11 Feb 21. Featured Paper

Neuropsychiatric symptoms associated with cerebral small vessel disease: a systematic review & meta-analysis.

Link to paper on The Lancet Psychiatry

Authors

Una Clancy MB BCh, Daniel Gilmartin MB BCh, Angela C C Jochems MSc, Lucy Knox MBChB, Fergus N Doubal PhD, Prof Joanna M Wardlaw MD

Abstract

Background: Cerebral small vessel disease, a common cause of vascular dementia, is often considered clinically silent before dementia or stroke become apparent.

However, some individuals have subtle symptoms associated with acute MRI lesions.

We aimed to determine whether neuropsychiatric & cognitive symptoms vary according to small vessel disease burden.

Methods: In this systematic review & meta-analysis, we searched MEDLINE, EMBASE, & PsycINFO for articles published in any language from database inception to Jan 24, 2020.

We searched for studies assessing anxiety, apathy, delirium, emotional lability, fatigue, personality change, psychosis, dementia-related behavioural symptoms or cognitive symptoms (including subjective memory complaints), & radiological features of cerebral small vessel disease.

We extracted reported odds ratios (OR), standardised mean differences (SMD), & correlations, stratified outcomes by disease severity or symptom presence or absence, & pooled data using random-effects meta-analyses, reporting adjusted findings when possible.

We assessed the bias on included studies using the Risk of Bias for Non-randomized Studies tool.

This study is registered with PROSPERO, CRD42018096673.

Findings: Of 7119 papers identified, 81 studies including 79 cohorts in total were eligible for inclusion (n=21 730 participants, mean age 69·2 years).

Of these 81 studies, 45 (8120 participants) reported effect estimates.

We found associations between worse white matter hyperintensity (WMH) severity & apathy (OR 1·41, 95% CI 1·05–1·89) & the adjusted SMD in apathy score between WMH severities was 0·38 (95% CI 0·15–0·61).

Worse WMH severity was also associated with delirium (adjusted OR 2·9, 95% CI 1·12–7·55) & fatigue (unadjusted OR 1·63, 95% CI 1·20–2·22).

WMHs were not consistently associated with subjective memory complaints (OR 1·34, 95% CI 0·61–2·94) & unadjusted SMD for WMH severity between these groups was 0·08 (95% CI −0·31 to 0·47).

Anxiety, dementia-related behaviours, emotional lability, & psychosis were too varied or sparse for meta-analysis; these factors were reviewed narratively.

Overall heterogeneity varied from 0% to 79%.

Only five studies had a low risk of bias across all domains.

Interpretation: Apathy, fatigue, & delirium associated independently with worse WMH, whereas subjective cognitive complaints did not.

The association of anxiety, dementia-related behaviours, emotional lability, & psychosis with cerebral small vessel disease require further investigation.

These symptoms should be assessed longitudinally to improve early clinical detection of small vessel disease & enable prevention trials to happen early in the disease course, long before cognition declines.

Keywords

• Anxiety
• Cerebral small vessel disease
• Dementia
• Meta-analysis
• Neuropsychiatric symptoms
• Stroke
• Systematic review