Recently, revised diagnostic criteria for Parkinson's disease (PD) were introduced (Postuma et al., 2015). Yet, except for well-established dopaminergic imaging, validated imaging biomarkers for PD are still missing, though they could improve diagnostic accuracy.We conducted systematic meta-analyses to identify PD-specific markers in whole-brain structural magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) and diffusion tensor imaging (DTI) studies. Overall, 74 studies were identified including 2323 patients and 1767 healthy controls. Studies were first grouped according to imaging modalities (MRI 50; PET 14; DTI 10) and then into subcohorts based on clinical phenotypes. To ensure reliable results, we combined established meta-analytical algorithms - anatomical likelihood estimation and seed-based D mapping - and cross-validated them in a conjunction analysis.Glucose hypometabolism was found using FDG-PET extensively in bilateral inferior parietal cortex and left caudate nucleus with both meta-analytic methods. This hypometabolism pattern was confirmed in subcohort analyses and related to cognitive deficits (inferior parietal cortex) and motor symptoms (caudate nucleus). Structural MRI showed only small focal gray matter atrophy in the middle occipital gyrus that was not confirmed in subcohort analyses. DTI revealed fractional anisotropy reductions in the cingulate bundle near the orbital and anterior cingulate gyri in PD.Our results suggest that FDG-PET reliably identifies consistent functional brain abnormalities in PD, whereas structural MRI and DTI show only focal alterations and rather inconsistent results. In conclusion, FDG-PET hypometabolism outperforms structural MRI in PD, although both imaging methods do not offer disease-specific imaging biomarkers for PD.

Corticobasal degeneration is a scarce neurodegenerative disease, which can only be confirmed by histopathological examination. Reported to be associated with various clinical syndromes, its classical clinical phenotype is corticobasal syndrome. Due to the rareness of corticobasal syndrome/corticobasal degeneration and low numbers of patients included in single studies, meta-analyses are particularly suited to disentangle features of the clinical syndrome and histopathology. Using PubMed, we identified 11 magnetic resonance imaging studies measuring atrophy in 22 independent cohorts with 200 patients contrasted to 318 healthy controls. The anatomic likelihood estimation method was applied to reveal affected brain regions across studies. Corticobasal syndrome was related to gray matter loss in the basal ganglia/thalamus, frontal, parietal, and temporal lobes. In corticobasal degeneration patients, atrophy in the thalamus, frontal, temporal, and occipital lobes were found. Finally, in a conjunction analysis, the bilateral thalamus, the bilateral posterior frontomedian cortex, posterior midcingulate cortex and premotor area/supplementary motor area, and the left posterior superior and middle frontal gyrus/precentral gyrus were identified as areas associated with both, corticobasal syndrome and corticobasal degeneration. Remarkably, atrophy in the premotor area/supplementary motor area and posterior midcingulate/frontomedian cortex seems to be specific for corticobasal syndrome/corticobasal degeneration, whereas atrophy in the thalamus and the left posterior superior and middle frontal gyrus/precentral gyrus are also associated with other neurodegenerative diseases according to anatomic likelihood estimation method meta-analyses. Our study creates a new conceptual framework to understand, and distinguish between clinical features (corticobasal syndrome) and histopathological findings (corticobasal degeneration) by powerful data-driven meta-analytic approaches. Furthermore, it proposes regional-specific atrophy as an imaging biomarker for diagnosis of corticobasal syndrome/corticobasal degeneration ante-mortem.

Balance dysfunction is a disabling symptom in people with Parkinson’s disease (PD). Evidence suggests that exercise can improve balance performance and induce neuroplastic effects. We hypothesised that a 10-week balance intervention (HiBalance) would improve balance, other motor and cognitive symptoms, and alter task-evoked brain activity in people with PD. We performed a double-blind randomised controlled trial (RCT) where 95 participants with PD were randomised to either HiBalance (n = 48) or a control group (n = 47). We found no significant group by time effect on balance performance (b = 0.4 95% CI [−1, 1.9], p = 0.57) or on our secondary outcomes, including the measures of task-evoked brain activity. The findings of this well-powered, double-blind RCT contrast previous studies of the HiBalance programme but are congruent with other double-blind RCTs of physical exercise in PD. The divergent results raise important questions on how to optimise physical exercise interventions for people with PD.Preregistration clinicaltrials.gov: NCT03213873.

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