Weight Loss and Alzheimer’s Disease in Down Syndrome

Abstract

Background: Virtually all adults with Down syndrome (DS) develop Alzheimer’s disease (AD) pathology, but research gaps remain in understanding early signs of AD in DS. Objective: The goal of the present study was to determine if unintentional weight loss is part of AD in DS. The specific aims were to: 1) examine relation between chronological age, weight, AD pathology, and AD-related cognitive decline were assessed in a large cohort of adults with DS, and 2) determine if baseline PET amyloid-β (Aβ) and tau PET status (–versus+) and/or decline in memory and mental status were associated with weight loss prior to AD progression. Methods: Analyses included 261 adults with DS. PET data were acquired using [11C] PiB for Aβ and [18F] AV-1451 for tau. Body mass index (BMI) was calculated from weight and height. Direct measures assessed dementia and memory. Clinical AD status was determined using a case consensus process. Percent weight decline across 16–20 months was assessed in a subset of participants (n = 77). Results: Polynomial regressions indicated an 0.23 kg/m2 decrease in BMI per year beginning at age 36.5 years, which occurs alongside the period during which Aβ and tau increase and memory and mental status decline. At a within-person level, elevated Aβ, decline in memory and mental status were associated with higher percent weight loss across 16–20 months. Conclusion: Unintentional weight loss occurs alongside Aβ deposition and prior to onset of AD dementia, and thus may be a useful sign of AD in DS.

Cerebrovascular disease emerges with age and Alzheimer’s disease in adults with Down syndrome

“…Hyperlipidemia was common but was not associated with cerebrovascular disease for a given age; hyperlipidemia may not operate as a vascular risk factor in the absence of metabolic disease (e.g., diabetes) in adults with DS. Lower BMI was associated with greater global WMH, highlighting a role of other disease related processes that affect diet, exercise, and weight 43 . While WMH may reflect Wallerian degeneration to some degree in advanced stages of late onset AD, tau burden was not associated with greater than expected WMH volume for participant age in adults with 26 , adults with autosomal dominant AD 22,23 , and adults with late onset AD 20,21 .…”

Balance and Gait

“…In the opposite direction, a recent study indicated an association between weight, cognitive decline, and AD pathology, suggesting that unintentional weight loss is associated with β-amyloid deposition in the brain before the onset of AD dementia in individuals with DS. 41 Indeed, other studies also indicated the association of weight loss and AD both in individuals with DS 42,43 and in the general population. 44,45 However, it is important to consider that our sample is young and may not be representative of populations with DS and prodromal dementia or dementia, which may explain why the BMI findings conflict with other studies, [41][42][43] where the mean age of dementia is considerably older.…”

“…41 Indeed, other studies also indicated the association of weight loss and AD both in individuals with DS 42,43 and in the general population. 44,45 However, it is important to consider that our sample is young and may not be representative of populations with DS and prodromal dementia or dementia, which may explain why the BMI findings conflict with other studies, [41][42][43] where the mean age of dementia is considerably older. In our analysis, we found no statistically significant differences related to sex, age, degree of intellectual disability, or use of medication.…”

“…In the present study, higher BMI was related to increased likelihood of prodromal dementia and dementia diagnosis. In the opposite direction, a recent study indicated an association between weight, cognitive decline, and AD pathology, suggesting that unintentional weight loss is associated with β-amyloid deposition in the brain before the onset of AD dementia in individuals with DS 41 . Indeed, other studies also indicated the association of weight loss and AD both in individuals with DS 42,43 and in the general population 44,45 .…”