Louis Chew-Seng Tan

Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies

Depression, anxiety and apathy are common mood disturbances in Parkinsons disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer‐reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single‐photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal−limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre‐processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra‐nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.

Progression of subcortical atrophy in mild Parkinson's disease and its impact on cognition

Mild cognitive impairment (MCI) is associated with pronounced grey matter atrophy in various brain regions. However, the association between atrophy patterns and progression from no cognitive impairment (NCI) to Parkinsons disease (PD)‐MCI is not clearly known. We investigated the pattern and progression of atrophy in subcortical structures and its impact on cognition in patients with mild PD.

Risk and prognostic factors for pneumonia and choking amongst Parkinson’s disease patients with dysphagia

OBJECTIVEnTo evaluate the time to hospitalisation and baseline factors associated with pneumonia/choking in Parkinsons Disease (PD) patients.nnnBACKGROUNDnAlthough dysphagia and pneumonia are common problems in PD, scarce research has been performed.nnnMETHODSnA total of 194 PD patients who underwent a VFS evaluation were retrospectively selected. The mode of feeding and admissions for pneumonia/choking were analyzed. Baseline clinical and demographic variables were compared between feeding groups. Kaplan-Meier survival analysis was performed to estimate time to pneumonia/choking. Clinical variables significantly associated with pneumonia/choking free survival were identified using Cox regression.nnnRESULTSnHospitalisation for pneumonia/choking occurred in 89 out of 194 patients, with the highest admission rate in rejected enteral feeding group (66.7%), followed by enteral feeding (61.8%) and oral feeding (38.8%) groups. The estimates of median time to event were 11, 14, and 47 months for rejected enteral feeding, enteral and oral feeding groups respectively (log-rank test pxa0<xa00.001). The rejected enteral feeding group had the highest risk of pneumonia/choking (HR 4.61, 95%CI:2.33-9.08, pxa0<xa00.001), followed by enteral feeding group (HR 2.29, 95%CI:1.25-4.19, pxa0=xa00.007), when compared to oral feeding group after adjusting for possible confounders. A stepwise Cox regression showed that the rejected enteral feeding (HR 4.89, 95%CI:2.19-10.88, pxa0<xa00.001), enteral mode of feeding (HR 2.43, 95%CI:1.11-5.32, pxa0=xa00.026), and Charlson weighted index of co-morbidity (HR 1.27, 95%CI:1.03-1.58, pxa0=xa00.028) were independently associated with higher hazard of pneumonia/choking.nnnCONCLUSIONSnCompliance to feeding recommendations is important to reduce the risk of hospitalisation for pneumonia/choking. The recommended mode of feeding and comorbidity index was significantly associated with pneumonia/choking risk.

Serum uric acid level and its association with motor subtypes and non-motor symptoms in early Parkinson's disease: PALS study

OBJECTIVEnUric acid has been found to be potentially neuroprotective in Parkinsons disease (PD). We investigated the relationship between serum uric acid levels and both motor and non-motor features in a prospective early PD cohort study.nnnMETHODSnFasting serum uric acid levels were measured from 125 early PD patients. Demographic, clinical characteristics, motor and non-motor assessments were performed. Patients were categorized into three motor subtypes: tremor-dominant (TD), postural instability/gait difficulty (PIGD), and mixed. Non-motor symptoms were classified as present or absent based on the appropriate cut-offs for each non-motor instrument.nnnRESULTSnMost patients had TD (nu202f=u202f51, 40.8%) and mixed (nu202f=u202f63, 50.4%) motor subtypes, while a minority had PIGD (nu202f=u202f11, 8.8%) motor subtype. The mean serum uric acid levels were significantly different between the three motor subtypes (pu202f=u202f0.0106), with the mixed subtype having the lowest serum uric acid levels. Using the TD subtype as reference, patients with higher serum uric acid levels were less likely to have the mixed (ORu202f=u202f0.684; pu202f=u202f0.0312) subtype as opposed to the TD subtype. Uric acid levels were not significantly different between the TD and PIGD subtypes. For non-motor symptoms, higher serum uric acid levels were significantly associated with less fatigue (ORu202f=u202f0.693; pu202f=u202f0.0408).nnnCONCLUSIONnHigher serum uric acid levels were associated with TD motor subtype and less fatigue in early PD, which could be related to its anti-oxidative properties. Uric acid could be an important biomarker for specific motor features and symptoms of fatigue in PD.

Mood and neural correlates of excessive daytime sleepiness in Parkinson's disease

For patients with Parkinsons disease (PD), excessive daytime sleepiness (PD‐EDS) is a debilitating non‐motor symptom and may be affected by mood symptoms, especially depression and anxiety. Few neuroimaging works have attempted to identify the neural features of PD‐EDS, but various findings were reported. The purpose of this study was to systematically review the literature on mood and neuroimaging correlates of PD‐EDS. A MEDLINE, PubMed, EMBASE, and PsycInfo search for peer‐reviewed original research articles on depression, anxiety, and neuroimaging in PD‐EDS identified 26 studies on depression, nine on anxiety, and eight on neuroimaging. Half of the studies reported greater depression in PD‐EDS‐positive patients compared with PD‐EDS‐negative patients. There was a significantly positive correlation between depression and PD‐EDS. Limited studies on anxiety in PD‐EDS suggested a weak correlation between anxiety and EDS. For depression and anxiety, the effect sizes were medium when EDS was subjectively measured, but became small when EDS was objective measured. Current neuroimaging studies generally suggested diminished neural structural and functional features (eg, brain volume, white matter integrity as indicated by fractional anisotropy, and cerebral metabolism) in patients with PD‐EDS. Future studies should apply objective and subjective measures of mood symptoms and EDS and improve the neuroimaging methodology via using multimodal techniques and whole‐brain analysis to provide new clues on the mood and neural correlates of PD‐EDS.

Higher serum triglyceride levels are associated with Parkinson's disease mild cognitive impairment

previously reported benign variants (Supplementary Table 4), suggesting that the identified VPS13C deletion might contribute to the CMT phenotype seen in our patient, which might help with the diagnosis of prospective VPS13C patients. In summary, we report the identification and characterization of a large L1 retrotransposition-mediated VPS13C deletion in a patient with parkinsonism, further confirming the role of the VPS13C in the pathogenesis of PD. This is the first large deletion identified and reported in the VPS13C gene. In addition to the strong effect of the identified mutation on the protein, our patient showed normal cognitive status and a milder clinical picture than that observed in previously reported patients. Last, the hypothesis that the identified VPS13C deletion might be responsible for the CMT phenotype seen in our patient needs to be further explored, as it also might be caused by mutations in an unknown CMT gene.

Non-motor symptoms in early Parkinson's disease with different motor subtypes and their associations with quality of life

The aim of this study was to examine non‐motor symptoms in different Parkinsons disease (PD) motor subtypes and their associations with quality of life (QoL).