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International audience; IntroductionProdromal non-motor symptoms precede, often by decades, motor signs and diagnosis of Parkinson's disease. It is however still uncertain if cognitive changes belong to the spectrum of non-motor prodromal Parkinson's disease. Thanks to the very long-term follow-up of the PAQUID population-based cohort, we assessed trajectories of cognitive complaints and functioning over a 13-year period before the diagnosis of late onset Parkinson's disease.MethodsThis study relies on a matched nested case-control sample selected from the cohort. Of the 3777 initial subjects of the cohort, 43 developed incident Parkinson's disease over the follow-up. The mean age at diagnosis was 78.0 (standard deviation = 5.8) years and 46.5% were men. These cases were matched to 86 elderly control subjects. Scores of different cognitive domains, daily function, and depressive symptoms were described throughout the follow-up using mixed-effects models.ResultsNo significant global cognitive decline preceded the diagnosis of late onset Parkinson's disease. However, psychomotor speed appeared significantly slower 2 years before the diagnosis and depressive symptoms 12 years before. Global score of instrumental activities of daily living became altered 2–3 years preceding the diagnosis of late onset Parkinson's disease, including the use of public transportation that was altered ten years before the diagnosis.ConclusionIn late onset Parkinson's disease, while global cognitive functions seem preserved, psychomotor speed starts to decline 2 years before the diagnosis and activities of daily living are also impacted. Depressive symptoms appear very early in the prediagnosic phase.

International audience; Dementia is a major public health issue worldwide and chronic use of benzodiazepine, which is very frequent in northern countries, was found to be a risk factor of dementia. This work aims at evaluating the impact of a reduction in chronic use of benzodiazepine on the future burden of dementia in France. Using estimations of dementia incidence and of benzodiazepine use and nation-wide projections of mortality and population sizes, a Monte Carlo approach based on an illness-death model provided projections of several indicators of dementia burden. With no change in benzodiazepine consumption, the prevalence of dementia between age 65 and 99 in France in 2040 was estimated at 2.16 millions (95% confidence interval (CI) 1.93–2.38), with a life expectancy without dementia at 65 years equal to 25.0 years (24.7–25.3) for women and 23.8 years (23.5–24.2) for men. Assuming a disappearance of chronic use of benzodiazepine in 2020, the prevalence would be reduced by about 6.6% in 2040 and the life expectancy without dementia would increase by 0.99 (0.93–1.06) year among women and 0.56 (0.50–0.62) among men. To conclude, a modest but significant reduction in future dementia burden could be obtained by applying current recommendation for duration of benzodiazepine use.

In line with declining trends in dementia incidence, this work thus aimed to compare the cognitive and functional evolution of two "generations" separated by 10 years and to evaluate the impact of specific risk factors on this evolution. This study was conducted on two "generations" of elderly individuals aged 78-88 years, who were included 10 years apart in the Personnes Agees QUID (PAQUID) cohort (France) (n = 612 in 1991-92 and n = 628 in 2001-02) and followed-up for 12 years, with assessments of cognition and disability. Differences between the generations in baseline levels and decline over time were estimated using a joint model to account for differential attrition. Compared with the first generation, the second generation had higher performances at baseline on four cognitive tests (from p < 0.005). Differences in global cognition, verbal fluency, and processing speed, but not in working memory were mostly explained by improvement in educational level. The second generation also exhibited less cognitive decline in verbal fluency and working memory. Regarding disability, we evidenced a lower progression over the follow-up period for the second generation compared to the first one. The cognitive state of this elderly population improved, partially due to improvements in educational level.

In line with declining trends in dementia incidence, this work thus aimed to compare the cognitive and functional evolution of two "generations" separated by 10 years and to evaluate the impact of specific risk factors on this evolution. This study was conducted on two "generations" of elderly individuals aged 78-88 years, who were included 10 years apart in the Personnes Agees QUID (PAQUID) cohort (France) (n = 612 in 1991-92 and n = 628 in 2001-02) and followed-up for 12 years, with assessments of cognition and disability. Differences between the generations in baseline levels and decline over time were estimated using a joint model to account for differential attrition. Compared with the first generation, the second generation had higher performances at baseline on four cognitive tests (from p < 0.005). Differences in global cognition, verbal fluency, and processing speed, but not in working memory were mostly explained by improvement in educational level. The second generation also exhibited less cognitive decline in verbal fluency and working memory. Regarding disability, we evidenced a lower progression over the follow-up period for the second generation compared to the first one. The cognitive state of this elderly population improved, partially due to improvements in educational level.

International audience; A simulation study is performed to investigate the robustness of the maximum likelihood estimator of fixed effects from a linear mixed model when the error distribution is misspecied. Inference for the fixed effects under the assumption of independent normally distributed errors with constant variance is shown to be robust when the errors are either non-gaussian or heteroscedastic, except when the error variance depends on a covariate included in the model with interaction with time. Inference is impaired when the errors are correlated. In the latter case, the model including a random slope in addition to the random intercept is more robust than the random intercept model. The use of Cholesky residuals and conditional residuals to evaluate the fit of a linear mixed model is also discussed.