In patients with Parkinson's disease (PD) disturbances of mental state constitute some of the most difficult treatment challenges of advanced disease, often limiting effective treatment of motor symptoms and leading to increased disability and poor quality of life. This article provides an update on the current knowledge of these complications and the use of old and new drugs in their management. Mental state alterations in PD include depression, anxiety, cognitive impairment, apathy, and treatment-related psychiatric symptoms. The latter range from vivid dreams and hallucinations to delusions, manic symptoms, hypersexuality, dopamine dysregulation syndrome and delirium. While some of these symptoms may be alleviated by anti-parkinsonian medication, especially if they are off-period related, treatment-related phenomena are usually exacerbated by increasing the number or dosage of antiparkinsonian drugs. Elimination of exacerbating factors and simplification of drug regimes are the first and most important steps in improvement of such symptoms. However, the advent of atypical antipsychotics such as clozapine has dramatically helped the management of treatment-related psychiatric complications in PD. In patients with dementia associated with PD cognitive functioning and behavioural problems appear to respond to cholinesterase inhibitors, such as rivastigmine or donepezil. Depression is a common problem in early as well as advanced PD, and selective serotonin reuptake inhibitors, reboxetine, and tricyclic antidepressants have been reported to be effective and well tolerated antidepressants. Randomised, controlled studies are required to assess the differential efficacy and tolerability of antidepressants in patients with PD, including the newer antidepressants with serotonergic and noradrenergic properties.
"Thus, these limitations did not allow for the formation of a solid conclusion. Previous studies have described the comorbidity between depression and neurological diseases (van der Werf et al., 2001;Carson et al., 2003; Surtees et al., 2003; Lobentanz et al., 2004; Schrag 2004). Following an evaluation of 300 patients with diseases such as Parkinson's, migraine, epilepsy, and multiple sclerosis, depression was reported in 40 % of the sample (Carson et al., 2003). "
[Show abstract][Hide abstract] ABSTRACT: This study aimed to conduct a systematic literature review regarding the associations between psychiatric symptoms, functional impairments, and quality of life in patients with CMT. The PUBMED, PsycInfo, SCIELO, and LILACS electronic databases were used, and the following search terms were employed: Charcot-Marie-Tooth, hereditary motor and sensory neuropathy (HMSN), mental disorder, quality of life, psychiatry, psychiatric, and psychological without the use of time-limit filters. According to the adopted inclusion criteria, 20 studies were included and appraised. These studies indicated that patients with CMT exhibited an increased trend toward depressive symptoms compared with the general population. In addition, CMT patients were exposed to a higher risk of reduced quality of life and significant sleep impairment. Considering the comorbidity of CMT with other psychiatric disorders, the heterogeneity of the instruments used to evaluate the psychiatric symptoms compromised the ability to compare the studies examined. Our results indicate a need for a systematic evaluation of these conditions to minimise the impairments and decreased quality of life caused by CMT.
"Loss of striatal dopamine (DA) as a result of degenerating DAergic neurons in the substantia nigra pars compacta (SNpc) is one of the pathological hallmarks of Parkinson's disease (PD), causing the characteristic motor symptoms of the disorder . It has recently become apparent that patients with PD also suffer from a myriad of non-motor symptoms , which strongly contribute to a reduced quality of life . One example is visuospatial deficits , exemplified by difficulties navigating through confined spaces and interacting with objects in their environment  . "
[Show abstract][Hide abstract] ABSTRACT: Unilateral intrastriatal and intra-medial forebrain bundle injections of 6-OHDA impair the performance in a lateralised choice reaction time task. However, the extent and pattern of deficits after nigral 6-OHDA injections is less well studied, as well as the impact of training regime or the modification of various task parameters. The nigral 6-OHDA lesion resulted in impaired response accuracy and an increased time to react to and execute the response on the side contralateral to the lesion as compared to sham-lesioned controls. Pre-training of the rats on the task prior to the lesion resulted in slightly faster reaction times as well as a reduced number of preservative panel presses compared to when rats were trained after the 6-OHDA injection. When the rat had to perform a longer sustained nose poke before responding to the lateralised stimuli, the number of useable trials was reduced in both controls and 6-OHDA rats as a result of an increased number of premature withdrawals from the centre hole. This study demonstrates that rats with a nigral 6-OHDA lesion display several distinct deficits in this operant task, which are similar to those seen after striatal and bundle 6-OHDA injections. In addition, by combining pre-training with the use of a short set of holds, improved sensitivity of this task can be achieved. This improvement in sensitivity may be of advantage when exploring new therapeutic interventions for PD, where subtle but relevant changes in performance may arise.
Behavioural brain research 03/2014; 266. DOI:10.1016/j.bbr.2014.02.043 · 3.03 Impact Factor
"One type of visuospatial deficit is disruption of the conceptual representation of external space, which is often exemplified as difficulties in navigating through doorways, narrow corridors and other confined spaces (Azulay et al., 2006). These deficits, as well as the other non-motor symptoms of PD, have been shown to have a great impact on the quality of life for the individuals with PD and their careers (Schrag, 2004) and effective treatment options are currently lacking. Unilateral 6-hydroxydopamine models of PD show marked impairments in detecting and responding to stimuli on the side contralateral to the lesion (Brown and Robbins, 1989; Carli et al., 1985, 1989; Dowd and Dunnett, 2004, 2005; Milton et al., 2004). "
[Show abstract][Hide abstract] ABSTRACT: Parkinson's disease (PD) patients often suffer from visuospatial deficits, which have been considered a disruption of the representation of external space. The lateralised choice reaction time (CRT) task is an operant task for rodents in which similar deficits can be assessed. It has been demonstrated that specific parameters in this task is disrupted after unilateral injections of 6-dydroxydopamine (6-OHDA), which have been associated with the dopamine (DA) depletion that inevitably follows this type of lesion. However, studies have demonstrated that this type of lesion also affects the serotonergic (5HT) and noradrenergic (NA) system. However, the impact of these systems on parameters in the CRT task had not yet been investigated. To this end, rats were pretrained on the CRT task before receiving selective lesions of the DAergic system, either alone or in combination with depletion of the NA- or 5HT system. All rats with a 6-OHDA lesion displayed a gradual decline in the selection, initiation and execution of lateralised movements compared to sham-lesion controls on the side contralateral to the lesion. They also displayed a reduced number of useable trials as well as an increased number of procedural errors. Interestingly, the group with an additional noradrenergic lesion was significantly slower in reacting to lateralised stimuli throughout the testing period compared to the other two groups with a 6-OHDA lesion. There was however no difference between the three different lesion groups in the other parameters assessed in the task. These data confirm previous findings demonstrating that that majority of the parameters assessed in the lateralised CRT task are strongly dependent on DA. However, this study has also shown that the NAergic system may play an important role in contributing to the attentive performance influencing the capacity to react to the presented lateralised stimuli.
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