METHODS: In this three-year longitudinal study, 125 subjects (77 PD patients and 48 spousal/sibling controls) underwent clinical, biochemical and body composition assessments using dual-energy X-ray absorptiometry.
RESULTS: Patients were older than controls (65.6 ± 8.9 vs. 62.6 ± 7.1, P = 0.049), with no significant differences in gender, comorbidities, dietary intake and physical activity. Clinically significant weight loss (≥5% from baseline weight) was recorded in 41.6% of patients, with a doubling of cases (6.5 to 13.0%) classified as underweight at study end. Over three years, patients demonstrated greater reductions in BMI (mean -1.2 kg/m2, 95%CI-2.0 to -0.4), whole-body fat percentage (-2.5% points, 95%CI-3.9 to -1.0), fat mass index (FMI) (-0.9 kg/m2, 95%CI-1.4 to -0.4), visceral fat mass (-0.1 kg, 95%CI-0.2 to 0.0), and subcutaneous fat mass (-1.9 kg, 95%CI-3.4 to -0.5) than in controls, with significant group-by-time interactions after adjusting for age and gender. Notably, 31.2% and 53.3% of patients had FMI<3rd (severe fat deficit) and <10th centiles, respectively. Muscle mass indices decreased over time in both groups, without significant group-by-time interactions. Multiple linear regression models showed that loss of body weight and fat mass in patients were associated with age, dyskinesia, psychosis and constipation.
CONCLUSIONS: We found progressive loss of weight in PD patients, with greater loss of both visceral and subcutaneous fat, but not muscle, compared to controls. Several associated factors (motor and non-motor disease features) were identified for these changes, providing insights on possible mechanisms and therapeutic targets.
METHODS: 93 patients and 78 spousal/sibling controls underwent comprehensive assessment of diet, clinical status, muscle strength/performance, frailty, body composition (using dual-energy X-ray absorptiometry), and serum levels of neurogastrointestinal hormones and inflammatory markers.
RESULTS: PD patients were older than controls (66.0 ± 8.5 vs. 62.4 ± 8.4years, P = 0.003). Mean body mass index (24.0 ± 0.4 vs. 25.6 ± 0.5kg/m2, Padjusted = 0.016), fat mass index (7.4 ± 0.3 vs. 9.0 ± 0.3kg/m2, Padjusted<0.001), and whole-body fat percentage (30.7 ± 0.8 vs. 35.7 ± 0.9%, Padjusted<0.001) were lower in patients, even after controlling for age and gender. There were no between-group differences in skeletal muscle mass index and whole-body bone mineral density. Body composition parameters did not correlate with disease duration or motor severity. Reduced whole-body fat percentage was associated with higher risk of motor response complications as well as higher levels of insulin-growth factor-1 and inflammatory markers. PD patients had a higher prevalence of sarcopenia (17.2% vs. 10.3%, Padjusted = 0.340) and frailty (69.4% vs. 24.2%, Padjusted = 0.010). Older age and worse PD motor severity were predictors of frailty in PD.
CONCLUSIONS: We found reduced body fat with relatively preserved skeletal muscle mass, and a high prevalence of frailty, in PD. Further studies are needed to understand the patho-mechanisms underlying these alterations.
METHODS: After systematic screening, raw 16S rRNA gene sequences were obtained from ten case-control studies totaling 1703 subjects (969 PD, 734 non-PD controls; seven predominantly Caucasian and three predominantly non-Caucasian cohorts). Quality-filtered gene sequences were analyzed using a phylogenetic placement approach, which precludes the need for the sequences to be sourced from similar regions in the 16S rRNA gene, thus allowing a direct comparison between studies. Differences in microbiome composition and correlations with clinical variables were analyzed using multivariate statistics.
RESULTS: Study and geography accounted for the largest variations in gut microbiome composition. Microbiome composition was more similar for subjects from the same study than those from different studies with the same disease status. Microbiome composition significantly differed between Caucasian and non-Caucasian populations. After accounting for study differences, microbiome composition was significantly different in PD vs. controls (albeit with a marginal effect size), with several distinctive features including increased abundances of Megasphaera and Akkermansia, and reduced Roseburia. Several bacterial genera correlated with PD motor severity, motor response complications and cognitive function.
CONCLUSION: Consistent microbial features in PD merit further investigation. The large variations in microbiome findings of PD patients underscore the need for greater harmonization of future research, and personalized approaches in designing microbial-directed therapeutics.
METHODS: A multi-ethnic cohort of PD patients from Malaysia (n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry.
RESULTS: Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK-PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and "loss of the swallow tail" sign, were documented.
CONCLUSIONS: This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK-PINK1. It also further supports the pathogenicity of the p. Leu347Pro variant.