Researchers found high levels of lean muscle may protect against Alzheimer's disease. However, more research is needed to elucidate the underlying biological pathways, as well as the clinical and public health implications.

This research was published in BMJ Medicine. Obesity has been linked to an increased risk of Alzheimer's disease in numerous studies, which may be explained by the associated increased inflammation, insulin resistance, and higher levels in fat tissue of the protein amyloid, which is harmful to brain health.

Lower levels of lean muscle have also been linked to an increased risk of the disease, though it's unclear whether this occurs before or after a diagnosis.

To find out, the researchers employed Mendelian randomisation, a technique that employs genetic variants as proxies for a specific risk factor--in this case, lean muscle--to obtain genetic evidence in support of a specific outcome--in this case, Alzheimer's disease risk.

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," 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," they added.

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 added.

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."