Long-term neurobehavioral correlates of brain cortical microinfarcts in a memory clinic cohort in Singapore

Abstract

Background Cortical cerebral microinfarcts are a small vessel disease biomarker underlying cognitive impairment and dementia. However, it is unknown whether cortical cerebral microinfarcts are associated with neuropsychiatric disturbances, and whether its effects are independent of conventional small vessel disease markers. Aims We investigated the associations of cortical cerebral microinfarcts burden with incidence and progression of neuropsychiatric subsyndromes in a memory clinic cohort of elderly in Singapore. Methods In this prospective cohort, 496 subjects underwent detailed neuropsychological and clinical assessments, 3T brain MRI, and Neuropsychiatric Inventory assessment at baseline and two years later. Cortical cerebral microinfarcts and other small vessel disease markers, including white matter hyperintensities, lacunes, and microbleeds, were graded according to established criteria. Neuropsychiatric symptoms (NPS) were clustered into subsyndromes of hyperactivity, psychosis, affective, and apathy following prior findings. Functional decline was determined using the clinical dementia rating (CDR) scale. Results The presence of multiple cortical cerebral microinfarcts (≥2) was associated with higher total NPS scores ( β = 4.19, 95% CI = 2.81–5.58, p < 0.001), particularly hyperactivity ( β = 2.01, 95% CI = 1.30–2.71, p < 0.01) and apathy ( β = 1.42, 95% CI = 0.65–2.18, p < 0.01) at baseline. Between baseline and year-2, multiple cortical cerebral microinfarcts were associated with accelerated progression in total NPS scores ( β = 0.29, 95% CI = 0.06–0.53, p = 0.015), driven by hyperactivity ( β = 0.45, 95% CI = 0.17–0.72, p < 0.01). Subjects with multiple cortical cerebral microinfarcts also had a faster functional decline, as measured with the CDR-sum-of-boxes scores, when accompanied with progression ( β = 0.31, 95% CI = 0.11–0.51, p < 0.01) or hyperactivity in total NPS ( β = 0.34, 95% CI = 0.13–0.56, p < 0.01). Conclusion Cortical cerebral microinfarcts are associated with incidence and progression of geriatric neurobehavioral disturbances, independent of conventional small vessel disease markers. The impact of incident cortical cerebral microinfarcts on neurocognitive and neuropsychiatric trajectories warrants further investigations.