Michelle E. Fullard

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 Parkinsons disease (PD). METHODS Parkinsons Progression Markers 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). Aβ1-42 was significantly lower, and tau/Aβ1-42 ratio was higher in those with worse olfaction. In longitudinal analyses, lower UPSIT score was associated with greater decline in MoCA score (β = 0.02 [0.01, 0.03], p = 0.001) over time, as were composite measures of UPSIT score and either Aβ1-42 or tau/Aβ1-42 ratio. In a Cox proportional hazards model, a composite measure of olfaction and Aβ1-42 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.

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.

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

Lower vitamin D levels have been associated with manifest Parkinsons disease, prompting the hypothesis that vitamin D insufficiency or deficiency may increase risk for PD.

Author response: Utilization of rehabilitation therapy services in Parkinson disease in the United States

We thank Drs. Bryant and Protas for the comment on our article,1 and for pointing out their supportive study.2 Together, our data suggest that underutilization of rehabilitation therapies in Parkinson disease (PD) is persistent and pervasive. During the time period of these 2 studies, several randomized controlled trials were published that supported the use of rehabilitation therapies in PD.3,4 Improvements in mobility, activities of daily living, speech volume, and quality of life were demonstrated in these and other studies. This is another example of the gap between PD research and implementation. The barriers to dissemination of proven treatments need to be addressed for PD outcomes to improve.

Patterns of Dementia Treatment and Frank Prescribing Errors in Older Adults With Parkinson Disease

Importance Dementia is common in Parkinson disease, but few data exist on dementia treatment patterns or the concurrent use of acetylcholinesterase inhibitors (ACHEIs) and anticholinergic medications, a frank prescribing error. Objectives To describe dementia treatment patterns, and to determine the extent to which the concurrent use of ACHEIs and drugs with strong anticholinergic activity occurs among individuals with Parkinson disease in the United States. Design, Setting, and Participants This cross-sectional analysis included adult Medicare beneficiaries (aged 65 years or older) with Parkinson disease diagnosis with 12 consecutive months of inpatient, outpatient, and prescription drug coverage from January 1, 2014, through December 31, 2014. Beneficiaries with other parkinsonian syndromes were excluded. Demographic, geographic, prescription claims, and other data were extracted from the 2014 Carrier, Beneficiary Summary, and Prescription Drug Event research identifiable files of the Centers for Medicare & Medicaid Services. Data analysis was conducted from August 1, 2017, to November 30, 2017. Main Outcomes and Measures Primary outcomes were use of dementia drug, specific dementia medication, and concurrent exposure to a high-potency anticholinergic drug and an ACHEI. Descriptive analyses and multivariable logistic regression models determined the extent to which patient characteristics and comorbid conditions were associated with dementia treatment or with a high-potency anticholinergic and ACHEI never event. Results Of 268 407 Medicare beneficiaries with Parkinson disease (mean [SD] age, 78.9 [7.5]; 134 575 male [50.1%]), most were identified in the files as white (232 831 [86.7%]), followed by black (14 629 [5.5%]), Hispanic (7176 [2.7%]), Asian (7115 [2.7%]), and Native American (874 [0.3%]). Among these beneficiaries, 73 093 (27.2%) were given a prescription for at least 1 antidementia medication. The most commonly prescribed medication was donepezil hydrochloride (46 027 [63.0%] users), followed by memantine hydrochloride (30 578 [41.8%] users) and rivastigmine tartrate (19 278 [26.4%] users). Dementia drugs were more likely to be prescribed to black (adjusted odds ratio [AOR], 1.33; 95% CI, 1.28-1.38) and Hispanic (AOR, 1.28; 95% CI, 1.22-1.35) beneficiaries and less likely for Native American beneficiaries (AOR, 0.62; 95% CI, 0.51-0.74). Women were less likely than men to be given a prescription for dementia medication (AOR, 0.85; 95% CI, 0.84-0.87). Of the 64 017 beneficiaries receiving an ACHEI, 28 495 (44.5%) experienced at least 1 high-potency anticholinergic–ACHEI event. Hispanic (AOR, 1.11; 95% CI, 1.00-1.23) and women (AOR, 1.30; 95% CI, 1.25-1.35) beneficiaries had greater odds of experiencing this never event. Statistically significant clusters of the prevalence of this prescribing error were observed across the United States (Moran I = 0.24; P < .001), with clusters of high prevalence in the southern and midwestern states. Conclusions and Relevance Dementia medication use by persons with Parkinson disease varies by race/ethnicity and sex; potentially inappropriate prescribing is common among those being treated for cognitive impairment and varies by race/ethnicity, sex, and geography. These findings may serve as national and local targets for improving care quality and outcomes for persons with Parkinson disease.

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.