Vitamin D in the Parkinson Associated Risk Syndrome (PARS) study.

BACKGROUND: Lower vitamin D levels have been associated with manifest Parkinson's disease, prompting the hypothesis that vitamin D insufficiency or deficiency may increase risk for PD. OBJECTIVES: To evaluate vitamin D levels in a population at risk for developing PD. METHODS: Plasma vitamin D levels were measured in the Parkinson Associated Risk Syndrome Study, a cohort of asymptomatic individuals, some of whom are at high risk for PD. Vitamin D levels were compared between subjects at high risk for PD (hyposmia and dopamine transporter scan deficit) versus all others and examined for correlations with dopaminergic system integrity. RESULTS: Mean vitamin D levels did not differ between groups, with a level of 27.8 ng/mL (standard deviation = 12.0) in the high-risk group versus 24.7 ng/mL (standard deviation = 9.0) in all others (P = 0.09). Vitamin D levels did not associate with putaminal dopamine transporter uptake. CONCLUSIONS: Our data from the asymptomatic Parkinson Associated Risk Syndrome cohort do not support the hypothesis that chronic vitamin D insufficiency threatens dopaminergic system integrity, contributing to PD pathogenesis. © 2017 International Parkinson and Movement Disorder Society.

Reducing the receipt of contraindicated medications in patients with Parkinson disease.

Background: The administration of antidopaminergic medications to patients with Parkinson's disease (PD) can exacerbate symptoms, and in the hospital setting, can lead to complications and increased length of stay. Despite efforts to improve medication administration through provider education and patient-centered interventions, the problem persists, with an estimated 21-43% of hospitalized PD patients receiving dopamine blocking medications. Methods: In this study, a best practice alert (BPA) was developed that was triggered when an antidopaminergic medication was ordered in the Emergency Department or hospital for a patient with a diagnosis of PD in the EMR. The primary outcomes were receipt of a contraindicated medication, length of stay (LOS) and readmission within 30 days. These outcomes were compared between the 12 months prior to the intervention and the 12 months post intervention. Data were also collected on admitting diagnosis, admitting service, neurology involvement and patient demographics. Results: For pre-intervention inpatient encounters, 18.3% involved the use of a contraindicated medication. This was reduced to 9.4% of all inpatient encounters for PD patients in the first 3 months post-intervention and remained lower at 13.3% for the full 12 months post-intervention. The overall rate of contraindicated medication use was low for ED visits at 4.7% pre-intervention and 5.7% post-intervention. Receipt of a contraindicated medication increased the risk of a longer length of stay, both before and after the intervention, but did not significantly affect 30-day readmission rate. Conclusion: An EMR BPA decreased the use of contraindicated medications for PD patients in the hospital setting, especially in the first 3 months. Strategies are still needed to reduce alert fatigue in order to maintain initial improvements.

Olfaction as an early marker of Parkinson's disease and Alzheimer's disease.

Olfactory impairment is a common and early sign of Parkinson's disease (PD) and Alzheimer's disease (AD), the two most prevalent neurodegenerative conditions in the elderly. This phenomenon corresponds to pathologic processes emerging in the olfactory system prior to the onset of typical clinical manifestations. Clinically available tests can establish hyposmia through odor identification assessment, discrimination, and odor detection threshold. There are significant efforts to develop preventative or disease-modifying therapies that slow down or halt the progression of PD and AD. Due to the convenience and low cost of its assessment, olfactory impairment could be used in these studies as a screening instrument. In the clinical setting, loss of smell may also help to differentiate PD and AD from alternative causes of Parkinsonism and cognitive impairment, respectively. Here, we discuss the pathophysiology of olfactory dysfunction in PD and AD and how it can be assessed in the clinical setting to aid in the early and differential diagnosis of these disorders.

A Review of the Relationship Between Vitamin D and Parkinson Disease Symptoms.

Vitamin D is a fat-soluble secosteroid that exerts its effects by binding to the vitamin D receptor (VDR), through which it directly and indirectly modulates the expression of hundreds to thousands of genes. While originally known for its role in regulating calcium homeostasis and metabolism, vitamin D is now associated with many other health conditions, including Parkinson's disease (PD). A high prevalence of vitamin D deficiency has been noted in PD for at least the past two decades. These findings, along with the discovery that the VDR and 1α-hydroxylase, the enzyme that converts vitamin D to its active form, are highly expressed in the substantia nigra, led to the hypothesis that inadequate levels of circulating vitamin D may lead to dysfunction or cell death within the substantia nigra. Studies investigating the relationship between vitamin D status and PD, however, have been inconsistent. Two prospective studies examined the association between mid-life vitamin D levels and risk of PD and produced conflicting results-one demonstrated an increased risk for PD with lower mid-life vitamin D levels, and the other showed no association between vitamin D and PD risk. One of the most consistent findings in the literature is the inverse association between serum vitamin D level and motor symptom severity in cross-sectional studies. While these data suggest that vitamin D may modify the disease, another likely explanation is confounding due to limited mobility. Fall risk has been associated with vitamin D in PD, but more study is needed to determine if supplementation decreases falls, which has been demonstrated in the general population. The association between vitamin D and non-motor symptoms is less clear. There is some evidence that vitamin D is associated with verbal fluency and verbal memory in PD. Studies in PD have also shown associations between vitamin D status and mood, orthostatic hypotension and olfactory impairment in PD. While more research is needed, given the numerous potential benefits and limited risks, vitamin D level assessment in PD patients and supplementation for those with deficiency and insufficiency seems justified.

State-level prevalence, health service use, and spending vary widely among Medicare beneficiaries with Parkinson disease.

State-level variations in disease, healthcare utilization, and spending influence healthcare planning at federal and state levels and should be examined to understand national disparities in health outcomes. This descriptive study examined state-level variations in Parkinson disease (PD) prevalence, patient characteristics, Medicare spending, out-of-pocket costs, and health service utilization using data on 27.5 million Medicare beneficiaries in the US in 2014. We found that 45.8% (n = 179,496) of Medicare beneficiaries diagnosed with PD were women; 26.1% (n = 102,205) were aged 85+. The District of Columbia, New York, Illinois, Connecticut, and Florida had the highest age-, race-, and sex-adjusted prevalence of Parkinson disease among Medicare beneficiaries in the US. Women comprised over 48.5% of PD patient populations in West Virginia, Kentucky, Mississippi, Louisiana, and Arkansas. More than 31% of the PD populations in Connecticut, Pennsylvania, Hawaii, and Rhode Island were aged 85+. PD patients who were "dual-eligible"-receiving both Medicare and Medicaid benefits-also varied by state, from <10% to >25%. Hospitalizations varied from 304 to 653 stays per 1000 PD patients and accounted for 26.5% of the 7.9 billion United States Dollars (USD) paid by the Medicare program for healthcare services delivered to our sample. A diagnosis of PD was associated with greater healthcare use and spending. This study provides initial evidence of substantial geographic variation in PD patient characteristics, health service use, and spending. Further study is necessary to inform the development of state- and federal-level health policies that are cost-efficient and support desired outcomes for PD patients.

Physical Activity in Early Parkinson Disease.

BACKGROUND: Physical activity and exercise improve outcomes in Parkinson disease (PD), however little is known about activity levels in early PD patients. OBJECTIVE AND METHODS: We examined self-reported activity scores and examined associations with clinical characteristics in 383 PD subjects and 175 healthy controls from the Parkinson Progression Markers Initiative (PPMI). RESULTS: Activity scores were 8% lower for PD subjects than HC (162.6±86.2 vs 175.0±78.5, p = 0.10). Higher scores were associated with younger age and male sex. Only 47% of PD subjects and 44% of HC reported activity consistent with standard recommendations for adults. CONCLUSIONS: Our findings highlight the need to encourage exercise even in early PD.

Sex disparities in health and health care utilization after Parkinson diagnosis: Rethinking PD associated disability.

OBJECTIVE: To examine sex differences and trends in comorbid disease and health care utilization in individuals with newly diagnosed Parkinson disease (PD). DESIGN: Retrospective cohort study. PARTICIPANTS: Over 133,000 Medicare beneficiaries with a new PD diagnosis in 2002 followed through 2008. METHODS: We compared the prevalence and cumulative incidence of common medical conditions, trends in survival and health care utilization between men and women with PD. RESULTS: Female PD patients had higher adjusted incidence rate ratio (IRR) of depression (IRR: 1.28, 1.25-1.31), hip fracture (IRR: 1.51, 1.45-1.56), osteoporosis (3.01, 2.92-3.1), and rheumatoid/osteoarthritis (IRR: 1.47, 1.43-1.51) than men. In spite of greater survival, women with PD used home health and skilled nursing facility care more often, and had less outpatient physician contact than men throughout the study period. CONCLUSIONS: Women experience a unique health trajectory after PD diagnosis as suggested by differing comorbid disease burden and health care utilization compared to men. Future studies of sex differences in care needs, care quality, comorbidity related disability, PD progression, and non-clinical factors associated with disability are needed to inform research agendas and clinical guidelines that may improve quality survival for women with PD.

Olfactory Dysfunction as an Early Biomarker in Parkinson's Disease.

Olfactory dysfunction is common in Parkinson's disease (PD) and often predates the diagnosis by years, reflecting early deposition of Lewy pathology, the histologic hallmark of PD, in the olfactory bulb. Clinical tests are available that allow for the rapid characterization of olfactory dysfunction, including tests of odor identification, discrimination, detection, and recognition thresholds, memory, and tests assessing the build-up of odor intensity across increasing suprathreshold stimulus concentrations. The high prevalence of olfactory impairment, along with the ease and low cost of assessment, has fostered great interest in olfaction as a potential biomarker for PD. Hyposmia may help differentiate PD from other causes of parkinsonism, and may also aid in the identification of "pre-motor" PD due to the early pathologic involvement of olfactory pathways. Olfactory function is also correlated with other non-motor features of PD and may serve as a predictor of cognitive decline. In this article, we summarize the existing literature on olfaction in PD, focusing on the potential for olfaction as a biomarker for early or differential diagnosis and prognosis.

Utilization of rehabilitation therapy services in Parkinson disease in the United States.

OBJECTIVE: To examine rehabilitation therapy utilization for Parkinson disease (PD). METHODS: We identified 174,643 Medicare beneficiaries with a diagnosis of PD in 2007 and followed them through 2009. The main outcome measures were annual receipt of physical therapy (PT), occupational therapy (OT), or speech therapy (ST). RESULTS: Outpatient rehabilitation fee-for-service use was low. In 2007, only 14.2% of individuals with PD had claims for PT or OT, and 14.6% for ST. Asian Americans were the highest users of PT/OT (18.4%) and ST (18.4%), followed by Caucasians (PT/OT 14.4%, ST 14.8%). African Americans had the lowest utilization (PT/OT 7.8%, ST 8.2%). Using logistic regression models that accounted for repeated measures, we found that African American patients (adjusted odds ratio [AOR] 0.63 for PT/OT, AOR 0.63 for ST) and Hispanic patients (AOR 0.97 for PT/OT, AOR 0.91 for ST) were less likely to have received therapies compared to Caucasian patients. Patients with PD with at least one neurologist visit per year were 43% more likely to have a claim for PT evaluation as compared to patients without neurologist care (AOR 1.43, 1.30-1.48), and this relationship was similar for OT evaluation, PT/OT treatment, and ST. Geographically, Western states had the greatest use of rehabilitation therapies, but provider supply did not correlate with utilization. CONCLUSIONS: This claims-based analysis suggests that rehabilitation therapy utilization among older patients with PD in the United States is lower than reported for countries with comparable health care infrastructure. Neurologist care is associated with rehabilitation therapy use; provider supply is not.

Olfactory impairment predicts cognitive decline in early Parkinson's disease.

OBJECTIVE: To evaluate the association between baseline olfaction and both cross-sectional and longitudinal cognitive assessments, motor symptoms, non-motor symptoms (NMS), and CSF biomarkers in early Parkinson's disease (PD). METHODS: Parkinson's Progression Marker's Initiative (PPMI) participants underwent baseline olfactory testing with the University of Pennsylvania Smell Identification Test (UPSIT). Serial assessments included measures of motor symptoms, NMS, neuropsychological assessment, and CSF biomarkers. Up to three years follow-up data were included. RESULTS: At baseline, worse olfaction (lowest tertile) was associated with more severe NMS, including anxiety and autonomic symptoms. Those in the lowest olfactory tertile were more likely to report cognitive impairment (37.4%) compared to those in the middle (24.4%) and highest olfactory tertiles (14.2%, p < 0.001). Aß1-42 was significantly lower, and tau/Aß1-42 ratio was higher in those with worse olfaction. In longitudinal analyses, lower UPSIT score was associated with greater decline in MoCA score (ß = 0.02 [0.01, 0.03], p = 0.001) over time, as were composite measures of UPSIT score and either Aß1-42 or tau/Aß1-42 ratio. In a Cox proportional hazards model, a composite measure of olfaction and Aß1-42 was a significant predictor of conversion from normal cognition to mild cognitive impairment (MCI; i.e., MoCA < 26), with subjects most impaired on both measures being 87% more likely to develop incident MCI (HR = 1.87 [1.16, 3.01], p = 0.01). CONCLUSIONS: Worse baseline olfaction is associated with long-term cognitive decline. The addition of AD CSF biomarkers to olfactory testing may increase the likelihood of identifying those at highest risk for cognitive decline and progression to MCI.