Apathy in drug-naïve patients with Parkinson's disease

ObjectiveThe aim of this study is to explore the prevalence and clinical correlates of apathy in early-stage Parkinson's disease (PD) from a cohort of Chinese patients.MethodsA cross-sectional analysis of 133 treatment-naive PD patients was conducted. Each subject was categorized as PD with or without apathy using the Lille Apathy Rating Scale (LARS).ResultsOf 133 patients, 30 PD patients (22.56%) reported apathy, of whom 23 (17.29%) did not have concomitant depression. The stepwise binary logistic regression model indicated that the lower Frontal assessment battery (FAB) score (OR = 0.623, 95% CI = 0.466–0.834, P = 0.001), the higher sleep/fatigue score from the Non-Motor Symptoms Scale (NMSS) (OR = 1.171, 95% CI = 1.071–1.279, P = 0.001), the higher Hamilton Depression Rating Scale including 24 items (HAMD-24) score (OR = 1.112, 95% CI = 1.005–1.230, P = 0.039) and the higher Unified Parkinson's Disease Rating Scale (UPDRS) part III score (OR = 1.119, 95% CI = 1.045–1.198, P = 0.001) were associated with apathy. No significant associations were found between apathy and other parameters such as age, sex distribution, disease duration, anxiety, Fatigue Severity Scale (FSS) score, Montreal Cognitive Assessment (MOCA) score and remaining domain scores for NMSS.ConclusionsApathy is not rare (22.56%) in Chinese treatment-naïve PD patients. Apathy in PD is not only related to the severity of motor symptoms of the disease but also to some non-motor symptoms, such as executive dysfunction, depression and sleep disturbances.     

Baseline predictors of worsening apathy in Parkinson's disease: A prospective longitudinal study

IntroductionApathy is one of the most common behavioural disorders in Parkinson's disease (PD) and contributes significantly to a reduced quality of life in PD patients.MethodsWe conducted a prospective longitudinal study of 89 mild PD patients over 18 months, measuring apathy symptoms at 6-monthly intervals using the Starkstein Apathy Scale, as well as measures of motor and non-motor symptoms, cognitive function, and functional disability at baseline. Mixed-effects models were used to characterise the individual trajectories of apathy symptom severity, and linear regression with stepwise elimination procedure was used to select significant baseline predictors.ResultsClinically significant levels of apathy were present in 42.7% of our sample at baseline, with symptom severity remaining relatively stable on average over the course of 18 months. Male gender, lower educational attainment, higher depression symptom severity, more severe functional disability, and the presence of dyskinesias at study entry predicted increasing apathy over the subsequent 18 months.ConclusionsPatients with these factors are at risk for progression of apathy, which may be prevented by treating depression and functional disability. Further studies are needed to address both the specific neurobiological pathways and psychosocial factors underpinning apathy in PD.     

The relation of testosterone levels with fatigue and apathy in Parkinson's disease

Objective

Fatigue and apathy are frequent in patients with Parkinson's disease (PD). Testosterone deficiency in male patients may contribute in development of fatigue and apathy as well. We investigated whether a possible relation exists between serum testosterone levels, fatigue and apathy in male PD patients.

Materials and methods

We included 29 non-demented and non-depressed PD patients and 30 age- and sex-matched healthy subjects. Fatigue Severity Scale (FSS) and Apathy Evaluation Scale (AES-C) were used for the evaluations. In PD patients and healthy subjects, a relationship between FSS, AES-C scores and plasma testosterone levels were assessed. In addition, a correlation between FSS, AES-C and Unified Parkinson's Disease Rating Scale was investigated in PD group.

Results

The mean scores of FSS and AES-C were significantly higher in PD patients than those of the control group. The Unified Parkinson's Disease Rating Scale (UPDRS) scores were significantly correlated with FSS and AES-C scores. Mean free testosterone level was significantly lower in PD patients than controls (p = 0.008). f-Testosterone levels of PD patients were not correlated with FSS or AES-C scores.

Conclusion

Apathy and fatigue are frequent in PD and show significant correlation with the severity of the disease. f-Testosterone levels are not related with apathy or fatigue in male PD patients and the role of testosterone in the pathophysiology of these non-motor symptoms is still controversial.     

Reduction of white matter integrity correlates with apathy in Parkinson's disease

Background: Apathy is a common non-motor symptom in Parkinson's disease (PD), but little is known about apathy and white matter (WM) change. In this study, we investigated whether fractional anisotropy (FA) of the WM can distinguish apathetic patients from non-apathetic PD patients, and whether the FA value correlates with the severity of apathy in PD.

Methods: Thirty-nine PD patients participated in our study, of which 18 participants were with apathy symptom, and 21 without apathy symptom. Diffusion tensor imaging was performed on all the subjects.

Results: Compared to non-apathetic PD patients, the apathetic group had reduced FA values in the genu and body of corpus callosum, bilateral anterior corona radiata, left superior corona radiata and left cingulum. Furthermore, in these WM regions, the FA values were negatively correlated with the Lille Apathy Rating Scale scores in apathetic subjects.

Conclusion: The WM change is associated with apathy in PD patients. In addition, the FA values of specific regions of WM could be a promising marker to predict the severity of apathy.     

Subjective perceived outcome of subthalamic deep brain stimulation in Parkinson's disease one year after surgery

ObjectivesDissatisfaction with subthalamic deep brain stimulation (STN-DBS) despite motor improvements has been observed in Parkinson's disease (PD). Hence, we compared patient's subjective perceived outcome 12 months after surgery (12mFU) with clinical measures to identify risk factors of dissatisfaction.MethodsPatients were examined at baseline and 12mFU. Quality of life (QoL), neuropsychiatric, cognitive and neurological functioning was measured. Patients were classified concerning their subjective outcome (negative = dissatisfaction; mixed; positive = satisfaction) at 12mFU using semi-structured interviews. First, the three groups were compared concerning interview statements. Second, repeated measures ANOVAs with group as between-subjects factor were applied to find significant effects of time, group, or interaction. Third, binary logistic regression determined predictors of dissatisfaction.ResultsOf the 28 enrolled patients, 25% perceived their outcome as negative, 32.1% as mixed, and 42.9% as positive. Concerning interview statements, dissatisfied patients mentioned significantly less often improved QoL and reduced medication, and reported worsening of mental state, and social interaction. For the whole sample, significant improvement over time was found for motor functioning, daily dopamine dosages, and QoL. Apathy significantly worsened over time, but dissatisfied patients were overall more apathetic and depressed than the other groups. Significant interaction of group and time was identified for QoL, which only improved in the mixed and satisfied group. Finally, preoperative apathy and axial symptoms predicted dissatisfaction with STN-DBS.ConclusionsAlthough motor symptoms and QoL improved in the whole sample, 25% of patients showed disappointment with STN-DBS. Especially apathy predicts dissatisfaction and should be considered preoperatively.     

The prevalence and clinical correlates of apathy and irritability in Alzheimer's disease

We examined the prevalence and correlates of apathy and irritability in a consecutive series of 101 patients with probable Alzheimer's disease (AD). Based on clinical criteria, 46 (46%) patients had apathy, and 13 (13%) patients had irritability. Apathy was significantly associated with more severe impairments in activities of daily living, significantly more severe extrapyramidal signs, and a significantly higher frequency of both major depression and dysthymia. Patients with irritability had significantly more severe impairments in activities of daily living and significantly higher depression and anosognosia scores. On the other hand, neither apathy nor irritability were significantly associated with deficits in specific cognitive domains.     

Cross‐sectional and longitudinal studies of three‐dimensional stereotactic surface projection SPECT analysis in Parkinson's disease

Although dementia is increasingly recognized as a common feature in Parkinson's disease (PD), its pathological substrate remains unknown. We conducted cross‐sectional and longitudinal brain perfusion SPECT analyses to explore changes during the course of developing dementia in PD. Fifty‐five patients originally diagnosed with PD were imaged in the cross‐sectional study. Twenty‐one of these, nine without dementia and 12 with dementia (PDD), were included in the longitudinal study to observe perfusion changes during the course of their disease. Data were analyzed using three‐dimensional stereotactic surface projection SPECT analysis. The UK Parkinson's Disease Society Brain Bank criteria were used to diagnose PD and the revised criteria for the clinical diagnosis of dementia with Lewy bodies for PDD. The cross‐sectional study showed that patients with PDD had significantly reduced perfusion in the right posterior cingulate, the right precuneus and the left posterior cingulate area. In the longitudinal study, significantly reduced perfusion was observed in the left anterior frontal gyrus in PD without dementia, and in the right inferior parietal lobule in those that developed PDD. We suggest that a relationship exists between developing dementia in PDD and reduced perfusion in the posterior parietal area. © 2009 Movement Disorder Society     

A review of studies describing the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia

OBJECTIVE: To review the literature relating to the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia (PDD). METHOD: MEDLINE (1966--December 2004), PsychINFO (1972--December 2004), EMBASE (1980--December 2004), CINHAL (1982--December 2004), and the Cochrane Collaboration were searched in December 2004. RESULTS: Three controlled trials and seven open studies were identified. Efficacy was assessed in three key domains: cognitive, neuropsychiatric and parkinsonian symptoms. CONCLUSION: Cholinesterase inhibitors have a moderate effect against cognitive symptoms. There is no clear evidence of a noticeable clinical effect against neuropsychiatric symptoms. Tolerability including exacerbation of motor symptoms--in particular tremor--may limit the utility of cholinesterase inhibitors.     

Impairments of speed and amplitude of movement in Parkinson's disease: A pilot study

Bradykinesia, characterized by slowness and decreased amplitude of movement, is often considered the most important deficit in Parkinson's disease (PD). The current clinical rating of bradykinesia in PD, based on the motor subscale of the Unified Parkinson's disease Rating Scale (UPDRS‐III), does not individually weigh the impairments in speed and amplitude of rapid alternating movements. We sought to categorize movement in PD to determine whether speed and amplitude have different relationships to current measures of motor impairment and disability. Categories of speed and amplitude (normal, slow/low, and very‐slow/very‐low) were ascertained using an electromagnetic tracking device. Amplitude was disproportionally more affected than speed in the “off” state. UPDRS‐III and the Schwab & England disability scale were worst in patients with very impaired amplitude and best in patients with normal amplitude. A similarly graded relationship was not found for categories of speed impairment. The examiner clinical global impression of change mirrored “off” state amplitude but not speed categories. Levodopa, however, normalized speed to a greater extent than amplitude. Our observations suggest that amplitude and speed impairments may be associated with different functional aspects in PD and deserve separate clinical assessment. © 2009 Movement Disorder Society     

Applause sign in advanced Parkinson's disease

BackgroundThe ‘applause sign’ a tendency to continue applauding in response to instructions to clap three times was described in 1995 and was considered specific to degenerative disease, especially to atypical parkinsonian disorders. In early phase Parkinson's disease (PD) the sign has been reported positive as well. In late stage PD it is unknown whether and to what extent the sign may be elicited and it remains unknown if and to what degree the sign correlates to cognitive impairment and PD related dementia.MethodsNursing home residents with PD (MMSE >17) were included. All patients underwent the clapping test and were tested for cognitive disturbance by making use of accepted clinimetrics (MMSE and Scopa-cog). T-testing was performed with the hypothesis that patients expressing the applause sign would score lower on the MMSE or Scopa-cog.ResultsSeventy three nursing home residents (mainly Hoehn and Yahr 4/5) with a mean disease duration of 10 years and a mean age of 78.7 years were included. The applause sign was found positive in 15 of 73 residents (20.5%). Residents expressing the applause sign had significantly lower mean scores on the MMSE (25.1 vs 22.9 points, p < 0.006) and Scopa-cog (14.8 vs 12.0 points, p < 0.039).ConclusionsThe applause sign is present in late stage PD and correlates with a higher degree of cognitive impairment as established with accepted clinimetric tests. A higher degree of frontal lobe involvement explains the presence of the applause sign.     

The current and projected economic burden of Parkinson's disease in the United States

Parkinson's disease (PD), following Alzheimer's disease, is the second‐most common neurodegenerative disorder in the United States. A lack of treatment options for changing the trajectory of disease progression, in combination with an increasing elderly population, portends a rising economic burden on patients and payers. This study combined information from nationally representative surveys to create a burden of PD model. The model estimates disease prevalence, excess healthcare use and medical costs, and nonmedical costs for each demographic group defined by age and sex. Estimated prevalence rates and costs were applied to the U.S. Census Bureau's 2010 to 2050 population data to estimate current and projected burden based on changing demographics. We estimate that approximately 630,000 people in the United States had diagnosed PD in 2010, with diagnosed prevalence likely to double by 2040. The national economic burden of PD exceeds $14.4 billion in 2010 (approximately $22,800 per patient). The population with PD incurred medical expenses of approximately $14 billion in 2010, $8.1 billion higher ($12,800 per capita) than expected for a similar population without PD. Indirect costs (e.g., reduced employment) are conservatively estimated at $6.3 billion (or close to $10,000 per person with PD). The burden of chronic conditions such as PD is projected to grow substantially over the next few decades as the size of the elderly population grows. Such projections give impetus to the need for innovative new treatments to prevent, delay onset, or alleviate symptoms of PD and other similar diseases. 2013 Movement Disorder Society     

Gender and onset age-related features of non-motor symptoms of patients with Parkinson's disease – A study from Southwest China

BackgroundNon-motor symptom (NMS) differences between male Parkinson's disease (PD) and female PD, and between early-onset PD (EOPD) and late-onset PD (LOPD) in Chinese populations remain largely unknown.MethodsA total of 522 PD patients from Southwest China were included. Patients were assessed using the Non-Motor Symptom Scale (NMSS) and Unified PD Rating Scale (UPDRS).ResultsMore NMS and significantly higher NMSS score were found in LOPD patients than in EOPD patients (9.3 ± 5.9 vs. 7.7 ± 5.6, P = 0.005; 37.4 ± 32.2 vs. 30.5 ± 28.9, P = 0.018), while no such differences were found between male and female patients. The NMS of gastrointestinal and urinary domains were more common in LOPD patients than in EOPD patients, whereas sexual dysfunction was more common in EOPD than in LOPD. The sleep/fatigue domain, the mood/apathy domain and “pain” symptoms were more prevalent and severe in female patients than in male patients while urinary symptoms were more common and severe in male patients. Significant positive correlations were observed between disease duration, Hoehn & Yahr stage, UPDRS Ⅲ, and NMSS score in the total sample, subgroups of both male and female patients as well as both EOPD and LOPD patients.ConclusionsNMS are common in the Chinese PD population. LOPD patients are likely to present with more and severe NMS than EOPD patients. Males are subjected to urinary symptoms and females are subjected to mood/apathy, sleep and pain symptoms.     

Alexithymia in Parkinson's disease: A systematic review of the literature

IntroductionIn this systematic review, we aimed to evaluate the role of alexithymia in Parkinson's disease (PD) and its relationship to neurological, neuropsychiatric, cognitive, and neuroimaging correlates.MethodsThe database was selected using PubMed Services, Cochrane, PsycNET and Scopus and a number of key words. Further studies were sought by manually searching for secondary sources, including relevant journals and references in primary articles. The search was restricted to articles written in English between January 1980 and August 2015.ResultsTen studies reported that alexithymia prevalence was about double in PD patients compared to control subjects and that specific dimensions of alexithymia might be related to depression, anxiety, apathy and impulsivity. Some studies investigated the relationship between alexithymia and neuropsychological symptoms and found correlations with frontal and parietal lobe functions. Two studies on neurological features reported a link between alexithymia and disease stage or a specific motor subtype of PD; the remaining studies found that alexithymia was independent from neurological symptoms, dopaminergic therapy and laterality of motor symptom onset.Data on neuroimaging correlates and therapeutic intervention on alexithymia in PD patients are still lacking.ConclusionAlthough results suggest that alexithymia is a primary characteristics of PD, further studies with larger patient samples are needed to definitively clarify the impact of alexithymia on the clinical features of PD patients.