Alzheimers Dement. 2025 Jun;21(6):e70387. doi: 10.1002/alz.70387.
ABSTRACT
INTRODUCTION: Weight loss has been linked to early Alzheimer’s disease (AD) pathology, possibly through metabolic dysregulation. We examined changes in body mass index (BMI) in relation to AD biomarkers (amyloid beta [Aβ] and tau) and cognitive decline in adults with Down syndrome (DS). We hypothesized that BMI decline would track with early AD pathology and cognitive decline.
METHODS: Adults with DS (N = 467; Mage = 43.67 ± 10.06) completed one to four data cycles (≈16 months apart). Linear mixed models examined BMI change over time by age, positron emission tomography (PET) Aβ and tau, and changes in memory and dementia symptoms.
RESULTS: BMI declined with age-by-time (β = -0.014, p = 0.002) and baseline PET Aβ-by-time (β = -0.005, p = 0.002). On average, BMI decline began in the early 40s and was related to decline in memory and overall cognitive functioning.
DISCUSSION: Weight loss is associated with the presence of Aβ and cognitive decline in adults with DS. Longitudinal studies need to clarify directionality and biological mechanisms.
HIGHLIGHTS: Adults with Down syndrome (DS) are at an elevated risk for Down Syndrome assocaited Alzheimer’s disease (DSAD). On average, adults with DS experience body mass index (BMI) decline beginning in their early 40s. Positron emission tomography amyloid beta deposition is associated with greater decline in BMI in adults with DS. Across time, AD-related memory declines are associated with BMI decline. BMI decline should be part of DSAD screening tools, as it is an important part of DSAD clinical disease expression.
PMID:40545561 | DOI:10.1002/alz.70387
