Perivascular spaces contribute to cognition beyond other small vessel disease markers.

Objective: To cross-sectionally relate multiple small vessel disease (SVD) neuroimaging markers to cognition among older adults.

Methods: Vanderbilt Memory & Aging Project participants free of clinical dementia and stroke (n = 327, age 73 ± 7 years, 59% male, 40% with mild cognitive impairment) completed neuropsychological assessment and 3T MRI to measure white matter hyperintensities (WMH), perivascular spaces (PVS), cerebral microbleeds (CMBs), and lacunes. Linear regressions related each SVD marker to neuropsychological performances and adjusted for age, sex, race/ethnicity, education, cognitive diagnosis, ε4 presence, Framingham Stroke Risk Profile, and intracranial volume.

Results: WMH related to the most neuropsychological measures, including the Boston Naming Test, Animal Naming, Coding, Number Sequencing, Executive Function Composite, and Hooper Visual Organization Test performances ( ≤ 0.01). PVS related to multiple information processing and executive function performances ( ≤ 0.02). Lacunes and CMBs related to fewer measures than expected. Combined models simultaneously testing multiple statistically significant SVD predictors suggested that WMH, PVS, and CMBs each independently related to information processing and executive function performances; however, compared to other SVD markers, PVS remained statistically significant in models related to information processing and executive functioning performances.

Conclusions: As expected, increased WMH corresponded to poorer performances across multiple cognitive domains. PVS, previously considered a benign neuroimaging feature in older adults, may have important clinical implications because PVS was related to information processing and executive function performances even in combined models. On the basis of models with multiple SVD predictors, WMH, PVS, and CMBs may each reflect a separate pathway of small vessel injury.