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.