Predictors of dementia in Parkinson's disease; findings from a 5-year prospective study using the SCOPA-COG

Zhu, Ke; Hilten, Jacobus J. van; Marinus, Johan

doi:10.1016/j.parkreldis.2014.06.006

Cited by 104 publications

(89 citation statements)

References 43 publications

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“…This outcome is inconsistent with previous studies reporting that lower education, increased age, male sex, motor disability, dysfunctional sense of smell, depression and anxiety are associated with cognitive impairment [31][32][33][34]. This inconsistency could be explained by the use of the MMSE as a cognitive assessment scale, and the relatively short disease duration of our subjects.…”

Section: Research Lei Chencontrasting

confidence: 98%

Cognitive Function in Early and Advanced Parkinson’s disease

Chen¹,

Wang²

2018

Neuropsychiatry

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Objective: To investigate the occurrence of mild cognitive impairment (MCI) in early and advanced Parkinson's disease (PD) and identify the risk factors for PD-MCI.Methods: A total of 138 PD patients were recruited between April 2015 and December 2017. We evaluated demographic and clinical data, including sex, age, age of onset, disease duration, Hoehn and Yahr stage, Unified Parkinson's Disease Rating Scale (UPDRS) part Ⅲ, 39-item Parkinson's Disease Questionnaire (PDQ-39), Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI) and Mini-Mental State Examination (MMSE) scores. Participants were divided into early and advanced PD groups according to Hoehn and Yahr stage. Group comparisons were performed using Student's t-tests or chi-square tests. Binary logistic regression was conducted to identify risk factors for PD-MCI. Results:There was no significant difference in MMSE scores between the early and advanced groups. According to PD-MCI Level 1 criteria, 27 individuals (30.0%) in the early group and 16 individuals (33.3%) in the advanced group were classified as having PD-MCI. The proportion of PD-MCI was not significantly different between the two groups (chi-square = 0.162, p = 0.687). No demographic or clinical factors were significantly associated with the development of PD-MCI. Conclusions:Cognitive impairment is stable in PD patients with short disease duration when the MMSE is used as a global cognitive test. The occurrence of PD-MCI is high, even in newly diagnosed PD patients.

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Section: Research Lei Chencontrasting

confidence: 98%

Cognitive Function in Early and Advanced Parkinson’s disease

Chen¹,

Wang²

2018

Neuropsychiatry

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“…Age-at-onset 2,3 , depression 2 , and education 2 have been nominated as predictors of dementia in multiple small or medium-sized cohorts (e.g. the largest published study examined 400 subjects for several years) 2,3 . Measures of baseline disease severity using motor and cognitive scores are linked to an increased risk of developing future dementia 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Prediction of cognition in Parkinson's disease with a clinical–genetic score: a longitudinal analysis of nine cohorts

Liu¹,

Locascio²,

Corvol³

et al. 2017

The Lancet Neurology

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148

157

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Summary Background Cognitive decline is a debilitating manifestation of disease progression in Parkinson’s disease. We aimed to develop a clinical-genetic score to predict global cognitive impairment in patients with the disease. Methods A prediction algorithm for global cognitive impairment (defined as Mini Mental State Exam (MMSE) ≤25) was built using data from 1,350 patients with 5,165 longitudinal visits over 12.8 (median, 2.8) years. Age at onset, MMSE, education, motor exam score, gender, depression and GBA mutations, machine selected through stepwise Cox’ hazards analysis and Akaike’s information criterion, were used to compute the multivariable predictor. Independent validation was achieved in another 1,132 patients with 19,127 visits over 8.6 (median, 6.5) years. Findings The cognitive risk score accurately predicted cognitive impairment within ten years of disease onset with an area under the curve (AUC) of >0.85 in both the discovery (95% CI, 0.821–0.902) and validation populations (95% CI, 0.779 – 0.913). 72.6% of patients scoring in the highest quartile were cognitively impaired by ten years vs. 3.7% in the lowest quartile (hazard ratio, 18.4, 95% CI, 9.4 – 36.1). Dementia or disabling cognitive impairment was predicted with an AUC of 0.877 (95% CI 0.788–0.943) and high negative predictive value (0.920, 95% 0.877–0.954) at the predefined cutoff (0.196). Performance was stable in 10,000 randomly resampled subsets. Interpretation Our predictive algorithm provides a potential test for future cognitive health or impairment in patients with Parkinson’s. It could improve trials of cognitive interventions and inform on prognosis.

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“…Beyond GBA , variants in other loci, such as MAPT 11 and SNCA ,43 are emerging that might contribute to modulating cognitive decline. Moreover, demographic, clinical, and environmental factors are likely to influence the rate of cognitive decline in a particular patient (eg, Zhu et al44). …”

Section: Discussionmentioning

confidence: 99%

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

Liu

Boot

Locascio

et al. 2016

Annals of Neurology

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229

240

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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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Predictors of dementia in Parkinson's disease; findings from a 5-year prospective study using the SCOPA-COG

Cited by 104 publications

References 43 publications

Cognitive Function in Early and Advanced Parkinson’s disease

Cognitive Function in Early and Advanced Parkinson’s disease

Prediction of cognition in Parkinson's disease with a clinical–genetic score: a longitudinal analysis of nine cohorts

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

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