Immune cell kinetics and antibody response in COVID-19 patients with low-count monoclonal B-cell lymphocytosis.

Low-count monoclonal B-cell lymphocytosis (MBLlo ) has been associated with an underlying immunodeficiency and has recently emerged as a new risk factor for severe COVID-19. Here, we investigated the kinetics of immune cell and antibody responses in blood during COVID-19 of MBLlo versus non-MBL patients. For this study, we analyzed the kinetics of immune cells in blood of 336 COVID-19 patients (74 MBLlo and 262 non-MBL), who had not been vaccinated against SARS-CoV-2, over a period of 43 weeks since the onset of infection, using high-sensitivity flow cytometry. Plasma levels of anti-SARS-CoV-2 antibodies were measured in parallel by ELISA. Overall, early after the onset of symptoms, MBLlo COVID-19 patients showed increased neutrophil, monocyte, and particularly, plasma cell (PC) counts, whereas eosinophil, dendritic cell, basophil, and lymphocyte counts were markedly decreased in blood of a variable percentage of samples, and with a tendency toward normal levels from week +5 of infection onward. Compared with non-MBL patients, MBLlo COVID-19 patients presented higher neutrophil counts, together with decreased pre-GC B-cell, dendritic cell, and innate-like T-cell counts. Higher PC levels, together with a delayed PC peak and greater plasma levels of anti-SARS-CoV-2-specific antibodies (at week +2 to week +4) were also observed in MBLlo patients. In summary, MBLlo COVID-19 patients share immune profiles previously described for patients with severe SARS-CoV-2 infection, associated with a delayed but more pronounced PC and antibody humoral response once compared with non-MBL patients.

The Effect of the Drug-Related Problems Prevention Bundle on Early Readmissions in Patients From the Emergency Department: A Randomized Clinical Trial.

BACKGROUND: Drug-related problems (DRPs) are prevalent and avoidable disease that patients experience due to drug use or nonuse. However, secondary prevention policies have not yet been systematized. OBJECTIVE: To assess the clinical impact of a secondary prevention bundle for DRPs in patients who visited the emergency department (ED) for medicine-related problems. METHODS: A single-center randomized clinical trial was conducted from August 28, 2019, to January 28, 2021, with 1-month follow-up. We included 769 adult patients who visited ED with a DRP associated with cardiovascular, alimentary tract, and metabolic system medications. For the intervention group, a DRP prevention bundle, consisting of a combined strategy initiated in the ED was applied. Patients in the control group received standard pharmaceutical care. Intervention was evaluated in terms of 30-day hospital readmission due to any cause. RESULTS: Final analysis included 769 patients, of which 68 (8.8%) were readmitted within 30 days (control group, 40 of 386 [cumulative incidence: 10.4%]; intervention group, 28 of 383 [cumulative incidence, 7.3%]). After adjustment of the model for chronic heart failure, there was a lower incidence of hospital readmission among patients in the intervention group compared with those in the control group, odds ratio: 0.59 [95% confidence interval: 0.37-0.97]; number needed to treat (NNT) = 32. No significant differences in other outcomes were observed. CONCLUSION AND RELEVANCE: In this clinical trial, DRP prevention bundle in adjusted analysis decreased the rate of 30-day hospital readmission for any cause in patients who visited ED for a DRP. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03607097).

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group.

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized, Double-Blind Primary Endpoint.

OBJECTIVE: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease. MATERIALS AND METHODS: Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life. RESULTS: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period. CONCLUSION: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.

Cancer in Parkinson's Disease: An Approximation to the Main Risk Factors.

BACKGROUND: Many evidences suggest a pathological link between neurodegenerative diseases and cancer. In fact, several epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson's disease (PD) patients and some PD genes are involved in cancer networks. OBJECTIVE: The aim of this study is to assess the influence of several factors in the risk of cancer in a cohort of 753 PD patients and to study how these variables interact with each other. METHODS: We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic or idiopathic PD), and two genetic variants, previously associated with cancer, rs5848-GRN and rs1042522-TP53. RESULTS: A higher age at PD onset was observed in patients who develop cancer before PD (p < 0.001). Alcohol consumption was a risk factor to develop cancer in PD patients (p = 0.011), while smoking was not a cancer risk factor in our cohort (p = 0.098). Among the genetic factors, the genotype TT GRN-rs5848 was statistically more frequent in PD patients without cancer (p = 0.05). CONCLUSIONS: Our study identified several factors, genetic and nongenetic, which contribute to the risk for cancer in PD.

The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight.

BACKGROUND: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. OBJECTIVES: To perform the largest PD genome-wide association study restricted to a single country. METHODS: We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. RESULTS: We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. CONCLUSIONS: Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain. © 2019 International Parkinson and Movement Disorder Society.

Research highlights in neurorehabilitation.

Recent studies of the mechanisms underlying plasticity and recovery following neurological injuries have originated innovative lines of research in neurorehabilitation. Additionally, the development of new technologies to facilitate the performance of evaluation and intervention procedures has stimulated research on novel rehabilitation paradigms and more effective rehabilitation strategies. However, translation of novel interventions into clinical practice remains a challenge. Further investigation to evaluate the effectiveness of novel rehabilitation approaches is needed. In this thematic series, six manuscripts summarize the results of current research with focus on evaluation and treatment strategies of relevance in neurorehabilitation.

Watershed management and public health: an exploration of the intersection of two fields as reported in the literature from 2000 to 2010.

Watersheds are settings for health and well-being that have a great deal to offer the public health community due to the correspondence between the spatial form of the watershed unit and the importance to health and well-being of water. However, managing watersheds for human health and well-being requires the ability to move beyond typical reductionist approaches toward more holistic methods. Health and well-being are emergent properties of inter-related social and biophysical processes. This paper characterizes points of connection and integration between watershed management and public health and tests a new conceptual model, the Watershed Governance Prism, to determine the prevalence in peer-reviewed literature of different perspectives relating to watersheds and public health. We conducted an initial search of academic databases for papers that addressed the interface between watershed management (or governance) and public health themes. We then generated a sample of these papers and undertook a collaborative analysis informed by the Watershed Governance Prism. Our analysis found that although these manuscripts dealt with a range of biophysical and social determinants of health, there was a tendency for social factors and health outcomes to be framed as context only for these studies, rather than form the core of the relationships being investigated. At least one cluster of papers emerged from this analysis that represented a cohesive perspective on watershed governance and health; "Perspective B" on the Watershed Governance Prism, "water governance for ecosystems and well-being," was dominant. Overall, the integration of watershed management/governance and public health is in its infancy.

An environmental justice perspective on ecosystem services.

Mainstreaming of ecosystem service approaches has been proposed as one path toward sustainable development. Meanwhile, critics of ecosystem services question if the approach can account for the multiple values of ecosystems to diverse groups of people, or for aspects of inter- and intra-generational justice. In particular, an ecosystem service approach often overlooks power dimensions and capabilities that are core to environmental justice. This article addresses the need for greater guidance on incorporating justice into ecosystem services research and practice. We point to the importance of deep engagement with stakeholders and rights holders to disentangle contextual factors that moderate justice outcomes on ecosystem service attribution and appropriation in socio-political interventions. Such a holistic perspective enables the integration of values and knowledge plurality for enhancing justice in ecosystem services research. This broadened perspective paves a way for transformative ecosystem service assessments, management, and research, which can help inform and design governance structures that nourish human agency to sustainably identify, manage, and enjoy ecosystem services for human wellbeing.

A participatory assessment of ecosystem services and human wellbeing in rural Costa Rica using photo-voice.

Human well-being is intricately connected to ecosystem services. A keystone contribution to the ecosystem service literature has been the Millennium Ecosystem Assessment, MA, (Ecosystems and human well-being: a framework for assessment, Island Press, Washington, DC; 2003, 2005). Much of the work on ecosystem services to date has focused on the assessment and classification of environmental functions. The need for inclusion of community perspectives in ecosystem assessments has been widely recognized in order to better understand the distribution of impacts and benefits resulting from natural resource use. Communities can offer a direct route to understanding the complex relationships between ecosystems and human well-being and how environmental management affects their livelihoods. Photovoice has been made popular as a tool for participatory needs assessment but it has had limited use in ecosystem assessments to date. The purpose of this paper is twofold: (1) to present the results of a community-level assessment of environmental services in a watershed dominated by pineapple monoculture in Costa Rica; and (2) to evaluate the strengths and the limitations of photovoice as a tool for mapping the relationship between ecosystems and people. I argue that photovoice is an underutilized methodology that has the potential to complement biophysical ecosystem service assessments in the context of impoverished and resource-dependent communities, particularly, since assessing ecosystem services and acting upon that information requires integrating the knowledges of diverse stakeholders, recognizing power imbalances, and grappling with the complexity of social-ecological systems. Processes such as photovoice have the potential to catalyze community self-organization, which is a critical component for empowerment.

Design and Application of Automated Algorithms for Diagnosis and Treatment Optimization in Neurodegenerative Diseases.

Neurodegenerative diseases represent a growing healthcare problem, mainly related to an aging population worldwide and thus their increasing prevalence. In particular, Alzheimer's disease (AD) and Parkinson's disease (PD) are leading neurodegenerative diseases. To aid their diagnosis and optimize treatment, we have developed a classification algorithm for AD to manipulate magnetic resonance images (MRI) stored in a large database of patients, containing 1,200 images. The algorithm can predict whether a patient is healthy, has mild cognitive impairment, or already has AD. We then applied this classification algorithm to therapeutic outcomes in PD after treatment with deep brain stimulation (DBS), to assess which stereotactic variables were the most important to consider when performing surgery in this indication. Here, we describe the stereotactic system used for DBS procedures, and compare different planning methods with the gold standard normally used (i.e., neurophysiological coordinates recorded intraoperatively). We used information collected from database of 72 DBS electrodes implanted in PD patients, and assessed the potentially most beneficial ranges of deviation within planning and neurophysiological coordinates from the operating room, to provide neurosurgeons with additional landmarks that may help to optimize outcomes: we observed that x coordinate deviation within CT scan and gold standard intra-operative neurophysiological coordinates is a robust matric to pre-assess positive therapy outcomes- "good therapy" prediction if deviation is higher than 2.5 mm. When being less than 2.5 mm, adding directly calculated variables deviation (on Y and Z axis) would lead to specific assessment of "very good therapy".

Mining, Colonial Legacies, and Neoliberalism: A Political Ecology of Health Knowledge : Mineria, legados coloniales y neoliberalismo: una ecologia politica del conocimiento en salud.

Scholarship on the health impacts of resource extraction displays prominent gaps and apparent corporate and neocolonial footprints that raise questions about how science is produced. We analyze production of knowledge, on the health impacts of mining, carried out in relation to the Canadian International Resources and Development Institute (CIRDI), a university-based organization with substantial extractive industry involvement and links to Canada's mining-dominated foreign policy. We use a "political ecology of knowledge" framework to situate CIRDI in the context of neoliberal capitalism, neocolonial sustainable development discourses, and mining industry corporate social responsibility techniques. We then document the interactions of specific health disciplinary conventions and knowledges within CIRDI-related research and advocacy efforts involving a major Canadian global health organization. This analysis illustrates both accommodation and resistance to large-scale political economic structures and the need to directly confront the global North governments and sectors pushing extractive-led neoliberal development globally.ResumenLa investigación sobre los impactos en la salud de la extracción de recursos naturales delata brechas importantes y huellas corporativas y neocoloniales, que plantean dudas acerca de cómo se produce la ciencia. Analizamos la producción de conocimiento sobre los impactos en la salud de la minería en relación con el Instituto Canadiense de Desarrollo y Recursos Internacionales (CIRDI, siglas en inglés), una organización universitaria que cuenta con participación sustancial de la industria extractiva y tiene vínculos con la política exterior de Canadá, la cual es dominada por intereses mineros. Utilizamos un marco de "ecología política del conocimiento" para situar a CIRDI en el contexto del capitalismo neoliberal, los discursos neocoloniales de desarrollo sostenible y las técnicas de responsabilidad social corporativa de la industria minera. Luego, documentamos las interacciones entre los conocimientos y convenciones disciplinarias de salud dentro de los esfuerzos de investigación y promoción relacionados con CIRDI que involucran a una importante organización canadiense de salud global. Este análisis muestra tanto la complacencia como la resistencia a las estructuras políticas económicas a gran escala, y la necesidad de confrontar directamente a los gobiernos y sectores del Norte global que manejan el desarrollo neoliberal impulsado por la extracción a nivel mundial.

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson's Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up.

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (ß = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (ß = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (ß = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.

Analysis of the Micro-RNA-133 and PITX3 genes in Parkinson's disease.

MicroRNAs are small RNA sequences that negatively regulate gene expression by binding to the 3' untranslated regions of mRNAs. MiR-133b has been implicated in Parkinson's disease (PD) by a mechanism that involves the regulation of the transcription factor PITX3. The variation in these genes could contribute to the risk of developing PD. We searched for DNA variants in miR-133 and PITX3 genes in PD patients and healthy controls from Spain. We found common DNA variants in the three miR-133 genes. Genotyping of a first set of patients (n = 777) and controls (n = 650) showed a higher frequency of homozygous for a miR-133b variant (-90 del A) in PD-patients (6/575; 1%) than in healthy controls (0/650) (P = 0.03). However, this association was not confirmed in a second set of patients (1/250; 0.4%) and controls (2/210; 1%). No common PITX3 variants were associated with PD, although a rare missense change (G32S) was found in only one patient and none of the controls. In conclusion, we report the variation in genes of a pathway that has been involved in dopaminergic neuron differentiation and survival. Our work suggests that miR-133 and PITX3 gene variants did not contribute to the risk for PD.

Lrrk2 R1441G-related Parkinson's disease: evidence of a common founding event in the seventh century in Northern Spain.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene together represent the most common genetic determinant of Parkinson's disease (PD) identified to date. The vast majority of patients with LRRK2-related PD reported in the literature carry one of three pathogenic substitutions: G2019S, R1441C, or R1441G. While G2019S and R1441C are geographically widespread, R1441G is most prevalent in the Basque Country and is rare outside of Northern Spain. We sought to better understand the processes that have shaped the current distribution of R1441G. We performed a haplotype analysis of 29 unrelated PD patients heterozygous for R1441G and 85 wild-type controls using 20 markers that spanned 15.1 Mb across the LRRK2 region. Nine of the patients were of Basque origin and 20 were non-Basques. We inferred haplotypes using a Bayesian approach and utilized a maximum-likelihood method to estimate the age of the most recent common ancestor. Significant but incomplete allele sharing was observed over a distance of 6.0 Mb and a single, rare ten-marker haplotype 5.8 Mb in length was seen in all mutation carriers. We estimate that the most recent common ancestor lived 1,350 (95% CI, 1,020-1,740) years ago in approximately the seventh century. We hypothesize that R1441G originated in the Basque population and that dispersion of the mutation then occurred through short-range gene flow that was largely limited to nearby regions in Spain.

5'-Upstream variants of CRHR1 and MAPT genes associated with age at onset in progressive supranuclear palsy and cortical basal degeneration.

Two different H1 sub-haplotypes at chromosome 17q21, H1C and H1E'A, have been associated with progressive supranuclear palsy (PSP) and cortical basal degeneration (CBD). We analyzed the SNPs included in the H1C and H1E'A haplotypes in a large Spanish PSP/CBD series and their interaction with age at onset (AAO). Survival analysis of rs1880753 marker was consistently associated with disease risk and with an earlier age at onset under an additive model. Its location at 160 kb and 50 kb upstream of tau and CRHR1 genes, respectively, suggests that it might act as a cis-element that regulates gene expression. Rs45502095(H1) was also associated with AAO under a recessive model. Haplotype analysis failed to replicate the association of H1C and H1E'A haplotypes with PSP/CBD. However, we found a strong association of two H1 sub-haplotypes with PSP and CBD (H1E'C and H1Q), which include MAPT and CRHR1 genes where the risk variant for PSP/CBD could lie.

Mutational screening of the mortalin gene (HSPA9) in Parkinson's disease.

Mortalin is a mitochondrial chaperone of the heat shock protein 70 family. Mortalin plays a central role in mitochondrial biogenesis through its capacity to direct the import of nuclear-encoded proteins into the mitochondria. As mitochondrial dysfunction has been involved in Parkinson's disease (PD), changes in mortalin function and expression could manifest as a higher risk of developing PD. In agreement with this, mortalin expression was decreased in the mitochondrial fraction of neurons from the substantia nigra of PD patients. We hypothesised that DNA variants in the mortalin gene (HSPA9) could contribute to the risk of developing PD. We analysed the 17 HSPA9 coding exons in 330 PD patients and 250 controls. In addition to several polymorphisms, found in patients and controls, three variants were found in 3 patients but none of the controls: two missense (R126 > W and P509 > S) and a 17 bp insertion in intron 8 (predicted to affect RNA splicing). Our study suggests that putative mutations in the mortalin, although rare, could contribute to the risk of developing PD.

HTT gene intermediate alleles in neurodegeneration: evidence for association with Alzheimer's disease.

Huntington's disease (HD) is an autosomal progressive neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene. Intermediate alleles (IAs) are in the range of 27-35 repeats and have been associated to a normal phenotype. The aim of this work was to analyze the association between intermediate huntingtin CAG-repeat alleles (IAs) and neurodegenerative diseases, other than HD. We screened the HTT CAG repeats in patients with Alzheimer's disease (AD) (n = 1126), Parkinson's disease (PD) (n = 610), and frontotemporal lobar degeneration (FTLD) (n = 225). We also studied 509 healthy controls (HCs). The relative frequency of IAs for each group was 6.03% in AD, 5.3% in FTLD, 3.5% in PD, and 2.9% in HCs. The frequency of IA was significantly higher among patients with AD when compared to HCs (p = 0.011, OR = 2.11, 95% CI = 1.19-3.74); no significant difference was observed in FTLD (p = 0.17; OR = 1.88, 95% CI = 0.85-4.03) and PD (p = 0.69; OR = 1.21; 95% CI (0.61-2.37) versus HCs. No atypical symptoms or clinical features distinctive of HD were found among carriers of IAs. We found 3 cases with CAG expansions within the pathological range, one diagnosed with AD, one with PD, and one with FTD. Results suggest that IAs might have a role in the pathogenesis of AD. In addition, HD patients might be misdiagnosed with other neurodegenerative diseases, particularly when CAG repeats are in the lower pathological range.