Research recently published in BMJ Medicine found evidence that may offer new ways to prevent the neurological condition. The findings

Obesity has been associated with an increased risk of Alzheimer’s disease in numerous studies, possibly related to concomitant increases in inflammation, insulin resistance, and higher levels of the brain-damaging protein amyloid-beta in adipose tissue.

Meanwhile, in other research, lower levels of lean muscle have also been associated with increased risk of the disease, but it was unclear whether this might precede or prove important for diagnosis.

To try to find out, a team of researchers from the University of California, San Francisco, USA, used Mendelian randomization, a technique that uses genetic variants as proxies for a particular risk factor, in this case lean muscle, to obtain genetic evidence to support a particular outcome. In this case, the specialists focused on detecting a possible risk of Alzheimer’s disease and their findings were published in BMJ Medicine.

In order to do so, they relied on 450,243 participants from the UK Biobank. That is why they focused on an independent sample of 21,982 people with the pathology and 41,944 without Alzheimer’s disease; plus an additional sample of 7329 with this condition and 252,879 without the pathology to validate the findings; and 269,867 participating in a study of genes and intelligence.

Bioimpedance, an electrical current flowing at different speeds 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 were located in the region of the APOE gene that is associated with vulnerability to Alzheimer’s disease. These combined genetic variants explained 10% of the difference in lean muscle mass in the arms and legs of the study participants.

exercise and physical activity

Lean mass was also associated with better performance on cognitive tasks (Getty Images)

Thus, they concluded that, on average, greater (genetically represented) lean muscle mass was associated with a modest, but statistically robust, reduction in the risk of Alzheimer’s disease. This finding was repeated in the additional sample of 7329 individuals with and 252,879 participants without Alzheimer’s disease, using different measures of lean muscle mass: trunk and whole body.

Strength vs. cognitive impairment

exercise and physical activity

“Promoting exercise and physical activity could reduce the burden of Alzheimer’s disease in the population,” said one of the study authors.

Lean mass was also associated with better performance on cognitive tasks, but this association did not account for its protective effect on Alzheimer’s disease risk. Body fat, adjusted for lean mass, was also not associated with disease risk, but was associated with worse cognitive performance on tasks.

These analyses provide new evidence supporting a cause-and-effect relationship between lean mass and risk of the disease,” said Iyas Daghlas, a specialist in the university’s Department of Neurology and one of the paper’s lead authors. Our findings also refute a large effect of fat mass on Alzheimer’s disease risk and highlight the importance of distinguishing lean from fat mass when investigating the effect of adiposity measures on health outcomes.

However, they also bring caveats to their conclusions. “Our findings,” notes Malik Nassan, Daghlas’ colleague and another of the paper’s authors, “need to be replicated with independent lines of complementary evidence before informing public health or clinical practice. In addition, more work is needed to determine cut-off values for age and degree of Alzheimer’s disease pathology after which lean mass modifications may no longer reduce risk. It is also unclear whether increased lean mass could reverse pathology in patients with preclinical disease or cognitive impairment.”

But they conclude that if future studies support their findings, “public health efforts to change the distribution of lean mass in the population, potentially through campaigns to promote exercise and physical activity, could reduce the burden of Alzheimer’s disease in the population,” concluded the paper’s third author, Dipender Gill.

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