Sporadic cerebral small vessel disease and cognitive decline in healthy older adults: A systematic review and meta-analysis

Jansma, Alexander; de Bresser, Jeroen; Schoones, Jan W; van Heemst, Diana; Akintola, Abimbola A · 2024 · Crossref

DOI: 10.1177/0271678x241235494

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Summary

This systematic review and meta-analysis investigates the association between sporadic cerebral small vessel disease (SVD) and cognitive decline in healthy older adults without baseline cognitive deficits. Motivated by the increasing prevalence of neurodegenerative diseases and the established link between SVD and vascular cognitive impairment, the study aims to quantify the specific impact of MRI markers of SVD—white matter hyperintensities (WMH), cerebral microbleeds (CMB), and lacunes—on distinct cognitive domains. This analysis addresses a gap in existing literature, which has largely focused on populations with existing pathologies like hypertension or stroke, rather than cognitively intact individuals. The researchers conducted a systematic search of seven databases (including PubMed, Embase, and Cochrane Library) for prospective longitudinal studies published up to June 2023. Inclusion criteria required studies to involve community-dwelling adults with a median age of 60 or older, normal baseline cognition, and quantitative neuropsychological testing alongside brain imaging. After screening 1,510 identified articles, 23 studies comprising 11,486 participants were included in the systematic review, with 21 studies contributing data to the meta-analysis. The average follow-up duration was 5.7 years. Statistical analysis involved pooling standardized effect estimates using random-effects models, assessing heterogeneity, and evaluating risk of bias through quality scoring and funnel plots. The results demonstrate that the presence of MRI markers of cerebral SVD predicts an increased risk of cognitive decline across multiple domains. Pooled effect sizes indicated significant negative associations for global cognition (−0.10), executive function (−0.18), memory (−0.12), and attention (−0.17). When analyzing individual markers, WMH showed statistically significant associations with decline in all four cognitive domains, with the strongest effects observed in executive function (−0.23) and attention (−0.24). CMBs were significantly associated with declines in executive function (−0.07), memory (−0.11), and attention (−0.13), though their impact was generally smaller than that of WMH. Lacunes showed negative correlations with cognition in several studies, but insufficient data prevented a robust pooled meta-analysis for this marker. The study concludes that sporadic SVD, particularly as evidenced by WMH and CMBs, is a significant predictor of cognitive decline in otherwise healthy older adults. WMH appears to have a broader and more pronounced impact on cognitive domains compared to CMBs. These findings underscore the importance of MRI markers as potential biomarkers for identifying individuals at risk of cognitive impairment, thereby informing future lifestyle interventions and treatment strategies aimed at preventing cognitive decline in aging populations.

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• cognitive impairment