Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians.

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

Optimizing Screening for Intrastriatal Interventions in Huntington's Disease Using Predictive Models.

BACKGROUND: Intrastriatal delivery of potential therapeutics in Huntington's disease (HD) requires sufficient caudate and putamen volumes. Currently, volumetric magnetic resonance imaging is rarely done in clinical practice, and these data are not available in large research cohorts such as Enroll-HD. OBJECTIVE: The objective of this study was to investigate whether predictive models can accurately classify HD patients who exceed caudate and putamen volume thresholds required for intrastriatal therapeutic interventions. METHODS: We obtained and merged data for 1374 individuals across three HD cohorts: IMAGE-HD, PREDICT-HD, and TRACK-HD/TRACK-ON. We imputed missing data for clinical variables with >72% non-missing values and used the model-building algorithm BORUTA to identify the 10 most important variables. A random forest algorithm was applied to build a predictive model for putamen volume >2500 mm3 and caudate volume >2000 mm3 bilaterally. Using the same 10 predictors, we constructed a logistic regression model with predictors significant at P < 0.05. RESULTS: The random forest model with 1000 trees and minimal terminal node size of 5 resulted in 83% area under the curve (AUC). The logistic regression model retaining age, CAG repeat size, and symbol digit modalities test-correct had 85.1% AUC. A probability cutoff of 0.8 resulted in 5.4% false positive and 66.7% false negative rates. CONCLUSIONS: Using easily obtainable clinical data and machine learning-identified initial predictor variables, random forest, and logistic regression models can successfully identify people with sufficient striatal volumes for inclusion cutoffs. Adopting these models in prescreening could accelerate clinical trial enrollment in HD and other neurodegenerative disorders when volume cutoffs are necessary enrollment criteria. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The gephyrin scaffold modulates cortical layer 2/3 pyramidal neuron responsiveness to single whisker stimulation.

Gephyrin is the main scaffolding protein at inhibitory postsynaptic sites, and its clusters are the signaling hubs where several molecular pathways converge. Post-translational modifications (PTMs) of gephyrin alter GABAA receptor clustering at the synapse, but it is unclear how this affects neuronal activity at the circuit level. We assessed the contribution of gephyrin PTMs to microcircuit activity in the mouse barrel cortex by slice electrophysiology and in vivo two-photon calcium imaging of layer 2/3 (L2/3) pyramidal cells during single-whisker stimulation. Our results suggest that, depending on the type of gephyrin PTM, the neuronal activities of L2/3 pyramidal neurons can be differentially modulated, leading to changes in the size of the neuronal population responding to the single-whisker stimulation. Furthermore, we show that gephyrin PTMs have their preference for selecting synaptic GABAA receptor subunits. Our results identify an important role of gephyrin and GABAergic postsynaptic sites for cortical microcircuit function during sensory stimulation.

Efficacy of the iron-chelating agent, deferiprone, in patients with Parkinson's disease: A systematic review and meta-analysis.

INTRODUCTION: Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have examined the efficacy of using the iron-chelating agent Deferiprone (DFP) for patients with PD. We conducted this meta-analysis to summarize and synthesize evidence from published randomized controlled trials about the efficacy of DFP for PD patients. METHODS: A comprehensive literature search of four electronic databases was performed, spanning until February 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan software. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS-III). RESULTS: Three RCTs with 431 patients were included in this analysis. DFP did not significantly improve UPDRS-III score compared to placebo (Standardized mean difference -0.06, 95% CI [-0.69, 0.58], low certainty evidence). However, it significantly reduced iron accumulation in the substantia nigra, putamen, and caudate as measured by T2*-weighted MRI (with high certainty evidence). CONCLUSION: Current evidence does not support the use of DFP in PD patients. Future disease-modification trials with better population selection, adjustment for concomitant medications, and long-term follow up are recommended.

Low-Income Older Adults' Vulnerability to Anticholinergic Medication-Associated Frailty.

BACKGROUND: A growing body of research supports the negative impact of anticholinergic drug burden on physical frailty. However, prior research has been limited to homogeneous white European populations, and few studies have evaluated how anticholinergic burden tools compare in their measurement function and reliability with minority community-dwelling adult populations. This study investigated the association between anticholinergic drug exposure and frailty by conducting a sensitivity analysis using multiple anticholinergic burden tools in a diverse cohort. METHODS: A comprehensive psychometric approach was used to assess the performance of five clinical Anticholinergic Burden Tools: Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), average daily dose, total standardized daily doses (TSDD), and Cumulative Anticholinergic Burden scale (CAB). Spearman correlation matrix and intraclass correlation coefficients (ICC) were used to determine the association among the variables. Ordinal logistic regression is used to evaluate the anticholinergic burden measured by each scale to determine the prediction of frailty. Model performance is determined by the area under the curve (AUC). RESULTS: The cohort included 80 individuals (mean age 69 years; 55.7% female, 71% African American). All anticholinergic burden tools were highly correlated (p < 0.001), ICC3 0.66 (p < 0.001, 95% confidence interval (CI) 0.53-0.73). Among individuals prescribed anticholinergics, 33% were robust, 44% were prefrail, and 23% were frail. All five tools predicted prefrail and frail status (p < 0.05) with low model misclassification rates for frail individuals (AUC range 0.78-0.85). CONCLUSION: Anticholinergic burden tools evaluated in this cohort of low-income African American older adults were highly correlated and predicted prefrail and frail status. Findings indicate that clinicians can select the appropriate instrument for the clinic setting and research question while maintaining confidence that all five tools will produce reliable results. Future anticholinergic research is needed to unravel the association between interventions such as deprescribing on incident frailty in longitudinal data.

Heart failure virtual consultation: caters for frailer, multimorbid and remote patients.

BACKGROUND: The heart failure (HF) virtual consultation (VC) is an eHealth tool for delivery of peer-to-peer specialist advice to general practitioners (GPs) to discuss HF diagnosis/management. We aim to investigate the impact of the VC service on onward referral rate and quality of assessment by GPs, as well as assess VC patient characteristics; Clinical Frailty Score (CSF), age and morbidity. METHODS: This prospective observational study collected VC data on: demographics, comorbidity, frailty, referral indication, the impact of VC on clinical care and the GP response to the question 'what would you have done without the VC service'. We compared patient characteristics to a control population of patients attending the HF unit (HFU) (n=118). REULTS: Between 2015 and 2021, 1681 VC cases were discussed. The majority of cases were discussed from remote areas (75%). Rediscussion cases increased from 0% to 34%. VC patients were older (76.2 (±11.3) vs 73.1 (±12.5) years, p<0.05), more frail (CSF=3.8 (±1.7) vs 3 (±1.6), p<0.01) and multimorbid (number of comorbidities=7.1 (±3.4) vs 3.8 (±1.9), p<0.001) compared with patients attending the HFU. Without the VC, 93% of cases would have been referred to face-to-face hospital services. Instead, VC resulted in only 9% of cases being referred to hospital services. The remainder of cases were managed by the VC service, in a shared GP-specialist approach. GP use of natriuretic peptide (NP) increased from 0% in 2015-2016 to 63% in 2021 and use of TTE increased from 0% in 2015-2016 to 69% by 2021. CONCLUSIONS: The VC service provides a platform for case discussion in particular for older, frailer patients and reduces onward hospital referrals. This may facilitate early diagnosis and management of suspected HF in the current era of long outpatient waiting times. The quality of community HF assessment improved as indicated by increased use of NP/TTE by GPs.

Challenges in heart failure care in four European countries: a comparative study.

BACKGROUND: In Europe, more than 15 million people live with heart failure (HF). It imposes an enormous social, organizational and economic burden. As a reaction to impending impact on healthcare provision, different country-specific structures for HF-care have been established. The aim of this report is to provide an overview and compare the HF-care approaches of Germany, Ireland, the Netherlands and the UK, and to open the possibility of learning from each other's experience. METHODS: A mixed methods approach was implemented that included a literature analysis, interviews and questionnaires with HF-patients and caregivers, and expert interviews with representatives from healthcare, health service research and medical informatics. RESULTS: The models of HF-care in all countries analyzed are based on the European Society of Cardiology guidelines for diagnosis and treatment of HF. Even though the HF-models differed in design and implementation in practice, key challenges were similar: (i) unequal distribution of care between urban and rural areas, (ii) long waiting times, (iii) unequal access to and provision of healthcare services, (iv) information and communication gaps and (v) inadequate implementation and financing of digital applications. CONCLUSION: Although promising approaches exist to structure and improve HF-care, across the four countries, implementation was reluctant to embrace novel methods. A lack of financial resources and insufficient digitalization making it difficult to adopt new concepts. Integration of HF-nurses seems to be an effective way of improving current models of HF-care. Digital solutions offer further opportunities to overcome communication and coordination gaps and to strengthen self-management skills.

Triceps Split and Snip Approach for Distal Humerus Fractures.

Background: The senior author adopted a Triceps Split and Snip approach in 2011. This paper details the results of patients for whom this approach was utilised for open reduction and internal fixation of complex AO type C distal humerus fractures. Methods: A retrospective analysis of a single surgeon's cases was conducted. Range of movement, as well as Mayo Elbow Performance Score (MEPS), and QuickDASH scores were evaluated. Two independent consultants with upper extremity practises evaluated pre- and post-operative radiographs. Results: Seven patients were available for clinical review. The mean age at the time of surgery was 47.7 years (range, 20.3-83.2) and the mean follow-up time was 3.6 years (range, 0.58-8). The average QuickDASH score was 15.85 (range, 0-52.3), average MEPS was 86.88 (range, 60-100) and average total arc of movement (TAM) was 103° (range, 70°-145°). All patients demonstrated 5/5 MRC triceps strength compared to the contralateral side. Conclusions: The Triceps Split and Snip approach for complex distal humerus fractures provided comparable mid-term clinical outcomes when compared to other published data regarding distal humerus fractures. It is versatile and does not compromise the intra-operative option of conversion to a total elbow arthroplasty. Level of Evidence: Level IV (Therapeutic).

Cholinergic Nucleus 4 Degeneration and Cognitive Impairment in Isolated Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD). OBJECTIVE: The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment. METHODS: We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age- and sex-matched healthy controls. Regional gray matter density (GMD) was calculated for Ch4 using probabilistic maps applied to brain magnetic resonance imaging (MRI). RESULTS: Ch4 GMD was significantly lower in the iRBD group compared to controls (0.417 vs. 0.441, P = 0.02). Ch4 GMD was also found to be a significant predictor of letter number sequencing (ß-coefficient = 58.31, P = 0.026, 95% confidence interval [7.47, 109.15]), a measure of working memory. CONCLUSIONS: iRBD is associated with Ch4 degeneration, and Ch4 degeneration in iRBD is associated with impairment in working memory. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cholinergic nucleus 4 grey matter density is associated with apathy in Parkinson's disease.

Objective: The generation and maintenance of goal-directed behavior is subserved by multiple brain regions that receive cholinergic inputs from the cholinergic nucleus 4 (Ch4). It is unknown if Ch4 degeneration contributes to apathy in Parkinson's disease (PD). Method: We analyzed data from 106 pre-surgical patients with PD who had brain MRIs and completed the Frontal Systems Behavior Scales (FrSBe). Eighty-eight patients also completed the Beck Depression Inventory-2nd Edition. Cholinergic basal forebrain grey matter densities (GMD) were measured by applying probabilistic maps to T1 MPRAGE sequences processed using voxel-based morphometry methods. We used linear and hierarchical regression modelling to examine the association between Ch4 GMD and the FrSBe Apathy subscale scores. We used similar methods to assess the specificity of this association and potential associations between Ch4 target regions and apathy. Results: Ch4 GMD (p = .021) and Ch123 GMD (p = .032) were significantly associated with Apathy subscale scores on univariate analysis. Ch4 GMD, but not Ch123 GMD, remained significantly associated with apathy when adjusting for age, sex, levodopa equivalent doses, and disease duration. Centromedial amygdala GMD, which receives cholinergic inputs from Ch4, was also associated with apathy. Ch4 GMD was not associated with depression or disinhibition, nor was it associated with executive dysfunction when adjusting for clinical and demographic variables. Conclusions: Ch4 GMD is specifically associated with apathy in PD. Ch4 degeneration results in cholinergic denervation of multiple cortical and limbic regions, which may contribute to the cognitive and emotional-affective processing deficits that underlie the behavioral symptoms of apathy.

Altered hemodynamics and vascular reactivity in a mouse model with severe pericyte deficiency.

Pericytes are the mural cells of the microvascular network that are in close contact with underlying endothelial cells. Endothelial-secreted PDGFB leads to recruitment of pericytes to the vessel wall, but this is disrupted in Pdgfbret/ret mice when the PDGFB retention motif is deleted. This results in severely reduced pericyte coverage on blood vessels. In this study, we investigated vascular abnormalities and hemodynamics in Pdgfbret/ret mice throughout the cerebrovascular network and in different cortical layers by in vivo two-photon microscopy. We confirmed that Pdgfbret/ret mice are severely deficient in pericytes throughout the vascular network, with enlarged brain blood vessels and a reduced number of vessel branches. Red blood cell velocity, linear density, and tube hematocrit were reduced in Pdgfbret/ret mice, which may impair oxygen delivery to the tissue. We also measured intravascular PO2 and found that concentrations were higher in cortical Layer 2/3 in Pdgfbret/ret mice, indicative of reduced blood oxygen extraction. Finally, we found that Pdgfbret/ret mice had a reduced capacity for vasodilation in response to an acetazolamide challenge during functional MRI imaging. Taken together, these results suggest that severe pericyte deficiency can lead to vascular abnormalities and altered cerebral blood flow, reminiscent of pathologies such as arteriovenous malformations.

One Minute of EEG Data Provides Sufficient and Reliable Data for Identifying Lewy Body Dementia.

OBJECTIVE: To determine the minimum duration of electroencephalography (EEG) data necessary to differentiate EEG features of Lewy body dementia (LBD), that is, dementia with Lewy bodies and Parkinson disease dementia, from non-LBD patients, that is, Alzheimer disease and Parkinson disease. METHODS: We performed quantitative EEG analysis for 16 LBD and 14 non-LBD patients. After artifact removal, a fast Fourier transform was performed on 90, 60, and thirty 2-second epochs to derive dominant frequency; dominant frequency variability; and dominant frequency prevalence. RESULTS: In LBD patients, there were no significant differences in EEG features derived from 90, 60, and thirty 2-second epochs (all P >0.05). There were no significant differences in EEG features derived from 3 different groups of thirty 2-second epochs (all P >0.05). When analyzing EEG features derived from ninety 2-second epochs, we found that LBD had significantly reduced dominant frequency, reduced dominant frequency variability, and reduced dominant frequency prevalence alpha compared with the non-LBD group (all P <0.05). These same differences were observed between the LBD and non-LBD groups when analyzing thirty 2-second epochs. CONCLUSIONS: There were no differences in EEG features derived from 1 minute versus 3 minutes of EEG data, and both durations of EEG data equally differentiated LBD from non-LBD.

Clinical effectiveness of patellar resurfacing, no resurfacing and selective resurfacing in primary total knee replacement: systematic review and meta-analysis of interventional and observational evidence.

BACKGROUND: Patellar resurfacing is optional during total knee replacement (TKR). Some surgeons always resurface the patella, some never resurface, and others selectively resurface. Which resurfacing strategy provides optimal outcomes is unclear. We assessed the effectiveness of patellar resurfacing, no resurfacing, and selective resurfacing in primary TKR. METHODS: A systematic review and meta-analysis was performed. MEDLINE, Embase, Web of Science, The Cochrane Library, and bibliographies were searched to November 2021 for randomised-control trials (RCTs) comparing outcomes for two or more resurfacing strategies (resurfacing, no resurfacing, or selective resurfacing) in primary TKR. Observational studies were included if limited or no RCTs existed for resurfacing comparisons. Outcomes assessed were patient reported outcome measures (PROMs), complications, and further surgery. Study-specific relative risks [RR] were aggregated using random-effects models. Quality of the evidence was assessed using GRADE. RESULTS: We identified 33 RCTs involving 5,540 TKRs (2,727 = resurfacing, 2,772 = no resurfacing, 41 = selective resurfacing). One trial reported on selective resurfacing. Patellar resurfacing reduced anterior knee pain compared with no resurfacing (RR = 0.65 (95% CI = 0.44-0.96)); there were no significant differences in PROMs. Resurfacing reduced the risk of revision surgery (RR = 0.63, CI = 0.42-0.94) and other complications (RR = 0.54, CI = 0.39-0.74) compared with no resurfacing. Quality of evidence ranged from high to very low. Limited observational evidence (5 studies, TKRs = 215,419) suggested selective resurfacing increased the revision risk (RR = 1.14, CI = 1.05-1.22) compared with resurfacing. Compared with no resurfacing, selective resurfacing had a higher risk of pain (RR = 1.25, CI = 1.04-1.50) and lower risk of revision (RR = 0.92, CI = 0.85-0.99). CONCLUSIONS: Level 1 evidence supports TKR with patellar resurfacing over no resurfacing. Resurfacing has a reduced risk of anterior knee pain, revision surgery, and complications, despite PROMs being comparable. High-quality RCTs involving selective resurfacing, the most common strategy in the UK and other countries, are needed given the limited observational data suggests selective resurfacing may not be effective over other strategies.

Bearing allostatic load: insights into a more equitable future within cardio-oncology.

Chronic stress is often regarded as a significant cause of morbidity and mortality; however, the mechanistic link between stress and various disease states has not yet been fully characterized. We explore the concept of allostatic load, a measurement of the physiological burden of chronic stress, as well as its potential role in disease pathogenesis as it relates to cardiovascular disease, cancer, and health-related disparities. Building from this framework, we then posit the potential implications of allostatic load on patient care and research in cardio-oncology. We identify allostatic load as a potential clinically actionable tool to improve health equity in cardio-oncology.

Disruption of proteostasis causes IRE1 mediated reprogramming of alveolar epithelial cells.

Disruption of alveolar type 2 cell (AEC2) protein quality control has been implicated in chronic lung diseases, including pulmonary fibrosis (PF). We previously reported the in vivo modeling of a clinical surfactant protein C (SP-C) mutation that led to AEC2 endoplasmic reticulum (ER) stress and spontaneous lung fibrosis, providing proof of concept for disruption to proteostasis as a proximal driver of PF. Using two clinical SP-C mutation models, we have now discovered that AEC2s experiencing significant ER stress lose quintessential AEC2 features and develop a reprogrammed cell state that heretofore has been seen only as a response to lung injury. Using single-cell RNA sequencing in vivo and organoid-based modeling, we show that this state arises de novo from intrinsic AEC2 dysfunction. The cell-autonomous AEC2 reprogramming can be attenuated through inhibition of inositol-requiring enzyme 1 (IRE1α) signaling as the use of an IRE1α inhibitor reduced the development of the reprogrammed cell state and also diminished AEC2-driven recruitment of granulocytes, alveolitis, and lung injury. These findings identify AEC2 proteostasis, and specifically IRE1α signaling through its major product XBP-1, as a driver of a key AEC2 phenotypic change that has been identified in lung fibrosis.

A lineage-specific Exo70 is required for receptor kinase-mediated immunity in barley.

In the evolution of land plants, the plant immune system has experienced expansion in immune receptor and signaling pathways. Lineage-specific expansions have been observed in diverse gene families that are potentially involved in immunity but lack causal association. Here, we show that Rps8-mediated resistance in barley to the pathogen Puccinia striiformis f. sp. tritici (wheat stripe rust) is conferred by a genetic module: Pur1 and Exo70FX12, which are together necessary and sufficient. Pur1 encodes a leucine-rich repeat receptor kinase and is the ortholog of rice Xa21, and Exo70FX12 belongs to the Poales-specific Exo70FX clade. The Exo70FX clade emerged after the divergence of the Bromeliaceae and Poaceae and comprises from 2 to 75 members in sequenced grasses. These results demonstrate the requirement of a lineage-specific Exo70FX12 in Pur1-mediated immunity and suggest that the Exo70FX clade may have evolved a specialized role in receptor kinase signaling.

Prodromal Dementia With Lewy Bodies: Evolution of Symptoms and Predictors of Dementia Onset.

BACKGROUND: Research criteria for prodromal dementia with Lewy bodies (DLB) were published in 2020, but little is known regarding prodromal DLB in clinical settings. METHODS: We identified non-demented participants without neurodegenerative disease from the National Alzheimer's Coordinating Center Uniform Data Set who converted to DLB at a subsequent visit. Prevalence of neuropsychiatric and motor symptoms were examined up to 5 years prior to DLB diagnosis. RESULTS: The sample included 116 participants clinically diagnosed with DLB and 348 age and sex-matched (1:3) Healthy Controls. Motor slowing was present in approximately 70% of participants 3 years prior to DLB diagnosis. In the prodromal phase, 50% of DLB participants demonstrated gait disorder, 70% had rigidity, 20% endorsed visual hallucinations, and over 50% of participants endorsed REM sleep behavior disorder. Apathy, depression, and anxiety were common prodromal neuropsychiatric symptoms. The presence of 1+ core clinical features of DLB in combination with apathy, depression, or anxiety resulted in the greatest AUC (0.815; 95% CI: 0.767, 0.865) for distinguishing HC from prodromal DLB 1 year prior to diagnosis. The presence of 2+ core clinical features was also accurate in differentiating between groups (AUC = 0.806; 95% CI: 0.756, 0.855). CONCLUSION: A wide range of motor, neuropsychiatric and other core clinical symptoms are common in prodromal DLB. A combination of core clinical features, neuropsychiatric symptoms and cognitive impairment can accurately differentiate DLB from normal aging prior to dementia onset.

Anticholinergic Medication Burden in Parkinson's Disease Outpatients.

BACKGROUND: Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications. OBJECTIVE: To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients. METHODS: We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Drug Burden Index-Anticholinergic component (DBI-Ach). Correlations between scales were assessed with weighted kappa coefficients. RESULTS: Between 31.5 to 46.3% of PD patients were taking medications with anticholinergic properties. Among the scales applied, the ACB produced the highest prevalence of medications with anticholinergic properties (46.3%). Considering only medications with definite anticholinergic activity (scores of 2 or 3 on ACB, ADS, or ARS), the most common anticholinergic drug classes were antiparkinsonian (8.2%), antipsychotic (6.4%), and urological (3.3%) medications. Cholinesterase inhibitors and medications with anticholinergic properties were co-prescribed to 5.4% of the total cohort. The most highly correlated scales were ACB and ADS (κ= 0.71), ACB and ARS (κ= 0.67), and ADS and ARS (κ= 0.55). CONCLUSION: A high proportion of PD patients (20%) were either taking antiparkinsonian, urological, or antipsychotic anticholinergic medications or were co-prescribed anticholinergic medications and cholinesterase inhibitors. By virtue of its detection of a high prevalence of anticholinergic medication usage and its high correlation with other scales, our data support use of the ACB scale to assess anticholinergic burden in PD patients.