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Tics are a common feature of early-onset neurodevelopmental disorders, characterized by involuntary and repetitive movements or sounds. Despite affecting up to 2% of children and having a genetic contribution, the underlying causes remain poorly understood. In this study, we leverage dense phenotype information to identify features (i.e., symptoms and comorbid diagnoses) of tic disorders within the context of a clinical biobank. Using de-identified electronic health records (EHRs), we identified individuals with tic disorder diagnosis codes. We performed a phenome-wide association study (PheWAS) to identify the EHR features enriched in tic cases versus controls (n = 1406 and 7030; respectively) and found highly comorbid neuropsychiatric phenotypes, including: obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, and anxiety (p < 7.396 × 10-5). These features (among others) were then used to generate a phenotype risk score (PheRS) for tic disorder, which was applied across an independent set of 90,051 individuals. A gold standard set of tic disorder cases identified by an EHR algorithm and confirmed by clinician chart review was then used to validate the tic disorder PheRS; the tic disorder PheRS was significantly higher among clinician-validated tic cases versus non-cases (p = 4.787 × 10-151; ß = 1.68; SE = 0.06). Our findings provide support for the use of large-scale medical databases to better understand phenotypically complex and underdiagnosed conditions, such as tic disorders.
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Bancos de Espécimes Biológicos , Registros Eletrônicos de Saúde , Fenótipo , Transtornos de Tique , Humanos , Transtornos de Tique/genética , Transtornos de Tique/diagnóstico , Transtornos de Tique/epidemiologia , Masculino , Feminino , Comorbidade , Criança , Adulto , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/diagnóstico , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/diagnóstico , Estudos de Casos e Controles , Fatores de RiscoRESUMO
INTRODUCTION: Anosognosia, defined as reduced awareness of one's deficit or symptom, is common in Huntington's disease (HD) and detectable at each disease stage. The impact of anosognosia on self-reporting in HD populations is critical to understand given growing use of patient-reported outcomes in HD clinical care and research. We aimed to determine the influence of anosognosia on patient-reported outcome measures assessing psychiatric symptoms and quality of life in HD. METHODS: We enrolled HD patients to complete a battery of patient-reported and rater-administered measures, including the Anosognosia Scale, at baseline and 6 months later. Patient-reported outcome measures included NeuroQoL short forms for depression, anxiety, satisfaction with social roles and activities, and positive affect and well-being and Patient-Reported Outcomes Measurement Information System short forms for emotional distress-anger and sleep-related impairment. Anosognosia Scale-Difference Score indexed patient-clinician agreement on patient motor, cognitive, and behavioral abilities. We conducted multivariable linear regression analyses to quantify the association of baseline anosognosia with 6-month patient-reported outcomes. RESULTS: Of 79 patients with complete Anosognosia Scale data at baseline, 25 (31.6 %) met the scale's criterion for anosognosia. In the regression analyses, baseline Difference Score improved prediction of 6-month patient-reported outcomes for depression, anxiety, anger, and positive affect and well-being (χ2(1) value range for likelihood ratio tests contrasting models with and without Difference Score: 13.1-20.9, p-values <0.001). Patients with more anosognosia self-reported less severe psychiatric symptoms and more positive affect and well-being. CONCLUSION: Study results suggest that anosognosia influences patient-reported outcomes for psychiatric symptoms and quality of life in HD populations.
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Agnosia , Doença de Huntington , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Doença de Huntington/complicações , Doença de Huntington/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Agnosia/etiologia , Idoso , Depressão/etiologiaRESUMO
Individuals with Tourette syndrome (TS) have poorer quality of life (QoL) than their peers, yet factors contributing to poor QoL in this population remain unclear. Research to date has predominantly focused on the impact of tics and psychiatric symptoms on QoL in TS samples. The aim of this cross-sectional, multi-informant study was to identify psychosocial variables that may impact adolescent QoL in TS. Thirty-eight adolescents aged 13 to 17 with TS and 28 age-matched controls participated with a caregiver. No group differences were found on QoL, although the TS group reported reduced QoL compared to population normative data. In the TS group, reduced QoL was associated with lower self-esteem, poorer family functioning, higher stress, and greater depression and anxiety; QoL was unrelated to tic severity. In regression analyses, after adjusting for covariates, family functioning was the strongest predictor of QoL. These results emphasize the need to further explore the influence of psychosocial factors, particularly family functioning, on QoL in adolescents with TS.
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Purpose: Adults with Tourette syndrome (TS) have worse mental health, physical health, and quality of life than the general population. The factors contributing to negative outcomes across multiple health domains in adults with TS remain uncertain, in part due to a lack of longitudinal studies in this population. In attempt to address these knowledge gaps, our center has initiated development of a regional registry for adults with TS. During the goal-setting and design phase of registry development, we conducted focus groups with adults with TS to identify research issues of greatest importance to this population and to obtain feedback on design and implementation of an adult TS registry. Patients and Methods: Participants were recruited from a tertiary care adult TS clinic and from institutional research registries. Focus groups were conducted online and were moderated by a qualitative research expert. Qualitative data analysis was performed using an iterative inductive/deductive approach. Results: Across four focus groups, adult TS participants (n=22) expressed a variety of research priorities, including developing more effective treatments for tics, identifying risk factors for tic persistence into adulthood, clarifying the interaction between TS symptoms and women's health, clarifying the relationships between TS and other mental and physical health disorders, and addressing day-to-day living issues. Focus group participants were generally enthusiastic about creation of an adult TS registry. They indicated that adults with TS are more likely to engage with a registry that logistically accommodates participants (eg, by offering a wide range of visit times, by providing telehealth options) and that fosters bidirectional interaction (eg, by disseminating results regularly, by involving participants in registry design and implementation, by notifying participants of support resources). Conclusion: Focus group input clarifies the research priorities of adults with TS and will inform the ongoing development of an adult TS registry.
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OBJECTIVE: Among adults with Tourette syndrome, depression and anxiety symptoms are widely prevalent and consistently associated with poor quality of life. Important knowledge gaps remain regarding mood and anxiety dimensions of the adult Tourette syndrome phenotype. Taking a dimensional approach, this study sought to determine the prevalence, severity, and clinical correlates of depression and anxiety symptoms in a clinical sample of adults with Tourette syndrome and other chronic tic disorders. METHODS: A retrospective chart review was conducted of all adults with a chronic tic disorder presenting to a tertiary care Tourette syndrome clinic between December 2020 and July 2022. Information extracted during chart review included data from scales administered as part of routine care: Quality of Life in Neurological Disorders (Neuro-QoL) Depression Short Form, Neuro-QoL Anxiety Short Form, Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale, Dimensional Obsessive-Compulsive Scale, and Yale Global Tic Severity Scale. Relationships between variables were examined by conducting between-group, correlation, and multivariable regression analyses. RESULTS: Data from 120 adult patients with a chronic tic disorder (77 men and 43 women) were analyzed. Neuro-QoL Anxiety scores were elevated in 66% of the cohort; Neuro-QoL Depression scores were elevated in 26%. Neuro-QoL Anxiety scores were significantly higher than general population norms, whereas Neuro-QoL Depression scores were not. After adjustment for covariates, depressive and anxiety symptom severity scores were significantly associated with each other and with obsessive-compulsive disorder symptom severity but not with tic severity. Sex-based differences emerged in the analyses. CONCLUSIONS: Among adults with chronic tic disorder, anxiety symptoms were more prevalent and severe than depressive symptoms, co-occurring psychiatric symptoms were more tightly linked with each other than with tic severity, and sex-based differences were evident.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtornos de Tique , Tiques , Síndrome de Tourette , Masculino , Humanos , Adulto , Feminino , Síndrome de Tourette/complicações , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/epidemiologia , Qualidade de Vida/psicologia , Tiques/diagnóstico , Tiques/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Transtornos de Tique/diagnóstico , Transtornos de Tique/epidemiologia , Transtornos de Tique/complicações , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/psicologiaRESUMO
Importance: Tics are a common feature of early-onset neurodevelopmental disorders, characterized by involuntary and repetitive movements or sounds. Despite affecting up to 2% of young children and having a genetic contribution, the underlying causes remain poorly understood, likely due to the complex phenotypic and genetic heterogeneity among affected individuals. Objective: In this study, we leverage dense phenotype information from electronic health records to identify the disease features associated with tic disorders within the context of a clinical biobank. These disease features are then used to generate a phenotype risk score for tic disorder. Design: Using de-identified electronic health records from a tertiary care center, we extracted individuals with tic disorder diagnosis codes. We performed a phenome-wide association study to identify the features enriched in tic cases versus controls (N=1,406 and 7,030; respectively). These disease features were then used to generate a phenotype risk score for tic disorder, which was applied across an independent set of 90,051 individuals. A previously curated set of tic disorder cases from an electronic health record algorithm followed by clinician chart review was used to validate the tic disorder phenotype risk score. Main Outcomes and Measures: Phenotypic patterns associated with a tic disorder diagnosis in the electronic health record. Results: Our tic disorder phenome-wide association study revealed 69 significantly associated phenotypes, predominantly neuropsychiatric conditions, including obsessive compulsive disorder, attention-deficit hyperactivity disorder, autism, and anxiety. The phenotype risk score constructed from these 69 phenotypes in an independent population was significantly higher among clinician-validated tic cases versus non-cases. Conclusions and Relevance: Our findings provide support for the use of large-scale medical databases to better understand phenotypically complex diseases, such as tic disorders. The tic disorder phenotype risk score provides a quantitative measure of disease risk that can be leveraged for the assignment of individuals in case-control studies or for additional downstream analyses.
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Background: Interoception refers to the sensing, interpretation, integration, and regulation of signals about the body's internal physiological state. Interoceptive sensibility is the subjective evaluation of interoceptive experience, as assessed by self-report measures, and is abnormal in numerous neuropsychiatric disorders. Research examining interoceptive sensibility in individuals with chronic tic disorders (CTDs), however, has yielded conflicting results, likely due to methodologic differences between studies and small sample sizes. Objective: We sought to compare interoceptive sensibility between adults with CTD and healthy controls, adjusting for co-occurring psychiatric symptoms, and to examine the relationship of interoceptive sensibility with other CTD clinical features, in particular, premonitory urge. Methods: We recruited adults with CTDs and sex- and age-matched healthy controls to complete the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2), as well as a battery of measures assessing psychiatric symptoms prevalent in CTD populations. CTD participants additionally completed scales quantifying tic severity, premonitory urge severity, and health-related quality of life. We conducted between-group contrasts (Wilcoxon rank-sum test) for each MAIA-2 subscale, analyzed the effect of psychiatric symptoms on identified between-group differences (multivariable linear regression), and examined within-group relationships between MAIA-2 subscales and other clinical measures (Spearman rank correlations, multivariable linear regression). Results: Between adults with CTD (n = 48) and healthy controls (n = 48), MAIA-2 Noticing and Not-Worrying subscale scores significantly differed. After adjusting for covariates, lower MAIA-2 Not-Worrying subscale scores were significantly associated with female sex (ß = 0.42, p < 0.05) and greater severity of obsessive-compulsive symptoms (ß = -0.028, p < 0.01), but not with CTD diagnosis. After adjusting for severity of tics and obsessive-compulsive symptoms, a composite of MAIA-2 Noticing, Attention Regulation, Emotional Awareness, Self-Regulation, Body Listening, and Trusting subscales (ß = 2.52, p < 0.01) was significantly associated with premonitory urge. Conclusion: Study results revealed three novel findings: adults with CTD experience increased anxiety-associated somatization and increased general body awareness relative to healthy controls; anxiety-associated somatization is more closely associated with sex and obsessive-compulsive symptoms than with CTD diagnosis; and increased general body awareness is associated with greater severity of premonitory urges.
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Neuropsychiatric manifestations of Huntington's disease (HD) can present years before motor symptoms. Nurses with specialized training provide superior care for HD patients, but HD exposure in nursing education is limited. Here we aimed to describe the historical neuropsychiatric burden in 50 HD patients and discuss implications for psychiatric nurses. Fifty patients with HD were assessed by a board-certified psychiatrist and completed surveys about symptoms, social history, medication use, and quality of life outcomes. Descriptive statistics were used to summarize patient characteristics, and correlation analyses assessed the relationships between neuropsychiatric symptoms and quality of life outcomes. Most patients (72%) reported a history of neuropsychiatric symptoms prior to their HD diagnosis. Prodromal anger/irritability was most common (52%), though few patients received treatment for this. Anxiety was the most common current symptom (78%), yet 40% of patients had never been prescribed an SSRI. Anxiety was associated with poorer patient-reported quality of life outcomes (p < .01). HD patients in this sample experienced frequent, early-onset neuropsychiatric symptoms. In coming years, psychiatric nurses in community settings will be more likely to encounter gene-positive HD patients before they develop motor symptoms. Psychiatric nurses can address identified gaps through enhanced screening and encouraging early intervention in those at risk.
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Doença de Huntington , Enfermagem Psiquiátrica , Psiquiatria , Ansiedade , Humanos , Qualidade de VidaRESUMO
BACKGROUND: Safer-at-home orders during the COVID-19 pandemic altered the structure of clinical care for Huntington's disease (HD) patients. This shift provided an opportunity to identify limitations in the current healthcare infrastructure and how these may impact the health and well-being of persons with HD. OBJECTIVE: The study objectives were to assess the feasibility of remote healthcare delivery in HD patients, to identify socioeconomic factors which may explain differences in feasibility and to evaluate the impact of safer-at-home orders on HD patient stress levels. METHODS: This observational study of a clinical HD population during the 'safer-at-home' orders asked patients or caregivers about their current access to healthcare resources and patient stress levels. A chart review allowed for an assessment of socioeconomic status and characterization of HD severity. RESULTS: Two-hundred and twelve HD patients were contacted with 156 completing the survey. During safer-at-home orders, the majority of HD patients were able to obtain medications and see a physician; however, 25% of patients would not commit to regular telehealth visits, and less than 50% utilized an online healthcare platform. We found that 37% of participants were divorced/single, 39% had less than a high school diploma, and nearly 20% were uninsured or on low-income health insurance. Patient stress levels correlated with disease burden. CONCLUSION: A significant portion of HD participants were not willing to participate in telehealth services. Potential explanations for these limitations may include socioeconomic barriers and caregiving structure. These observations illustrate areas for clinical care improvement to address healthcare disparities in the HD community.
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COVID-19 , Doença de Huntington , Telemedicina , Adulto , Efeitos Psicossociais da Doença , Feminino , Disparidades em Assistência à Saúde , Humanos , Doença de Huntington/epidemiologia , Doença de Huntington/terapia , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , SARS-CoV-2 , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Tics are the hallmark feature of Tourette syndrome (TS), but psychiatric and sensory symptoms are widely prevalent and increasingly recognized as core manifestations of the disorder. Accumulating evidence suggests that these psychiatric and sensory symptoms exert greater influence on quality of life (QOL) than tics themselves. However, much remains uncertain about determinants of QOL in TS due to the complexity of the clinical presentation. Here, we sought to clarify the association between health-related QOL (HRQOL) and common psychiatric and sensory symptoms in adults with TS and other chronic tic disorders. To do so, we prospectively recruited 52 patients from a tertiary care clinic to complete self-report measures assessing HRQOL (Gilles de la Tourette-Quality of Life Scale, GTS-QOL), depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder Scale-7, GAD-7), obsessive-compulsive symptoms (Dimensional Obsessive-Compulsive Scale, DOCS), attention deficit hyperactivity disorder symptoms (Adult ADHD Self-Report Screening Scale for DSM-5, ASRS-V), and premonitory urge (Premonitory Urge to Tic Scale, PUTS). All participants were also administered the Yale Global Tic Severity Scale (YGTSS) to quantify tic severity. Using correlational analysis and multivariable linear regression modeling, we found that GTS-QOL score was significantly associated with scores from all other rating scales, with the exception of the PUTS. GTS-QOL was most strongly associated with PHQ-9, followed by ASRS-V, GAD-7, DOCS, and YGTSS total tic score. The regression model including these five independent variables, as well as sex, explained 79% of GTS-QOL score variance [F (6,40) = 29.6, p < 0.001]. Specific psychiatric symptoms differentially impacted physical, psychological, and cognitive HRQOL. Systematic assessment of psychiatric comorbidities is imperative for clinical care and clinical research efforts directed at improving QOL in adults with chronic tic disorders.
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OBJECTIVE: To evaluate the performance of telehealth as a screening tool for spasticity compared to direct patient assessment in the long-term care setting. DESIGN: Cross-sectional, observational study. SETTING: Two long-term care facilities: a 140-bed veterans' home and a 44-bed state home for individuals with intellectual and developmental disabilities. SUBJECTS: Sixty-one adult residents of two long-term care facilities (aged 70.1 ± 16.2 years) were included in this analysis. Spasticity was identified in 43% of subjects (Modified Ashworth Scale rating mode = 2). Contributing diagnoses included traumatic brain injury, spinal cord injury, birth trauma, stroke, cerebral palsy, and multiple sclerosis. MAIN MEASURES: Movement disorders neurologists conducted in-person examinations to determine whether spasticity was present (reference standard) and also evaluated subjects with spasticity using the Modified Ashworth Scale. Telehealth screening examinations, facilitated by a bedside nurse, were conducted remotely by two teleneurologists using a three-question screening tool. Telehealth screening determinations of spasticity were compared to the reference standard determination to calculate sensitivity, specificity, and the area under the curve (AUC) in receiver operating characteristics. Teleneurologist agreement was evaluated using Cohen's kappa. RESULTS: Teleneurologist 1 had a specificity of 89% and sensitivity of 65% to identify the likely presence of spasticity (n = 61; AUC = 0.770). Teleneurologist 2 showed 100% specificity and 82% sensitivity (n = 16; AUC = 0.909). There was almost perfect agreement between the two examiners at 94% (kappa = 0.875, 95% CI: 0.640-1.000). CONCLUSION: Telehealth may provide a useful, efficient method of identifying residents of long-term care facilities that likely need referral for spasticity evaluation.
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Assistência de Longa Duração , Espasticidade Muscular/diagnóstico , Telemedicina , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Encaminhamento e Consulta , Traumatismos da Medula Espinal/complicações , Acidente Vascular Cerebral/complicaçõesAssuntos
Antipsicóticos/efeitos adversos , Discinesia Induzida por Medicamentos/fisiopatologia , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Risperidona/efeitos adversos , Adulto , Antipsicóticos/administração & dosagem , Preparações de Ação Retardada , Discinesia Induzida por Medicamentos/etiologia , Humanos , Injeções , Masculino , Risperidona/administração & dosagemRESUMO
BACKGROUND: Thalamic ventral intermediate nucleus (VIM) deep brain stimulation (DBS) is an effective therapy for medication-refractory essential tremor (ET). However, 13-40% of patients with an initially robust tremor efficacy lose this benefit over time despite reprogramming attempts. At our institution, a cohort of ET patients with VIM DBS underwent implantation of a second anterior (ventralis oralis anterior; VOA) DBS lead to permit "confined stimulation." We sought to assess whether confined stimulation conferred additional tremor capture compared to VIM or VOA stimulation alone. METHODS: Seven patients participated in a protocol-based programming session during which a video-recorded Fahn-Tolosa-Marin Part A (FTM-A) tremor rating scale was used in the following 4 DBS states: off stimulation, VIM stimulation alone, VOA stimulation alone, and dual lead (confined) stimulation. RESULTS: The average (SD) baseline FTM-A off score was 17.6 (4.0). VIM stimulation alone lowered the average FTM-A total score to 6.9 (4.0). Confined stimulation further attenuated the tremor, reducing the total score to 5.7 (2.8). CONCLUSIONS: Confined thalamic DBS can provide additional symptomatic benefits in patients with unsatisfactory tremor control from VIM or VOA stimulation alone.
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Estimulação Encefálica Profunda/métodos , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/terapia , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Núcleos Ventrais do Tálamo/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Tremor Essencial/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Acquired neurogenic stuttering has been considered a fairly uncommon clinical occurrence; speech-activated myoclonus is a rare entity that can mimic stuttering and is caused by a wide array of etiologies. CASE REPORT: Here we report a patient with myoclonus-dystonia syndrome (MDS), due to an identified disease-causing mutation, who displayed speech-activated myoclonus mimicking stuttering. DISCUSSION: In MDS, myoclonus has only infrequently been reported to affect speech. This case further expands the spectrum of conditions causing the rare clinical phenomenon of speech-activated myoclonus.
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Advancing age and disease duration both contribute to cortical thinning in Parkinson's disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson's Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2(nd), or 3(rd) order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning.
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BACKGROUND: Parkinson's Disease patients with predominant gait dysfunction appear to have reduced cortical thickness compared to other motor phenotypes. The extent to which advancing age or disease duration impact the pattern of these distinctions is unclear. OBJECTIVE: We examine if PD patients with predominant signs of postural instability and gait dysfunction are distinguished by distinct patterns of cerebral atrophy, and how these differences are influenced by age and disease duration. METHODS: The Unified Parkinson's Disease Rating Score (UPDRS) was administered to 196 PD patients (ageâ=â61.4±8.9yrs) in the Off and On dopamine state. All completed a structural T1-weighted brain MRI. We defined 3 motor phenotypes: tremor dominant, akinetic-rigid, and postural instability with gait disorder. General linear modeling quantified cortical thickness in relation to disease duration, and motor improvement after dopaminergic therapy. Cortical thickness and subcortical volumes were compared between the three motor subtypes, after controlling for disease duration and age. RESULTS: We identified 177/196 patients who met criteria for a motor subtype. When corrected for disease duration, postural-instability patients had marked cortical thinning of the bilateral frontal-temporal and posterior cortical regions (cuneus/precuneus). After regressing for age, reduced frontal thickness was evident in patients with gait dysfunction. Widespread cortical thinning was associated with increasing disease duration and reduced motor improvement to dopaminergic therapy. CONCLUSIONS: Results emphasize that the profile of motor signs, especially prominent gait manifestations, relate to cortical thinning in distinct regions. Unique patterns of atrophy appear to be driven by advancing pathology related to age and disease duration.