NeuroExercise: The Effect of a 12-Month Exercise Intervention on Cognition in Mild Cognitive Impairment—A Multicenter Randomized Controlled Trial

Abstract

Exercise intervention studies in mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease (AD), have demonstrated inconsistent yet promising results. Addressing the limitations of previous studies, this trial investigated the effects of a 12-month structured exercise program on the progression of MCI. The NeuroExercise study is a multicenter randomized controlled trial across three European countries (Ireland, Netherlands, Germany). Hundred and eighty-three individuals with amnestic MCI were included and were randomized to a 12-month exercise intervention (3 units of 45 min) of either aerobic exercise (AE; n = 60), stretching and toning exercise (ST; n = 65) or to a non-exercise control group (CG; n = 58). The primary outcome, cognitive performance, was determined by an extensive neuropsychological test battery. For the primary complete case (CC) analyses, between-group differences were analyzed with analysis of covariance under two conditions: (1) the exercise group (EG = combined AE and ST groups) compared to the CG and (2) AE compared to ST. Primary analysis of the full cohort (n = 166, 71.5 years; 51.8% females) revealed no between-group differences in composite cognitive score [mean difference (95% CI)], 0.12 [(−0.03, 0.27), p = 0.13] or in any cognitive domain or quality of life. VO2 peak was significantly higher in the EG compared to the CG after 12 months [−1.76 (−3.39, −0.10), p = 0.04]. Comparing the two intervention groups revealed a higher VO2peak level in the aerobic exercise compared to the stretching and toning group, but no differences for the other outcomes. A 12-month exercise intervention did not change cognitive performance in individuals with amnestic MCI in comparison to a non-exercise CG. An intervention effect on physical fitness was found, which may be an important moderator for long term disease progression and warrants long-term follow-up investigations.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02913053, identifier: NCT02913053.

Exploring bi-directional temporal associations between timed-up-and-go and cognitive domains in the Irish longitudinal study on ageing (TILDA)

“…The multiple significant associations between other covariates and mobility in the repeated-measures mixed models investigating cognitive functions as predictors, suggest that there may be scope for interventions to slow down adverse trajectories of mobility decline even in the presence of baseline cognitive impairment, by acting on potentially modifiable factors (e.g., improving muscle strength, addressing fear of falling, optimising medications). Intervention approaches including physical exercise may also be appropriate [57][58][59], although not necessarily effective in improving cognition [60]. Indeed, in community-based samples, comprehensive geriatric assessment and individuallytailored interventions may contribute to improvements in the health and functional status of older persons with multimorbidity [61].…”

ESO Guideline on covert cerebral small vessel disease

“…RCTs with participants with memory complaints or MCI and no definition of SVD at enrolment (NeuroExercice, AIBL Active) have found no intervention effects of aerobic exercise on cognitive or imaging outcomes. 113,114 However, an RCT with elderly individuals at-risk for dementia from the general population (FINGER) has shown that a multidomain intervention including diet, exercise, cognitive training and vascular risk monitoring has beneficial effects in improving and maintaining…”

“…RCTs with participants with memory complaints or MCI and no definition of SVD at enrolment (NeuroExercice, AIBL Active) have found no intervention effects of aerobic exercise on cognitive or imaging outcomes. 113 , 114 However, an RCT with elderly individuals at-risk for dementia from the general population (FINGER) has shown that a multidomain intervention including diet, exercise, cognitive training and vascular risk monitoring has beneficial effects in improving and maintaining cognitive functioning. 115 A pooled analysis of 322 individuals from two RCTs targeting lifestyle and vascular risk factors with multi-domain interventions to prevent post-stroke cognitive impairment found limited evidence of benefit on attention but not on other cognitive domains.…”

Recruitment of a multi‐site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial

“… 2 NeuroExercise screened 1528 individuals over 18 months, including 835 (54.6%) deemed ineligible at screening. 2 , 18 In another 12‐month RCT of home‐based aerobic exercise in adults with aMCI, a total of 1620 individuals were screened, including 1550 (95.7%) who did not meet eligibility criteria over a 4‐year recruitment period. 19 EXERT experienced greater recruitment success, with screen failure rates of 46.1% and 44.7% after telephone and in‐person screening visits, respectively, during 3.5 years of recruitment.…”