effects in A+.

Highlights
Amyloid beta (Aβ; A) was predictive for cognitive decline, dementia, and mortality. Small vessel disease (SVD) had no additional deleterious effects in A+. SVD modestly predicted dementia in A-. Aβ should be assessed even when magnetic resonance imaging indicates vascular cognitive impairment.