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

INTRODUCTIONWe assessed whether co-morbid small vessel disease (SVD) has clinical predictive value in preclinical or prodromal Alzheimer's disease.METHODSIn 1090 non-demented participants (65.4 +/- 10.7 years) SVD was assessed with magnetic resonance imaging and amyloid beta (A beta) with lumbar puncture and/or positron emission tomography scan (mean follow-up for cognitive function 3.1 +/- 2.4 years).RESULTSThirty-nine percent had neither A beta nor SVD (A-V-), 21% had SVD only (A-V+), 23% A beta 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.DISCUSSIONIn non-demented persons A beta was predictive of cognitive decline, dementia, and mortality. SVD modestly predicts dementia in A-, but did not increase deleterious effects in A+.HighlightsAmyloid beta (A beta; 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-.A beta should be assessed even when magnetic resonance imaging indicates vascular cognitive impairment.