To investigate the prevalence of incidental MRI findings among neurologically healthy older adults and the relationship of those incidental findings to cognitive and mental health outcomes.

Distinguishing between healthy brain aging and prodromal neurological disease is vital for early detection and prevention of neurological disorders, especially dementia, stroke, movement disorders, and epilepsy. Volume loss and white matter changes both occur with healthy aging and with development of neurological disease.

The Cleveland Clinic Brain Study is a longitudinal, observational study of neurologically healthy older adults collecting annual multimodal data including neuroimaging, self-report questionnaires, and neuropsychological testing. The baseline structural MRIs of 1125 participants (77.2% female, 87.9% white, aged 50 to 86, mean 61.4 years) have been qualitatively evaluated for incidental findings and systematically documented by a team of neuroradiologists. Groups were compared with two-sample t-tests or one-way ANOVA followed by Benjamini-Hochberg multiple testing correction.

Seventy percent of participants had abnormal MRI findings, including 60 participants requiring clinical action. Additionally, 12.6% showed volume loss, while 60.9% had white matter changes. Participants with volume loss were older (t(1124) = -10.52), had worse memory performance (t(987)  = 3.09), and lower stress (t(831) = 2.49) than those without. Depression symptoms increased with volume loss severity (F(1,134)= 10.64). Only age differed (t(1124) = -4.92) between those with and without any white matter changes. More severe white matter changes were associated with increased age (F(2,678)= 22.21) and depression (F(2,678)= 4.57), yet with reduced anxiety (F(2,678)= 3.10) and stress (F(2,678)= 4.61). All reported tests had adjusted p-values less than 0.05.

Our data demonstrate that, at baseline, volume loss severity and white matter change severity relate to several cognitive and mental health outcomes. Evaluating the relationship between these outcomes and structural MRI features over time will allow us to explore age- and disease-related patterns.