Objective: To investigate whether a 12-week aerobic interval training (AIT) can preserve subcortical brain structures in early Parkinson’s disease (PD) and whether these effects are hemisphere-specific and related to dopaminergic degeneration, brain-derived neurotrophic factor (BDNF), and clinical outcomes.

Background: Although physical exercise improves motor and non-motor symptoms, its potential neuroprotective effects on brain structure remain unclear. Most studies report averaged bilateral brain effects, potentially masking PD-related hemisphere-specific effects.

Method: Patients with early-stage idiopathic PD (N=26) were randomized to a training group (PD-TR; n=13), completing a 12-week AIT program on a cycle ergometer, or a non-training control group (PD-NTR; n=13). Baseline putaminal dopaminergic degeneration was assessed using [¹⁸F]FDOPA_PET/CT. Hemispheres were classified as more-affected (MA) and less-affected (LA) based on posterior putamen uptake. Pre- and post-intervention assessments included: (i) 3T MRI T1-weighted scans for subcortical volumetry, (ii) serum BDNF levels, and (iii) clinical evaluation using the Unified Parkinson’s Disease Rating Scale (UPDRS). Training effects were analyzed with linear mixed-effects models and mechanistic associations with generalized additive models.

Results: Compared with PD-NTR, the PD-TR group demonstrated AIT-induced increases in serum BDNF levels and a neuroprotective structural pattern with preserved subcortical volumes (primarily in the LA-hemisphere), whereas the PD-NTR group showed no change in BDNF and significant progressive atrophy. Structural preservation in PD-TR included the MA-accumbens, LA-putamen, LA-hippocampus and LA-amygdala. Clinically, the PD-TR cohort remained stable, while the PD-NTR group worsened in UPDRS Parts I, II, and Total scores. In PD-TR: (i) MA-accumbens and LA-putamen volume changes were predicted by baseline [¹⁸F]FDOPA_PET/CT, (ii) LA-hippocampal volume changes were associated with BDNF boost, and (iii) MA-accumbens and LA-putamen volume changes predicted clinical stabilization (UPDRS Part I and Total scores).

Conclusion: A 12-week AIT induced neuroprotective effects on subcortical structures in early PD, predominantly in the LA-hemisphere, suggesting that even short-term exercise interventions may slow neurodegeneration and promote clinical stabilization.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/12-week-aerobic-interval-training-induces-hemisphere-specific-neuroprotection-in-parkinsons-disease-a-multimodal-mri-18ffluorodopa-pet-ct-and-bdnf-study/