Study finds body composition impacts neurodegenerative disease risk

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Jul 28 2024

A recent study published in the journal Neurology determines whether identifiable body composition patterns can be associated with an increased risk of neurodegenerative diseases and whether this association is due to the effects of cardiovascular disease (CVD).

Study: Association Between Body Composition Patterns, Cardiovascular Disease, and Risk of Neurodegenerative Disease in the UK Biobank. Image Credit: Sebastian Kaulitzki / Shutterstock.com

How does body weight impact the risk of neurodegenerative disease?

There remains a lack of effective treatments for neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD), which remain the leading causes of death and disability in the elderly. Therefore, it is crucial to identify modifiable risk factors to develop targeted and customized preventive strategies.

CVD increases the risk of neurodegenerative disease; however, additional research is needed to clarify the mechanisms involved in this association. The “obesity paradox phenomenon” denotes a lower risk of dementia and PD among obese individuals; however, this may be attributed to unintentional weight loss that occurs in the early stages of neurodegenerative diseases.

The use of body mass index (BMI) to define obesity is also a limiting factor, as this measurement was created on data from homogenous populations and fails to consider variations in body composition. For example, BMI cannot distinguish between fat and muscle, causing highly muscular individuals to be misclassified as overweight due to higher BMI values.

About the study

The current study was a retrospective analysis of data on 412,691 individuals obtained from the United Kingdom Biobank. All study participants had no neurodegenerative disease at baseline and were monitored for five years after the recruitment time point until April 1, 2023.

The researchers were interested in determining how different body composition characteristics, such as fat, muscle, and bone, could be used to predict the future risk of neurodegenerative disease. The susceptibility to neurodegenerative disease was also adjusted by the polygenetic risk scores for the apolipoprotein E (APOE) genotype and a family history of neurodegenerative disease.

Mediation analytic methods were also applied for CVD. Moreover, the potential relationship between body composition patterns and brain atrophy or cerebral small vessel disease, both of which indicate brain aging, was also examined in 40,790 study participants.

What did the study show?

The mean age of the study cohort at the beginning was 56 years, 55% female. A total of 8,224 new cases of neurodegenerative disease were reported during the 9.1-year follow-up period.

Various body composition patterns were identified, which included fat-to-lean mass, muscle strength, bone density, leg-dominant fat distribution, central obesity, and arm-dominant fat distribution patterns. All body composition patterns were associated with a high BMI, except for muscle strength patterns.

Fat-to-lean mass, muscle strength, bone density, and leg-dominant fat distribution patterns were associated with a 6-26% reduction in the risk of neurodegenerative disease development during the follow-up period. Conversely, central obesity and arm-dominant fat distribution were associated with a 13-18% increased risk of these conditions. There was no difference in the observed associations between participants with varying degrees of susceptibility, except for the bone density pattern.

The direction of risk did not vary when the participants were stratified by subtype or specific neurodegenerative conditions. However, the lean mass pattern was associated with a greater risk of vascular neurodegenerative disease and reduced risk of AD.

Brain aging and atrophy were associated with central obesity and arm-dominant fat distribution patterns. Comparatively, muscle strength, bone density, and leg-dominant fat distribution patterns were associated with reduced brain aging.

The mediation analysis indicated that 10.7-35.3% of the association of neurodegenerative disease with these parameters could be attributed to CVDs, particularly cerebrovascular disease.

Conclusions

Certain body composition patterns that are characterized by central obesity, muscle strength, and arm-dominant fat distribution are at a greater risk of neurodegenerative diseases and brain aging, with this risk mitigated by the presence of CVD.

Compared to previous studies reporting similar findings, the current study considered diverse components of body mass and their interrelationships using neurodegenerative disease and brain aging as outcomes.

These findings underscore the potential of improving body composition and early CVD management in mitigating risk of neurodegenerative diseases.”

Reducing excess fat deposition in the arms and trunk and increasing muscle development to healthy levels may protect against neurodegenerative disease compared to overall weight loss. Nevertheless, further research on more diverse samples is necessary to validate this study.