Body mass index decline and cognitive trajectories in mild cognitive impairment: the role of maternal history of Alzheimer’s disease

Background: Maternal history of Alzheimer’s disease (MH) has been associated with increased risk of Alzheimer’s disease (AD), earlier onset, and distinct neurobiological features. In parallel, an anthropometric-metabolic phenotype characterized by body mass index (BMI) decline and unintentional weight loss has been described as an early feature preceding cognitive decline in the prodromal stages of AD. Objective: To investigate whether MH is associated with a distinctive anthropometric-metabolic and cognitive phenotype in individuals with mild cognitive impairment (MCI), focusing on longitudinal trajectories of body mass index (BMI), memory, and executive function. Methods: Participants with MCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed over up to 24 months of follow-up. Longitudinal changes in BMI, memory, and executive function were examined using repeated-measures ANOVA. MH, APOE4 status, age, sex, and conversion to AD were included as between-subject factors. Results: Among 397 participants with MCI, 270 (68%) remained clinically stable and 127 (32%) converted to AD during follow-up. APOE4 positivity was more frequent among converters. BMI declined over time, with a steeper reduction observed in individuals who converted to AD and in those with MH. MH was associated with differential longitudinal cognitive trajectories, characterized by subtle non-linear changes in memory performance and relative preservation of executive function. Changes in BMI showed modest associations with memory and executive function trajectories. Conclusions: MH is associated with distinctive longitudinal patterns of anthropometric-metabolic and cognitive change in individuals with MCI. Incorporating maternal history may help refine phenotypic characterization in prodromal AD, supporting a more nuanced understanding of disease heterogeneity in the prodromal stages.