Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease

Abstract

Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline.

Trial registration: ClinicalTrials.gov NCT00220441.

Fig. 1

Subject flow from initial contact through study completion.

Fig. 2

Treatment effects on cognitive outcomes of executive function. Means (standard error of measurement) represent 6-month change relative to baseline, expressed as difference scores. All means are adjusted for age and gender as well as other task-specific variables when indicated. A) Trails B time to complete the task (seconds, log transformed, adjusted for Trails A time) was faster for subjects in the aerobic group relative to controls, p = 0.04. B) Task Switching response latency for all trials, adjusted for accuracy, was faster for the aerobic group relative to controls, p = 0.03. C) Stroop voice onset latency to interference stimuli was faster for subjects in the aerobic group versus controls, p = 0.04. D) SOPT performance, indexed by number of correct responses across all trials, tended to improve for aerobic exercisers relative to controls, p = 0.10.