Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Abstract

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.

Figure 1. Flow chart of the study.

Figure 2. Changes in cognitive score at the ADAS-score during the 7-months intervention

. Mean change in ADAS-Cog score from baseline (negative differences correspond to lower scores at T7 than T0, indicating performance improvement). Error bars are s.e.m.; p value from mixed model repeated measure analysis, group × time interaction.

Figure 3. Estimated mean changes from baseline (T0) to T7 in cognitive score at the Rey-Osterrieth Complex Figure test immediate recall and Phonemic verbal fluency.

Positive differences correspond to higher scores at T7 than T0, indicating performance improvement. Error bars are s.e.m.; p value from mixed model repeated measure analysis (group × time interaction).

Figure 4. Train the Brain intervention increases Cerebral Blood Flow (CBF) in Medial Temporal Lobe (MTL) regions.

Voxel-wise paired t-test analysis between T0 and T7 for both the MCI-training and –no training groups (a) Increase of CBF in the MCI-training group (n = 48) at T7 with respect to T0 (p threshold 0.001). (b) No significant change of CBF between T0 and T7 was found in the MCI-no training group (n = 22). Lower line/row). Change of CBF during the 7 months intervention in (c) the hippocampus and (d) the parahippocampal regions Mean change from baseline is presented (positive differences correspond to higher CBF at T7 than T0. Error bars are s.e.m. In the parahippocampal region, two way mixed model ANOVA, time x treatment, revealed a significant time x treatment interaction (p < 0.05) with MCI-training subjects showing a significant improvement (*) and MCI-no training subjects showing a not significant decrease.

Figure 5. Training maintains neural efficiency as measured by task-related fMRI.

(A) No effect of training on task accuracy was evident for MCI-training and -no training subjects. (B) T0 task-related regions of interest obtained by pooling MCI-training and -no training subjects together. (C) Effects of training on BOLD signal: brain regions showing a significant effect for the ‘Time’ factor (L MT: left middle temporal motion-related region; L IPS: left intraparietal sulcus; L PMC: left premotor cortex). (D) Post-hoc analysis for each of the regions in section C, MCI-no training subjects showed an increase of BOLD signal between T0 and T7, while MCI-no training subjects did not, suggesting that our training program maintains neural efficiency.