Repeated brain MRI utility in identifying neurodegenerative disorders at the pre-dementia stage

Despite the increasing availability of biomarkers in clinical settings, diagnosing individuals with subtle cognitive/behavioral symptoms and normal structural brain imaging remains challenging. In real-world settings, it is not feasible to subject all such patients to costly and invasive second-level assessments, and there are no clear guidelines for identifying those who should undergo these procedures beyond clinical follow-up and structural imaging. The present study explores the potential of repeated magnetic resonance imaging (MRI) in this context. We investigated whether detecting pathological brain volume (BV) changes exceeding normal aging could aid in deciding whether advanced biomarker testing is reasonable. Individuals with subtle cognitive/behavioral complaints underwent baseline and 18-month follow-up assessments (neuropsychological evaluation, MRI, and biomarker tests). Annualized percentage of BV change (PBVC/y), adjusted for age, sex, and scanner, was calculated with SIENA, and classified whether exceeding the 80th/95th percentiles of normative data. At follow-up, participants were classified (I) Converters/Non-Converters based on clinical information, (II) Non-converters+/Non-Converters- based on biomarkers status, and (III) Underlying disease based on both clinical follow-up and biomarkers. Logistic regressions assessed PBVC/y, baseline BV, and Mini-Mental State Examination change as predictors of participants' classification. Among 110 participants, PBVC/y exceeding both the 80th/95th percentiles increased the probability of being classified Converters or Alzheimer's disease/Frontotemporal dementia. Exceeding the 80th percentile increased the odds of being classified Non-Converters+. Our results suggest that the application of SIENA normative data to repeated MRIs may help in deciding whether or not performing more invasive and high-cost second-level procedures in individuals with early-stage and subtle cognitive/behavioural changes.