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Study Shows Aerobic Exercise Helps Cognitive Function in Older Adults

Treadmill, Older Adult, Exercise, Alzheimer's Disease, Brain Health, Brain Function, Cognition, Biomarkers, Dementia

The enhanced physical activity group underwent 26 weeks of supervised treadmill training. Blood samples for both groups were taken at baseline and after 26 weeks.


By gisele galoustian | 6/10/2021

Increasing evidence shows that physical activity and exercise training may delay or prevent the onset of Alzheimer鈥檚 disease (AD). In aging humans, aerobic exercise training increases gray and white matter volume, enhances blood flow, and improves memory function. The ability to measure the effects of exercise on systemic biomarkers associated with risk for AD and relating them to key metabolomic alterations may further prevention, monitoring, and treatment efforts. However, systemic biomarkers that can measure exercise effects on brain function and that link to relevant metabolic responses are lacking.

To address this issue, , Ph.D., from 91制片厂鈥檚 and Stiles-Nicholson Brain Institute and Ozioma Okonkwo, Ph.D., Wisconsin Alzheimer鈥檚 Disease Research Center and Department of Medicine at the and their collaborators, tested the hypotheses that three specific biomarkers, which are implicated in learning and memory, would increase in older adults following exercise training and correlate with cognition and metabolomics markers of brain health. They examined myokine Cathepsin B (CTSB), brain derived neurotrophic factor (BDNF), and klotho, as well as metabolomics, which have become increasingly utilized to understand biochemical pathways that may be affected by AD.

Researchers performed a metabolomics analysis in blood samples of 23 asymptomatic late middle-aged adults, with familial and genetic risk for AD (mean age 65 years old, 50 percent female) who participated in the 鈥渁eRobic Exercise And Cognitive Health (REACH) Pilot Study鈥 (NCT02384993) at the University of Wisconsin. The participants were divided into two groups: usual physical activity (UPA) and enhanced physical activity (EPA). The EPA group underwent 26 weeks of supervised treadmill training. Blood samples for both groups were taken at baseline and after 26 weeks.

Results of the study, published in the journal , showed that plasma CTSB levels were increased following this 26-week structured aerobic exercise training in older adults at risk for AD. Verbal learning and memory correlated positively with change in CTSB but was not related to BDNF or klotho. The present correlation between CTSB and verbal learning and memory suggests that CTSB may be useful as a marker for cognitive changes relevant to hippocampal function after exercise in a population at risk for dementia. Plasma BDNF levels decreased in conjunction with metabolomic changes, including reductions in ceramides, sphingo- and phospholipids, as well as changes in gut microbiome metabolites and redox homeostasis. Indeed, multiple lipid metabolites relevant to AD were modified by exercise in a manner that may be neuroprotective. Serum klotho was unchanged but was associated with cardiorespiratory fitness.

鈥淥ur findings position CTSB, BDNF, and klotho as exercise biomarkers for evaluating the effect of lifestyle interventions on brain function,鈥 said van Praag, corresponding author, an associate professor of biomedical science, 91制片厂鈥檚 Schmidt College of Medicine, and a member of the 91制片厂 Brain Institute and the 91制片厂 Institute for Human Health & Disease Intervention (I-HEALTH). 鈥淗uman studies often utilize expensive and low throughput brain imaging analyses that are not practical for large population-wide studies. Systemic biomarkers that can measure the effect of exercise interventions on Alzheimer鈥檚-related outcomes quickly and at low-cost could be used to inform disease progression and to develop novel therapeutic targets.鈥

CTSB, a lysosomal enzyme, is secreted from muscle into circulation after exercise and is associated with memory function and adult hippocampal neurogenesis. Older adults with cognitive impairment have lower serum and brain CTSB levels. BDNF is a protein that is upregulated in the rodent hippocampus and cortex by running and is important for adult neurogenesis, synaptic plasticity, and memory function. Klotho is a circulating protein that can enhance cognition and synaptic function and is associated with resilience to neurodegenerative disease, possibly by supporting brain structures responsible for memory and learning.

鈥淭he positive association between CTSB and cognition, and the substantial modulation of lipid metabolites implicated in dementia, support the beneficial effects of exercise training on brain function and brain health in asymptomatic individuals at risk for Alzheimer鈥檚 disease,鈥 said van Praag. 聽

Study co-first authors are Julian M. Gaitan, a researcher and exercise physiologist at the University of Wisconsin-Madison; Hyo Youl Moon, Ph.D., a faculty member at the ; co-authors Matthew Stremlau, Ph.D., , ; and faculty members, professors Dena B. Dubal, M.D., ; and Dane B. Cook, Ph.D., .

This work was supported by grants from the Alzheimer鈥檚 Association (NIRGD-305257), the Extendicare Foundation, and the National Institutes of Health (K23 AG045957, R01AG027161, P50 AG033514, and UL1RR025011). This work also was supported in part by the NIA Intramural Research Program, the 91制片厂 Brain Institute, Jupiter Life Sciences Initiative, and the Florida Department of Health鈥檚 Ed and Ethel Moore Alzheimer鈥檚 Disease Research program.

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