From the Journals

Muscle fat: A new risk factor for cognitive decline?



Muscle adiposity may be a novel risk factor for cognitive decline in older adults, new research suggests.

Investigators assessed muscle fat in more than 1,600 adults in their 70s and evaluated their cognitive function over a 10-year period. They found that increases in muscle adiposity from year 1 to year 6 were associated with greater cognitive decline over time, independent of total weight, other fat deposits, muscle characteristics, and traditional dementia risk factors.

The findings were similar between Black and White people and between men and women.

“Increasing adiposity – or fat deposition – in skeletal muscles predicted faster cognitive decline, irrespective of demographics or other disease, and this effect was distinct from that of other types of fat or other muscle characteristics, such as strength or mass,” study investigator Caterina Rosano MD, MPH, professor of epidemiology at the University of Pittsburgh, said in an interview.

The study was published in the Journal of the American Geriatrics Society.

Biologically plausible

“There has been a growing recognition that overall adiposity and muscle measures, such as strength and mass, are individual indicators of future dementia risk and both strengthen the algorithms to predict cognitive decline,” said Dr. Rosano, associate director for clinical translation at the University of Pittsburgh’s Aging Institute. “However, adiposity in the muscle has not been examined.”

Some evidence supports a “biologically plausible link” between muscle adiposity and dementia risk. For example, muscle adiposity increases the risk for type 2 diabetes and hypertension, both of which are dementia risk factors.

Skeletal muscle adiposity increases with older age, even in older adults who lose weight, and is “highly prevalent” among older adults of African ancestry.

The researchers examined a large, biracial sample of older adults participating in the Health, Aging and Body Composition study, which enrolled men and women aged between 70 and 79 years. Participants were followed for an average of 9.0 ± 1.8 years.

During years 1 and 6, participants’ body composition was analyzed, including intermuscular adipose tissue (IMAT), visceral and subcutaneous adiposity, total fat mass, and muscle area.

In years 1, 3, 5, 8, and 10, participants’ cognition was measured using the modified Mini-Mental State (3MS) exam.

The main independent variable was 5-year change in thigh IMAT (year 6 minus year 1), and the main dependent variable was 3MS decline (from year 5 to year 10).

The researchers adjusted all the models for traditional dementia risk factors at baseline including 3MS, education, apo E4 allele, diabetes, hypertension, and physical activity and also calculated interactions between IMAT change by race or sex.

These models also accounted for change in muscle strength, muscle area, body weight, abdominal subcutaneous and visceral adiposity, and total body fat mass as well as cytokines related to adiposity.

‘Rich and engaging crosstalk’

The final sample included 1634 participants (mean age, 73.38 years at baseline; 48% female; 35% Black; mean baseline 3MS score, 91.6).

Thigh IMAT increased by 39.0% in all participants from year 1 to year 6, which corresponded to an increase of 4.85 cm2 or 0.97 cm2/year. During the same time period, muscle strength decreased by 14.0% (P < .05), although thigh muscle area remained stable, decreasing less than 0.5%.

There were decreases in both abdominal subcutaneous and visceral adiposity of 3.92% and 6.43%, respectively (P < .05). There was a decrease of 3.3% in 3MS from year 5 to year 10.

Several variables were associated with 3MS decline, independent of any change in thigh IMAT: older age, less education, and having at least one copy of the APOe4 allele. These variables were included in the model of IMAT change predicting 3MS change.

A statistically significant association of IMAT increase with 3MS decline was found. The IMAT increase of 4.85 cm2 corresponded to a 3MS decline of an additional 3.6 points (P < .0001) from year 5 to year 10, “indicating a clinically important change.”

The association between increasing thigh IMAT with declining 3MS “remained statistically significant” after adjusting for race, age, education, and apo E4 (P < .0001) and was independent of changes in thigh muscle area, muscle strength, and other adiposity measures.

In participants with increased IMAT in years 1-6, the mean 3MS score fell to approximately 87 points at year 10, compared with those without increased IMAT, with a 3MS score that dropped to approximately 89 points.

Interactions by race and sex were not statistically significant (P > .08).

“Our results suggest that adiposity in muscles can predict cognitive decline, in addition to (not instead of) other traditional dementia risk factors,” said Dr. Rosano.

There is “a rich and engaging crosstalk between muscle, adipose tissue, and the brain all throughout our lives, happening through factors released in the bloodstream that can reach the brain, however, the specific identity of the factors responsible for the crosstalk of muscle adiposity and brain in older adults has not yet been discovered,” she noted.

Although muscle adiposity is “not yet routinely measured in clinical settings, it is being measured opportunistically on clinical CT scans obtained as part of routine patient care,” she added. “These CT measurements have already been validated in many studies of older adults; thus, clinicians could have access to this novel information without additional cost, time, or radiation exposure.”

Causality not proven

In a comment, Bruce Albala, PhD, professor, department of environmental and occupational health, University of California, Irvine, noted that the 3MS assessment is scored on a 100-point scale, with a score less than 78 “generally regarded as indicating cognitive impairment or approaching a dementia condition.” In the current study, the mean 3MS score of participants with increased IMAT was still “well above the dementia cut-off.”

Moreover, “even if there is a relationship or correlation between IMAT and cognition, this does not prove or even suggest causality, especially from a biological mechanistic approach,” said Dr. Albaba, an adjunct professor of neurology, who was not involved in the study. “Clearly, more research is needed even to understand the relationship between these two factors.”

The study was supported by the National Institute on Aging. Dr. Rosano and coauthors and Dr. Albala declared no relevant financial relationships.

A version of this article originally appeared on

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