Mara Getz, Larry Charleston IV, Cynthia E. Armand, Allison W. Willis, and Elizabeth Seng declare no conflicts of interest.

INTRODUCTION:Clinicians and researchers frequently ask informants about changes in a person's cognition, but whether informant assessments correspond to objectively measured change is unclear. METHODS:A subset (n = 2710) of US Health and Retirement Study participants and their informants completed the Harmonized Cognitive Assessment Protocol (HCAP). Using generalized estimating equations, we compared informant-reported change in memory and daily functioning to prospectively collected delayed word recall and instrumental activities of daily living (iADL) in the 10 years preceding HCAP. RESULTS:Informant reports of worsened memory were associated with declining word recall, and informant-reported iADL loss was associated with declining iADLs. Informant-reported memory impairment was more strongly associated with declining word recall when informants saw the respondent weekly or more compared to one to three times monthly or less (p < 0.0001 for interaction). DISCUSSION:Informant assessments of memory and iADLs are generally consistent with prospective measurements, but this relationship depends significantly on frequency of informant contact. Highlights:Informant ratings of a person's memory and daily functioning are generally reliable.Quality of reporting depends on frequency of informant contact.Knowing an informant's characteristics is important for interpreting responses.

Neurodevelopmental disorders (NDDs) are lifelong conditions that affect brain development and functioning, with varying levels of impairment on daily life. Advances in technology have extended life expectancy for individuals with NDDs; however, little is known about their health in older adulthood. Using a 20% random sample of Medicare beneficiaries in 2021, we identified adults aged 65 and older with autism spectrum disorder, cerebral palsy, muscular dystrophy, or spina bifida. Demographic characteristics and comorbidities were compared to a control group without NDDs. Compared with controls, older adults with NDDs were younger on entry into Medicare, had distinct sex distributions, and were less racially and ethnically diverse. Neurological conditions—including epilepsy, multiple sclerosis, and migraine—were markedly more prevalent among NDD groups, as were psychiatric disorders such as anxiety, depression, and psychosis. Substance use disorders, particularly alcohol abuse and dependence, occurred at nearly twice the rate of controls. Vascular conditions, including myocardial infarction, atrial fibrillation, heart failure, ischemic heart disease, and stroke, were also elevated, averaging twofold higher in NDD groups. Neurodegenerative diseases, notably Alzheimer’s dementia and Parkinson’s disease, were up to three times more common among individuals aging with NDDs, underscoring the dual impact of lifelong neurodevelopmental conditions and aging-related decline. These findings demonstrate that while vascular and substance use disorders contribute to the excess burden of disease, the most pronounced disparities lie in neurological, psychiatric, and neurodegenerative comorbidities. This highlights the urgent need for research on neurodegeneration risk in NDD populations and for healthcare adaptations to better support individuals with lifelong NDDs.

Introduction:Parkinson disease psychosis (PDP) is a common complication of PD. Until 2016, the only drugs available to treat PDP in the U.S. were antipsychotics with variable degrees of dopamine-receptor antagonism (DRA) that may worsen PD motor symptoms. We evaluated the impact that pimavanserin, a selective serotonin receptor inverse agonist/antagonist atypical antipsychotic (AAP) with no known DRA, had on PDP treatment practices in a commercially insured population. Methods:We included adults diagnosed with PD who filled at least one AAP prescription from 2016 to 2022. AAP dispensings were categorized into (1) pimavanserin, (2) clozapine and quetiapine (i.e., PDP-"preferred" mixed receptor antagonist AAPs), and (3) the remaining AAPs (i.e., PDP-"nonpreferred" mixed receptor antagonist AAPs). Trends in quarterly dispensing rates per 1000 persons treated were compared across categories. Secondary analyses focused on the 65+ subpopulations insured by Medicare Advantage programs. Results:Dispensing rates varied between 4 and 697/1000 persons treated for pimavanserin, 1434-1821 for preferred, and 394-746 for nonpreferred AAPs. Pimavanserin dispensings surpassed the nonpreferred category after quarter 3 of 2018. However, preferred AAPs, particularly quetiapine, remained the most dispensed category in the sixth year after pimavanserin's approval. We observed similar trends among Medicare Advantage enrollees. Conclusion:The availability of pimavanserin was followed by a decline in the use of the most harmful AAPs in persons living with PD. Quetiapine remained the most prescribed AAP. Comparative safety and effectiveness studies are needed to define the relative risks and benefits of treatment options in PDP.

Purpose Anticholinergic medication use measured via the Anticholinergic Cognitive Burden (ACB) scale has been associated with an increased dementia incidence in older adults but has not been explored specifically for Parkinson disease dementia (PDD). We used adjusted Cox models to estimate the risk of incident PDD associated with demographic factors, clinical characteristics, and time-varying total ACB in a longitudinal, deeply-phenotyped prospective PD cohort. Major findings 56.5% of study participants were taking ACB-scale drugs at enrollment. Increasing age, motor symptom burden and psychosis were associated with PDD risk. Female sex and educational achievement were protective against PDD. ACB categories were not associated with PDD overall, but depression and impulse control disorder were strongly associated with PDD in a subsample with high baseline ACB. Conclusions Patient and clinical factors modify PDD risk. PD drug safety and drug-disease interaction studies may require considering multiple mechanisms and including dose-based, prospectively acquired medication exposure measures.

Complex regional pain syndrome is a chronic pain disorder marked by symptoms such as swelling, impaired motor function, and sympathetic dysfunction. Our primary objective was to determine the total number of complex regional pain syndrome type 1 (CRPS-1) emergency department (ED) visits and hospitalizations by race/ethnicity, as well as to assess sex and age distributions by race/ethnicity. Secondary objectives were to examine whether race/ethnicity, as well as select characteristics, are associated with hospitalization and longer length of stay. We completed a cross-sectional study of adults (19+ years) using acute and inpatient care data from the 2020 Nationwide Emergency Department Sample and the National Inpatient Sample. The overall rate of CRPS-1 diagnosis among ED visits and hospitalizations was 0.02% and 0.04%, respectively. Most CRPS-1 care was provided to White (ED: 83.1%; inpatient: 82.8%) patients. Within race/ethnicity groups, CRPS-1 ED visits and hospitalizations generally increased with age. Secondary findings included: 1) ED visits by Black individuals (compared with White) were significantly negatively associated with immediate hospitalization (adjusted odds ratio (AOR) 0.74, 95% CI 0.55 to 0.99); 2) hospitalizations by Black patients (compared with White) were independently associated with increased length of stay (odds ratio (OR) 1.45, 95% CI 1.07 to 1.96), though the association diminished with adjustment; and 3) drug abuse was significantly associated with hospitalization (AOR 4.67, 95% CI 3.53 to 6.18) and longer length of stay (AOR 1.81, 95% CI 1.34 to 2.46). Race/ethnicity was minimally associated with studied CRPS-1 outcomes. Additional studies are required to determine the impact of race/ethnicity on seeking care for CRPS-1.

PURPOSE:Self-reported visual difficulty is consistently associated with dementia and other neuropsychiatric outcomes, but studies of specific age-related eye diseases have yielded conflicting results. METHODS:We conducted a retrospective cohort study using data from The National Health and Aging Trends Study, an ongoing nationally representative survey of older U.S. adults (n = 10,089). All subjects are screened for self-reported visual difficulty annually. Using linked Medicare claims data, we identified subjects with age-related macular degeneration (AMD), primary open-angle glaucoma (POAG), diabetic retinopathy, and cataract. For each condition, controls with complete Medicare eligibility and at least one eye care encounter were selected. We used semiparametric discrete time proportional hazards models to measure associations with incident dementia, and generalized estimating equations to examine longitudinal associations with depression, anxiety, and hallucinations, adjusting for baseline demographics and time-varying comorbidities. RESULTS:Self-reported visual difficulty was associated with dementia (HR 1.16, 95% CI: 1.00-1.34), depression (OR 1.14, 95% CI: 1.04-1.26), anxiety (OR 1.17, 95% CI: 1.06-1.29), and hallucinations (OR 1.54, 95% CI: 1.29-1.84). Diabetic retinopathy was associated with depression (OR 1.31, 95% CI: 1.05-1.64), and cataracts were associated with a lower risk of depression (OR 0.84, 95% CI: 0.74-0.95) and anxiety (OR 0.86, 95% CI: 0.75-0.99). There were no other associations between age-related eye disease and neuropsychiatric outcomes. CONCLUSION:Self-reported visual difficulty is associated with dementia and other neuropsychiatric outcomes to a greater degree than age-related eye disease. These findings highlight the distinction between self-reported vision and clinically diagnosed eye disease with regard to health outcomes in older adults.

Abstract This is an inception cohort study protocol to enroll people with Parkinson's disease into a biobanking protocol at the clinic-wide level collecting clinical information and blood for future research use. The informed consent process includes optional recontact for future research studies, access to the medical record, and use of samples for future studies. Blood products (plasma and genomic DNA) are banked for future use. Clinical data is obtained through a questionnaire. Each visit lasts between 10-20 min between a clinical research coordinator and patient at the time of their return visit to the medical office. The strength of this protocol is the broad research enrollment across a whole clinic target for recruitment, optional consents for future research and access to the medical record. Weakness include the time needed for enrollment and limited clinical information collected.

BACKGROUND:Stopping or reducing risky or unneeded medications ("deprescribing") could improve older adults' health. Electronic health data can support observational and intervention studies of deprescribing, but there are no standardized measures for key variables, and healthcare systems have differing data types and availability. We developed definitions for chronic medication use and discontinuation based on electronic health data and applied them in a case study of benzodiazepines and Z-drugs in five diverse US healthcare systems. METHODS:We conducted a retrospective cohort study of adults age 65+ from 2017 to 2019 with chronic benzodiazepine or Z-drug use. We determined whether sites had access to medication orders and/or dispensings. We developed definitions for chronic use and discontinuation using both data types. Discontinuation definitions were based on (1) gaps in medication availability during follow-up or (2) not having medication available at a fixed time point. We examined the impact of varying the gap length and requiring a 30-day period without orders/dispensings ("halo") around the fixed time point. We compared results derived from orders versus dispensings at one site. RESULTS:Approximately 1.6%-2.6% of older adults had chronic benzodiazepine/Z-drug use (total N = 6775, ranging from 431 to 2122 across sites). Depending on the definition and site, the proportion discontinuing use during 12 months ranged from 6% to 49%. Requiring a longer gap or a 30-day "halo" resulted in lower estimates. At one site, only 56% of those with chronic use defined from orders also qualified based on dispensings, and the discontinuation rate at 180 days was 20% from orders versus 32% from dispensings. CONCLUSIONS:Requiring a gap of ≥90 days or a "halo" around a time point may more accurately capture discontinuation than using a shorter gap or no halo. Orders data underestimate discontinuation compared to dispensings. Work is needed to adapt these definitions for other drug classes and settings.

The global rise in polypharmacy has increased both the necessity and complexity of drug-drug interaction (DDI) assessments, given the growing potential for interactions involving more than two drugs. Leveraging large-scale healthcare claims data, we piloted a semi-automated, high-throughput case-crossover-based approach for drug-drug-drug interaction (3DI) screening. Cases were direct-acting oral anticoagulant (DOAC) users with either a major bleeding event during ongoing dispensings for potentially interacting, enzyme-inhibiting antihypertensive drugs (AHDs) (Study 1), or a thromboembolic event during ongoing dispensings for potentially interacting, enzyme-inducing antiseizure medications (ASMs) (Study 2). 3DI detection was based on screening for additional drug exposures that served as acute outcome triggers. To mitigate direct effects and confounding by concomitant drugs, self-controlled estimates were adjusted using negative cases (external "control" DOAC users with the same outcomes but co-dispensings for non-interacting AHDs or ASMs). Signal thresholds were set based on P-values and false discovery rate q-values to address multiple comparisons. Study 1: 285 drugs were examined among 3,306 episodes. Self-controlled assessments with q-value thresholds yielded 9 3DI signals (cases) and 40 DDI signals (negative cases). External adjustment generated 10 3DI signals from the P-value threshold and no signals from the q-value threshold. Study 2: 126 drugs were examined among 604 episodes. Assessments with P-value thresholds yielded 3 3DI and 26 DDI signals following self-control, as well as 4 3DI signals following adjustment. No 3DI signals met the q-value threshold. The presented self- and externally-controlled approach aimed to advance paradigms for real-world higher order drug interaction screening among high-susceptibility populations with pre-existent DDI risk.

BACKGROUND AND OBJECTIVES:It is widely cited that dementia occurs in up to 80% of patients with Parkinson disease (PD), but studies reporting such high rates were published over two decades ago, had relatively small samples, and had other limitations. We aimed to determine long-term dementia risk in PD using data from two large, ongoing, prospective, observational studies. METHODS:Participants from the Parkinson's Progression Markers Initiative (PPMI), a multisite international study, and a long-standing PD research cohort at the University of Pennsylvania (Penn), a single site study at a tertiary movement disorders center, were recruited. PPMI enrolled de novo, untreated PD participants and Penn a convenience cohort from a large clinical center. For PPMI, a cognitive battery is administered annually, and a site investigator makes a cognitive diagnosis. At Penn, a comprehensive cognitive battery is administered either annually or biennially, and a cognitive diagnosis is made by expert consensus. Interval-censored survival curves were fit for time from PD diagnosis to stable dementia diagnosis for each cohort, using cognitive diagnosis of dementia as the primary end point and Montreal Cognitive Assessment (MoCA) score <21 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I cognition score ≥3 as secondary end points for PPMI. In addition, estimated dementia probability by PD disease duration was tabulated for each study and end point. RESULTS:For the PPMI cohort, 417 participants with PD (mean age 61.6 years, 65% male) were followed, with an estimated probability of dementia at year 10 disease duration of 9% (site investigator diagnosis), 15% (MoCA), or 12% (MDS-UPDRS Part I cognition). For the Penn cohort, 389 participants with PD (mean age 69.3 years, 67% male) were followed, with 184 participants (47% of cohort) eventually diagnosed with dementia. The interval-censored curve for the Penn cohort had a median time to dementia of 15 years (95% CI 13-15); the estimated probability of dementia was 27% at 10 years of disease duration, 50% at 15 years, and 74% at 20 years. DISCUSSION:Results from two large, prospective studies suggest that dementia in PD occurs less frequently, or later in the disease course, than previous research studies have reported.

BACKGROUND:Deprescribing of potentially inappropriate medications is recommended for older adults and may improve health outcomes and quality of life in persons living with Parkinson disease (PD). Patient attitudes, beliefs, and preferences play a crucial role in the success of deprescribing interventions. We aimed to examine the attitudes and beliefs about medication burden and deprescribing among persons living with PD. METHODS:We administered a survey to participants of Fox Insight, a prospective longitudinal study of persons living with PD. The survey included the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire and additional questions about adverse drug effects. We used logistic regression models to explore potential predictors of treatment dissatisfaction and willingness to deprescribe. RESULTS:Of the 4945 rPATD respondents, 31.6% were dissatisfied with their current medications, and 87.1% would be willing to deprescribe medications. Male sex was associated with a greater willingness to deprescribe (adjusted odds ratio [aOR] 1.62, 95% confidence interval [CI] 1.37-1.93). A greater belief that the medication burden was high or that some medications were inappropriate was associated with treatment dissatisfaction (aORs 3.74, 95% CI 3.26-4.29 and 5.61, 95% CI 4.85-6.50), and more willingness to deprescribe (aORs 1.74, 95% CI 1.47-2.06 and 2.87, 95% CI 2.41-3.42). Cognitive impairment was the adverse drug effect participants were most concerned about when prescribed new medications to treat nonmotor symptoms. CONCLUSIONS:Persons with PD are often dissatisfied with their overall medication load and are open to deprescribing. Medications that are associated with cognitive impairment might be prioritized targets for deprescribing interventions in this population.

BACKGROUND:Visual impairment (VI) is associated with dementia and other neuropsychiatric outcomes, but previous studies have not considered genetic sources of confounding or effect modification. METHODS:We analysed data from the Health and Retirement Study, an ongoing nationally representative survey of older US adults, a subset of whom underwent genetic testing from 2006 to 2012 (n = 13 465). Using discrete time proportional hazards models and generalised estimating equations, we measured the association between VI and dementia, depression and hallucinations adjusting for demographics and comorbidities, ancestry-specific principal components and polygenic risk scores (PRS) for Alzheimer's disease, major depressive disorder or schizophrenia. Effect modification was assessed using VI-PRS interaction terms and stratified analyses. RESULTS:VI was associated with dementia, depression and hallucinations after adjusting polygenic risk and other confounders. There was no VI-PRS interaction for dementia or depression. However, the association between VI and hallucinations varied by genetic risk of schizophrenia. Within the bottom four quintiles of schizophrenia PRS, VI was not associated with hallucinations among White (OR 1.16, 95% CI: 0.87-1.55) or Black participants (OR 0.96, 95% CI: 0.49-1.89). In contrast, VI was strongly associated with hallucinations among White (OR 2.08, 95% CI: 1.17-3.71) and Black (OR 10.63, 95% CI: 1.74-65.03) participants in the top quintile of schizophrenia PRS. CONCLUSIONS:The association between VI and neuropsychiatric outcomes is not explained by shared genetic risk factors, and there is a significant interaction between VI and polygenic risk of hallucinations in older adults.

BACKGROUND AND OBJECTIVES:Although neurodegenerative diseases are a leading cause of death, little is known about health care utilization and cost during the end-of-life (EoL) period or how it compares with that of other life-limiting conditions. We aimed to describe and compare resource utilization among US Medicare decedents with neurodegenerative diseases with decedents with cancer. METHODS:We conducted a retrospective study of Medicare Part A and B beneficiaries with Alzheimer disease (AD), Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS) who died in 2018. Decedents diagnosed with malignant brain tumors or pancreatic cancer served as non-neurodegenerative comparators. Descriptive analyses examined demographic and clinical characteristics in the last year of life. The probabilities and associated costs of emergency department (ED), inpatient, skilled nursing facility (SNF), and hospice utilization during the last 12 and 6 months of life were also compared between persons with neurodegenerative diseases and cancer, adjusting for sociodemographic factors and comorbidity burden. RESULTS:A total of 1,126,799 Medicare beneficiaries died in 2018, of which 357,926 had a qualifying diagnosis. Persons with neurodegenerative diseases were older and more frequently received Medicaid assistance than persons with brain or pancreatic cancer. In all groups, health care service utilization increased over the last year of life, and total costs were predominantly attributable to inpatient care. In the last 6 months of life, neurologist care was infrequent among patients with neurodegenerative disease (AD: 1.5%; PD: 8.6%; ALS: 32.0%). Persons with neurodegenerative diseases as compared to persons with malignant brain tumors also had greater odds of ED use (AD: adjusted odds ratio [aOR] 1.17, 95% CI 1.11-1.23; PD: aOR 1.18, 95% CI 1.11-1.25; ALS: aOR 1.11, 95% CI 1.01-1.23), lower odds of hospitalization (AD: aOR 0.64, 95% CI 0.60-0.68; PD: aOR 0.65, 95% CI 0.61-0.69; ALS: aOR 0.33, 95% CI 0.30-0.37), and lower odds of hospice enrollment (AD: aOR 0.33, 95% CI 0.31-0.36; PD: aOR 0.33, 95% CI 0.31-0.36; ALS: aOR 0.41, 95% CI 0.36-0.46). The findings were similar in pancreatic cancer. DISCUSSION:Persons with neurodegenerative diseases in the United States are more likely to visit the ED and less likely to use inpatient and hospice services at EoL than persons with brain or pancreatic cancer. These group differences may stem from prognostic uncertainty and reflect inadequate EoL care practices, requiring further investigation to ensure more timely palliative care and hospice referrals.

Importance Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency of and the association between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing (EI) ASMs may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk. Objective To assess the rates of thromboembolic and major bleeding events in adults with AF and epilepsy dispensed DOACs and EI ASMs vs DOACs with non-EI ASMs. Design, Setting, and Participants This active-comparator, new-user cohort study included US health care data from the Clinformatics Data Mart database from October 2010 to September 2021 for a nationally representative population of adults with AF and epilepsy. Exposure Evaluations included episodes of contiguous coadministration of DOACs for AF with EI ASMs (exposed) or non-EI ASMs (referent) for epilepsy. Main Outcomes and MeasuresThromboembolic events (primary outcome) and major bleeding events (secondary outcome) were identified based on a series of validated, diagnosis-based coding algorithms. Data-adaptive, high-dimensional propensity score matching was used to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regression models with robust variance estimators to account for clustering within matched pairs. Results This study included 14 078 episodes (median age, 74 [IQR, 67-81]; 52.4% female) and 14 158 episodes (median age, 74 [IQR, 67-81]; 52.4% female) of incident DOAC and ASM use that met eligibility criteria for assessment of thromboembolic and major bleeding outcomes, respectively. Incidence was 88.5 per 1000 person-years for thromboembolic events and 68.3 per 1000 person-years for bleeding events. Compared with use of non-EI ASMs, use of EI ASMs with DOACs was not associated with a difference in risk of thromboembolic events (AHR, 1.10; 95% CI, 0.82-1.46) but was associated with a reduction in risk of major bleeding events (AHR, 0.63; 95% CI, 0.44-0.89). Conclusions and RelevanceIn this cohort study, EI ASMs were not associated with alteration in DOAC efficacy. Further research is needed on the reduction in bleeding risk associated with EI ASMs, as this may suggest that pharmacokinetic interactions are associated with lowering DOAC levels without negating therapeutic effects.

Background High-dimensional propensity scoring (HDPS) is a method for empirically identifying potential confounders within large healthcare databases such as administrative claims data. However, this method has not yet been applied to large national health surveys such as the National Health and Aging Trends Study (NHATS), an ongoing nationally representative survey of older adults in the United States and important resource in gerontology research.Methods In this Research Practice article, we present an overview of HDPS and describe the specific data transformation steps and analytic considerations needed to apply it to national health surveys. We applied HDPS within NHATS to investigate the association between self-reported visual difficulty and incident dementia, comparing HDPS to conventional confounder selection methods.Results Among 7 207 dementia-free NHATS Wave 1 respondents, 528 (7.3%) had self-reported visual difficulty. In an unadjusted discrete time proportional hazards model accounting for the complex survey design of NHATS, self-reported visual difficulty was strongly associated with incident dementia (odds ratio [OR] 2.34, 95% confidence interval [CI]: 1.95-2.81). After adjustment for standard investigator-selected covariates via inverse probability weighting, the magnitude of this association decreased, but evidence of an association remained (OR 1.44, 95% CI: 1.11-1.85). Adding 75 HDPS-prioritized variables to the investigator-selected propensity score model resulted in further attenuation of the association between visual impairment and dementia (OR 0.94, 95% CI: 0.70-1.23).Conclusions HDPS can be successfully applied to national health surveys such as NHATS and may improve confounder adjustment. We hope developing this framework will encourage future consideration of HDPS in this setting.

BACKGROUND:Population reflective research enrollment improves study generalizability and disease knowledge. Nevertheless, the proportion of underrepresented groups (URGs) in Parkinson's disease (PD) research remains low. Hence, the current manuscript describes the process of designing a study to analyze the effectiveness of strategies to overcome barriers to URG recruitment in PD research.METHODS:The Fostering Inclusivity in Research Engagement for Underrepresented Populations in Parkinson's Disease (FIRE-UP PD) study asked participating sites to identify a URG or geographical region to target to assess knowledge and attitudes toward PD research as well as increase Fox Insight (an online study with The Michael J. Fox Foundation) participation across eight months. URGs were defined as racial and ethnic minorities, women, rural populations, and low socioeconomic status groups. Participating sites were paired based on their proposed interventions and were randomly assigned to either the intervention or control condition.RESULTS:The FIRE-UP PD study was divided into pre-intervention, intervention, and post-intervention periods to measure changes in awareness and trust in PD research along with engagement and interest in PD protocols through the use of several surveys. Interventions included developing educational tools to engage local communities, building partnerships within local PD communities, and recruiting stakeholders to reimagine medical and research information for the community.CONCLUSION:Improving representation in research is a crucial step toward improving access to PD diagnoses and treatments. This is one of the first multi-site PD research studies to include community engagement to address barriers to research participation and improve research recruitment of URGs.

Observational studies in Parkinson's disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular and clinical features of every PD patient at the University of Pennsylvania (UPenn). The objectives of this study are to determine the feasibility of genetic characterization in PD and assess clinical features by sex and GBA1/LRRK2 status on a clinic-wide scale. All PD patients with clinical visits at the UPenn PD Center between 9/2018 and 12/2022 were eligible. Blood or saliva were collected, and a clinical questionnaire administered. Genotyping at 14 GBA1 and 8 LRRK2 variants was performed. PD symptoms were compared by sex and gene groups. 2063 patients were approached and 1,689 (82%) were enrolled, with 374 (18%) declining to participate. 608 (36%) females were enrolled, 159 (9%) carried a GBA1 variant, and 44 (3%) carried a LRRK2 variant. Compared with males, females across gene groups more frequently reported dystonia (53% vs 46%, p = 0.01) and anxiety (64% vs 55%, p < 0.01), but less frequently reported cognitive impairment (10% vs 49%, p < 0.01) and vivid dreaming (53% vs 60%, p = 0.01). GBA1 variant carriers more frequently reported anxiety (67% vs 57%, p = 0.04) and depression (62% vs 46%, p < 0.01) than non-carriers; LRRK2 variant carriers did not differ from non-carriers. We report feasibility for near-clinic-wide enrollment and characterization of individuals with PD during clinical visits at a high-volume academic center. Clinical symptoms differ by sex and GBA1, but not LRRK2, status.