|dc.description.abstract||Objectives—To examine the effects of aerobic exercise on cognition and other biomarkers
associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and
assess the role of sex as a predictor of response.
Design—Six-month, randomized, controlled, clinical trial.
Setting—Veterans Affairs Puget Sound Health Care System clinical research unit.
Participants—Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging
in age from 55 to 85 years (mean age,70 years).
Intervention—Participants were randomized either to a high-intensity aerobic exercise or
stretching control group. The aerobic group exercised under the supervision of a fitness trainer at
75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group
carried out supervised stretching activities according to the same schedule but maintained theirheart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic
and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray
absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive
tests were administered.
Main Outcome Measures—Performance measures on Symbol-Digit Modalities, Verbal
Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels
of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids
40 and 42.
Results—Six months of high-intensity aerobic exercise had sex-specific effects on cognition,
glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite
comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise
improved performance on multiple tests of executive function, increased glucose disposal during
the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived
neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor
I and had a favorable effect only on Trails B performance.
Conclusions—This study provides support, using rigorous controlled methodology, for a potent
nonpharma-cologic intervention that improves executive control processes for older women at
high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response
may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis
responses to aerobic exercise.||en_US