1·8 billion people of diverse ethnicities and cultures live in the Western Pacific Region. The increasing longevity of populations in this region is a major contributor to the exponential increase in Parkinson's disease prevalence worldwide. Differences exist between Parkinson's disease in the Western Pacific Region and in Europe and North America that might provide important insights into our understanding of the disease and approaches to management. For example, some genetic factors (such as LRRK2 mutations or variants) differ, environmental exposures might play differential roles in modulating the risk of Parkinson's disease, and fewer dyskinesias are reported, with some differences in the profile of non-motor symptoms and comorbidities. Gaps in awareness of the disease and inequitable access to treatments pose challenges. Further improvements in infrastructure, clinical governance, and services, and concerted collaborative efforts in training and research, including greater representation of the Western Pacific Region in clinical trials, will improve care of patients with Parkinson's disease in this region and beyond.

Parkinson's disease in the Western Pacific Region

The core symptoms of different dementia subtypes are the behavioral and psychological symptoms of dementia (BPSD) and its neuropsychiatric symptoms (NPS). BPSD symptoms may occur at any stage in the case of dementia due to Alzheimer's disease (AD), whereas they tend to occur early on in the case of its behavioral variant frontotemporal dementia or dementia with Lewy bodies and are essential for diagnosis. BPSD treatment consists of non-pharmacological as well as pharmacological interventions, with non-pharmacological interactions being suggested as first-line treatment. Agitation, psychotic features, apathy, depression, and anxiety may not respond to acetylcholinesterase inhibitors or memantine in AD cases; therefore, antipsychotics, antidepressants, sedative drugs or anxiolytics, and antiepileptic drugs are typically prescribed. However, such management of BPSD can be complicated by hypersensitivity to antipsychotic drugs, as observed in DLB, and a lack of effective pro-cognitive treatment in the case of frontotemporal dementia. The present paper reviews current knowledge of the management of BPSD and its limitations and discusses on-going clinical trials and future therapeutic options.

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Pharmacotherapy of Behavioral and Psychological Symptoms of Dementia: State of the Art and Future Progress.

Introduction There are several new and emerging antipsychotic medication strategies recently marketed or under clinical development for the treatment of several mental disorders. There is the need to provide an up-to-date overview on the safety of this new generation of antipsychotic medications, which includes also the third-generation antipsychotics (TGA). Areas covered The authors aimed at providing a synthesis of the most current evidence about the safety profile of the recently developed and/or marketed antipsychotics. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library from inception until March 2020, combining free terms and MESH headings for the topics of TGA and recently developed and/or marketed antipsychotics as following: ((safety OR adverse events OR side effects) AND ((brexpiprazole OR cariprazine OR inhaled loxapine OR lumateperone (ITI-007) OR lurasidone OR pimavanserin OR roluperidone (MIN-101) OR transdermal patch asenapine)). Expert opinion Overall, newer antipsychotics display a good safety profile, with a well-demonstrated lower metabolic liability compared to second-generation antipsychotics. Furthermore, TGA appear to specifically target negative symptomatology and improving cognitive domains. Abbreviations Aps=Antipsychotic Drugs; AEs = Adverse Effects; EPS = Extrapyramidal Symptoms; NMS = Neuroleptic malignant syndrome; D = Dopamine; Ki = Inhibitory Constant; 5-HT = Serotonin; ECG = Electrocardiogram; H = Histamine; M = Muscarinic; BMI = Body Mass Index.

Up-to-date expert opinion on the safety of recently developed antipsychotics.

Background: The complexity of speech motor control, and the incomplete conceptualisation of phases in the transformation of the speech code from linguistic symbols to a code amenable to a motor sys...

New perspectives on speech motor planning and programming in the context of the four- level model and its implications for understanding the pathophysiology underlying apraxia of speech and other motor speech disorders

Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies.

Objective Dysarthric speech of persons with Huntington disease (HD) is typically described as hyperkinetic; however, studies suggest that dysarthria can vary and resemble patterns in other neurologic conditions. To test the hypothesis that distinct motor speech subgroups can be identified within a larger cohort of patients with HD, we performed a cluster analysis on speech perceptual characteristics of patient audio recordings. Methods Audio recordings of 48 patients with mild to moderate dysarthria due to HD were presented to 6 trained raters. Raters provided scores for various speech features (e.g., voice, articulation, prosody) of audio recordings using the classic Mayo Clinic dysarthria rating scale. Scores were submitted to an unsupervised k-means cluster analysis to determine the most salient speech features of subgroups based on motor speech patterns. Results Four unique subgroups emerged from the cohort of patients with HD. Subgroup 1 was characterized by an abnormally fast speaking rate among other unique speech features, whereas subgroups 2 and 3 were defined by an abnormally slow speaking rate. Salient speech features for subgroup 2 overlapped with subgroup 3; however, the severity of dysarthria differed. Subgroup 4 was characterized by mild deviations of speech features with typical speech rate. Length of CAG repeats, Unified Huntington’s Disease Rating Scale total motor score, and percent intelligibility were significantly different for pairwise comparisons of subgroups. Conclusion This study supports the existence of distinct presentations of dysarthria in patients with HD, which may be due to divergent pathologic processes. The findings are discussed in relation to previous literature and clinical implications.

Motor speech patterns in Huntington disease.

Psychosis is common in Parkinson’s disease-related disorders and is associated with significant morbidity Pimavanserin is a newly approved treatment for Parkinson’s disease psychosis, but real-world experience with pimavanserin has been limited by small sample sizes and limited assessment of longitudinal outcomes The aim was to summarize the clinical experience with pimavanserin in a large cohort of patients with Parkinson’s disease-related psychosis We conducted a retrospective chart review of patients who were prescribed pimavanserin at Vanderbilt University Medical Center in the southeast United States between May 2016 and July 2018 We used Chi-squared analyses to compare efficacy and tolerability of pimavanserin, considering patient diagnosis, presence of dementia or delusions, use of deep brain stimulation, and prior antipsychotic failure Additionally, we compared the clinical characteristics of patients who started treatment and those who did not, to evaluate safety outcomes We identified 107 patients prescribed pimavanserin, and 91 began treatment Clinical improvement in psychosis was documented in 76% of patients (69/91) and did not differ based on diagnosis, presence of dementia, delusions, use of deep brain stimulation, or prior antipsychotic failure Adverse effects were reported in 20 patients (22%), the most common of which was worsening gait instability (5/91, 5%) Side effects led to cessation of therapy in 11 of the 91 patients (12%) At current follow-up, 50 (65%) of 77 living patients remain on treatment, with a mean treatment duration of 146 months Although most of these patients are on pimavanserin monotherapy (33/50, 66%), 17 patients (34%) are on a dual-antipsychotic regimen The living patients no longer on treatment stopped pimavanserin primarily because of a lack of perceived benefit (11/77, 14%), side effects (9/77, 12%), or both (1/77, 1%), though six patients (8%) stopped for reasons unrelated to medication effects, including the desire to reduce overall medication burden and negative media reporting on pimavanserin Study results emphasize long-term efficacy and tolerability of pimavanserin for psychosis in Parkinson’s disease-related disorders, including patients with dementia, delusions, deep brain stimulation use, or prior antipsychotic failure

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Pimavanserin for Psychosis in Parkinson's Disease-Related Disorders: A Retrospective Chart Review

Objective:Neuropsychiatric symptoms are known to increase caregiver burden and decrease patient quality of life among patients with Huntington’s disease. Functional capacity is an outcome commonly ...

Jessie Sellers

Papers

Motor speech patterns in Huntington disease.

Pimavanserin for Psychosis in Parkinson's Disease-Related Disorders: A Retrospective Chart Review

A Systematic Review of Neuropsychiatric Symptoms and Functional Capacity in Huntington’s Disease