Summary: High lean muscle levels may be protective against Alzheimer’s disease.
The study, which involved genetic analyses of hundreds of thousands of participants, suggested a correlation between lean muscle mass and a reduced risk of Alzheimer’s. Despite these findings, researchers caution that further investigations are required to clarify the biological mechanisms and implications for public health.
They suggest that if confirmed, physical activity campaigns might help reduce the overall burden of Alzheimer’s disease.
Key Facts:
- The study used genetic analysis of over 700,000 participants to explore the correlation between lean muscle mass and Alzheimer’s disease risk.
- Higher lean muscle mass, determined through genetic proxies, was associated with a modest but statistically significant decrease in Alzheimer’s disease risk.
- The researchers stress the need for additional research to validate these findings, understand the underlying mechanisms, and determine possible interventions.
Source: BMJ
High levels of lean muscle might protect against Alzheimer’s disease, suggests a large study published in the open access journal BMJ Medicine. But further research is needed to tease out the underlying biological pathways, along with the clinical and public health implications, say the study authors.
Obesity has been associated with a heightened risk of Alzheimer’s disease in numerous studies, possibly explained by the attendant increased inflammation, insulin resistance, and higher levels in fat tissue of the protein harmful to brain health, amyloid β.
Lower levels of lean muscle have also been associated with a heightened risk of the disease, but it’s not clear if this might precede or succeed a diagnosis.
To try and find out, the researchers used Mendelian randomisation, a technique that uses genetic variants as proxies for a particular risk factor—in this case lean muscle—to obtain genetic evidence in support of a particular outcome—in this study, Alzheimer’s disease risk.
They drew on 450, 243 UK Biobank participants; an independent sample of 21,982 people with, and 41,944 people without, Alzheimer’s disease; a further sample of 7329 people with, and 252,879 people without, Alzheimer’s disease to validate the findings; and 269,867 people taking part in a genes and intelligence study.
Bioimpedance—an electric current that flows at different rates through the body depending on its composition—was used to estimate lean muscle and fat tissue in the arms and legs, the results of which were adjusted for age, sex, and genetic ancestry.
Some 584 genetic variants were associated with lean muscle mass; none was located in the APOE gene region that is associated with vulnerability to Alzheimer’s disease. These genetic variants combined explained 10% of the difference in lean muscle mass in the arms and legs of the study participants.
On average, higher (genetically proxied) lean muscle mass was associated with a modest, but statistically robust, reduction in Alzheimer’s disease risk.
This finding was replicated in the further sample of 7329 people with, and 252,879 people without, Alzheimer’s disease, using different measures of lean muscle mass—trunk and whole body.
Lean mass was also associated with better performance on cognitive tasks, but this association didn’t explain the protective effect of lean mass on Alzheimer’s disease risk.
Nor was body fat, adjusted for lean mass, associated with the risk of Alzheimer’s disease, but it was associated with poorer cognitive task performance.
“These analyses provide new evidence supporting a cause-and-effect relation between lean mass and risk of Alzheimer’s disease,” say the researchers.
The findings also “refute a large effect of fat mass on the risk of Alzheimer’s disease and highlight the importance of distinguishing between lean mass and fat mass when investigating the effect of adiposity measures on health outcomes,” they add.
But they caution: “Our findings need to be replicated with independent lines of complementary evidence before informing public health or clinical practice. Also, more work is needed to determine the cut-off values for age and degree of pathology of Alzheimer’s disease after which modifications of lean mass might no longer reduce the risk.”
Nor is it clear whether increasing lean mass could reverse the pathology of Alzheimer’s disease in patients with preclinical disease or mild cognitive impairment, they add.
But they conclude that if future studies back their findings, “public health efforts to shift the population distribution of lean mass, potentially through campaigns to promote exercise and physical activity, might reduce the population burden of Alzheimer’s disease.”
About this Alzheimer’s disease research news
Author: Caroline White
Source: BMJ
Contact: Caroline White – BMJ
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Genetically proxied lean mass and risk of Alzheimer’s disease: mendelian randomisation study” by Iyas Daghlas et al. BMJ Medicine
Abstract
Genetically proxied lean mass and risk of Alzheimer’s disease: mendelian randomisation study
Objective
To examine whether genetically proxied lean mass is associated with risk of Alzheimer’s disease.
Design
Mendelian randomisation study.
Setting
The UK Biobank study and genome wide association study meta-analyses of Alzheimer’s disease and cognitive performance.
Participants
Summary level genetic data from: 450 243 UK Biobank participants with impedance measures of lean mass and fat mass; an independent sample of 21 982 patients with Alzheimer’s disease and 41 944 controls without Alzheimer’s disease; a replication sample of 7329 patients with Alzheimer’s disease and 252 879 controls; and 269 867 individuals taking part in a genome wide association study of cognitive performance.
Main outcome measure
Effect of genetically proxied lean mass on the risk of Alzheimer’s disease, and the related phenotype of cognitive performance.
Results
An increase in genetically proxied appendicular lean mass of one standard deviation was associated with a 12% reduced risk of Alzheimer’s disease (odds ratio 0.88, 95% confidence interval 0.82 to 0.95, P=0.001). This finding was replicated in an independent cohort of patients with Alzheimer’s disease (0.91, 0.83 to 0.99, P=0.02) and was consistent in sensitivity analyses that are more robust to the inclusion of pleiotropic variants.
Higher genetically proxied appendicular lean mass was also associated with increased cognitive performance (standard deviation increase in cognitive performance for each standard deviation increase in appendicular lean mass 0.09, 95% confidence interval 0.06 to 0.11, P=0.001), and adjusting for potential mediation through genetically proxied cognitive performance did not reduce the association between appendicular lean mass and risk of Alzheimer’s disease.
Similar results were found for the outcomes of Alzheimer’s disease and cognitive performance when the risk factors of genetically proxied trunk lean mass and whole body lean mass were used, respectively, adjusted for genetically proxied fat mass.
Conclusions
These findings suggest that lean mass might be a possible modifiable protective factor for Alzheimer’s disease. The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.
