# Longitudinal study of body mass index in relation to Alzheimer's disease pathology and symptomatology in Down syndrome

## TL;DR

This study shows that adults with Down syndrome experience BMI decline in their 40s, which is linked to Alzheimer's disease pathology and cognitive decline.

## Contribution

The study links longitudinal BMI decline to AD biomarkers and cognitive decline in adults with Down syndrome.

## Key findings

- BMI decline in adults with Down syndrome is associated with amyloid beta deposition and cognitive decline.
- BMI decline begins in the early 40s and is linked to memory and cognitive functioning decline.
- BMI decline is an important clinical indicator for Down syndrome-associated Alzheimer's disease.

## Abstract

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.

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.

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.

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.

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.

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.