Longitudinal effects of physical activity on sleep in association with hippocampal-amygdala subfield structure and functional connectivity in Alzheimer's disease.
Dadsena R, Costa A, et al. • Alzheimer's & dementia : the journal of the Alzheimer's Association • 2026
Exercise was associated with short-term MTL preservation and network reorganization linked to sleep and activity, supporting continuous physical activity for lasting benefits in individuals on the AD continuum.
Key Findings
Results
After 6 months of multimodal exercise intervention, the intervention group showed increased hippocampus-amygdala connectivity compared to the psychoeducation control group.
46 individuals on the AD continuum were randomized to 6 months of multimodal exercise (n=25) or psychoeducation (n=21)
Resting-state functional MRI was used to assess hippocampus-amygdala connectivity
Increased connectivity was observed at the post-intervention timepoint (T2) in the exercise group
The study followed participants for 18 months total with measurements at T1-T4
Results
The exercise intervention group showed attenuated hippocampal and amygdala subfield atrophy after the 6-month intervention period.
High-resolution T1 MRI was used to measure hippocampal and amygdala subfield volumes longitudinally
Attenuation of subfield atrophy was observed in the exercise group relative to the psychoeducation group at 6 months
This effect represents short-term medial temporal lobe preservation associated with multimodal exercise
Results
One year after the intervention ended, both groups showed progression in cognitive decline and hippocampal atrophy, suggesting exercise benefits were not maintained without continued activity.
Follow-up assessments were conducted at 12 and 18 months (T3 and T4) after the start of the study
Both the exercise and psychoeducation groups progressed in cognitive decline during the follow-up period
Both groups showed hippocampal atrophy progression at the one-year post-intervention follow-up
This finding supports the need for continuous physical activity to maintain lasting benefits
Results
Hippocampal and amygdalar volumes and connectivity were associated with sleep parameters in individuals on the AD continuum.
Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), sleep diaries, and wearable devices
Both structural (subfield volumes) and functional (connectivity) measures of the medial temporal lobe were associated with sleep outcomes
Sleep is described as a modifiable risk factor in Alzheimer's disease in this study
Results
Hippocampal and amygdalar volumes and connectivity were associated with both physical activity and cognitive parameters.
Activity measures were obtained via wearables alongside clinical and cognitive testing
Associations were found between MTL structure/connectivity and activity levels across the longitudinal follow-up
Clinical and cognitive testing was included alongside neuroimaging and sleep/activity measures at each timepoint (T1-T4)
Methods
The study design involved a randomized controlled trial with longitudinal neuroimaging follow-up over 18 months in participants on the Alzheimer's disease continuum.
The study is called the Dementia-Multi-Objective Validation of Exercise (MOVE) study
46 participants were randomized: 25 to multimodal exercise and 21 to psychoeducation
Assessments included high-resolution T1 MRI, resting-state fMRI, PSQI, sleep diaries, wearables, and clinical/cognitive testing
Four timepoints (T1-T4) were assessed spanning the 6-month intervention and 12-month follow-up
What This Means
This research suggests that regular physical exercise may temporarily protect brain regions critical for memory and emotion — specifically the hippocampus and amygdala — in people who are at risk for or in early stages of Alzheimer's disease. In this study, participants who completed a 6-month multimodal exercise program showed less brain tissue loss and stronger connections between the hippocampus and amygdala compared to those who received psychoeducation. These brain regions are important for sleep regulation, memory, and emotional processing, and all three of these functions were found to be interrelated in this population.
However, the protective effects of the exercise program did not appear to last. When researchers followed up one year after the exercise program ended, both the exercise and non-exercise groups showed similar levels of cognitive decline and hippocampal shrinkage. This finding implies that the brain benefits seen from exercise are not permanent — they seem to require ongoing physical activity to be maintained.
This research also highlights the relationship between sleep quality, brain structure, and physical activity in Alzheimer's disease. The fact that sleep measures were linked to the size and connectivity of hippocampal and amygdala regions suggests that sleep health and brain health may reinforce each other. Together, these findings point to the potential value of sustained, long-term physical activity — rather than a short-term program — as part of a lifestyle approach to supporting brain health in people on the Alzheimer's disease continuum.
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Dadsena R, Costa A, David S, Haberl L, Schulz J, Reetz K, et al.. (2026). Longitudinal effects of physical activity on sleep in association with hippocampal-amygdala subfield structure and functional connectivity in Alzheimer's disease.. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71651