PROJECT ABSTRACT/SUMMARY
People with Down syndrome (DS) have a 75-90% lifetime risk for developing Alzheimer’s disease (AD).2,3
However, there is marked variability in the timing of AD, with a 30+ year range in the age of onset of clinical
dementia8, suggesting that factors beyond trisomy 21 may influence AD in DS. Outside of DS, mid-life obesity
or being overweight is an identified risk factor for later life AD, such that efforts to reduce body mass index
(BMI) and increase physical activity have been proposed to be promising AD prevention programs. Adults with
DS are at risk for being overweight and obese40--42, yet virtually nothing is known about whether mid-life BMI is
associated with the timing of AD pathology and symptomology in DS. To date, studies examining BMI and AD
in DS have focused on BMI after a clinical AD dementia diagnosis,49,51 used primarily cross-sectional
methods,49,50 and/or relied on small sample sizes.51 The proposed F31 will provide training on advanced
statistical analytic methods to assess longitudinal data, grow my knowledge on the valid assessment of AD
pathology and cognition in DS, and develop professional skills for engaging in multisite research consortiums.
The project will leverage already existing data to address three specific aims: 1) evaluate the effect of BMI and
weight change on AD biomarkers (PET Aß and tau PET) across 36 months, 2) examine the effect of BMI and
weight change on cognitive performance (episodic memory, executive functioning, motor planning and control,
and dementia symptoms) and clinical dementia status (cognitively stable, mild cognitive impairment, and
dementia) across 36 months, and 3) explore if inflammatory biomarkers (serum c-reactive protein, IL-6, IL-10,
and tumor necrosis factor alpha) are related to BMI and mediate the link between BMI and AD pathology and
cognitive decline. This work will help me launch an independent program of research on healthy aging in DS
that can inform social policy and intervention for preventing or delaying AD in DS and other at-risk populations.