The effects of medical comorbidity, cognition, and age on patient-reported outcomes in Parkinson's disease.

OBJECTIVE: The purpose of this cross-sectional study was to compare the independent contributions of medical comorbidity, cognition, and age on patient-reported outcomes in Parkinson's disease (PD). METHODS: 572 PD patients completed the Patient-Reported Outcome Measurement Information System (PROMIS®)-29 v2.0 Profile (physical function, anxiety, depression, fatigue, sleep disturbance, satisfaction with participation in social roles, pain interference) and PROMIS Global Health (mental health and physical health) scales. Comorbidity was measured with the Cumulative Illness Rating Scale-Geriatric (CIRS-G) and cognition with the Montreal Cognitive Assessment (MoCA). Multiple regression models examined the 9 PROMIS measures as predicted by comorbidity, cognition, and age, adjusting for demographic and clinical characteristics (UPDRS and disease duration). RESULTS: Comorbidity was associated with poorer outcomes in all nine PROMIS domains. Cognition was associated with two of nine domains: physical function and anxiety. Age was associated with five domains: anxiety, depression, sleep disturbance, satisfaction with participation in social roles, and global mental health. Comorbidity showed greater effects on all nine domains than cognition or age (higher standardized beta coefficients). CONCLUSION: Medical comorbidity, cognition, and age have different impacts on patient-reported outcomes in PD. Medical comorbidity has a greater impact than either cognition or age on a range of patient-reported physical and mental health domains. Medical comorbidity is an important contributor to the patient's perspective of their physical and mental health.

Spirituality in Parkinson's Disease within a Sample from the USA.

Spirituality and religious beliefs are important for coping with medical conditions. The dopaminergic system is involved in reward behavior, and its dysfunction in Parkinson Disease (PD) raises questions about religiosity and spirituality in people with PD. This study examines the association between levels of spirituality and religiosity and the severity of PD motor and non-motor symptoms. The secondary aim investigates the perceived impact of PD diagnosis on spirituality and religiosity. This was a cross-sectional analysis of demographic, physical, mental, and spirituality and religiosity status in patients with PD recruited for the Health Outcomes Measurement (HOME) Study at the University of Maryland Parkinson Disease and Movement Disorders Center, Baltimore, USA. Spirituality and religiosity were assessed using the Spiritual Well-being Scale, and the World Health Organization Quality of Life Spiritual Religious and Personal Belief field-test instrument. The sample size was 85 PD patients. The mean age (standard deviation) was 65.5 (9.4) years and 67.1% were male. Higher levels of spirituality and religiosity were associated with younger age, sex (female), less education, religious affiliation (Christian), and mental health status. After adjusting for age, education, gender, race, marital status, religion, physical health, mental health, and comorbidity, only anxiety was associated with all of the spirituality/religiosity assessments. The majority of patients reported no change in their religious or spiritual beliefs following diagnosis. Greater spirituality and religiosity were associated with less anxiety. Also, younger women with PD showed higher levels of spirituality and religiosity. Longitudinal studies on more diverse populations are needed.

Somatoform Symptoms in Parkinson Disease.

BACKGROUND: Co-occurring somatoform symptoms complicate the diagnosis and treatment of Parkinson disease (PD). OBJECTIVE: To learn more about the relationship between somatoform symptoms and PD by comparing demographic and clinical features across PD groups differing in somatoform symptom severity. METHOD: Using standardized Brief Symptom Inventory-18 (BSI-18) scores to measure somatoform symptom severity, we assigned 1093 individuals with PD to one of four subgroups using comparisons to normative means: low (M < -½ SD), average (M ± ½ SD), high (M +½ SD to +1 SD), very high (M > +1 SD). We used demographics and disease severity measures to assess each subgroup. RESULTS: Most of the individuals with PD (56%) had high or very high somatoform symptom levels. Increased somatoform symptom levels were associated with female gender, lower socioeconomic status, greater disease duration, increased PD severity (Total Unified Parkinson's Disease Rating Scale), greater disability (Older Americans Resource and Services Disability subscale), increased BSI-18 Depression and Anxiety subscale scores, lower cognitive function (Mini-Mental State Examination), lower self-efficacy scores (Self-Efficacy to Manage Chronic Disease Scale), lower quality of life scores (SF-12 Health Status Survey), and greater medical comorbidity (Cumulative Illness Rating Scale-Geriatrics) (all comparisons: P < 0.001). We found no significant between-group differences for age, race, or marital status. CONCLUSION: Somatoform symptom severity in individuals with PD is associated with greater PD severity and disability and is more common in females and in individuals with low socioeconomic status. Greater awareness of somatoform symptoms should help improve PD treatment.

Genome Sequencing in the Parkinson Disease Clinic.

Background and Objectives: Genetic variants affect both Parkinson disease (PD) risk and manifestations. Although genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to examine interest in comprehensive genetic testing among patients with PD and document reactions to possible findings from genome sequencing in 2 academic movement disorder clinics. Methods: In 203 subjects with PD (age = 63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Based on the results, 231 patients (age = 67 years, 63% male) were surveyed on interest in genetic testing and responses to vignettes covering (1) familial risk of PD (LRRK2); (2) risk of PD dementia (GBA); (3) PD genetic risk score; and (4) secondary, medically actionable variants (BRCA1). Results: Genome sequencing revealed a LRRK2 variant in 3% and a GBA risk variant in 10% of our clinical sample. The genetic risk score was normally distributed, identifying 41 subjects with a high risk of PD. Medically actionable findings were discovered in 2 subjects (1%). In our survey, the majority (82%) responded that they would share a LRRK2 variant with relatives. Most registered unchanged or increased interest in testing when confronted with a potential risk for dementia or medically actionable findings, and most (75%) expressed interest in learning their PD genetic risk score. Discussion: Our results highlight broad interest in comprehensive genetic testing among patients with PD and may facilitate integration of genome sequencing in clinical practice.

Confirming Parkinson Disease Diagnosis: Patterns of Diagnostic Changes by Movement Disorder Specialists.

Background: The American Academy of Neurology Parkinson Disease (PD) quality measures include an annual diagnostic review. Objective: To investigate the frequency and pattern of changes in diagnoses between PD and other causes of parkinsonism. Methods: This prospective longitudinal cohort study included consented patients diagnosed with PD at least once and a minimum of two times at the Movement Disorders Center between 2002 and 2017. Movement disorder specialists confirmed and documented diagnoses at every visit. Longitudinal changes in diagnoses were identified across visits. Results: Of 1567 patients with parkinsonism, 174 had non-PD parkinsonism with no change over time. Of 1393 patients diagnosed with PD at least once, 94% (N = 1308) had no change of diagnosis over time and 6% (N = 85) had a change of diagnosis including PD ⟷ drug-induced parkinsonism (DIP) (27.1%), PD ⟷ multiple system atrophy (MSA) (20.0%), PD ⟷ progressive supranuclear palsy (PSP) (18.8%), PD ⟷ Lewy body dementia (DLB) (16.5%), PD⟷ vascular parkinsonism (9.4%), more than two diagnoses (4.7%), and PD ⟷ corticobasal syndrome (CBS) (3.5%). The direction of diagnostic switches was as follows: PD ⟶ other parkinsonism diseases (36.5%), other parkinsonism diseases ⟶ PD (31.8%), and 31.8% of multiple switches. There were no significant differences in duration of follow-up, age at first visit, gender, race, marital status, education, income, cognition, or employment between the stable and unstable groups. Diagnostic change was associated with greater PD severity and greater medical comorbidity. Conclusion: Over a 15-year period, movement disorder specialists changed their clinical diagnosis of PD in 6% of patients. The most common diagnostic switches, to or from PD, were DIP, MSA, PSP, and DLB. This study describes routine clinical diagnostic patterns in the absence of pathologic confirmation. The presence of diverse diagnostic changes over time underscores the value of confirming PD diagnosis.

The economic burden of Parkinson disease among Medicare beneficiaries.

BACKGROUND: The progressive nature of Parkinson disease (PD), together with a lack of curative treatments, contributes to its economic burden. OBJECTIVE: To estimate the longitudinal incremental costs attributable to PD among Medicare beneficiaries. METHODS: In this retrospective cohort study, we used data from the Chronic Conditions Data Warehouse to identify Medicare beneficiaries with and without PD-related claims identified from 2006 to 2014 with follow-up until 2015. We grouped PD cases and controls based on their survival profiles using a grouping algorithm that used the following baseline measures: age, race, sex, and comorbidity. We identified 3 survival groups and used them to stratify the descriptive annual cost estimates in the 9 years after the index date. We estimated the incremental 1-, 3-, and 5-year costs of PD using generalized linear models (GLM) that controlled for baseline factors. RESULTS: We identified 27,394 cases and controls who were grouped into 3 survival groups. The mean age of the full study sample was 73 years. No material differences were found in the incremental cost of PD across the survival groups. Based on the multivariable GLM, the 1-year incremental cost of PD was $9,625 (95% CI, $9,054-$10,197). The 3-year incremental cost of PD was $20,832 (95% CI, $19,390-$22,274). The 5-year incremental cost of PD was $27,466 (95% CI, 25,088-$29,844). CONCLUSIONS: Among Medicare beneficiaries, PD is associated with excess costs compared with controls. We did not identify substantial differences in the incremental cost of PD across the survival groups. DISCLOSURES:This study was funded by Pfizer Inc. The funding agreement did not impact the authors' independence in designing the study, collecting the data, interpreting the data, writing the manuscript, and submitting the manuscript for publication. Dr Onukwugha reports grants from Pfizer Inc for the conduct of this study and is an employee of University of Maryland, Baltimore, which received financial support from Pfizer Inc in connection with the development of this manuscript; Dr Shulman reports research funding from Pfizer Inc related to the current work, is an employee of University of Maryland, Baltimore, which received financial support from Pfizer Inc in connection with the development of this manuscript, and reports research funding from the NIH, The Rosalyn Newman Foundation, and the Eugenia and Michael Brin family unrelated to the current work and royalties from Oxford University Press and Johns Hopkins University Press; Ms Myers and Dr Alvir are employees and stockholders of Pfizer Inc; Dr Gray was an employee and stockholder of Pfizer Inc at the time of analysis.

Comparison of motor, non-motor, and quality of life phenotype in Black and White patients with Parkinson's disease.

OBJECTIVE: To determine phenotypic differences between Black and White patients with Parkinson's disease (PD). DESIGN/METHODS: Patients with PD in a movement disorders clinic were approached to participate. After consent, a battery of tests was completed, including MDS-UPDRS Part III and the motor domains of the NIH Toolbox, Montreal Cognitive Assessment, Single Digit Modality Test, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, Parkinson's Disease Questionnaire (PDQ39), Schwab and England, Epworth Sleepiness Scale, UPSIT smell test, and others. RESULTS: Twenty-four Black PD and 25 White PD patients participated. There were no differences in demographics and MDS-UPDRS Part III scores. White PD participants performed better on the 4-m walk gait speed test (p < 0.0005), standing balance test (p < 0.001), Montreal Cognitive Assessment (p < 0.0005), and Single Digit Modality Test (p < 0.005). Black PD participants had lower scores on PROMIS Satisfaction with Participation (p = 0.023), PROMIS Physical Function Mobility (p = 0.007), total PDQ39 (p = 0.008), PDQ39 mobility (p = 0.012), PDQ39 ADL (p = 0.014), PDQ39 cognition (p = 0.023), and PDQ39 body discomfort (p = 0.041) scales. CONCLUSIONS: Significant differences were found in motor, non-motor and quality of life scales in Black and White PD participants with similar demographics. Further work will need to be done to identify the underlying reasons and ways to mitigate these disparities.

The Corpse: Time for Another Look A Review of the Culture of Embalming, Viewing and the Social Construction.

Embalming of the dead is more common in the United States than anywhere else in the world. Battles far from home during the Civil War with concern for contagion from dead bodies being shipped home compelled President Lincoln to direct the troops to use embalming to allow the return of the Union dead to their homes. Viewings were common with war heroes and culminated with the viewing of Lincoln himself. In the 20th century embalming became a tradition despite substantial evidence indicating environmental and occupational hazards related to embalming fluids and carbon dioxide generated from manufacturing steel coffins before placing in concrete burial vaults. Embalming is promoted and considered helpful to the grieving process. Embalmers are expected to produce an illusion of rest, an image that in some ways disguises death for the benefit of mourners. The dead are carefully displayed in a condition of liminal repose where the 'true' condition is hidden, and death is removed from the actual event. In this paper we highlight the spiritual and cultural complexities of embalming related issues. We propose an innovative process to empower people facing serious illness, and their families to make shared and informed decisions, especially when death is an expected outcome.

Comparison of Mini-Mental State Examination and Montreal Cognitive Assessment Ratings Across Levels of Parkinson's Disease Severity.

BACKGROUND: Cognitive impairment (CI) is common in Parkinson's disease (PD) and an important cause of disability. Screening facilitates early detection of CI and has implications for management. Preclinical disability is when patients have functional limitations but maintain independence through compensatory measures. OBJECTIVE: The objective of this study was to investigate the relationship between scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) with levels of PD severity and disability. METHODS: PD patients (n = 2,234) in a large observational study were stratified by disease severity, based on Total Unified Parkinson's Disease Rating Scale (Total UPDRS) and Hoehn and Yahr (HY) stage. Using MMSE (n = 1,184) or MoCA (n = 1,050) and basic (ADL) and instrumental activities of daily living (IADL) scales for disability, linear regression analysis examined associations between cognitive status and disability. RESULTS: Cognition and disability were highly correlated, with the strongest correlation between IADL and MoCA. Only 16.0% of mean MMSE scores were below threshold for CI (28) and only in advanced PD (Total UPDRS 60+, HY≥3). MoCA scores fell below CI threshold (26) in 66.2% of the sample and earlier in disease (Total UPDRS 30+, HY≥2), corresponding with impairments in ADLs. CONCLUSION: In a large clinical dataset, a small fraction of MMSE scores fell below cutoff for CI, reinforcing that MMSE is an insensitive screening tool in PD. MoCA scores indicated CI earlier in disease and coincided with disability. This study shows that MoCA, but not MMSE is sensitive to the emergence of early cognitive impairment in PD and correlates with the concomitant onset of disability.

Health Care Resource Utilization Associated With Parkinson Disease Among Medicare Beneficiaries.

OBJECTIVE: To compare differences in health care resource utilization (HcRU) over time between Medicare beneficiaries with and without Parkinson disease (PD). METHODS: This retrospective observational study used the Chronic Conditions Data Warehouse (5% Medicare sample) between 2005 and 2015. In a propensity score-matched (age, sex, race, and comorbidity adjusted) sample of beneficiaries with and without PD, we examined all-cause HcRU due to inpatient admissions, emergency department (ED) admissions, skilled nursing facility (SNF) admissions, health care provider encounters, neurologist visits, rehabilitation service visits, and non-PD medication fills. Relative to beneficiaries without PD, we reported adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for beneficiaries with PD using generalized linear models with log link and negative binomial variance functions. RESULTS: A total of 467,064 Medicare enrollees (unmatched sample) met the inclusion criteria. Of these, 3.3% had PD. In the matched sample and relative to beneficiaries without PD, beneficiaries with PD displayed higher rates of inpatient admissions (IRR 1.29, 95% CI 1.24-1.34), ED admissions (IRR 1.31, 95% CI 1.27-1.34), SNF admissions (IRR 2.00, 95% CI 1.92-2.09), health care provider encounters (IRR 1.18, 95% CI 1.16-1.20), neurologist visits (IRR 5.57, 95% CI 5.35-5.78), rehabilitation service visits (IRR 1.47, 95% CI 1.41-1.53), and non-PD medication fills (IRR 1.10, 95% CI 1.08-1.11) over time. CONCLUSION: These results reflect patterns of medical care among Medicare beneficiaries with PD. The findings can help clinicians, payers, and policy makers make evidence-based decisions for the allocation of scarce health care resources for PD management. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that Medicare beneficiaries with PD use more health care resources than matched controls without PD.

Longitudinal Change in Quality of Life in Neurological Disorders Measures Over 3 Years in Patients with Early Parkinson's Disease.

BACKGROUND: The Quality of Life in Neurological Disorders (Neuro-QoL) is a publicly available health-related quality-of-life measurement system. OBJECTIVE: The aim of this study was to evaluate the utility of Neuro-QoL item banks as outcome measures for clinical trials in Parkinson's disease. METHODS: An analysis of Neuro-QoL responsiveness to change and construct validity was performed in a multicenter clinical trial cohort. RESULTS: Among 310 participants over 3 years, changes in five of eight Neuro-QoL domains were significant (P < 0.05) but very modest. The largest effect sizes were seen in the cognition and mobility domains (0.35-0.39). The largest effect size for change over the year in which levodopa was initiated was -0.19 for lower extremity function-mobility. For a similarly designed clinical trial, estimated sample size required to demonstrate a 50% reduction in worsening ranged from 420 to more than 1000 participants per group. CONCLUSIONS: More sensitive tools will be required to serve as an outcome measure in early Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society.

Genome-Wide Association Study Meta-Analysis for Parkinson Disease Motor Subtypes.

OBJECTIVE: To discover genetic determinants of Parkinson disease (PD) motor subtypes, including tremor dominant (TD) and postural instability/gait difficulty (PIGD) forms. METHODS: In 3,212 PD cases of European ancestry, we performed a genome-wide association study (GWAS) examining 2 complementary outcome traits derived from the Unified Parkinson's Disease Rating Scale, including dichotomous motor subtype (TD vs PIGD) or a continuous tremor/PIGD score ratio. Logistic or linear regression models were adjusted for sex, age at onset, disease duration, and 5 ancestry principal components, followed by meta-analysis. RESULTS: Among 71 established PD risk variants, we detected multiple suggestive associations with PD motor subtype, including GPNMB (rs199351, p subtype = 0.01, p ratio = 0.03), SH3GL2 (rs10756907, p subtype = 0.02, p ratio = 0.01), HIP1R (rs10847864, p subtype = 0.02), RIT2 (rs12456492, p subtype = 0.02), and FBRSL1 (rs11610045, p subtype = 0.02). A PD genetic risk score integrating all 71 PD risk variants was also associated with subtype ratio (p = 0.026, ß = -0.04, 95% confidence interval = -0.07-0). Based on top results of our GWAS, we identify a novel suggestive association at the STK32B locus (rs2301857, p ratio = 6.6 × 10-7), which harbors an independent risk allele for essential tremor. CONCLUSIONS: Multiple PD risk alleles may also modify clinical manifestations to influence PD motor subtype. The discovery of a novel variant at STK32B suggests a possible overlap between genetic risk for essential tremor and tremor-dominant PD.

Frequency of Parkinsonism and Parkinson Disease in African Americans in the Chicago Community.

BACKGROUND: There is paucity of data about African American (AA) patients with Parkinson's disease (PD) and parkinsonism which may precede PD in older adults. Prior studies suggest that there are lower rates of PD in the AA population, with more cognitive impairment in AA with PD. This study aimed to investigate differences in PD, parkinsonism, and cognition between White and AA populations in 3 longitudinal epidemiologic cohort studies of aging. METHODS: This study examined parkinsonism, PD frequency, and cognition of community-dwelling older individuals in 3 longitudinal epidemiologic cohort studies. Parkinsonism was based on an exam utilizing the modified Unified Parkinson's Disease Rating Scale performed by a nurse. PD was based on self-report, medications used for treatment of PD, and examination findings. Cognition was assessed using 19 performance-based tests that assess 5 cognitive domains. RESULTS: AA participants were less likely to have parkinsonism compared to Whites, even with age and gender differences. Frequency of PD was not significant between groups. AA were more likely to have lower cognitive scores as compared to Whites. AA were less likely to have parkinsonism even with controlling for cognitive differences between groups. CONCLUSIONS: Parkinsonian signs are present among AA in the community at lower rates than in White individuals. Cognitive profiles of AA and Whites with parkinsonism may be different, suggesting differing contributions of pathology to cognitive decline and parkinsonism between groups. Additional research is needed to understand the progression of parkinsonism to PD, as well as to understanding the cognitive differences in AA with parkinsonism.

Quantitative mobility measures complement the MDS-UPDRS for characterization of Parkinson's disease heterogeneity.

INTRODUCTION: Emerging technologies show promise for enhanced characterization of Parkinson's Disease (PD) motor manifestations. We evaluated quantitative mobility measures from a wearable device compared to the conventional motor assessment, the Movement Disorders Society-Unified PD Rating Scale part III (motor MDS-UPDRS). METHODS: We evaluated 176 PD subjects (mean age 65, 65% male, 66% H&Y stage 2) during routine clinic visits using the motor MDS-UPDRS and a 10-min motor protocol with a body-fixed sensor (DynaPort MT, McRoberts BV), including the 32-ft walk, Timed Up and Go (TUG), and standing posture with eyes closed. Regression models examined 12 quantitative mobility measures for associations with (i) motor MDS-UPDRS, (ii) motor subtype (tremor dominant vs. postural instability/gait difficulty), (iii) Montreal Cognitive Assessment (MoCA), and (iv) physical functioning disability (PROMIS-29). All analyses included age, gender, and disease duration as covariates. Models iii-iv were secondarily adjusted for motor MDS-UPDRS. RESULTS: Quantitative mobility measures from gait, TUG transitions, turning, and posture were significantly associated with motor MDS-UPDRS (7 of 12 measures, p < 0.05) and motor subtype (6 of 12 measures, p < 0.05). Compared with motor MDS-UPDRS, several quantitative mobility measures accounted for a 1.5- or 1.9-fold increased variance in either cognition or physical functioning disability, respectively. Among minimally-impaired subjects in the bottom quartile of motor MDS-UPDRS, including subjects with normal gait exam, the measures captured substantial residual motor heterogeneity. CONCLUSION: Clinic-based quantitative mobility assessments using a wearable sensor captured features of motor performance beyond those obtained with the motor MDS-UPDRS and may offer enhanced characterization of disease heterogeneity.

Weight loss and weight gain in Parkinson disease.

INTRODUCTION: Parkinson disease (PD) has been associated with both weight loss and gain in different stages of the disease. Our study aimed to determine the prevalence and associations with weight change over two years based on 3% and 5% weight change. METHODS: In this longitudinal analysis, weight at baseline and follow-up was used to classify patients into groups of weight loss, stable, and weight gain. Differences between these groups at baseline and then with change over time were tested. RESULTS: The sample was 668 patients with mean(SD) age 66.1(10) and disease duration 5.3(5.4) years. Using 3% weight change criteria: 32.6% lost, 23.1% gained, and 55.7% had stable weight. Using 5% criteria: 22.6% lost, 15.7% gained, and 61.7% had stable weight. Age was associated with both 3% and 5% change in weight. Other associations with 5% weight change were disease duration, Total and Motor Unified Parkinson's Disease Rating Scale, Older Americans Resource and Services disability, and Hoehn & Yahr staging. The effects of 3% weight loss on Motor UPDRS, IADLs, and depression, and the effects of 5% weight loss on IADLs remained statistically significant when controlling for baseline differences in age, levodopa use, and Total UPDRS. CONCLUSION: PD patients are more likely to experience 3% than 5% weight change and this lower threshold of weight change was associated with greater disease severity and disability over time. Attention to more subtle weight change may help identify those at greater risk of disability.

Emotional Traumatic Brain Injury.

The definition of traumatic brain injury (TBI) has expanded to include mild TBI and postconcussive syndrome. This evolution has resulted in difficulty disentangling the physical trauma of mild TBI from the emotional trauma of posttraumatic stress disorder (PTSD). Advances in stress neurobiology and knowledge of brain injury at the macroscopic, microscopic, biochemical, and molecular levels call for a redefinition of TBI that encompasses both physical and emotional TBI. Conceptualizing a spectrum of TBI with both physical and emotional causation resolves the irreconcilable tangle between diagnostic categories and acknowledges overlapping forms of brain injury and shared systemic effects due to hormonal and inflammatory mediators. Recognizing emotional TBI shifts the interpretation of emotional trauma from a confound to a comorbid, related cause of brain injury. The mechanism of emotional TBI includes the intricate actions of stress hormones on diverse brain functions due to changes in synaptic plasticity, where chronically elevated hormone levels reduce neurogenesis, resulting in dendritic atrophy and impaired cognition. The overlapping effects of physical and emotional trauma are seen in neuropathology (ie, reduction of hippocampal volume in TBI and PTSD); fMRI (similar regional activations in physical and emotional pain); and systemic sequelae, including changes in proinflammatory cytokine levels and immune cell function. Accumulating evidence favors a change in the definition of TBI to encompass emotional TBI. The definition of TBI will be strengthened by the inclusion of both physical and emotional trauma that result in diverse and overlapping forms of brain injury with sequelae for physical and mental health.

Identifying and predicting Parkinson's disease subtypes through trajectory clustering via bipartite networks.

Chronic medical conditions show substantial heterogeneity in their clinical features and progression. We develop the novel data-driven, network-based Trajectory Profile Clustering (TPC) algorithm for 1) identification of disease subtypes and 2) early prediction of subtype/disease progression patterns. TPC is an easily generalizable method that identifies subtypes by clustering patients with similar disease trajectory profiles, based not only on Parkinson's Disease (PD) variable severity, but also on their complex patterns of evolution. TPC is derived from bipartite networks that connect patients to disease variables. Applying our TPC algorithm to a PD clinical dataset, we identify 3 distinct subtypes/patient clusters, each with a characteristic progression profile. We show that TPC predicts the patient's disease subtype 4 years in advance with 72% accuracy for a longitudinal test cohort. Furthermore, we demonstrate that other types of data such as genetic data can be integrated seamlessly in the TPC algorithm. In summary, using PD as an example, we present an effective method for subtype identification in multidimensional longitudinal datasets, and early prediction of subtypes in individual patients.

Assessment of Parkinson disease quality measures on 12-month patient outcomes.

BACKGROUND: Quality measures (QMs) exist to operationalize guidelines by measuring adherence to guidelines through documentation, ultimately leading to improved patient outcomes. Studies are rare looking at the relationship between adherence to Parkinson disease (PD) QMs and patient outcomes. METHODS: We assessed adherence of our movement disorders specialists (MDSs) to the American Academy of Neurology's 2010 PD QM set through chart review using the measure set work group's criteria of documentation. We then evaluated patient outcomes to see whether there was a correlation with adherence to these QMs. RESULTS: Ninety-seven consecutive patients met the inclusion criteria. The mean disease duration was 9.3 (5.8) years. All patients were assessed by 1 of 4 MDSs. A total of 68% of QMs were documented across all patients. There was a small positive correlation between the number of documented QMs the year before the index visit and the number of calls/emails both the year before and after the index visit (r = 0.20, p = 0.04 and r = 0.26, p = 0.01, respectively.) There was a small negative correlation between the number of documented QMs and the number of PD follow-up visits the year after the index visit (r = -0.19, p = 0.05.) No other outcome showed a statistically significant correlation with the adherence to documented QMs. CONCLUSIONS: We found no clinically important improvement in patient outcomes with higher adherence levels. It is important that QM developers validate QMs to ensure that they fulfill the intended goal of improved patient outcomes.

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies.

BACKGROUND: Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. METHODS: We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. FINDINGS: Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16-36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10-7). INTERPRETATION: These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. FUNDING: The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources).