Parkinson's disease (PD) usually presents in older adults and typically has both motor and non-motor dysfunctions. PD is a progressive neurodegenerative disorder resulting from dopaminergic neuronal cell loss in the mid-brain substantia nigra pars compacta region. Outlined here is an integrative medicine and health strategy that highlights five treatment options for people with Parkinson's (PwP): rehabilitate, therapy, restorative, maintenance, and surgery. Rehabilitating begins following the diagnosis and throughout any additional treatment processes, especially vis-a-vis consulting with physical, occupational, and/or speech pathology therapist(s). Therapy uses daily administration of either the dopamine precursor levodopa (with carbidopa) or a dopamine agonist, compounds that preserve residual dopamine, and other specific motor/non-motor-related compounds. Restorative uses strenuous aerobic exercise programs that can be neuroprotective. Maintenance uses complementary and alternative medicine substances that potentially support and protect the brain microenvironment. Finally, surgery, including deep brain stimulation, is pursued when PwP fail to respond positively to other treatment options. There is currently no cure for PD. In conclusion, the best strategy for treating PD is to hope to slow disorder progression and strive to achieve stability with neuroprotection. The ultimate goal of any management program is to improve the quality-of-life for a person with Parkinson's disease.

https://www.mdpi.com/2218-273X/11/4/612/pdf

Treatment Options for Motor and Non-Motor Symptoms of Parkinson's Disease.

Mental health care for older adults: recent advances and new directions in clinical practice and research

Abstract Abrupt onset of severe neuropsychiatric symptoms including obsessive–compulsive disorder, tics, anxiety, mood swings, irritability, and restricted eating is described in children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Symptom onset is often temporally associated with infections, suggesting an underlying autoimmune/autoinflammatory etiology, although direct evidence is often lacking. The pathological mechanisms are likely heterogeneous, but we hypothesize convergence on one or more biological pathways. Consequently, we conducted whole exome sequencing (WES) on a U.S. cohort of 386 cases, and whole genome sequencing (WGS) on ten cases from the European Union who were selected because of severe PANS. We focused on identifying potentially deleterious genetic variants that were de novo or ultra-rare (MAF) &lt; 0.001. Candidate mutations were found in 11 genes ( PPM1D, SGCE, PLCG2, NLRC4, CACNA1B, SHANK3, CHK2, GRIN2A , RAG1 , GABRG2 , and SYNGAP1 ) in 21 cases, which included two or more unrelated subjects with ultra-rare variants in four genes. These genes converge into two broad functional categories. One regulates peripheral immune responses and microglia ( PPM1D, CHK2, NLRC4, RAG1, PLCG2 ). The other is expressed primarily at neuronal synapses ( SHANK3, SYNGAP1, GRIN2A, GABRG2, CACNA1B, SGCE ). Mutations in these neuronal genes are also described in autism spectrum disorder and myoclonus-dystonia. In fact, 12/21 cases developed PANS superimposed on a preexisting neurodevelopmental disorder. Genes in both categories are also highly expressed in the enteric nervous system and the choroid plexus. Thus, genetic variation in PANS candidate genes may function by disrupting peripheral and central immune functions, neurotransmission, and/or the blood-CSF/brain barriers following stressors such as infection. 

/pdf/identification-of-ultra-rare-genetic-variants-in-pediatric-2hko53dl.pdf

Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing

Objective Administrative claims data are used to study the incidence and outcomes of dementia-related hallucinations, but the validity of International Classification of Diseases (ICD) codes for identifying dementia-related hallucinations is unknown. Methods We analyzed Medicare-linked survey data from 2 nationally representative studies of U.S. older adults (the National Health and Aging Trends Study and the Health and Retirement Study) which contain validated cognitive assessments and a screening question for hallucinations. We identified older adults who had dementia or were permanent nursing home residents, and we combined this with questionnaire responses to define dementia-related hallucinations. Using Medicare claims data, we calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ICD codes for dementia-related hallucinations overall and within prespecified strata of age, neurologic comorbidity, and health care utilization. Results We included 2,337 older adults with dementia in our cohort. Among 3,789 person-years of data, 1,249 (33.0%) had hallucations, and of these 286 had a qualifying ICD code for dementia-related hallucinations or psychosis (sensitivity 22.9%). Of 2,540 person-years of dementia without hallucinations, 284 had a diagnosis code for hallucinations (specificity 88.8%). PPV was 50.2%, and NPV was 70.1%. Sensitivity was greatest (57.0%) among those seeing a psychiatrist. Otherwise, there were no significant differences in sensitivity, specificity, PPV, or NPV by age, neurologic diagnosis, or neurologist care. Conclusion Dementia-related hallucinations are poorly captured in administrative claims data, and estimates of their prevalence and outcomes using these data are likely to be biased.

Medicare Claims Data Underestimate Hallucinations in Older Adults With Dementia.

Objective Administrative claims data are used to study the incidence and outcomes of dementia-related hallucinations, but the validity of International Classification of Diseases (ICD) codes for identifying dementia-related hallucinations is unknown. Methods We analyzed Medicare-linked survey data from 2 nationally representative studies of U.S. older adults (the National Health and Aging Trends Study and the Health and Retirement Study) which contain validated cognitive assessments and a screening question for hallucinations. We identified older adults who had dementia or were permanent nursing home residents, and we combined this with questionnaire responses to define dementia-related hallucinations. Using Medicare claims data, we calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ICD codes for dementia-related hallucinations overall and within prespecified strata of age, neurologic comorbidity, and health care utilization. Results We included 2,337 older adults with dementia in our cohort. Among 3,789 person-years of data, 1,249 (33.0%) had hallucations, and of these 286 had a qualifying ICD code for dementia-related hallucinations or psychosis (sensitivity 22.9%). Of 2,540 person-years of dementia without hallucinations, 284 had a diagnosis code for hallucinations (specificity 88.8%). PPV was 50.2%, and NPV was 70.1%. Sensitivity was greatest (57.0%) among those seeing a psychiatrist. Otherwise, there were no significant differences in sensitivity, specificity, PPV, or NPV by age, neurologic diagnosis, or neurologist care. Conclusion Dementia-related hallucinations are poorly captured in administrative claims data, and estimates of their prevalence and outcomes using these data are likely to be biased. 

Medicare Claims Data Underestimate Hallucinations in Older Adults With Dementia

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinical diagnosis in children who have an acute manifestation of varied neuropsychiatric symptoms, including obsessive compu...

Evaluation of Intravenous Immunoglobulin in Pediatric Acute-Onset Neuropsychiatric Syndrome.

Objective To determine the association of dementia-related psychosis (DRP) with death and use of long-term care (LTC); we hypothesized that DRP would be associated with increased risk of death and use of LTC in patients with dementia. Methods A retrospective cohort study was performed. Medicare claims from 2008 to 2016 were used to define cohorts of patients with dementia and DRP. Outcomes were LTC, defined as nursing home stays of >100 consecutive days, and death. Patients with DRP were directly matched to patients with dementia without psychosis by age, sex, race, number of comorbid conditions, and dementia index year. Association of DRP with outcomes was evaluated using a Cox proportional hazard regression model. Results We identified 256,408 patients with dementia. Within 2 years after the dementia index date, 13.9% of patients developed DRP and 31.9% had died. Corresponding estimates at 5 years were 25.5% and 64.0%. Mean age differed little between those who developed DRP (83.8 ± 7.9 years) and those who did not (83.1 ± 8.7 years). Patients with DRP were slightly more likely to be female (71.0% vs 68.3%) and white (85.7% vs 82.0%). Within 2 years of developing DRP, 16.1% entered LTC and 52.0% died; corresponding percentages for patients without DRP were 8.4% and 30.0%, respectively. In the matched cohort, DRP was associated with greater risk of LTC (hazard ratio [HR] 2.36, 2.29–2.44) and death (HR 2.06, 2.02–2.10). Conclusions DRP was associated with a more than doubling in the risk of death and a nearly 2.5-fold increase in risk of the need for LTC.

https://n.neurology.org/content/neurology/96/12/e1620.full.pdf

Association of Dementia-related Psychosis with Long-term Care Use and Death.

BACKGROUND: More than 5.6 million Americans suffer from dementia, and that number is expected to double by 2060. This comes at a considerable burden to the health care system with costs estimated at $157-$215 billion in 2010. Depending on dementia type and disease progression, approximately 20%-70% of patients experience dementia-related psychosis (DRP), characterized by hallucinations and/or delusions resulting in worse clinical outcomes and greater caregiver burden compared with patients without DRP. OBJECTIVE: To compare real-world clinical events, health care resource utilization (HCRU), and health care costs among matched cohorts of DRP versus dementia-only patients. METHODS: This retrospective database analysis examined commercial and Medicare Advantage with Part D enrollees aged ≥ 40 years with evidence of DRP and dementia from January 1, 2010, through March 31, 2017. The first observed indicator of psychosis (≥ 2 diagnoses and/or antipsychotic pharmacy fills) co-occurring with or following evidence of dementia (≥ 2 diagnoses and/or dementia medication pharmacy fills) was the index date among patients with DRP. DRP patients were propensity score matched 1:1 to patients with dementia only based on demographics, comorbidities, dementia type, dementia severity, and pre-index all-cause HCRU. Continuous health plan enrollment ≥ 12 months before evidence of dementia through the index date and ≥ 12 months following the index date was required. Outcomes included clinical events, HCRU, and health care costs. RESULTS: A significantly higher percentage of DRP patients had ≥1 diagnosis for behavioral health conditions in the pre-index period compared with dementia-only patients (depression: 32.4% vs. 22.8%; anxiety: 19.1% vs. 11.5%; and insomnia: 9.0% vs. 6.3%; P < 0.001 for all comparisons). Diagnoses of post-index clinical events were significantly more likely among DRP patients compared with dementia-only patients including falls/fractures (28.3% vs. 14.1%), neurologic effects (17.7% vs. 12.9%), sedation (15.0% vs. 2.4%), cardiovascular effects (7.0% vs. 4.1%), and extrapyramidal reactions (3.2% vs. 1.7%; P < 0.001 for all comparisons). Higher percentages of DRP patients had an all-cause outpatient visit (80.2% vs. 68.9%), emergency visit (65.0% vs. 36.6%), or inpatient stay (47.2% vs. 20.0%) during the post-index period (P < 0.001 for all comparisons). The proportions of DRP patients with a post-index dementia-related office visit, outpatient visit, emergency visit, or inpatient stay was 48%, 147%, 339%, and 286% higher, respectively, compared with patients with dementia only. Compared with patients with dementia only, patients with DRP had significantly higher mean total post-index all-cause costs ($21,657 vs. $12,026; P < 0.001) and dementia-related costs ($11,852 vs. $3,013; P < 0.001). CONCLUSIONS: Patients with DRP were more likely to have diagnoses for behavioral health conditions, experience clinical events, and have higher mean all-cause and dementia-related HCRU and costs compared with patients with dementia only. These results reflect the unmet need of patients with DRP and an urgency for new treatment options to reduce substantial clinical and economic burden in this population. DISCLOSURES: This study was funded by Acadia Pharmaceuticals, which participated in the study design, interpretation of study results, and critical review of the manuscript. Abler, Skoog, and Rashid were employees of Acadia Pharmaceuticals at the time this study was conducted. Frazer and Halpern were employees of Optum at the time this study was conducted and were funded by Acadia Pharmaceuticals to conduct the study.

Burden of illness among patients with dementia-related psychosis.

Objectives: This study evaluated treatment patterns and factors associated with medication treatment changes in residents with dementia-related psychosis in a long-term care (LTC) setting. Methods:...

https://journals.sagepub.com/doi/pdf/10.1177/23337214211016565

Real-World Medication Treatment Patterns for Long-Term Care Residents with Dementia-Related Psychosis.

This study assessed treatment change patterns in Parkinson's disease psychosis (PDP) residents receiving antipsychotic (AP) therapies in U.S. long-term care (LTC) facilities. Residents with PDP in LTC between 01/01/13 and 06/30/16 were identified with ≥1 claim of psychosis, hallucinations, or delusions after PD diagnosis. Treatment patterns were evaluated during the 12 months post index. We identified 864 PDP residents: 408 (47.2%) on AP therapy and 456 (52.8%) on no AP therapy. A total of 335 residents (82.1%) continued, 13 (3.2%) discontinued, 11 (2.7%) switched, and 49 (12.0%) augmented (used ≥2 APs) their index AP therapy. Based on the multivariate regression analysis, younger age, male gender, anemia, anxiolytic use or anxiety, sedatives/hypnotic use, bladder disorders including urinary tract infections, coronary conditions, diabetes, hypertension, and dementia were associated with a higher likelihood of treatment change. Understanding the factors associated with treatment change may inform ways to improve management of PDP in the U.S. LTC setting.

Nazia Rashid

Papers

Evaluation of Intravenous Immunoglobulin in Pediatric Acute-Onset Neuropsychiatric Syndrome.

Association of Dementia-related Psychosis with Long-term Care Use and Death.

Burden of illness among patients with dementia-related psychosis.

Real-World Medication Treatment Patterns for Long-Term Care Residents with Dementia-Related Psychosis.

Treatment Patterns With Antipsychotics in Long-Term Care Patients With Parkinson’s Disease Psychosis: