- Numerous factors are associated with increased or decreased Alzheimer’s disease risk.
- A new study indicates lean muscle mass may play a preventive role in disease onset.
- However, the reasons why muscle mass influences Alzheimer’s remain unclear.
- More research is needed to investigate the relationship and its mechanisms.
Experts have long recommended regular exercise as a potential approach to help reduce the risk of Alzheimer’s disease.
Now new research published in the British Medical Journal supports this thinking — suggesting that developing lean muscle might offer a level of protection against the neurological condition.
University of California San Francisco scientists found that individuals with higher, lifelong levels of lean muscle mass had a 12% reduction in Alzheimer’s risk.
Previous studies have explored the role of obesity and body mass index (BMI) in Alzheimer’s development. However, these “did not find evidence for a causal effect,” said Dr. Iyas Daghlas, a third-year neurology resident at the University of California San Francisco and co-author of the study.
Uncertain whether BMI alone was a significant enough determinant of Alzheimer’s risk, the researchers wanted to explore body composition more closely.
“[We] hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease,” Daghlas told Healthline.
The researchers used data from hundreds of thousands of individuals, the largest group of which came from the UK Biobank — an ongoing database collecting half a million individuals’ health and genetic information.
Data was studied by employing Mendelian randomization, which uses gene variations as proxies for certain risk factors.
Further, bioimpedance measures — an electrical current that runs through the body at various speeds depending on muscle and fat composition — were used to estimate individuals’ lean muscle and fat mass.
A total of 584 genetic variants were linked to lean muscle mass, none of which were found in the area of the brain associated with vulnerability to Alzheimer’s.
On average, participants with greater levels of (genetically proxied) lean muscle had a statistically significant (12%) lower risk of developing the disease.
To affirm these findings, the researchers repeated the analytical process using data from a further 260,208 individuals, of which 7,329 had an Alzheimer’s diagnosis. Rather than in the legs and arms, they measured lean muscle mass in the trunk and whole body.
Again, they found that greater lean muscle was associated with reduced chances of developing Alzheimer’s.
One result was somewhat unexpected: while body fat was linked to poorer performance on cognitive tasks, once adjusted for lean mass, the analysis did not find a link between body fat and Alzheimer’s risk.
“I was surprised by the striking discordance between the protective effect of lean mass on dementia risk and the absence of an effect of fat mass on dementia risk,” stated Daghlas.
What the findings didn’t tell us
While the findings support a cause-and-effect association between muscle mass and Alzheimer’s risk, some unanswered questions remain.
For instance, it is unclear whether lean muscle has to be “built” before a certain age to positively influence Alzheimer’s development, or if it only impacts certain Alzheimer’s pathologies.
Further, “this study does not directly address the question of whether factors behind the DNA — such as proactively building muscle mass — benefits from the association,” said Dr. Anna Nordvig, a neurologist at NewYork-Presbyterian and Weill Cornell Medicine, who was not associated with the research.
It’s also unknown whether those with mild signs of Alzheimer’s or cognitive impairment would experience symptom regression after building lean muscle.
That said, “this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” asserted Daghlas. “It is a hopeful finding which gives patients agency in their neurologic health.”
Another limitation of the study is that the mechanisms behind the relationship between lean muscle and Alzheimer’s remain unclear.
The researchers briefly speculated on potential links. For instance, cardiovascular disease has long been affiliated with Alzheimer’s, although Daghlas noted the association is “complicated.”
Vascular dementia is driven by heart disease concerns such as stroke and hypertension, Daghlas said. “In contrast, the most recent causal evidence suggests weaker evidence for an effect of vascular risk factors on Alzheimer’s disease risk,” he explained — “though this is a controversial notion.”
While further exploration is required, “It may very well be the case that lean mass reduces the risk of vascular dementia via a reduction in cardiovascular disease risk,” Daghlas said. “This can be investigated in future studies.”
The researchers also speculated in the paper that “new” mechanisms may be at play — such as circulating centrally acting myokines.
“Myokines are proteins released by muscles that affect other tissues,” Daghlas revealed. “They have been shown in experimental studies to be induced by exercise and to positively influence brain function.”
Aside from these, other muscle-related factors “may explain the larger picture,” said Dr. Anna Nordvig, a neurologist at NewYork-Presbyterian and Weill Cornell Medicine, who was not associated with the research. For instance, “bone hormones, cardio vs strength training differences, sex hormones, glymphatic drainage depending on exercise, and sleep, to name a few.”
Ultimately, more clinical intervention studies are needed to confirm the effect of lean muscle on Alzheimer’s and the drivers behind the relationship.
While there’s no foolproof measure to prevent Alzheimer’s, experts believe various measures can aid in reducing your risk profile.
These fall into two categories, said Nordvig: “protect” and “stimulate” — and “physical activity falls into both of these.”
“‘Protect’ includes keeping an eye on things we discuss at a yearly physical,” she explained — such as blood pressure, sugar levels, weight, diet, and sleep.
There are environmental risk factors linked to Alzheimer’s that we should also aim to protect ourselves from, said Dr. Rena Sukhdeo Singh, a vascular neurologist with the University of Maryland Shore Regional Health.
Systemic inflammation is another factor associated with Alzheimer’s onset, Sukhdeo Singh said. Chronic inflammation can occur for many reasons, ranging from medications to high sugar and processed food intake to smoking and excessive alcohol consumption.
Meanwhile, “stimulate” involves optimizing other daily inputs that impact cognition. For instance, “learning a new skill, hobby, language, or instrument,” suggested Sukhdeo Singh, or engaging in shorter activities like “sudokus, puzzles, and number games.”
Unfortunately, we’re unable to influence some elements. “Non-modifiable risk factors include age, genetics, and sex,” she added.
How to build lean muscle
Increasing your lean muscle mass is simpler than you might think, said Rachel Lovitt, certified personal trainer and founder of Mindful Movement and Living.
It involves “challenging your muscles to do more than they normally do, recovering from that challenge, and providing your muscles proper fuel to both meet and recover from that challenge,” she told Healthline.
Building lean muscle doesn’t have to involve lifting heavy weights. “Resistance training (or strength training) is any form of movement that uses resistance or external loads to challenge your muscle,” Lovitt said.
When it comes to moves, Lovitt recommended engaging in weighted actions that simultaneously target multiple areas so you train your whole body.
For instance, squats are a great option for the lower body as they “work so many muscle groups at once [and are] one of the most functional exercises out there,” she stated. To target the upper body, moves to try include push-ups, shoulder presses, or rows.
The American College of Sports Medicine (ACSM)
“The ACSM recommends that novice, healthy resistance trainers do 1-3 sets per exercise, doing 8-12 reps, at 70-85% of one repetition max,” she added.
But exercise is only one piece of the lean muscle picture.
“Properly fueling your exercise is vital to increasing muscle mass,” Lovitt stated. This means “eating enough protein so your muscle has the building blocks to grow,” she said, and ensuring your diet includes a good balance of micronutrients and macronutrients so your body can function properly.
Proper recovery is also essential. “Muscles aren’t built in the gym, they’re built in your sleep,” said Lovitt. “Exercise is the stimulus that provokes muscle growth, but rest is when your muscles actually grow.”
All of this can feel a little overwhelming, and exercises that work for one individual might not be so suited to another.
“When it comes to increasing muscle mass, I highly recommend working with a qualified personal trainer or movement specialist so that you can come up with a plan that works for your unique life, body, and goals,” Lovitt stated.