RESUMO
AIMS: Lewy body diseases (LBD) are characterized by alpha-synuclein (SYN) pathology, but comorbid Alzheimer's disease (AD) pathology is common and the relationship between these pathologies in microanatomic hippocampal subfields is understudied. Here we use digital histological methods to test the association between hippocampal SYN pathology and the distribution of tau and amyloid-beta (Aß) pathology in LBD and contrast with AD subjects. We also correlate pathologic burden with antemortem episodic memory testing. METHODS: Hippocampal sections from 49 autopsy-confirmed LBD cases, 30 with no/low AD copathology (LBD - AD) and 19 with moderate/severe AD copathology (LBD + AD), and 30 AD patients were stained for SYN, tau, and Aß. Sections underwent digital histological analysis of subfield pathological burden which was correlated with antemortem memory testing. RESULTS: LBD - AD and LBD + AD had similar severity and distribution of SYN pathology (P > 0.05), CA2/3 being the most affected subfield (P < 0.02). In LBD, SYN correlated with tau across subfields (R = 0.49, P < 0.001). Tau burden was higher in AD than LBD + AD (P < 0.001), CA1/subiculum and entorhinal cortex (ERC) being most affected regions (P = 0.04 to <0.01). However, tau pathology in LBD - AD was greatest in CA2/3, which was equivalent to LBD + AD. Aß severity and distribution was similar between LBD + AD and AD. Total hippocampal tau and CA2/3 tau was inversely correlated with memory performance in LBD (R = -0.52, -0.69, P = 0.04, 0.009). CONCLUSIONS: Our findings suggest that tau burden in hippocampal subfields may map closely with the distribution of SYN pathology in subfield CA2/3 in LBD diverging from traditional AD and contribute to episodic memory dysfunction in LBD.
Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Hipocampo/patologia , Doença por Corpos de Lewy/patologia , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Córtex Entorrinal/metabolismo , Feminino , Humanos , Masculino , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismoRESUMO
INTRODUCTION: Objective, portable measures of motor function for out-of-office assessments are needed in Parkinson's Disease (PD). This study had 3 objectives. First, to examine change in objective motor measurements in PD (as assessed with the Objective PD Measurement (OPDM) system). Second, to correlate objective measures with clinical features and putative PD cerebrospinal fluid (CSF) and dopaminergic imaging biomarkers. Third, to assess participant compliance with and perceptions of serial in-home motor assessments. METHODS: De novo PD subjects participating in this pilot study of the Parkinson Progression Markers Initiative (PPMI) completed OPDM assessments at home weekly for 3 months and in the clinic at baseline and 3-, 6-, and 12-months. Tasks included (i)digitography (ii)a repetitive hand tapping task and (iii)timed pegboard task. A global objective motor score (OMS) was derived from the latter three. MDS-UPDRS-III score was obtained at each time point, and CSF and dopamine transporter (DAT) SPECT at baseline. RESULTS: 27 participants, mean age 62.6 years, 19 male were included. A mean of 10.5 in-home assessments were completed. There was no significant change in in-home OMS over 12 weeks (p = 0.48). There was strong correlation between mean baseline OMS and MDS-UPDRS-III scores (spearman's rho = 0.60, p=<0.0001). Baseline OMS predicted 6-month MDS-UPDRS-III (ß = 0.80, p = 0.0002) but not change in MDS-UPDRS-III score, DAT SPECT, or putative CSF biomarkers. CONCLUSIONS: This study suggests that administration of in-home motor tasks as part of a large multi-center study is feasible and scores derived from these assessments may serve as surrogates of in-person clinician-assessed motor score.
Assuntos
Mãos/fisiopatologia , Movimento/fisiologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Desempenho Psicomotor/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Examine the correlates of Health Related Quality of Life (HRQL) in a large cohort of Parkinson's disease (PD) patients from National Parkinson Foundation (NPF) Centers of Excellence (COEs). BACKGROUND: Improving outcomes for PD will depend upon uncovering disease features impacting HRQL to identify targets for intervention and variables for risk-adjustment models. Differences in HRQL outcomes between COEs could uncover modifiable aspects of care delivery. METHODS: This cross-sectional study examined the relative contribution of demographic, social, clinical and treatment features potentially related to HRQL, as measured by the PDQ-39, in 4601 consecutive subjects from 18 COEs. Stepwise linear regression was utilized to identify correlates of HRQL. RESULTS: The variability in the PDQ-39 summary index score correlated with H&Y stage (R(2) = 22%), Timed up and Go (TUG) (17%), disease duration (11%), comorbidities (8%), cognitive status (8%), antidepressant use (6%) and center at which a patient received care (5%). Stepwise regression reordered the importance of the variables, with the H&Y first and TUG and the center becoming equal and the second most important variables determining the PDQ-39 total score. All independent variables together accounted for 44% of the variability in HRQL. CONCLUSIONS: We confirmed many but not all HRQL associations found in smaller studies. A novel observation was that the site of care was an important contributor to HRQL, suggesting that comparison of outcomes and processes among centers may identify best practices.
Assuntos
Afeto , Limitação da Mobilidade , Ambulatório Hospitalar , Doença de Parkinson/epidemiologia , Doença de Parkinson/psicologia , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar/normas , Doença de Parkinson/diagnósticoRESUMO
OBJECTIVE: To address the need for brief, reliable, valid, and standardized quality of life (QOL) assessment applicable across neurologic conditions. METHODS: Drawing from larger calibrated item banks, we developed short measures (8-9 items each) of 13 different QOL domains across physical, mental, and social health and evaluated their validity and reliability. Three samples were utilized during short form development: general population (Internet-based, n = 2,113); clinical panel (Internet-based, n = 553); and clinical outpatient (clinic-based, n = 581). All short forms are expressed as T scores with a mean of 50 and SD of 10. RESULTS: Internal consistency (Cronbach α) of the 13 short forms ranged from 0.85 to 0.97. Correlations between short form and full-length item bank scores ranged from 0.88 to 0.99 (0.82-0.96 after removing common items from banks). Online respondents were asked whether they had any of 19 different chronic health conditions, and whether or not those reported conditions interfered with ability to function normally. All short forms, across physical, mental, and social health, were able to separate people who reported no health condition from those who reported 1-2 or 3 or more. In addition, scores on all 13 domains were worse for people who acknowledged being limited by the health conditions they reported, compared to those who reported conditions but were not limited by them. CONCLUSION: These 13 brief measures of self-reported QOL are reliable and show preliminary evidence of concurrent validity inasmuch as they differentiate people based upon number of reported health conditions and whether those reported conditions impede normal function.
Assuntos
Nível de Saúde , Doenças do Sistema Nervoso/psicologia , Neurologia/instrumentação , Qualidade de Vida , Inquéritos e Questionários/normas , Idoso , Feminino , Humanos , Internet/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neurologia/métodos , Pacientes Ambulatoriais/psicologia , Reprodutibilidade dos Testes , AutorrelatoRESUMO
OBJECTIVE: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). METHODS: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. RESULTS: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004). CONCLUSION: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.
Assuntos
Disfunção Cognitiva/genética , Análise Mutacional de DNA , Triagem de Portadores Genéticos , Glucosilceramidase/genética , Testes Neuropsicológicos , Doença de Parkinson/genética , Adulto , Doenças dos Gânglios da Base/diagnóstico , Doenças dos Gânglios da Base/genética , Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Demência/genética , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/genética , Feminino , Testes Genéticos , Genótipo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/genética , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/genética , Doença de Parkinson/diagnóstico , Fenótipo , Proteínas Serina-Treonina Quinases/genética , Ubiquitina-Proteína Ligases/genética , beta-Glucosidase/genéticaRESUMO
BACKGROUND: No recent analysis details Parkinson's Disease (PD) costs or survival for Medicare beneficiaries. This study assesses excess direct costs and survival in Medicare beneficiaries with early and advanced PD. METHODS: Patients with ≥ 2 PD diagnoses (ICD-9-CM: 332.0), ≥ age 65, continuously enrolled in Parts A&B during one-year baseline and study periods were selected from the Medicare 5% sample (N = 3.2 million, 1999-2008). Newly diagnosed patients were defined as having no baseline claims for movement disorder, dementia, Alzheimer's, bipolar disorder, psychosis, falls or related injuries, ambulatory assistance device (walker or wheelchair), or skilled nursing facility. Controls without PD were demographically matched 1:1. Costs to Medicare were compared via Wilcoxon rank-sum tests and inverse probability weighted multivariate regression. Survival was assessed via Cox proportional hazards analysis. RESULTS: Costs in the year post-diagnosis were higher for newly diagnosed patients (N = 9,201, $7423) than controls ($5024), resulting in excess PD-associated costs of $2399 (p < 0.001). Cumulative excess costs were $28,422 from the year prior to index quarter to five years following (p < 0.01). PD patients receiving their first claim for an ambulatory assistance device (N = 11,294) had excess cumulative costs of $50,923 (p < 0.001) over the same period; those receiving their first claim for a skilled nursing facility (N = 10,152) had excess costs of $102,750 (p < 0.001). Hazard rates of mortality were higher among newly diagnosed PD (1.43, p < 0.001), ambulatory assistance device (2.37, p < 0.001) and skilled nursing facility (3.34, p < 0.001) cohorts than in corresponding non-PD groups. CONCLUSIONS: Medicare beneficiaries with PD have substantially and progressively higher costs and mortality compared with controls.
Assuntos
Custos de Cuidados de Saúde , Medicare/economia , Doença de Parkinson , Sobrevida , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Doença de Parkinson/economia , Doença de Parkinson/epidemiologia , Doença de Parkinson/mortalidade , Estudos Retrospectivos , Estatísticas não Paramétricas , Estados UnidosRESUMO
BACKGROUND: Mutations in parkin are a known genetic risk factor for early onset Parkinson's disease (EOPD) but their role in non-motor manifestations is not well established. Genetic factors for depression are similarly not well characterized. We investigate the role of parkin mutations in depression among those with EOPD and their relatives. METHODS: We collected psychiatric information using the Patient Health Questionnaire and Beck Depression Inventory II on 328 genotyped individuals including 88 probands with early onset PD (41 with parkin mutations, 47 without) and 240 first and second-degree relatives without PD. RESULTS: Genotype was not associated with depression risk among probands. Among unaffected relatives of EOPD cases, only compound heterozygotes (n = 4), and not heterozygotes, had significantly increased risk of depressed mood (OR = 14.1; 95% CI 1.2-163.4), moderate to severe depression (OR = 17.8; 95% CI 1.0-332.0), depression (score ≥ 15) on the Beck Depression Inventory II (BDI-II) (OR = 51.9; 95% CI 4.1-657.4), and BDI-II total depression score (ß = 8.4; 95% CI 2.4-11.3) compared to those without parkin mutations. CONCLUSIONS: Relatives of EOPD cases with compound heterozygous mutations and without diagnosed PD may have a higher risk of depression compared to relatives without parkin mutations. These findings support evidence of a genetic contribution to depression and may extend the phenotypic spectrum of parkin mutations to include non-motor manifestations that precede the development of PD.
Assuntos
Depressão/genética , Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Doença de Parkinson/psicologia , Ubiquitina-Proteína Ligases/genética , Adulto , Idade de Início , Análise Mutacional de DNA , Feminino , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Mutação , Testes Neuropsicológicos , Fenótipo , Fatores de RiscoRESUMO
BACKGROUND: While Parkinson disease (PD) is consistently associated with impaired olfaction, one study reported better olfaction among Parkin mutation carriers than noncarriers. Whether olfaction differs between Parkin mutation heterozygotes and carriers of 2 Parkin mutations (compound heterozygotes) is unknown. OBJECTIVE: To assess the relationship between Parkin genotype and olfaction in PD probands and their unaffected relatives. METHODS: We administered the University of Pennsylvania Smell Identification Test (UPSIT) to 44 probands in the Consortium on Risk for Early-Onset Parkinson Disease study with PD onset ≤50 years (10 Parkin mutation heterozygotes, 9 compound heterozygotes, 25 noncarriers) and 80 of their family members (18 heterozygotes, 2 compound heterozygotes, 60 noncarriers). In the probands, linear regression was used to assess the association between UPSIT score (outcome) and Parkin genotype (predictor), adjusting for covariates. Among family members without PD, we compared UPSIT performance in heterozygotes vs noncarriers using generalized estimating equations, adjusting for family membership, age, gender, and smoking. RESULTS: Among probands with PD, compound heterozygotes had higher UPSIT scores (31.9) than heterozygotes (20.1) or noncarriers (19.9) (p < 0.001). These differences persisted after adjustment for age, gender, disease duration, and smoking. Among relatives without PD, UPSIT performance was similar in heterozygotes (32.5) vs noncarriers (32.4), and better than in heterozygotes with PD (p = 0.001). CONCLUSION: Olfaction is significantly reduced among Parkin mutation heterozygotes with PD but not among their heterozygous relatives without PD. Compound heterozygotes with PD have olfaction within the normal range. Further research is required to assess whether these findings reflect different neuropathology in Parkin mutation heterozygotes and compound heterozygotes.
Assuntos
Doença de Parkinson/genética , Olfato , Ubiquitina-Proteína Ligases/genética , Adulto , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Doença de Parkinson/fisiopatologiaRESUMO
OBJECTIVE: To identify antemortem CSF diagnostic biomarkers that can potentially distinguish between the 2 main causes of frontotemporal lobar degeneration (FTLD), i.e., FTLD with TDP-43 pathology (FTLD-TDP) and FTLD with tau pathology (FTLD-tau). METHODS: CSF samples were collected antemortem from 23 patients with FTLD with known pathology to form a autopsy cohort as part of a comparative biomarker study that additionally included 33 living cognitively normal subjects and 66 patients with autopsy-confirmed Alzheimer disease (AD). CSF samples were also collected from 80 living patients clinically diagnosed with frontotemporal dementia (FTD). Levels of 151 novel analytes were measured via a targeted multiplex panel enriched in neuropeptides, cytokines, and growth factors, along with levels of CSF biomarkers for AD. RESULTS: CSF levels of multiple analytes differed between FTLD-TDP and FTLD-tau, including Fas, neuropeptides (agouti-related peptide and adrenocorticotropic hormone), and chemokines (IL-23, IL-17). Classification by random forest analysis achieved high sensitivity for FTLD-TDP (86%) with modest specificity (78%) in the autopsy cohort. When the classification algorithm was applied to a living FTD cohort, semantic dementia was the phenotype with the highest predicted proportion of FTLD-TDP. When living patients with behavioral variant FTD were examined in detail, those predicted to have FTLD-TDP demonstrated neuropsychological differences vs those predicted to have FTLD-tau in a pattern consistent with previously reported trends in autopsy-confirmed cases. CONCLUSIONS: Clinical cases with FTLD-TDP and FTLD-tau pathology can be potentially identified antemortem by assaying levels of specific analytes that are well-known and readily measurable in CSF.
Assuntos
Biomarcadores/líquido cefalorraquidiano , Proteínas de Ligação a DNA/metabolismo , Degeneração Lobar Frontotemporal/líquido cefalorraquidiano , Tauopatias/líquido cefalorraquidiano , Hormônio Adrenocorticotrópico/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Estudos de Coortes , Feminino , Degeneração Lobar Frontotemporal/complicações , Humanos , Interleucina-17/líquido cefalorraquidiano , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estatísticas não Paramétricas , Tauopatias/complicaçõesRESUMO
OBJECTIVE: Cognitive decline associated with Parkinson disease (PD) is common and highly disabling. Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease. METHODS: A total of 45 patients with PD were enrolled in this prospective cohort study and had at least 1 yearly longitudinal follow-up evaluation. CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale (DRS-2). CSF was tested for amyloid ß 1-42 (Aß(1-42)), p-tau(181p), and total tau levels using the Luminex xMAP platform. Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time. RESULTS: Lower baseline CSF Aß(1-42) was associated with more rapid cognitive decline. Subjects with CSF Aß(1-42) levels ≤192 pg/mL declined an average of 5.85 (95% confidence interval 2.11-9.58, p = 0.002) points per year more rapidly on the DRS-2 than subjects above that cutoff, after adjustment for age, disease duration, and baseline cognitive status. CSF total tau and p-tau(181p) levels were not significantly associated with cognitive decline. CONCLUSIONS: Reduced CSF Aß(1-42) was an independent predictor of cognitive decline in patients with PD. This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD. This biomarker may provide clinically useful prognostic information, particularly if combined with other risk factors for cognitive impairment in PD.
Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Transtornos Cognitivos/líquido cefalorraquidiano , Progressão da Doença , Doença de Parkinson/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Transtornos Cognitivos/complicações , Transtornos Cognitivos/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: Depression and antidepressant use, especially selective serotonin reuptake inhibitors (SSRIs), are common in Parkinson disease (PD). The objective of this clinical trial was to assess the efficacy of atomoxetine, a selective norepinephrine reuptake inhibitor (SNRI), for the treatment of clinically significant depressive symptoms and common comorbid neuropsychiatric symptoms in PD. METHODS: A total of 55 subjects with PD and an Inventory of Depressive Symptomatology-Clinician (IDS-C) score > or = 22 were randomized to 8 weeks of atomoxetine or placebo treatment (target dosage = 80 mg/day). Depression response (> 50% decrease in IDS-C score or Clinical Global Impression-Improvement [CGI-I] score of 1 or 2) was assessed using intention-to-treat modeling procedures. Secondary outcomes included global cognition, daytime sleepiness, anxiety, apathy, and motor function. RESULTS: There were no between-groups differences in a priori-defined response rates. Using a more liberal response criterion of > 40% decrease in IDS score from baseline, there was a trend (p = 0.08) favoring atomoxetine. Patients receiving atomoxetine experienced significantly greater improvement in global cognition (p = 0.003) and daytime sleepiness (p = 0.001), and atomoxetine was well-tolerated. CONCLUSIONS: Atomoxetine treatment was not efficacious for the treatment of clinically significant depressive symptoms in PD, but was associated with improvement in global cognitive performance and daytime sleepiness. Larger studies of SNRIs in PD for disorders of mood, cognition, and wakefulness are appropriate. CLASSIFICATION OF EVIDENCE: This interventional study provides Class II evidence that atomoxetine (target dosage = 80 mg/day) is not efficacious in improving clinically significant depression in PD.
Assuntos
Inibidores da Captação Adrenérgica/uso terapêutico , Depressão/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Propilaminas/uso terapêutico , Inibidores da Captação Adrenérgica/efeitos adversos , Idoso , Cloridrato de Atomoxetina , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/epidemiologia , Comorbidade , Depressão/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Propilaminas/efeitos adversos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Due to the high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson disease (PD), routine cognitive screening is important for the optimal management of patients with PD. The Montreal Cognitive Assessment (MoCA) is more sensitive than the commonly used Mini-Mental State Examination (MMSE) in detecting MCI and dementia in patients without PD, but its validity in PD has not been established. METHODS: A representative sample of 132 patients with PD at 2 movement disorders centers was administered the MoCA, MMSE, and a neuropsychological battery with operationalized criteria for deficits. MCI and PD dementia (PDD) criteria were applied by an investigator blinded to the MoCA and MMSE results. The discriminant validity of the MoCA and MMSE as screening and diagnostic instruments was ascertained. RESULTS: Approximately one third of the sample met diagnostic criteria for a cognitive disorder (12.9% PDD and 17.4% MCI). Mean (SD) MoCA and MMSE scores were 25.0 (3.8) and 28.1 (2.0). The overall discriminant validity for detection of any cognitive disorder was similar for the MoCA and the MMSE (receiver operating characteristic area under the curve [95% confidence interval]): MoCA (0.79 [0.72, 0.87]) and MMSE (0.76 [0.67, 0.85]), but as a screening instrument the MoCA (optimal cutoff point = 26/27, 64% correctly diagnosed, lack of ceiling effect) was superior to the MMSE (optimal cutoff point = 29/30, 54% correctly diagnosed, presence of ceiling effect). CONCLUSIONS: The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, has adequate psychometric properties as a screening instrument for the detection of mild cognitive impairment or dementia in Parkinson disease. However, a positive screen using either instrument requires additional assessment due to suboptimal specificity at the recommended screening cutoff point.
Assuntos
Transtornos Cognitivos/diagnóstico , Demência/diagnóstico , Entrevista Psiquiátrica Padronizada , Testes Neuropsicológicos , Idoso , Transtornos Cognitivos/complicações , Transtornos Cognitivos/epidemiologia , Coleta de Dados , Demência/complicações , Demência/epidemiologia , Feminino , Avaliação Geriátrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Psicometria/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Disparities of Parkinson's disease (PD) care have not been assessed. METHODS: We examined the medical records of 309 (83%) non-Hispanic White and 65 (17%) non-White Los Angeles veterans with PD from 1998 to 2004 to determine if care quality as measured by 10 PD indicators different by race/ethnicity. RESULTS: In multivariate modeling, adherence to indicators was higher among non-Hispanic Whites (71% vs. 65%, risk ratio 1.15, 95% CI [1.07-1.32]) compared to non-Whites. Differences in adherence by race/ethnicity were greatest for depression treatment (p<0.05). CONCLUSIONS: We detected disparities in quality of PD care, particularly in depression treatment. Future research should determine causes for these so that interventions can be designed to reduce such disparities.
Assuntos
Doença de Parkinson/etnologia , Doença de Parkinson/terapia , Qualidade da Assistência à Saúde , Veteranos , Negro ou Afro-Americano , Idoso , Idoso de 80 Anos ou mais , Asiático , Estudos de Coortes , Hispânico ou Latino , Humanos , Indígenas Norte-Americanos , Masculino , Pessoa de Meia-Idade , Indicadores de Qualidade em Assistência à Saúde , Estudos Retrospectivos , População BrancaRESUMO
As predictive testing for Parkinson's disease (PD) becomes available, it will be important to understand in whom such testing will be used. To address this issue, we conducted a mail survey of 138 first-degree relatives of PD patients. In the absence of treatment, 60% reported that they would either "definitely" or "probably" be interested in predictive testing. In the setting of a clinical trial, this number increased to 71% (p=0.04) and when neuroprotective therapy is available, interest increased to 90% (p<0.001). Interest in predictive testing for PD is moderate in the absence of effective therapy, and goes up significantly when both clinical trial participation and neuroprotective therapy are offered.
Assuntos
Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Análise de Variância , Correio Eletrônico/estatística & dados numéricos , Família , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/genética , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
Based on published prevalence studies, we used two different methodologies to project the number of individuals with Parkinson disease (PD) in Western Europe's 5 most and the world's 10 most populous nations. The number of individuals with PD over age 50 in these countries was between 4.1 and 4.6 million in 2005 and will double to between 8.7 and 9.3 million by 2030.
Assuntos
Previsões/métodos , Internacionalidade , Doença de Parkinson/epidemiologia , Densidade Demográfica , Crescimento Demográfico , Modelos de Riscos Proporcionais , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
We conducted a retrospective chart review of all ALS patients seen at our institution over four years to determine the incidence of venous thromboembolism and to identify risk factors in this population. Events occurred in 13 of 438 patients (2.97%), yielding an annual incidence rate of 33.1 events per 1,000 patients (95% CI 17.5-55.3). ALS patients have a risk of venous thromboembolism that is higher than the general population but lower than the population of patients with acute stroke or spinal cord injury. Immobility was significantly associated with increased risk of venous thrombosis (RR = 4.96; 95% CI 1.39-17.78).
Assuntos
Esclerose Lateral Amiotrófica/complicações , Tromboembolia , Trombose Venosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Trombose Venosa/epidemiologia , Trombose Venosa/etiologiaRESUMO
OBJECTIVE: To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD). METHODS: This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5-10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog). RESULTS: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale.There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant. CONCLUSIONS: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study.
Assuntos
Inibidores da Colinesterase/uso terapêutico , Demência/tratamento farmacológico , Indanos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Piperidinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Colinesterase/efeitos adversos , Estudos Cross-Over , Demência/diagnóstico , Donepezila , Método Duplo-Cego , Feminino , Humanos , Indanos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico , Piperidinas/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD). OBJECTIVE: To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD. METHODS: Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated. RESULTS: UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant. CONCLUSIONS: Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.
Assuntos
Agnosia/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/análise , Compostos de Organotecnécio , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos , Agnosia/etiologia , Agnosia/fisiopatologia , Ligação Competitiva/fisiologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Progressão da Doença , Dopamina/deficiência , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Exame Neurológico , Condutos Olfatórios/diagnóstico por imagem , Condutos Olfatórios/metabolismo , Condutos Olfatórios/fisiopatologia , Compostos de Organotecnécio/metabolismo , Compostos de Organotecnécio/farmacocinética , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos , Olfato/fisiologia , Transmissão Sináptica/fisiologia , Tropanos/metabolismo , Tropanos/farmacocinéticaRESUMO
A woman presenting with levodopa responsive Parkinsonism developed rapidly progressive bulbar signs, quadriparesis, and upper and lower motor neurone signs. At necropsy, she was found to have three pathological diagnoses: amyotrophic lateral sclerosis, Parkinson's disease, and abundant tau-positive argyrophilic neuritic pathology, known as argyrophilic grain disease. This case raises the possibility that three distinct neuropathological diagnoses share a common aetiology.
Assuntos
Esclerose Lateral Amiotrófica/patologia , Encefalopatias/patologia , Doença de Parkinson/patologia , Esclerose Lateral Amiotrófica/complicações , Autopsia , Encefalopatias/complicações , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Proteínas tau/análiseRESUMO
We evaluated the diagnostic accuracy of SPECT imaging using [(99m)Tc]TRODAT-1 (TRODAT), a relatively inexpensive technetium-labeled dopamine transporter ligand, in distinguishing 29 patients with early PD from 38 healthy volunteers. Mean TRODAT uptake values were significantly decreased in the caudate (p=0.0097) and anterior and posterior putamen (p < 0.0001) of PD patients compared to controls. Using the posterior putamen as the main region of interest resulted in the greatest accuracy (sensitivity 0.79, specificity 0.92). These findings show that TRODAT imaging can accurately differentiate early PD patients from controls and has the potential to improve the diagnosis of patients with early signs of PD.