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

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.