Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer\u2019s disease

Stephan Müller,Susanne Gräber,Randall J Bateman,Martin N Rossor ,Bernardino Ghetti,Oliver Preische,Stephen Salloway,Chengjie Xiong,Reisa A Sperling ,Peter R Schofield,Mathias Jucker,Neill R Graff‐Radford ,Colin L Masters,Janko Dietzsch,Hamid R Sohrabi,Virginia Buckles,Eric Mcdade,Douglas Galasko,Kimberly A Quaid,John C Morris,Ralph N Martins,John M Ringman,Tammie L.s Benzinger ,Christoph Laske

doi:10.1038/s41598-017-01327-w

Abstract

The relationship between body-mass index (BMI) and Alzheimer´s disease (AD) has been extensively investigated. However, BMI alterations in preclinical individuals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before expected symptom onset. However, the BMI curves begun to diverge already at 17.8 years before expected symptom onset. Lower BMI in preclinical MCs was significantly associated with less years before estimated symptom onset, higher global Aβ brain burden, and with lower delayed total recall scores in the logical memory test. The study provides cross-sectional evidence that weight loss starts one to two decades before expected symptom onset of ADAD. Our findings point toward a link between the pathophysiology of ADAD and disturbance of weight control mechanisms. Longitudinal follow-up studies are warranted to investigate BMI changes over time.

Highlights

All participants included in the present study showed no relevant signs of cognitive impairment that interfere with activities of daily living as indicated by a Clinical Dementia Rating (CDR) score of zero
The main findings were as follows: (1) Preclinical mutation carriers (MCs) showed weight loss starting one to two decades before expected symptom onset of autosomal-dominant AD (ADAD); (2) In preclinical MCs, body mass index (BMI) was significantly correlated with estimated years to symptom onset (EYO), whereas in NCs a negative association between BMI and EYO could be observed
Previous studies examining the association between BMI and Alzheimer’s disease (AD) risk have all been performed in elderly people who were cognitively normal or already presented signs of MCI or mild AD4, 17–19

Summary

Introduction

Low BMI and accelerated weight loss in later life have been associated with increased risk of AD4–8. Up to now, it is still unclear at what time point BMI decreases during the preclinical stage of AD. To address these research questions, we examined cross-sectional data of asymptomatic autosomal-dominant AD (ADAD) family members participating in the Dominantly Inherited Alzheimer Network (DIAN)[9]. Study of ADAD allows examining BMI across the whole spectrum of the disease beginning more than 20 years prior to the estimated symptom onset. In the present study we were interested (1) to examine the relationship between BMI and estimated years to expected symptom onset in preclinical ADAD and (2) whether BMI was associated with cognitive and imaging data in preclinical ADAD

Methods

Results

Conclusion