AUTHOR=Stuckenschneider Tim , Sanders Marit L. , Devenney Kate E. , Aaronson Justine A. , Abeln Vera , Claassen Jurgen A. H. R. , Guinan Emer , Lawlor Brian , Meeusen Romain , Montag Christian , Olde Rikkert Marcel G. M. , Polidori M. Cristina , Reuter Martin , Schulz Ralf-Joachim , Vogt Tobias , Weber Bernd , Kessels Roy P. C. , Schneider Stefan 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.621947

DOI=10.3389/fnagi.2020.621947

ISSN=1663-4365

ABSTRACT=<p>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; <italic>n</italic> = 60), stretching and toning exercise (ST; <italic>n</italic> = 65) or to a non-exercise control group (CG; <italic>n</italic> = 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 (<italic>n</italic> = 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), <italic>p</italic> = 0.13] or in any cognitive domain or quality of life. VO<sub>2</sub> peak was significantly higher in the EG compared to the CG after 12 months [−1.76 (−3.39, −0.10), <italic>p</italic> = 0.04]. Comparing the two intervention groups revealed a higher VO<sub>2</sub>peak 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.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02913053" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/ct2/show/NCT02913053</ext-link>, identifier: NCT02913053.</p>