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

Justine E.F. Moonen, Renée Haan, Isabelle Bos, Charlotte Teunissen, Elsmarieke van de Giessen, Jori Tomassen, Anouk den Braber, Sophie M. van der Landen, Eco J.C. de Geus, Nienke Legdeur, Argonde C. van Harten, Calvin Trieu, Casper de Boer, Lior Kroeze, Frederik Barkhof, Pieter Jelle Visser, Wiesje M. van der Flier

    Research output: Contribution to journalArticleAcademicpeer-review


    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.

    Original languageEnglish
    Pages (from-to)1868-1880
    JournalAlzheimer's and Dementia
    Issue number3
    Early online date25 Dec 2023
    Publication statusPublished - Mar 2024


    • amyloid beta
    • cognitive decline
    • dementia
    • mortality
    • small vessel disease

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