Facial emotion decoding in patients with Parkinson's disease

Purpose. In line with the growing attention on non-motor symptoms and disturbance of affective and emotional processing in Parkinson’s disease, we aimed to study the different aspects of facial emotion expression evaluation in a group of Parkinson’s disease without cognitive decline in treatment with common antiparkinsonian drugs, matched for sex, age and education with healthy subjects.

Materials and methods. The study was conducted on 30 patients (13 male; mean age: 63.3 ± 6.7; mean age of disease onset: 56.5 ± 7.1; mean duration of the disease: 6.7 ± 2.6) with a diagnosis of Parkinson’s disease and receiving dopaminergic therapy, as compared with 30 healthy controls. Different tasks of facial expression evaluation were used. All patients were assessed for neuropsychological and psychological profiles during optimized medication-on condition.

Results. The total number of errors in facial emotion recognition task is higher (p < 0.001) in patients than controls and it is due to errors in identifying sadness (p < 0.001), anger (p = 0.01) and fear (p < 0.001). No differences in the total amount of activation, valence and intensity ratings were found. The difference between patients and controls in emotion recognition appears to be independent by the severity of depressive symptoms.

Conclusions. The present study provides further evidence of altered non-verbal emotional information processing in Parkinson’s disease patients, suggesting that nigrostriatal dopaminergic depletion leads also to emotional information processing dysfunction. The consequences of these emotional encoding disturbances in daily living and their relationship to mood and behavioural disorders remain to be clarified.     

Facial expression recognition in people with medicated and unmedicated Parkinson's disease

Recognition of facial expressions of emotion was investigated in people with medicated and unmedicated Parkinson's disease (PD) and matched controls (unmedicated PD, n=16; medicated PD, n=20; controls, n=40). Participants in the medicated group showed some visual impairment (impaired contrast sensitivity) and performed less well on perception of unfamiliar face identity, but did not show significant deficits in the perception of sex, gaze direction, or familiar identity from the face. For both Parkinson's disease groups, there was evidence of impaired recognition of facial expressions in comparison to controls. These deficits were more consistently noted in the unmedicated group, who were also found to perform worse than the medicated group at recognising disgust from prototypical facial expressions, and at recognising anger and disgust in computer-manipulated images. Although both Parkinson's disease groups showed impairments of facial expression recognition, the consistently worse recognition of disgust in the unmedicated group is consistent with the hypothesis from previous studies that brain regions modulated by dopaminergic neurons are involved in the recognition of disgust.     

Deficits in decoding emotional facial expressions in Parkinson's disease

INTRODUCTION: The basal ganglia have numerous connections not only with the motor cortex but also with the prefrontal and limbic cortical areas. Therefore, basal ganglia lesions can disturb motor function but also cognitive function and emotion processing. The aim of the present study was to assess the consequences of Parkinson's disease (PD) on ability to decode emotional facial expressions (EFEs)-a method commonly used to investigate non-verbal emotion processing. METHODS: Eighteen PD patients participated in the study, together with 18 healthy subjects strictly matched with respect to age, education and sex. The patients were early in the course of the disease and had not yet received any antiparkinsonian treatment. Decoding of EFEs was assessed using a standardized, quantitative task where the expressions were of moderate intensity, i.e. quite similar to those experienced in everyday life. A set of tests also assessed executive function. Visuospatial perception, depression and anxiety were measured. RESULTS: Early in the course of the disease, untreated PD patients were significantly impaired in decoding EFEs, as well as in executive function. The deficits were significantly interrelated, although neither was significantly related to severity of the motor symptoms. Visuospatial perception was not impaired, and the patients' impairment was related neither to their depression nor to their anxiety score. The PD patients' impairment in decoding EFEs was related to a systematic response bias. CONCLUSION: Early in the course of PD, non-verbal emotional information processing is disturbed. This suggests that in PD, nigrostriatal dopaminergic depletion leads not only to motor and cognitive disturbances but also to emotional information processing deficits. The observed correlation pattern does not enable adoption of a clear-cut position in the debate over totally or partially segregated functional organization of the basal ganglia circuits.     

Distractibility in early Parkinson's disease

Post-mortem evidence has shown a depletion of dopamine in the mesocortical and mesolimbic pathways in brains of Parkinson patients. Since these dopaminergic pathways have been implicated in the control of attention in animals, selective attention to visual stimuli was studied in eight patients with early Parkinson's disease (Stage I or II as defined by the Hoehn and Yahr Scale) and eight normal controls of comparable age, sex and Full Scale Intelligence Quotient. Subjects with dementia, psychiatric disease and other neurological abnormalities were excluded. The Parkinson patients were more prone to interference in the presence of distractor items than the normal controls as shown on the focussing + distraction and switching + distraction of attention paradigms on the Distractor task. There findings are not accounted for by mood, intellectual status or memory and thus may be as a result of the loss of dopamine in the mesocortico-limbic projections.     

Tremors in early Parkinson's disease

We examined 50 untreated parkinsonian patients with a complaint of tremor for the presence of a resting, postural, or kinetic tremor. Tremors were recorded by an accelerometer to determine amplitude and frequency. A postural tremor was present in 92% and a resting tremor in 76%. The amplitude of postural tremor was greater than resting tremor in 50%, the same in 25%, and less in 25%. The average tremor frequency of resting and postural tremor was not significantly different. Carbidopa/levodopa reduced testing tremor in 58% and postural tremor in 46% of patients. The dopamine agonist naxoglide (PHNO) reduced resting tremor in 77% and postural tremor in 70% of patients. Postural tremor was not worsened by either drug. It is concluded that tremors in both the resting and postural positions are an integral part of the symptoms of Parkinson's disease and that both tremors have a similar frequency and pharmacological responsiveness in the early phases of the disease.     

Skin conditions in early Parkinson's disease

ObjectiveSkin conditions have been associated with increased risk of Parkinson's disease (PD). Little is known about clinical and biomarker differences according to presence of skin conditions among PD patients. Studying these differences might provide insight into PD pathogenesis.MethodsWe examined the association between common skin conditions and risk of PD in a case-control study of 423 early drug-naïve PD cases and 196 healthy controls (HC) in the Parkinson's Progression Markers Initiative (PPMI). Among PD participants, we examined if skin conditions were associated with clinical and PD-relevant biomarkers.ResultsSkin conditions occurred more frequently among PD participants (41%) relative to HC (32%). In multivariate analyses, we observed an association between any skin condition and PD (OR = 1.49, 95% CI = 1.03–2.16) and basal cell carcinoma and PD (OR = 2.05, 95% CI = 1.02–4.08). PD participants who reported skin conditions were older (OR = 1.68, 95% CI = 1.21–2.35) more educated (OR = 1.70, 95% CI = 0.99–2.91), had higher Semantic Fluency Test (SFT) scores (OR = 1.45, 95% CI = 1.07–1.96) and Hopkins Verbal Learning Test (HVLT) retention scores (OR = 1.55, 95% CI = 1.09–2.22) compared to PD patients without skin conditions. None of the associations remained significant after Bonferroni correction for multiple comparisons.ConclusionsWe observed a positive association between any skin condition as well as basal cell carcinoma and PD. PD participants with skin conditions were older, more educated, had higher SFT and HVLT retention scores compared to those without skin conditions. However, all associations were no longer significant after Bonferroni multiple comparisons correction. Observed associations should be confirmed in larger, longitudinal studies.     

Cognitive decline in early Parkinson's disease

Data on the prevalence and severity of cognitive impairment among patients with newly diagnosed idiopathic Parkinson's disease (PD) is limited. Using a prospectively collected clinical database, we studied the longitudinal trend of mini‐mental state examination (MMSE) change and baseline factors predictive for MMSE decline. One hundred six patients with mean age of 61.2 years and mean baseline MMSE of 27.8 ± 2.3 were studied. MMSE increased by 0.4 points/year among patients without cognitive decline (n = 73) and decreased by 2.39 points/year among patients with cognitive decline (n = 33). Univariate analysis demonstrated education, age of diagnosis, depression, and diabetes mellitus to be associated with cognitive decline. Motor scores and hallucination were not associated with cognitive decline. Multivariate analysis demonstrated higher level of education to be protective (HR = 0.91, 95% CI 0.82–0.99, P = 0.047) and depression having borderline significance in predicting cognitive decline (HR = 2.00, 95% CI 0.97–4.15, P = 0.061). We found that 31% of newly diagnosed idiopathic PD patients have measurable cognitive decline at an early stage of disease. Higher education is protective while depression may be predictive of cognitive decline. © 2009 Movement Disorder Society     

Levodopa response in early Parkinson's disease

To further characterize the short‐term levodopa response in early PD, we performed a retrospective analysis of the ELLDOPA study which randomized 361 early PD subjects to placebo, levodopa 150, 300, or 600 mg/day. We evaluated change in UPDRS motor scores (UPDRSm) from baseline to weeks 9 and 24, and identified changes in UPDRSm that best discriminated treatment with levodopa from placebo. Linear regressions were used to determine associations between baseline characteristics and changes in UPDRSm. Mean percent improvement in UPDRSm in levodopa‐treated subjects was greater than that for placebo‐treated subjects (27.4% vs. 5.8% at 9 weeks, P < 0.001 and 26.2% vs. 4.0% at 24 weeks, P < 0.001). UPDRSm change at 9 weeks ranged from –92.9% (improvement) to 85.7% (worsening) for levodopa and –86.7% to 160% for placebo, and at 24 weeks ranged from –100.0% to 242.9% for levodopa and –87.5% to 112.5% for placebo. UPDRSm improvements of 22.0% at 9 weeks and 23.8% at 24 weeks best discriminated treatment with levodopa 300 mg/day (a common initial maintenance dosage in clinical practice) from placebo. Significant associations were not observed between baseline subject characteristics and magnitude of response from baseline to week 24. We conclude that although levodopa treatment significantly improved PD signs when compared with placebo, there was a wide range and considerable overlap in clinical responses to levodopa and placebo. A substantial proportion of subjects with early PD did not experience a robust response to levodopa. An improvement in UPDRSm of ～22% best discriminated levodopa treatment from placebo. © 2009 Movement Disorder Society     

Treatment of early Parkinson's disease

Levodopa is still the most effective therapeutic agent for the treatment of Parkinson's disease (PD). Initially, levodopa provides a stable therapeutic response but, during long-term treatment its beneficial effect declines and a gradually increasing number of patients experience fluctuations in motor response. Therefore, in the management of PD it is important to minimise the risks for the development of motor fluctuations. In this context, recent double-blind long-term studies have confirmed the earlier results, suggesting that it appears advisable to initiate dopaminergic treatment in early PD by initially using a dopamine agonist and by adding levodopa when the benefit is no longer adequate with dopamine agonist alone. Another alternative would be to start with selegiline alone, then depending on the disability of the patient, add a dopamine agonist and finally levodopa.     

Combined bromocriptine-levodopa therapy early in Parkinson's disease

Compared with levodopa, treatment of parkinsonism for 3 years with bromocriptine alone resulted in less fluctuation and peak-dose dyskinesia, but also less improvement in parkinsonian disability. Only a few of the 76 patients had long-term benefit on chronic bromocriptine therapy. However, combined bromocriptine and levodopa therapy had a therapeutic response equal to that of levodopa alone, with fewer fluctuations and peak-dose dyskinesias. Treatment should begin with a low dose of levodopa and a dopamine agonist.     

Parkin analysis in early onset Parkinson's disease

We analysed the parkin gene in a large consecutive series (146) of unrelated early onset Parkinson's disease (onset ⩽40 years of age) patients. Twelve cases (8.2%) had homozygous or compound heterozygous point mutations and/or exon rearrangements, while a single mutation was found in four subjects (2.7%). We identified eight exon rearrangements and nine point mutations, two of which were novel: c.735delT (p.C212/X224) and c.815C>G (p.C238W). Genotype–phenotype correlation revealed that parkin carriers had features similar to those of non-carrier early onset Parkinson disease patients.     

Motor subtype changes in early Parkinson's disease

IntroductionDistinct motor subtypes of Parkinson's disease (PD) have been described through both clinical observation and through data-driven approaches. However, the extent to which motor subtypes change during disease progression remains unknown. Our objective was to determine motor subtypes of PD using an unsupervised clustering methodology and evaluate subtype changes with disease duration.MethodsThe Parkinson's Progression Markers Initiative database of 423 newly diagnosed PD patients was utilized to retrospectively identify unique motor subtypes through a data-driven, hierarchical correlational clustering approach. For each patient, we assigned a subtype to each motor assessment at each follow-up visit (time points) and by using published criteria. We examined changes in PD subtype with disease duration using both qualitative and quantitative methods.ResultsFive distinct motor subtypes were identified based on the motor assessment items and these included: Tremor Dominant (TD), Axial Dominant, Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait Disorder Dominant. About half of the patients had consistent subtypes at all time points. Most patients met criteria for TD subtype soon after diagnosis. For patients with inconsistent subtypes, there was an overall trend to shift away from a TD phenotype with disease duration, as shown by chi-squared test, p < 0.001, and linear regression analysis, p < 0.05.ConclusionThese results strongly suggest that classification of motor subtypes in PD can shift with increasing disease duration. Shifting subtypes is a factor that should be accounted for in clinical practice or in clinical trials.     

Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson's disease

BACKGROUND: Bilateral subthalamic nucleus (STN) stimulation is recognised as a treatment for parkinsonian patients with severe levodopa related motor complications. Although adverse effects are infrequent, some behavioural disturbances have been reported. OBJECTIVE: To investigate the consequences of STN stimulation on emotional information processing in Parkinson's disease by assessing the performance of an emotional facial expression (EFE) decoding task in a group of patients before and after surgery. METHODS: 12 non-demented patients with Parkinson's disease were studied. They were assessed one month before surgery and three months after. Their ability to decode EFEs was assessed using a standardised quantitative task. Overall cognitive function, executive function, visuospatial perception, depression, and anxiety were also measured. Twelve healthy controls were matched for age, sex, and duration of education. RESULTS: Before surgery, the patients showed no impairment in EFE decoding compared with the controls. Their overall cognitive status was preserved but they had a moderate dysexecutive syndrome. Three months after surgery, they had significant impairment of EFE decoding. This was not related to their overall cognitive status or to depression/anxiety scores. Visuospatial perception was not impaired. There was no change in the extent of the dysexecutive syndrome except for a reduction in phonemic word fluency. CONCLUSIONS: Bilateral STN stimulation disturbs negative emotional information processing in Parkinson's disease. The impairment appears specific and unrelated to certain secondary variables. This behavioural complication of STN may have implications for the patient's social life.     

Diagnostic aspects of early Parkinson's disease

Insidious onset of mild, unspecific, sensitive, vegetative, psychopathological, cognitive and perceptive disturbances, i. e., visual and olfactory dysfunction, with a resulting change of personal behavior, i. e., reduced stress tolerance, precede the initially intermittently occurring motor symptoms in patients with Parkinson's disease (PD). Novel neuropathological findings suggest an expansion pattern of the neurodegenerative process beyond the nigral dopaminergic neurons with the initial event located outside the brain. This underlines the clinical concept of an initial premotor phase, which starts in nondopaminergic areas in PD. Moreover a more global general understanding of chronic neurodegeneration enables the performance of clinical trials on neuroprotection, since there is increasing evidence that diagnosis of PD at the threshold of onset of motor symptoms or cognitive symptoms in Alzheimer's disease is too late. Such an earlier diagnosis of chronic neurodegeneration will allow a more convincing demonstration of the efficacy of a neuroprotective or disease modifying compound. It will also support the concept of a clinically effective pharmacological intervention on a disease process, which is also more and more demanded by the health authorities for drug approval.     

帕金森病早期诊断的生物学标志物

帕金森病是一种慢性进行性中枢神经系统退行性疾病.早在临床前期尚未出现典型临床症状时,帕金森病患者即已出现神经系统退行性病变.因此,如果能在退行性病变早期及时明确诊断并予以治疗,将会减缓疾病进程,提高患者生活质量.虽然目前尚未发现早期诊断帕金森病的理想标志物,但是已有许多生物学标志物具有研究和应用前景.     

Levodopa in the early treatment of Parkinson's disease

L-dopa has many advantages as initial therapy for Parkinson's disease (PD). It is safer, more efficacious, associated with fewer adverse effects, few interactions, easier for patients to use and for clinicians to prescribe, and cheaper than dopamine (DA) agonists. Although L-dopa is more likely than DA agonists to introduce motor fluctuations and dyskinesia, L-dopa is also more effective in improving motor function. Furthermore, there is no long-term benefit from delaying L-dopa based on the risk of motor complications or psychiatric symptoms. Many investigations have shown that L-dopa does not accelerate disease progression. Now is the time to re-evaluate L-dopa for initial treatment of PD.