Using longitudinal analyses, we showed that a high level of physical activity and total energy expenditure suppressed the frontal lobe atrophy progression that is induced by aging.
An inactive daily life appears to be a risk factor for frontal lobe atrophy progression. In male participants, those with the lowest activity energy expenditure (first quintile, <143.2 kcal) had a 3.408-fold risk of frontal lobe atrophy progression compared with those with the highest activity energy expenditure (fifth quintile, ≥284.4 kcal) (Table 4). Similarly, men with the fewest number of steps (first quintile, <5736.0 steps) had a 3.651-fold risk of frontal lobe atrophy progression compared with those with the most number of steps (fifth quintile, ≥10,407.4 steps) (Table 4). An activity energy expenditure of 143.2 kcal is equivalent to activity in 4 METs (e.g., raking the lawn and table tennis) for 33 min in 62.5-kg men. Thirty minutes of middle-intensity or greater activities per day, such as 5700 steps or more walking per day, may be necessary to reduce the risk of frontal lobe atrophy progression. In addition, daily physical activity decreases with aging. An increase in planned physical activities may be necessary to prevent frontal lobe atrophy progression in older people.
Not only the expenditure of energy with physical activity but also the energy metabolic rate of the whole body appears to be associated with frontal lobe atrophy. Low total energy expenditure tended to be a risk for frontal lobe atrophy in male and female participants (Table 4 and Table 5. In a study of prosimians and anthropoid apes and humans, brain volume is correlated with basal metabolism. The amount of basal metabolism may determine frontal lobe atrophy progression. It is well known that basal metabolism decreases with aging. Age-related skeletal muscle loss (sarcopenia) may be a risk factor for frontal lobe atrophy progression due to decreasing basal metabolism. Physical activity may compensate for a reduction in basal metabolism in the elderly.
Although a low-activity energy expenditure and a low number of steps were risk factors for frontal lobe atrophy progression in male participants, they were not risk factors in female participants (Table 4 and Table 5. Generally, there are many more men with brain atrophy than women. In this study, the ratios of frontal lobe atrophy progression were different between male and female participants (Table 2). Sex hormones may also affect the relationship between physical activity and frontal lobe atrophy. Androgens and estrogens are associated with brain volume,[13,24] and the adaptability of the brain to physical activity may be higher in men than that in women.
In contrast to activity energy expenditure, total energy expenditure was associated with frontal lobe atrophy progression in both men and women. Basal metabolism is the maximal occupation ratio in total energy expenditure. The brain metabolic rate is included in the basal metabolism. In women, total energy expenditure including basal metabolism appears to be a better index of the risks for frontal lobe atrophy progression compared with physical activity parameters. However, because some of the odds ratios were exceedingly large in female participants, our logistic regression model may not have precisely estimated the risk of frontal lobe atrophy. There were 55 male participants with frontal lobe atrophy progression (Table 2), but only 35 female participants had frontal lobe atrophy progression (Table 2). These sex differences in the brain atrophy progression rate may have influenced estimation of the odds ratio. In women in particular, further investigations may be needed to determine the association of frontal lobe atrophy progression with total energy expenditure.
Brain atrophy is caused in part by obesity, metabolic syndrome, and its components.[4,12] A high level of physical activity improves obesity and metabolic syndrome. Cross-sectional research suggests that prevention of obesity by physical activity causes the relationship between physical activity and brain volume. However, in this study, frontal lobe atrophy progression was associated with the physical activity level in logistic regression models that controlled for BMI. Physical activity or the total energy expenditure may be independent factors for preventing frontal lobe atrophy progression, regardless of obesity.
In this study, the activity energy expenditure, the number of steps, and the total energy expenditure were quantitative data collected by an accelerometer. The objectivity of our study is higher than that of past studies that estimated the physical activity level with a questionnaire.[5,19]
A limitation of this study is the noninvasive approach using MRI. We could not elucidate the mechanism of frontal lobe atrophy progression induced by a low level of physical activity or total energy expenditure. In an animal study, the beta amyloid cumulative dose is active mass dependent in mouse brain. The death of neurons may be inhibited by physical activity. Some growth factors, such as nerve growth factor or brain-derived neurotrophic factor, contribute to neuronal survival or neurogenesis.[31,39] The serum level of nerve growth factors fluctuates with physical exercise, and thus, exercise stimulus with physical activity may modify expression of nerve growth factors.
Exercise and physical activity have been reported to change the volume of every region of the brain, including the frontal lobe, the temporal lobe, the parietal lobe, and the hippocampus.[3,5,8,19] Interestingly, our results showed associations between brain atrophy progression and physical activity or total energy expenditure only in the frontal lobe, but not in the temporal lobe. We hypothesize that the regional differences in brain atrophy progression were due to differences in the patterns of physical activities (including types, intensities, or frequencies). A previous study suggests that increased blood flow in the brain due to physical exercise promotes neurogenesis. Blood flow in the brain varies with exercise type and intensity.[20,28] In this study, because the activity energy expenditure, the number of steps, and the total energy expenditure data were collected as the total amount per day with accelerometer sensors, the differences in the patterns of physical activities between participants were not determined. Further investigations that define these details may clearly uncover an association between physical activities and regional differences in brain atrophy progression.
In summary, using the longitudinal design of the NILS-LSA cohort, we evaluated the association between brain atrophy progression and daily physical activity and total energy expenditure in 774 community-living, middle-age, and elderly Japanese people with an 8-yr follow-up duration. Our data confirm that low levels of physical activity and total energy consumption are significant predictors of the risk for brain atrophy, and the effect of atrophy suppression is seen only in the frontal lobe. Promoting participation in physical activities may be beneficial in attenuating age-related frontal lobe atrophy and in preventing dementia.
This work was supported by The Research Funding for Longevity Sciences (23–33) from the National Center for Geriatrics and Gerontology, Japan.
The authors thank all of the participants and the health professionals and researchers from the Department for Development of Preventive Medicine, National Center for Geriatrics and Gerontology, who were involved in the data collection and analyses.
The results of the present investigation do not constitute endorsement by the American College of Sports Medicine.
Med Sci Sports Exerc. 2012;44(12):2362-2368. © 2012 American College of Sports Medicine