Activities of Daily Living, Depression, and Quality of Life in Parkinson’s Disease

This study examined whether activities of daily living (ADL) mediate the relationship between depression and health-related quality of life (HR-QOL) in people with Parkinson’s disease (PD). A cross-sectional, correlational research design examined data from 174 participants who completed the Geriatric Depression Scale (GDS-15), Parkinson’s Disease Questionnaire-39 (PDQ-39), and Unified Parkinson’s Disease Rating Scale-section 2 (UPDRS-section 2 [ADL]). Multiple Regression Analysis (MRA) was used to examine the mediator model. Depression and ADL significantly (p<.001) predicted HR-QOL, and depression significantly (p<.001) predicted ADL. Whilst ADL did not impact on the relationship between depression and HRQOL, there was a significant (p<.001) indirect effect of depression on HR-QOL via ADL, suggesting both direct and indirect (via ADL) effects of depression on HR-QOL. The magnitude of this effect was moderate (R2 = .13). People with PD who report depression also experience greater difficulty completing ADL, which impacts upon their HR-QOL. It is recommended that clinicians adopt a multidisciplinary approach to care by combining pharmacological treatments with psycho/occupational therapy, thereby alleviating the heterogeneous impact of motor and non-motor symptoms on HR-QOL in people with PD

Destruction of Dopaminergic Neurons in the Midbrain by 6-Hydroxydopamine Decreases Hippocampal Cell Proliferation in Rats: Reversal by Fluoxetine

Background Non-motor symptoms (e.g., depression, anxiety, and cognitive deficits) in patients with Parkinson disease (PD) precede the onset of the motor symptoms. Although these symptoms do not respond to pharmacological dopamine replacement therapy, their precise pathological mechanisms are currently unclear. The present study was undertaken to examine whether the unilateral 6-hydroxydopamine (6-OHDA) lesion to the substantia nigra pars compacta (SNc), which represents a model of long-term dopaminergic neurotoxicity, could affect cell proliferation in the adult rat brain. Furthermore, we examined the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the selective noradrenaline reuptake inhibitor maprotiline on the reduction in cell proliferation in the subgranular zone (SGZ) by the unilateral 6-OHDA lesion. Methodology/Principal Findings A single unilateral injection of 6-OHDA into the rat SNc resulted in an almost complete loss of tyrosine hydroxylase (TH) immunoreactivity in the striatum and SNc, as well as in reductions of TH-positive cells and fibers in the ventral tegmental area (VTA). On the other hand, an injection of vehicle alone showed no overt change in TH immunoreactivity. A unilateral 6-OHDA lesion to SNc significantly decreased cell proliferation in the SGZ ipsilateral to the 6-OHDA lesion, but not in the contralateral SGZ or the subventricular zone (SVZ), of rats. Furthermore, subchronic (14 days) administration of fluoxetine (5 mg/kg/day), but not maprotiline significantly attenuated the reduction in cell proliferation in the SGZ by unilateral 6-OHDA lesion. Conclusions/Significance The present study suggests that cell proliferation in the SGZ of the dentate gyrus might be, in part, under dopaminergic control by SNc and VTA, and that subchronic administration of fluoxetine reversed the reduction in cell proliferation in the SGZ by 6-OHDA. Therefore, SSRIs such as fluoxetine might be potential therapeutic drugs for non-motor symptoms as well as motor symptoms in patients with PD, which might be associated with the reduction in cell proliferation in the SGZ

Gray matter vulnerabilities predict longitudinal development of apathy in Huntington's disease

Background: Apathy, a common neuropsychiatric disturbance in Huntington's disease (HD), is subserved by a complex neurobiological network. However, no study has yet employed a whole-brain approach to examine underlying regional vulnerabilities that may precipitate apathy changes over time. Objectives: To identify whole-brain gray matter volume (GMV) vulnerabilities that may predict longitudinal apathy development in HD. Methods: Forty-five HD individuals (31 female) were scanned and evaluated for apathy and other neuropsychiatric features using the short-Problem Behavior Assessment for a maximum total of six longitudinal visits (including baseline). In order to identify regions where changes in GMV may describe changes in apathy, we performed longitudinal voxel-based morphometry (VBM) on those 33 participants with a magnetic resonance imaging (MRI) scan on their second visit at 18 ± 6 months follow-up (78 MRI datasets). We next employed a generalized linear mixed-effects model (N = 45) to elucidate whether initial and specific GMV may predict apathy development over time. Results: Utilizing longitudinal VBM, we revealed a relationship between increases in apathy and specific GMV atrophy in the right middle cingulate cortex (MCC). Furthermore, vulnerability in the right MCC volume at baseline successfully predicted the severity and progression of apathy over time. Conclusions: This study highlights that individual differences in apathy in HD may be explained by variability in atrophy and initial vulnerabilities in the right MCC, a region implicated in action-initiation. These findings thus serve to facilitate the prediction of an apathetic profile, permitting targeted, time-sensitive interventions in neurodegenerative disease with potential implications in otherwise healthy populations