Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons. Exercise has been reported to slow the clinical progression of PD. We evaluated the dopaminergic system of patients with mild and early PD before and after a six-month program of intense exercise. Using 18F-FE-PE2I PET imaging, we measured dopamine transporter (DAT) availability in the striatum and substantia nigra. Using NM-MRI, we evaluated the neuromelanin content in the substantia nigra. Exercise reversed the expected decrease in DAT availability into a significant increase in both the substantia nigra and putamen. Exercise also reversed the expected decrease in neuromelanin concentration in the substantia nigra into a significant increase. These findings suggest improved functionality in the remaining dopaminergic neurons after exercise. Further research is needed to validate our findings and to pinpoint the source of any true neuromodulatory and neuroprotective effects of exercise in PD in large clinical trials.

Synaptic loss and its association with symptom severity in Parkinson's disease.

Parkinson's disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [11C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain. We also examined a measure of relative brain perfusion from the early part of the same PET scan. Our results provide evidence for synaptic density loss in the substantia nigra that had been previously reported, but also extend this to other early-Braak stage regions known to be affected in PD (brainstem, caudate, olfactory cortex). Importantly, we also found a direct association between synaptic density loss in the nigra and severity of symptoms in patients. A greater extent and wider distribution of synaptic density loss in PD patients with longer illness duration suggests that [11C]UCB-J PET can be used to measure synapse loss with disease progression. We also demonstrate lower brain perfusion in PD vs. HC groups, with a greater extent of abnormalities in those with longer duration of illness, suggesting that [11C]UCB-J PET can simultaneously provide information on changes in brain perfusion. These results implicate synaptic imaging as a useful PD biomarker for future disease-modifying interventions.

Objective response to ethanol in essential tremor: results from a standardized ethanol challenge study.

BACKGROUND AND OBJECTIVES: Ethanol has been reported to improve tremor severity in approximately two thirds of patients with essential tremor (ET), but the accuracy of that proportion is not certain and the mechanism of action is unknown. The goal of this study was to investigate alcohol response on tremor by applying an a priori objective response definition and subsequently to describe the responder rate to a standardized ethanol dose in a cohort of 85 ET patients. A secondary analysis evaluated other tremor and nontremor features, including demographics, tremor intensity, breath alcohol concentration, nontremor effects of alcohol, self-reported responder status to ethanol, and prior ethanol exposure. METHODS: This was a prospective, open-label, single-dose challenge of oral ethanol during which motor and nonmotor measurements were obtained starting immediately prior to ethanol administration and subsequently every 20 min for 120 min. We defined tremor reduction as a 35% decline in power in the patient's tremor frequency recorded during spiral drawing 60 min after ethanol administration. RESULTS: In total, 80% of patients were considered alcohol responsive using our objective definition. Responder status and change in the objective tremor metrics were significantly correlated with the change in breath alcohol concentration levels after ethanol administration, but no other relationships to nontremor metrics were found. DISCUSSION: A high percentage of patients actually respond to acute ethanol. However, their self-reported response does not correlate well with their objective response. Objective response correlates with breath alcohol level but not with sedation, indicating a specific effect of ethanol on tremor.

Magnetic resonance imaging modalities aid in the differential diagnosis of atypical parkinsonian syndromes.

Accurate and timely diagnosis of atypical parkinsonian syndromes (APS) remains a challenge. Especially early in the disease course, the clinical manifestations of the APS overlap with each other and with those of idiopathic Parkinson's disease (PD). Recent advances in magnetic resonance imaging (MRI) technology have introduced promising imaging modalities to aid in the diagnosis of APS. Some of these MRI modalities are also included in the updated diagnostic criteria of APS. Importantly, MRI is safe for repeated use and more affordable and accessible compared to nuclear imaging. These advantages make MRI tools more appealing for diagnostic purposes. As the MRI field continues to advance, the diagnostic use of these techniques in APS, alone or in combination, are expected to become commonplace in clinical practice.

Stroke in Parkinson's disease: a review of epidemiological studies and potential pathophysiological mechanisms.

Parkinson's disease (PD) is the fastest growing neurological disorder and one of the leading neurological causes of disability worldwide following stroke. An overall aging global population, as well as general changes in lifestyle associated with mass industrialization in the last century, may be linked to both increased incidence rates of PD and an increase in cumulative cardiovascular risk. Recent epidemiological studies show an increased risk of stroke, post-stroke complications, and subclinical ischemic insults in PD. PD patients have a host of characteristics that might contribute to increasing the risk of developing ischemic stroke including motor impairment, dysautonomia, and sleep disorders. This increases the urgency to study the interplay between PD and other neurological disorders, and their combined effect on mortality, morbidity, and quality of life. In this review, we provide a comprehensive overview of the studied etiological factors and pathological processes involved in PD, specifically with regard to their relationship to stroke. We hope that this review offers an insight into the relationship between PD and ischemic stroke and motivates further studies in this regard.

Mental imagery content is associated with disease severity and specific brain functional connectivity changes in patients with Parkinson's disease.

Mental imagery is the mental re-creation of perceptual experiences, events and scenarios, and motor acts. In our previous study, we assessed whether motor imagery (MI) training combined with functional magnetic resonance imaging-based neurofeedback could improve the motor function of nondemented subjects with mild Parkinson's disease (PD) (N = 22). We used visual imagery (VI) (e.g., of scenes or events, but not of self-movements) training without neurofeedback for the control group (N = 22). Notably, both groups showed significant and comparable improvement in motor function after four weeks of daily imagery practice. In this study, we further examined the neural correlates of the motor enhancement as a result of the VI training by analyzing the self-reported VI content during daily practice and relating its quality to the functional connectivity characteristics of the same subjects. We demonstrated that the VI practice encompassed multisensory, spatial, affective, and executive processes all of which are also important for motor function in real life. Subjects with worse global disease severity also showed poorer quality of the VI content. Finally, the quality of the VI content showed significant positive correlations with the functional connectivity changes during the VI tasks in brain areas supporting visuospatial and sensorimotor processes. Our findings suggest that mental imagery training combining VI and MI may enhance motor function in patients with mild PD, and more broadly, underline the importance of incorporating self-reports of thoughts and experiences in neuroimaging studies that examine the brain mechanisms of complex cognitive processes especially in neuropsychiatric patient populations.

Measuring Heart Rate Accurately in Patients With Parkinson Disease During Intense Exercise: Usability Study of Fitbit Charge 4.

BACKGROUND: Parkinson disease (PD) is the second most common neurodegenerative disease, affecting approximately 1% of the world's population. Increasing evidence suggests that aerobic physical exercise can be beneficial in mitigating both motor and nonmotor symptoms of the disease. In a recent pilot study of the role of exercise on PD, we sought to confirm exercise intensity by monitoring heart rate (HR). For this purpose, we asked participants to wear a chest strap HR monitor (Polar Electro Oy) and the Fitbit Charge 4 (Fitbit Inc) wrist-worn HR monitor as a potential proxy due to its convenience. Polar H10 has been shown to provide highly accurate R-R interval measurements. Therefore, we treated it as the gold standard in this study. It has been shown that Fitbit Charge 4 has comparable accuracy to Polar H10 in healthy participants. It has yet to be determined if the Fitbit is as accurate as Polar H10 in patients with PD during rest and exercise. OBJECTIVE: This study aimed to compare Fitbit Charge 4 to Polar H10 for monitoring HR in patients with PD at rest and during an intensive exercise program. METHODS: A total of 596 exercise sessions from 11 (6 male and 5 female) participants were collected simultaneously with both devices. Patients with early-stage PD (Hoehn and Yahr ≤2) were enrolled in a 6-month exercise program designed for patients with PD. They participated in 3 one-hour exercise sessions per week. They wore both Fitbit and Polar H10 during each session. Sessions included rest, warm-up, intense exercise, and cool-down periods. We calculated the bias in the HR of the Fitbit Charge 4 at rest (5 min) and during intense exercise (20 min) by comparing the mean HR during each of the periods to the respective means measured by Polar H10 (HRFitbit - HRPolar). We also measured the sensitivity and specificity of Fitbit Charge 4 to detect average HRs that exceed the threshold for intensive exercise, defined as 70% of an individual's theoretical maximum HR. Different types of correlations between the 2 devices were investigated. RESULTS: The mean bias was 1.68 beats per minute (bpm) at rest and 6.29 bpm during high-intensity exercise, with an overestimation by Fitbit Charge 4 in both conditions. The mean bias of the Fitbit across both rest and intensive exercise periods was 3.98 bpm. The device's sensitivity in identifying high-intensity exercise sessions was 97.14%. The correlation between the 2 devices was nonlinear, suggesting Fitbit's tendency to saturate at high values of HR. CONCLUSIONS: The performance of Fitbit Charge 4 is comparable to Polar H10 for assessing exercise intensity in a cohort of patients with PD (mean bias 3.98 bpm). The device could be considered a reasonable surrogate for more cumbersome chest-worn devices in future studies of clinical cohorts.

Neurofeedback-guided kinesthetic motor imagery training in Parkinson's disease: Randomized trial.

BACKGROUND: Parkinson's disease (PD) causes difficulty with maintaining the speed, size, and vigor of movements, especially when they are internally generated. We previously proposed that the insula is important in motivating intentional movement via its connections with the dorsomedial frontal cortex (dmFC). We demonstrated that subjects with PD can increase the right insula-dmFC functional connectivity using fMRI-based neurofeedback (NF) combined with kinesthetic motor imagery (MI). The current study is a randomized clinical trial testing whether NF-guided kinesthetic MI training can improve motor performance and increase task-based and resting-state right insula-dmFC functional connectivity in subjects with PD. METHODS: We assigned nondemented subjects with mild PD (Hoehn & Yahr stage ≤ 3) to the experimental kinesthetic MI with NF (MI-NF, n = 22) and active control visual imagery (VI, n = 22) groups. Only the MI-NF group received NF-guided MI training (10-12 runs). The NF signal was based on the right insula-dmFC functional connectivity strength. All subjects also practiced their respective imagery tasks at home daily for 4 weeks. Post-training changes in 1) task-based and resting-state right insula-dmFC functional connectivity were the primary imaging outcomes, and 2) MDS-UPDRS motor exam and motor function scores were the primary and secondary clinical outcomes, respectively. RESULTS: The MI-NF group was not significantly different from the VI group in any of the primary imaging or clinical outcome measures. The MI-NF group reported subjective improvement in kinesthetic body awareness. There was significant and comparable improvement only in motor function scores in both groups (secondary clinical outcome). This improvement correlated with NF regulation of the right insula-dmFC functional connectivity only in the MI-NF group. Both groups showed specific training effects in whole-brain functional connectivity with distinct neural circuits supporting kinesthetic motor and visual imagery (exploratory imaging outcome). CONCLUSIONS: The functional connectivity-based NF regulation was unsuccessful, however, both kinesthetic MI and VI practice improved motor function in our cohort with mild PD.

Hierarchical Denoising of Ordinal Time Series of Clinical Scores.

Clinical scores (disease rating scales) are ordinal in nature. Longitudinal studies which use clinical scores produce ordinal time series. These time series tend to be noisy and often have a short-duration. This paper proposes a denoising method for such time series. The method uses a hierarchical approach to draw statistical power from the entire population of a study's patients to give reliable, subject-specific results. The denoising method is applied to MDS-UPDRS motor scores for Parkinson's disease.

Characterization of Early Stage Parkinson's Disease From Resting-State fMRI Data Using a Long Short-Term Memory Network.

Parkinson's disease (PD) is a common and complex neurodegenerative disorder with five stages on the Hoehn and Yahr scaling. Characterizing brain function alterations with progression of early stage disease would support accurate disease staging, development of new therapies, and objective monitoring of disease progression or treatment response. Functional magnetic resonance imaging (fMRI) is a promising tool in revealing functional connectivity (FC) differences and developing biomarkers in PD. While fMRI and FC data have been utilized for diagnosis of PD through application of machine learning approaches such as support vector machine and logistic regression, the characterization of FC changes in early-stage PD has not been investigated. Given the complexity and non-linearity of fMRI data, we propose the use of a long short-term memory (LSTM) network to distinguish the early stages of PD and understand related functional brain changes. The study included 84 subjects (56 in stage 2 and 28 in stage 1) from the Parkinson's Progression Markers Initiative (PPMI), the largest-available public PD dataset. Under a repeated 10-fold stratified cross-validation, the LSTM model reached an accuracy of 71.63%, 13.52% higher than the best traditional machine learning method and 11.56% higher than a CNN model, indicating significantly better robustness and accuracy compared with other machine learning classifiers. Finally, we used the learned LSTM model weights to select the top brain regions that contributed to model prediction and performed FC analyses to characterize functional changes with disease stage and motor impairment to gain better insight into the brain mechanisms of PD.

Functional Connectome in Parkinson's Disease and Parkinsonism.

PURPOSE OF REVIEW: There has been an exponential growth in functional connectomics research in neurodegenerative disorders. This review summarizes the recent findings and limitations of the field in Parkinson's disease (PD) and atypical parkinsonian syndromes. RECENT FINDINGS: Increasingly more sophisticated methods ranging from seed-based to network and whole-brain dynamic functional connectivity have been used. Results regarding the disruption in the functional connectome vary considerably based on disease severity and phenotypes, and treatment status in PD. Non-motor symptoms of PD also link to the dysfunction in heterogeneous networks. Studies in atypical parkinsonian syndromes are relatively scarce. An important clinical goal of functional connectomics in neurodegenerative disorders is to establish the presence of pathology, track disease progression, predict outcomes, and monitor treatment response. The obstacles of reliability and reproducibility in the field need to be addressed to improve the potential of the functional connectome as a biomarker for these purposes in PD and atypical parkinsonian syndromes.

Distinct neural circuits are associated with subclinical neuropsychiatric symptoms in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) can present with neuropsychiatric symptoms (here, anxiety, depression, and apathy) at any stage of the disease. We investigated the neural correlates of subclinical neuropsychiatric symptoms in relation to motor and cognitive symptoms in a high-functioning PD cohort. METHODS: Brain morphometry of the cognitively intact, early-stage (Hoehn & Yahr 2) PD group (n = 48) was compared to matched controls (n = 37). Whole-brain, pairwise, resting-state functional connectivity measures were correlated with neuropsychiatric symptom, motor exam, and global cognitive scores of the PD group. RESULTS: Factor analysis of highly collinear anxiety, depression, and apathy scores revealed a single principal component (i.e., composite neuropsychiatric symptom score) explaining 71.6% of variance. There was no collinearity between the neuropsychiatric, motor, and cognitive scores. Compared to controls, PD group showed only subcortical changes including amygdala and nucleus accumbens atrophy, and greater pallidal volume. Reduced functional connectivity in the limbic cortical-striatal circuits and increased functional connectivity between the cerebellum and occipito-temporal regions were associated with a more impaired neuropsychiatric profile. This functional connectivity pattern was distinct from those associated with motor deficits and global cognitive functioning. The individual components of the neuropsychiatric symptoms also exhibited unique connectivity patterns. LIMITATIONS: Patients were scanned in "on-medication" state only and a control group with similar neuropsychiatric symptoms was not included. CONCLUSION: Abnormal functional connectivity of distinct neural circuits is present even at the subclinical stage of neuropsychiatric symptoms in PD. Neuropsychiatric phenotyping is important and may facilitate early interventions to "reorganize" these circuits and delay/prevent clinical symptom onset.

Structural and functional brain changes in hepatic and neurological Wilson disease.

Wilson disease (WD) can manifest with hepatic or neuropsychiatric symptoms. Our understanding of the in vivo brain changes in WD, particularly in the hepatic phenotype, is limited. Thirty subjects with WD and 30 age- and gender-matched controls participated. WD group underwent neuropsychiatric assessment. Unified WD Rating Scale neurological exam scores were used to determine neurological (WDN, score > 0) and hepatic-only (WDH, score 0) subgroups. All subjects underwent 3 Tesla anatomical and resting-state functional MRI. Diffusion tensor imaging (DTI) and susceptibility-weighted imaging (SWI) were performed only in the WD group. Volumetric, DTI, and functional connectivity analyses were performed to determine between-group differences. WDN and WDH groups were matched in demographic and psychiatric profiles. The entire WD group compared to controls showed significant thinning in the bilateral superior frontal cortex. The WDN group compared to control and WDH groups showed prominent structural brain changes including significant striatal and thalamic atrophy, more subcortical hypointense lesions on SWI, and diminished white matter integrity in the bilateral anterior corona radiata and corpus callosum. However, the WDH group also showed significant white matter volume loss compared to controls. The functional connectivity between the frontostriatal nodes was significantly reduced in the WDN group, whereas that of the hippocampus was significantly increased in the WDH group compared to controls. In summary, structural and functional brain changes were present even in neurologically non-manifesting WD patients in this cross-sectional study. Longitudinal brain MRI scans may be useful as biomarkers for prognostication and optimization of treatment strategies in WD.

Robust Bayesian Analysis of Early-Stage Parkinson's Disease Progression Using DaTscan Images.

This paper proposes a mixture of linear dynamical systems model for quantifying the heterogeneous progress of Parkinson's disease from DaTscan Images. The model is fitted to longitudinal DaTscans from the Parkinson's Progression Marker Initiative. Fitting is accomplished using robust Bayesian inference with collapsed Gibbs sampling. Bayesian inference reveals three image-based progression subtypes which differ in progression speeds as well as progression trajectories. The model reveals characteristic spatial progression patterns in the brain, each pattern associated with a time constant. These patterns can serve as disease progression markers. The subtypes also have different progression rates of clinical symptoms measured by MDS-UPDRS Part III scores.

Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging.

OBJECTIVE: Parkinson disease is characterized by motor and nonmotor symptoms, reduced striatal dopamine signaling, and loss of dopamine neurons in the substantia nigra. It is now known that the pathological process in Parkinson disease may begin decades before the clinical diagnosis and include a variety of neuronal alterations in addition to the dopamine system. METHODS: This study examined the density of all synapses with synaptic vesicle glycoprotein 2A (SV2A) in Parkinson disease subjects with mild bilateral disease (n = 12) and matched normal controls (n = 12) using in vivo high-resolution positron emission tomographic imaging as well as postmortem autoradiography in an independent sample with Parkinson disease (n = 15) and normal controls (n = 13) in the substantia nigra and putamen. RESULTS: A group-by-brain region interaction effect (F10, 22 = 3.52, p = 0.007) was observed in the primary brain areas with in vivo SV2A binding. Post hoc analyses revealed that the Parkinson disease group exhibited lower SV2A in the substantia nigra (-45%; p < 0.001), red nucleus (-31%; p = 0.03), and locus coeruleus (-17%; p = 0.03). Exploratory analyses also revealed lower SV2A binding in clinically relevant cortical areas. Using autoradiography, we confirmed lower SV2A in the substantia nigra (-17%; p < 0.005) and nonsignificant findings in the putamen (-4%; p = 0.06). INTERPRETATION: This work provides the first evidence of synaptic loss in brainstem nuclei involved in the pathogenesis of Parkinson disease in living patients. SV2A imaging holds promise for understanding synaptic changes central to the disease. Ann Neurol 2020;87:329-338.

Goal-directed behavior in individuals with mild Parkinson's disease: Role of self-efficacy and self-regulation.

INTRODUCTION: Deficits in goal-directed behavior are common in individuals with Parkinson's disease (PD) and have been ascribed to apathy. In addition to apathy, individuals' beliefs in their competence (self-efficacy) and capacity to regulate emotions, thoughts, and actions (self-regulation) are critical skills for goal-directed behavior. We investigated these skills and their relationship to motor and non-motor symptoms in individuals with PD. We also examined the neural correlates of these skills using functional magnetic resonance imaging (fMRI). METHODS: We enrolled 35 subjects with mild PD (Hoehn and Yahr stage ≤2.5) and used the new general self-efficacy (NGSES) and self-regulation scales (SRS). We correlated the scores on these scales with measures of cognition, anxiety, depression, apathy, fatigue, quality of life, and disease burden using stepwise regression analyses. We collected resting-state fMRI data in a 3-Tesla scanner and computed the pairwise functional connectivity among nodes of major networks. We correlated the connectivity maps with the NGSES and SRS scores. RESULTS: Our PD cohort demonstrated intact NGSES and SRS scores compared with respective population data. These scores showed significant negative correlation with apathy and disease burden. Stronger connectivity in the salience network and decoupling from the default mode network supported self-efficacy and self-regulation. CONCLUSIONS: Self-efficacy and self-regulation capacity seems preserved, but vulnerable to disease-related factors in individuals with mild PD. Educational programs cultivating this capacity could improve the coping skills of these individuals. Functional connectivity changes in salience and default mode networks may serve as neurobiological markers to demonstrate the effectiveness of such interventions.

An online curriculum in movement disorders for neurology housestaff.

INTRODUCTION: In many neurology residency programs, outpatient neurology subspecialties are underrepresented. Trainee exposure to these subspecialties, including movement disorders, is limited by paucity and variability of clinical experiences. We designed a structured educational tool to address this variability and allow for standardization of elements of movement disorders teaching. METHODS: We designed and implemented a web-based curriculum in movement disorders for neurology housestaff, in order to improve participant knowledge. The curriculum includes an introduction with a structured framework for the description of abnormal movements and 10 interactive modules focusing on common movement disorders. The curriculum was piloted with nine neurology housestaff at Yale-New Haven Hospital. Evaluation of the curriculum was performed using pre- and post-tests, a survey, and semi-structured interviews. RESULTS: The mean pre-test score was 0.7 (±0.19), and the mean post-test score was 0.95 (±0.05) (t = 3.27). Surveys demonstrated mean Likert values >4/5 for all questions in all categories (knowledge acquisition, quantity, enthusiasm and technical). Semi-structured interviews revealed the following themes: 1) the modules increased participant comfort with the topic, 2) the format was engaging, and 3) the curriculum accommodated different learning styles. All participants remarked that the structured framework was a particular strength. CONCLUSION: We have created, implemented, and evaluated a foundational curriculum in movement disorders for neurology trainees, using readily-available technology. Housestaff responded positively to the curriculum, both in terms of content and format. This curriculum can be implemented in a variety of educational settings, as a central component of a standardized approach to movement disorders teaching.

Suicidal risk and demoralization in Parkinson disease.

OBJECTIVE: We aimed to determine suicide risk and lifetime suicidal ideation in Parkinson disease (PD) patients versus controls and how depression, demoralization, and insomnia are associated with suicidality. METHODS: In this case-control study, PD patients and matched controls were recruited from movement disorder clinics, Michael J. Fox Foundation, and Research Match websites. Suicide risk and suicidal ideation were assessed using the Suicidal Behavior Questionnaire-revised (SBQ-R) and Columbia-Suicide Severity Rating Scale. Lifetime depression was assessed using the Brief Lifetime Depression Scale, sleep using Insomnia Severity Index (ISI), demoralization using Diagnostic Criteria for Psychosomatic Research and Kissane Demoralization Scales, and non-motor symptoms using UPDRS Non-Motor Aspects of Experiences of Daily Living scale (nM-EDL). RESULTS: 186 PD participants and 177 controls were matched for age (64.2 ± 7.7 years), sex (48.8% female), and socioeconomics. PD participants were not more likely than controls to have high suicide risk (SBQ-R ≥ 7) (7.5% vs. 11.3%; p = 0.22) or to have had a lifetime suicide plan or attempt (2.7% vs. 5.1%; p = 0.24), but were less likely to have had lifetime suicidal ideation (23.1% vs. 35.0%; p = 0.01). PD participants were more likely than controls to have lifetime depression history (34.4% vs. 20.9%; p = 0.004), and demoralization (19.9% vs. 10.7%; p = 0.02), and had higher ISI scores (8.7 ± 5.8 vs. 5.1 ± 4.5; p < 0.0001). PD patients with high versus normal suicide risk had higher nM-EDL scores (16.5 ± 6.8 vs. 10.7 ± 5.9; p = 0.002), and more demoralization (71.4% vs. 21.5%; p < 0.0001). CONCLUSIONS: Suicide risk is not elevated and suicidal ideation is uncommon in PD, despite the high prevalence of depression and demoralization.

Parkinson's Disease Dementia and Lewy Body Disease.

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PD-D) are Lewy body-related neurodegenerative disorders sharing common clinical and neuropathological findings. The clinical features of both conditions include cognitive impairment, behavioral symptoms, autonomic dysfunction, sleep disorders, and parkinsonism. The cognitive profile of both disorders is characterized by particularly severe deficits in executive and visuospatial functions as well as attention. Clinical differentiation between DLB and PD-D is based on an arbitrary distinction between the time of onset of parkinsonism and cognitive symptoms; extrapyramidal symptoms precede dementia in PD-D, whereas it coincides with or follows dementia within 1 year in DLB. When the clinical picture is fully developed, DLB and PD-D are practically indistinguishable. Although the diagnosis is basically clinical, structural and functional neuroimaging as well as cerebrospinal fluid biomarkers may help the clinician in the diagnosis. Placebo-controlled randomized trials of the cholinesterase inhibitors have shown modest but significant benefits in cognition, global function, and neuropsychiatric symptoms in both disorders. Behavioral symptoms such as hallucinations and delusions should be treated with caution with antipsychotics, as they have the potential to worsen motor and cognitive symptoms.