Higher muscle mass and lower visceral fat associated with younger brain age — Evidence Review

People with more muscle mass and a lower ratio of visceral fat to muscle tend to have younger biological brain ages, according to a new study from the Mallinckrodt Institute of Radiology at Washington University School of Medicine. Related research broadly supports these findings, consistently linking higher muscle mass and lower visceral fat with better brain health and cognitive function.

• Multiple large observational studies and interventional trials indicate that both greater muscle mass and lower visceral adiposity independently correlate with slower brain aging, improved cognitive performance, and larger brain volumes across diverse age groups and populations 1 3 4 8.
• Experimental and mechanistic studies provide evidence that visceral fat promotes inflammation and metabolic dysfunction affecting brain health, while muscle mass may exert protective effects via myokine secretion and improved metabolic regulation 5 7.
• Some population-based studies highlight potential sex-specific and age-related nuances, with certain findings suggesting the relationship between visceral fat, muscle, and cognition may differ by demographic factors or cognitive domain assessed 1 6 10.

Study Overview and Key Findings

As the global population ages, understanding modifiable risk factors for brain health is increasingly important. This study examined how the balance of muscle mass and visceral fat in middle-aged adults relates to biological brain age, as estimated by MRI. By leveraging advanced imaging and AI analysis, the research provides new insight into how body composition metrics—particularly the ratio of visceral fat to muscle—reflect underlying brain aging processes. The findings are timely given the growing use of GLP-1 medications and the clinical focus on preventing neurodegenerative conditions such as Alzheimer's disease.

Property	Value
Organization	Mallinckrodt Institute of Radiology at Washington University School of Medicine
Authors	Cyrus Raji, Somayeh Meysami, Soojin Lee, Saurabh Garg, Nasrin Akbari, Rodrigo Solis Pompa, Ahmed Gouda, Thanh Duc Nguyen, Saqib Abdullah Basar, Yosef G. Chodakiewitz, David A. Merrill, Alex Exuzides, Amar P. Patel, Daniel J. Durand, Sam Hashemi
Population	Healthy adults
Sample Size	1,164 participants
Methods	Observational Study
Outcome	Muscle mass, visceral fat, brain age
Results	Higher muscle and lower visceral fat linked to younger brain age.

Literature Review: Related Studies

To provide broader scientific context, we searched the Consensus paper database, which includes over 200 million research articles. The following search queries were used to identify relevant studies:

1. muscle mass brain age correlation
2. visceral fat cognitive function impact
3. aging brain physical fitness relationship

Topic	Key Findings
How do muscle mass and visceral fat independently and jointly affect brain aging and cognition?	- Higher lean muscle mass correlates with improved cognitive performance and fluid intelligence, while greater visceral fat predicts cognitive decline 1 3 5. - The ratio of muscle to visceral fat is a stronger predictor of brain volume and cognitive function than either alone 3.
What mechanisms link body composition (muscle and fat) to brain structure and function?	- Visceral fat is associated with inflammation and metabolic dysfunction that can impair cognition, while muscle mass may protect brain health via myokine secretion and improved metabolism 5 7. - Physical activity and aerobic fitness reduce brain tissue loss and oxidative stress 11 14.
Are these relationships consistent across age, sex, and population groups?	- Associations between muscle, fat, and cognition are observed in children, adolescents, adults, and older populations, though some sex-specific and age-related nuances exist 1 6 8 9 10. - Some studies suggest visceral fat may be partially protective in specific subgroups 10.
What is the impact of interventions (e.g., exercise, pharmacological) on body composition and brain?	- Physical activity interventions reduce visceral fat and improve cognitive function, particularly in children with obesity 9. - Aerobic fitness and exercise training are linked to preserved brain volume, reduced brain aging, and improved cognition in older adults 11 12 13 15.

How do muscle mass and visceral fat independently and jointly affect brain aging and cognition?

A substantial body of research supports the view that both higher muscle mass and lower visceral fat are beneficial for brain health, with their combined ratio offering an even stronger association with cognitive outcomes and brain structure. The new study's findings are consistent with previous work showing that the muscle-to-visceral fat ratio best reflects integrated effects on brain aging.

• Greater lean muscle mass is associated with higher fluid intelligence and cognitive function in both men and women, while visceral adipose mass predicts cognitive decline 1.
• The ratio of thigh muscle to visceral fat correlates positively with the volume of brain regions important for cognition and movement, outperforming single measures of muscle or fat 3.
• These relationships hold across a range of ages and populations, reinforcing the importance of considering body composition holistically 1 3.
• Subcutaneous fat (fat under the skin) appears less relevant to brain aging and cognitive function than visceral fat 6.

What mechanisms link body composition (muscle and fat) to brain structure and function?

Mechanistic studies indicate that excess visceral fat drives inflammation and metabolic disturbances that can negatively affect brain health, while skeletal muscle provides protective effects through myokines and metabolic regulation. Physical activity, which helps maintain muscle and reduce visceral fat, also appears neuroprotective.

• Dysfunctional myokine secretion from low muscle mass may lead to inflammation, impaired metabolism, and oxidative stress, contributing to cognitive decline 5.
• Visceral adipose tissue can trigger neuroinflammation through NLRP3-IL1β signaling, impairing cognition in obesity models 7.
• Aerobic fitness and regular physical activity are linked to reduced brain tissue loss, improved white matter structure, and lower risk of neurodegenerative disease 11 12 13 14.
• Exercise interventions in animal models reduce oxidative stress and amyloid pathology, supporting neuroprotection 14.

Are these relationships consistent across age, sex, and population groups?

The associations between body composition and brain health are observed across diverse populations, though some studies suggest the strength and direction of these relationships may vary by age, sex, or cognitive domain. For example, certain studies report partially protective effects of visceral fat in specific subgroups.

• In adolescents and children, higher visceral fat is linked to poorer executive function, with some evidence of stronger effects in females 6 9.
• Large cohort studies in adults and older populations consistently find links between higher muscle mass, lower visceral fat, and better cognitive performance 1 8.
• A study in older Japanese women found that higher visceral fat was associated with a lower risk of mild cognitive impairment, suggesting possible context-dependent or threshold effects 10.
• Longitudinal and genetic studies support the causal role of visceral adiposity and BMI in cognitive decline across ethnic groups 4 8.

What is the impact of interventions (e.g., exercise, pharmacological) on body composition and brain?

Interventional research demonstrates that modifying body composition through exercise can slow brain aging and enhance cognitive function. The new study's findings may also have implications for optimizing pharmacological treatments affecting muscle and fat distribution.

• Physical activity interventions in children lead to reductions in visceral fat and improvements in cognitive control, especially in those who are obese 9.
• Aerobic fitness training in older adults is associated with preserved brain tissue, improved connectivity of critical brain networks, and reduced risk of dementia 11 12 13 15.
• Exercise-induced improvements in body composition (more muscle, less visceral fat) may help prevent or delay pathological brain aging and neurodegenerative diseases 14 15.
• The current study highlights the need to balance fat loss and muscle preservation in pharmacological therapies such as GLP-1 agonists, given their differing effects on muscle and fat compartments.

Future Research Questions

Although the current study and related literature provide compelling evidence linking body composition to brain aging, important questions remain. Future research should address causal relationships, underlying mechanisms, and optimal intervention strategies, as well as population-specific effects.

Research Question	Relevance
Does improving muscle mass through intervention directly reduce brain aging?	Establishing causality is critical for designing targeted interventions; current evidence is largely observational 1 3 11.
What are the biological mechanisms linking visceral fat to brain aging and cognitive decline?	Understanding pathways (e.g., inflammation, insulin resistance, myokines) can inform prevention and treatment strategies 5 7.
How do sex and age moderate the relationship between body composition and brain health?	Some studies report differential effects by sex and age; clarifying these patterns will support personalized medicine approaches 1 6 10.
Can GLP-1 weight loss drugs be optimized to reduce visceral fat while preserving muscle mass?	Given the popularity of GLP-1 drugs and their potential to cause muscle loss, optimizing dosing/regimens may maximize brain health benefits [study, news article].
What are the long-term effects of changing body composition on brain structure and function in different populations?	Longitudinal studies across diverse groups are needed to assess whether interventions have sustained benefits for brain aging and cognitive health 4 8 9.