Human head next to damaged neurons to indicate Alzheimer's disease
Credit: Science Photo Library - PASIEKA/Getty Images

Researchers from the University of California San Francisco and pharma company Novo Nordisk have found that high levels of lean muscle mass could be protective against Alzheimer’s disease (AD). Obesity has been associated with a higher AD risk due to increase inflammation, insulin resistance, and higher levels of amyloid β, as has lower levels of lean muscle.

Until now, it has not been clear whether lower muscle mass was an indicator that preceded AD diagnosis or developed after diagnosis. To look for the answer to this question, the investigators tapped the data of 450,243 participants in the U.K. Biobank broken down as follows:

  • An independent sample of 21,982 people with AD and 41,944 people without disease.
  • A further sample of 7,329 people with AD and 252,879 people without to validate the findings.
  • 269,867 people taking part in a genes and intelligence study.

In their study, published in the journal BMJ Medicine, the researchers used Mendelian randomization that used genetic proxies to determine lean muscle in order to obtain genetic evidence to support a particular outcome, in this case, AD. The researchers also used bioimpedance, the use of an electric current that flows at different rates through the body depending on tissue composition, to determine the lean muscle and fat in the arms and legs, then adjusted the results based on the age, sex, and genetic history of each individual.

The team uncovered a broad collection of 584 genetic variants that were associated with lean muscle mass, and noted that none of the variants were located in the APOE gene region that is associated with the risk of developing AD. These genetic variants combined explained 10% of the difference in lean muscle of the people in the study.

“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),” the researchers wrote noting that these results were replicated in the independent cohort of patients with Alzheimer’s disease.

Lean muscle mass was also associated with higher scores on cognitive tests, but the results didn’t help explain what provided the protective effect from lean muscle mass related to AD development. Body fat, adjusted for lean muscle mass, also was not associated with AD risk, though it was associated with poorer cognitive performance.

“These analyses provide new evidence supporting a cause-and-effect relation between lean mass and risk of Alzheimer’s disease,” said 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.”

The researchers cautioned that this is an early study, drawing this links to muscle mass and protection from AD and that more research is also needed to understand the biological pathways.

“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,” the investigators noted. Adding that their study did not provide evidence whether increasing lean muscle mass could reverse AD pathology.

Also of Interest