Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Moonen JEF

PROVIDER: S-EPMC10984432 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Moonen Justine E F JEF Haan Renée R Bos Isabelle I Teunissen Charlotte C van de Giessen Elsmarieke E Tomassen Jori J den Braber Anouk A van der Landen Sophie M SM de Geus Eco J C EJC Legdeur Nienke N van Harten Argonde C AC Trieu Calvin C de Boer Casper C Kroeze Lior L Barkhof Frederik F Visser Pieter Jelle PJ van der Flier Wiesje M WM

Alzheimer's & dementia : the journal of the Alzheimer's Association 20231225 3

<h4>Introduction</h4>We assessed whether co-morbid small vessel disease (SVD) has clinical predictive value in preclinical or prodromal Alzheimer's disease.<h4>Methods</h4>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).<h4>Results</h4>Thirty-nine percent had neither Aβ nor SVD (A-V-), 21% had SVD only ( ...[more]

PMID: 38146222

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Project description:BackgroundAlthough its incidence is relatively low, delayed-onset post-stroke cognitive decline (PSCD) may offer valuable insights into the "vascular contributions to cognitive impairment and dementia," particularly concerning the roles of vascular and neurodegenerative mechanisms. We postulated that the functional segregation observed during post-stroke compensation could be disrupted by underlying amyloid pathology or cerebral small vessel disease (cSVD), leading to delayed-onset PSCD.MethodsUsing a prospective stroke registry, we identified patients who displayed normal cognitive function at baseline evaluation within a year post-stroke and received at least one subsequent assessment. Patients suspected of pre-stroke cognitive decline were excluded. Decliners [defined by a decrease of ≥3 Mini-Mental State Examination (MMSE) points annually or an absolute drop of ≥5 points between evaluations, confirmed with detailed neuropsychological tests] were compared with age- and stroke severity-matched non-decliners. Index-stroke MRI, resting-state functional MRI, and 18F-florbetaben PET were used to identify cSVD, functional network attributes, and amyloid deposits, respectively. PET data from age-, sex-, education-, and apolipoprotein E-matched stroke-free controls within a community-dwelling cohort were used to benchmark amyloid deposition.ResultsAmong 208 eligible patients, 11 decliners and 10 matched non-decliners were identified over an average follow-up of 5.7 years. No significant differences in cSVD markers were noted between the groups, except for white matter hyperintensities (WMHs), which were strongly linked with MMSE scores among decliners (rho = -0.85, p < 0.01). Only one decliner was amyloid-positive, yet subthreshold PET standardized uptake value ratios (SUVR) in amyloid-negative decliners inversely correlated with final MMSE scores (rho = -0.67, p = 0.04). Decliners exhibited disrupted modular structures and more intermingled canonical networks compared to non-decliners. Notably, the somato-motor network's system segregation corresponded with the decliners' final MMSE (rho = 0.67, p = 0.03) and was associated with WMH volume and amyloid SUVR.ConclusionDisruptions in modular structures, system segregation, and inter-network communication in the brain may be the pathophysiological underpinnings of delayed-onset PSCD. WMHs and subthreshold amyloid deposition could contribute to these disruptions in functional brain networks. Given the limited number of patients and potential residual confounding, our results should be considered hypothesis-generating and need replication in larger cohorts in the future.

Dataset Information

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

Introduction

Methods

Results

Discussion

Highlights

Publications

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

Similar Datasets

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