Association of MRI-Visible Perivascular Spaces With Longitudinal Cognitive Decline Over a Decade

Clinical Snapshot

Key Findings

• P Value: All significant associations had confidence intervals excluding zero

• Effect Size: Executive function composite: β = -9.51 (independent analysis: β = -7.47); Hooper Visual Organization Test: β = -26.06 (independent: β = -22.11)

• Primary Outcome: Longitudinal cognitive decline across multiple neuropsychological domains over mean 4.9±3.1 years follow-up

• Nnt Or Sensitivity: Basal ganglia PVS independently predicted executive function and visuospatial decline beyond other SVD markers

• Confidence Interval: Executive function: 95% CI -14.33 to -4.68 (independent: -12.84 to -2.10); Hooper: 95% CI -50.53 to -1.59 (independent: -42.38 to -1.85)

Clinical Application

Requires 3T MRI with specialised PVS analysis software, limiting routine clinical application but feasible in specialist memory clinics Relevant for Australian memory clinics and neurologists. MRI accessibility through Medicare for appropriate indications. Aligns with RACGP cognitive assessment guidelines for early detection strategies Older adults without dementia or stroke undergoing cognitive assessment, particularly those with vascular risk factors

Abstract

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the most common vascular contributor to dementia. SVD markers often coexist, contributing to difficulty assessing their independent contributions to cognitive domains. MRI-visible perivascular spaces (PVSs) are an emerging SVD marker visualized by MRI. We previously showed that basal ganglia PVSs cross-sectionally contribute to worse cognition, independent of other SVD markers. To further characterize the clinical relevance of PVS, we studied its role as a unique SVD marker of longitudinal cognitive decline. METHODS: Participants without stroke or dementia were included in the Vanderbilt Memory and Aging Project, a longitudinal observational cohort study based in Nashville, TN. Participants completed 3T MRI at study entry to measure SVD burden (PVS volume fraction, white matter hyperintensities volume, lacune counts, and cerebral microbleeds counts). PVS volumes were segmented using a deep learning algorithm. Participants underwent comprehensive serial neuropsychological testing over an 11-year follow-up period (mean follow-up = 4.9 ± 3.1 years). Each SVD marker was related to longitudinal neuropsychological performances using a linear mixed-effects model adjusting for age, sex, race/ethnicity, education, baseline cognitive status, apolipoprotein E-ε4 presence, Framingham Stroke Risk Profile, and intracranial volume. Head-to-head comparisons simultaneously tested multiple statistically significant SVD markers. RESULTS: Among participants (n = 750, age 68 ± 9 years, 52% female), higher basal ganglia PVS burden at baseline was associated with worse longitudinal performances in Boston Naming Test (β = -29.63; 95% CI -56.66 to -2.60), Animal Naming (β = -33.09; 95% CI -65.66 to -0.51), Wechsler Adult Intelligence Scale IV Coding (β = -86.36; 95% CI -150.9 to -21.82), executive function composite (β = -9.51; 95% CI -14.33 to -4.68), Hooper Visual Organization Test (β = -26.06; 95% CI -50.53 to -1.59), and episodic memory composite (β = -7.05; 95% CI -11.9 to -2.21). In head-to-head comparisons, basal ganglia PVS remained independent associations with executive function composite (β = -7.47; 95% CI -12.84 to -2.10) and Hooper Visual Organization Test (β = -22.11; 95% CI -42.38 to -1.85). DISCUSSION: Basal ganglia PVS burden independently contributes to worse longitudinal executive function and visuospatial skills independent of other SVD markers, highlighting PVS as an emerging marker of domain-specific cognitive decline in aging. Although causation cannot be established, findings further support PVS as a vascular contributor to deep brain structure damage underlying cognitive decline over time.

References

1. 1.Kohno, K., Sun, Y., LeFevre, J. D., Robb, W. H., Jackson, T. B., Liu, D., Vyas, Y., Sweely, B., Pechman, K. R., Shashikumar, N., Peterson, A., Landman, B., Davis, L. T., Hohman, T. J., & Jefferson, A. L. (2026). Association of MRI-visible perivascular spaces with longitudinal cognitive decline over a decade. Neurology. https://doi.org/10.1212/WNL.0000000000214803