Determinants of delayed diagnosis in Parkinson’s disease

Breen, David P.; Evans, Jonathan; Farrell, Krista; Brayne, Carol; Barker, Roger A.

doi:10.1007/s00415-013-6905-3

Cited by 73 publications

(108 citation statements)

References 8 publications

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“…Physicians therefore recruited and longitudinally assessed the participants without knowledge of their GBA genotype. This design should be less vulnerable to recruitment and ascertainment bias than previous case‐control studies given that patients were assigned to one of two groups simply based on the presence or absence of mutated GBA alleles in a form of “double‐blinded Mendelian randomization.” The meta‐analysis included two community‐based cohorts6, 14 and six from academic centers with cohort‐specific eligibility criteria, differences in enrollment ages, and recruitment from distinct source populations.…”

Section: Discussionmentioning

confidence: 99%

“…Seven longitudinal cohorts6, 10, 11, 12, 13, 14, 15, 16 from North America and Europe representing 2,304 patients with PD (and available DNA) were analyzed (Table 1). The analysis included two population‐based, incident cohort studies (Cambridgeshire Parkinson's Incidence from GP to Neurologist [CamPaIGN],17 Parkinsonism: Incidence, Cognition and Non‐motor heterogeneity in Cambridgeshire (PICNICS)14, 18; five purpose‐built biomarkers and clinical observational studies from academic centers (Harvard Biomarker Study [HBS],19, 20, 21, 22 PROfiling PARKinson's disease [PROPARK],16 and the French Drug Interaction with Genes in PD [DIGPD]); as well as two well‐phenotyped, failed phase III clinical trials with longitudinal, observational extension studies (Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism [DATATOP]15; Parkinson Research Examination of CEP‐1347 Trial/A Longitudinal Follow‐up of the PRECEPT Study Cohort [PreCEPT/PostCEPT]13.…”

Section: Methodsmentioning

confidence: 99%

“…In DATATOP, the eligibility criteria required a diagnosis of early, idiopathic PD (Hoen & Yahr [HY] stages 1 or 2) not on antiparkinsonian medications23. Detailed eligibility criteria for the cohorts have been previously reported 10, 13, 14, 16, 22, 23, 24, 25. For all cohorts, diagnostic certainty was increased by confirming the clinical diagnosis of PD during longitudinal follow‐up visits 26.…”

Section: Methodsmentioning

confidence: 99%

“…The study names are Harvard Biomarkers Study (HBS)10, 21, 22; Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP)15, 23; Parkinson Research Examination of CEP‐1347 Trial/A Longitudinal Follow‐up of the PRECEPT Study Cohort (PreCEPT/PostCEPT)13; Cambridgeshire Parkinson's Incidence from GP to Neurologist (CamPaIGN)6, 11, 24; Parkinsonism: Incidence, Cognition and Non‐motor heterogeneity in Cambridgeshire (PICNICS)14; Drug Interaction with Genes in PD (DIGPD)25; and PROfiling PARKinson's disease (PROPARK) study 16. HBS was examined in two parts: 383 participants for whom targeted genotyping of three GBA mutations was performed; 173 individuals for whom full sequencing of the GBA locus was performed (targeted sequencing).…”

Section: Methodsmentioning

confidence: 99%

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Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

Liu

Boot

Locascio

et al. 2016

Annals of Neurology

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ObjectiveWe hypothesized that specific mutations in the β‐glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non‐neuropathic GD mutations confer intermediate progression rates.MethodsA total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models.ResultsOverall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60–6.25) and a hastened decline in Mini–Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18–8.73; p = 0.022). By contrast, the common, non‐neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92–4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89–2.05) did not reach significance.InterpretationMutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into “high gear.” These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674–685

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

Liu

Boot

Locascio

et al. 2016

Annals of Neurology

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230

240

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“…Al revisar la literatura sólo encontramos tres trabajos que compartían un grado de similitud con el nuestro [4][5][6] . Al comparar los datos generales hallamos que al momento del diagnóstico la edad en nuestro grupo fue ligeramente mayor que el promedio de 67 años obtenido en dos informes previos 4,5 .…”

Section: Discussionunclassified

Latencia diagnóstica en la enfermedad de Parkinson: Estudio en 200 pacientes de novo en un hospital público de Chile

2015

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Functional Impairment in Individuals With Prodromal or Unrecognized Parkinson Disease

et al. 2023

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ImportanceDaily functioning in individuals with prodromal Parkinson disease requires more detailed description.ObjectiveTo evaluate whether functional limitations exist in individuals with Parkinson disease prior to diagnosis compared with the general population.Design, Setting, and ParticipantsThis case-control study used Medicare-linked data from the National Health and Aging Trends Study (NHATS), a longitudinal survey in the US, for a random subsample of Medicare beneficiaries aged 65 years or older, with Black and older individuals oversampled by design. Patients with incident Parkinson disease were defined as having 2 or more Medicare diagnoses from January 2011 to December 2017, with Medicare eligibility 2 or more consecutive years prior to the first diagnosis. Controls were defined as individuals with Medicare eligibility at a baseline year and 2 or more years prior, with no Parkinson disease diagnosis. Analyses were conducted from November 2021 to June 2022.ExposuresResponses to survey questions addressing dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.Main Outcome and MeasuresAssociations between survey responses and Parkinson disease diagnosis in the first year of diagnosis (baseline) and up to 3 years prior to diagnosis (ie, during the prodromal phase) were examined using logistic regression.ResultsA total of 6674 participants were included. The participant numbers and case prevalence each year varied from 3492 to 5049 and from 700 to 1180 per 100 000 population, respectively. The median age groups were 75 to 79 years and 80 to 84 years, and the percentage of females varied from 48.21% (27 of 56 cases) to 59.98% (2079 of 3466 controls) across all years, with similar proportions among cases and controls. Individuals with prodromal Parkinson disease were less likely to report being able to walk 6 blocks (odds ratio [OR], 0.34; 95% CI, 0.15-0.82), stand independently from a kneeling position (OR, 0.30; 95% CI, 0.11-0.85), or lift a heavy object above one’s head (OR, 0.36; 95% CI, 0.15-0.87) and were more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.Conclusions and RelevanceThe findings suggest that individuals with prodromal or unrecognized Parkinson disease may have greater impairment in activities involving mobility and strength up to 3 years prior to diagnosis compared with the general population. Identification of prodromal disease may facilitate earlier intervention to improve function.

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Determinants of delayed diagnosis in Parkinson’s disease

Cited by 73 publications

References 8 publications

Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

Latencia diagnóstica en la enfermedad de Parkinson: Estudio en 200 pacientes de novo en un hospital público de Chile

Functional Impairment in Individuals With Prodromal or Unrecognized Parkinson Disease

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