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Objective: To assess whether temporal trends in very early (within 48 hours) case-fatality rates may differ from those occurring between 48 hours and 30 days in patients with spontaneous intracerebral hemorrhage (ICH)., Methods: All cases of ICH that occurred in Dijon, France (151,000 inhabitants), were prospectively collected between 1985 and 2011, using a population-based registry. Time trends in 30-day case fatality were analyzed in 3 periods: 1985-1993, 1994-2002, and 2003-2011. Cox regression models were used to evaluate associations between time periods and case fatality within 48 hours and between 48 hours and 30 days, after adjustments for demographics, risk factors, severity, and ICH location., Results: A total of 531 ICH cases were recorded (mean age 72.9 ± 15.8, 52.7% women). Thirty-day case fatality gradually decreased with time from 40.9% in 1985-1993 to 33.5% 1994-2002 and to 29.6% in 2003-2011 (adjusted hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.47-1.07, p = 0.106, for 1994-2002, and adjusted HR 0.49, 95% CI 0.32-0.73, p < 0.001, for 2003-2011). Over the whole study period, 43.6% of 1-month deaths occurred within the first 48 hours following ICH onset. There was no temporal change in case fatality occurring within the first 48 hours but a decrease in deaths occurring between 48 hours and 30 days was observed with time (HR 0.53, 95% CI 0.31-0.90, p = 0.02, for 1994-2002, and HR 0.32, 95% CI 0.32-0.55, p < 0.01, for 2003-2011, compared with 1985-1993)., Conclusion: Although 30-day case fatality significantly decreased over the last 27 years, additional improvements in acute management of ICH are needed since very early case-fatality rates (within 48 hours) did not improve., (© 2017 American Academy of Neurology.)

Objective: We aimed to investigate the impact of endogenous estradiol (E2) on dementia and to evaluate the contribution of vascular risk factors and inflammatory and blood coagulation markers to this association., Methods: Using data from a French population-based prospective study (the Three-City Study) including 5,644 postmenopausal women aged 65 years or older, we investigated the association of endogenous total-E2 and bioavailable-E2 and total-testosterone with the 4-year incidence of all-cause dementia. We further focused on the role of dementia and cardiovascular risk factors as well as inflammation (C-reactive protein, fibrinogen) and hypercoagulability (fibrin d-dimers, thrombin generation) in these associations. We used a case-cohort design consisting of a random subcohort of 562 women not using hormone therapy and 132 incident dementia cases., Results: Adjusted Cox proportional hazards models showed a J-shaped relationship between total-E2 and risk of dementia (p = 0.001). Total-E2 values in the lower and upper quartiles were associated with an increased dementia risk (adjusted hazard ratio [HR] [95% confidence interval] = 2.2 [1.1-4.5] and HR = 2.4 [1.2-5.2], respectively). Importantly, the risk associated with higher E2 levels was dramatically increased in women with diabetes compared with nondiabetic women (adjusted HR associated with the upper E2 quartile = 14.2 [1.60-123] and HR = 3.4 [0.1-147], respectively, p interaction <0.05). Similar results were found for bioavailable-E2. Adjustment for inflammatory and blood coagulation markers did not modify our results. No significant association was found for total-testosterone., Conclusion: High E2 level is an independent predictor of incident dementia, particularly in postmenopausal women with diabetes.

Objective: To describe CSF biomarker profiles in posterior cortical atrophy (PCA), which induces high-order visual deficits often associated with Alzheimer disease (AD) pathology, and relate these findings to clinical and neuropsychological assessment., Methods: This prospective observational study included 22 patients with PCA who underwent CSF biomarker analysis of total tau (t-tau), phosphorylated tau on amino acid 181 (p-tau181), and amyloid β (Aβ(42)). At group level, the CSF profiles of patients with PCA were compared to those of patients with typical AD and patients with other dementia (OD). Individually, the clinical presentation of patients with PCA was correlated to their CSF profile to assess the predictability of clinical features for diagnosis of underlying AD pathology., Results: At group level, the PCA biomarker profile was not different from that of the AD group, but very different from that of the OD group (p < 0.001). More than 90% of patients with PCA had CSF profiles consistent with AD. All patients with PCA with either isolated higher-order visual deficit (n = 8) or visual deficit associated with memory impairment (n = 11) had CSF profiles consistent with AD. Only one of the 3 patients with PCA with asymmetric motor signs fulfilled biological CSF criteria for AD., Conclusions: PCA syndrome is usually associated with CSF biomarkers suggestive of AD, as shown by previous neuropathologic studies. This does not apply in case of motor signs suggesting associated corticobasal syndrome. CSF biomarkers help to discriminate AD from non-AD processes associated with this condition.

Objective: There is accumulating evidence that involvement in leisure activities may be related to risk of dementia; however, there is no consensus concerning the underlying mechanism of this association. Hypothesizing that leisure activities may contribute to cognitive reserve (CR), we examined the association between leisure activities and risk of incident dementia and its subtypes within a general population sample, categorizing leisure activity as stimulating, passive, physical, and social. The possibility that these associations may be driven by other proxies of CR was also examined., Methods: Analyses were carried out on 5,698 dementia-free participants aged 65 and over included in the Three-City cohort study in Dijon and Montpellier (France) in 1999-2001. Hazard ratios (HR) were calculated for incident dementia and its subtypes (mixed/vascular dementia and Alzheimer disease) in relation to category of leisure activity., Results: Stimulating leisure activities were found to be significantly associated with a reduced risk of dementia (n = 161, HR = 0.49, 95% confidence interval [CI]: 0.31; 0.79) and Alzheimer disease (n = 105, HR = 0.39, 95% CI: 0.21; 0.71) over the 4-year follow-up 1) independently of other proxies of CR, 2) after adjusting for vascular risk factors, depressive symptoms, and physical functioning, and 3) independently of other leisure activities. Furthermore, no significant association was found with other leisure activities and dementia after controlling for the potential confounders., Conclusion: Our findings support the hypothesis that cognitively stimulating leisure activities may delay the onset of dementia in community-dwelling elders.

Objective: Several lines of evidence indicate that a decrease in the CSF concentration of amyloid beta(42) (Abeta(42)) is a potential biomarker for incident Alzheimer disease. In contrast, studies on plasma Abeta(1-40) and Abeta(1-42) peptide levels have yielded contradictory results. Here, we explored the links between incident dementia and plasma Abeta(1-40) and Abeta(1-42) peptide concentrations in the prospective, population-based Three-City (3C) Study. We also assessed the association between plasma concentrations of truncated Abeta (Abeta(n-40) and Abeta(n-42)) and the risk of dementia., Methods: During a subsequent 4-year follow-up period, 257 individuals presented incident dementia from 8,414 participants, and a subcohort of 1,185 individuals without dementia was drawn as a control cohort. Plasma levels of Abeta(1-40), Abeta(1-42), Abeta(n-40), and Abeta(n-42) were measured using an xMAP-based assay technology. The association between plasma Abeta peptide levels and the risk of dementia was assessed using Cox proportional hazard models., Results: Of the various Abeta variables analyzed, the Abeta(1-42)/Abeta(1-40) and Abeta(n-42)/Abeta(n-40) ratios presented the strongest association with the risk of dementia: people with a high Abeta(1-42)/Abeta(1-40) or Abeta(n-42)/Abeta(n-40) ratio had a lower risk of developing dementia. These associations were restricted to individuals diagnosed at 2 years of follow-up and the Abeta(n-42)/Abeta(n-40) ratio was mainly associated with the risk of mixed/vascular dementia., Conclusion: Plasma Abeta peptide concentrations and Abeta(1-42)/Abeta(1-40) and Abeta(n-42)/Abeta(n-40) ratios may be useful markers to indicate individuals susceptible to short-term risk of dementia.

Objective: To examine the association between caffeine intake, cognitive decline, and incident dementia in a community-based sample of subjects aged 65 years and over., Methods: Participants were 4,197 women and 2,820 men from a population-based cohort recruited from three French cities. Cognitive performance, clinical diagnosis of dementia, and caffeine consumption were evaluated at baseline and at 2 and 4 year follow-up., Results: Caffeine consumption is associated with a wide range of sociodemographic, lifestyle, and clinical variables which may also affect cognitive decline. Multivariate mixed models and multivariate adjusted logistic regression indicated that women with high rates of caffeine consumption (over three cups per day) showed less decline in verbal retrieval (OR = 0.67, CI = 0.53, 0.85), and to a lesser extent in visuospatial memory (OR = 0.82, CI = 0.65, 1.03) over 4 years than women consuming one cup or less. The protective effect of caffeine was observed to increase with age (OR = 0.73, CI = 0.53, 1.02 in the age range 65 to 74; OR = 0.3, CI = 0.14, 0.63 in the range 80+). No relation was found between caffeine intake and cognitive decline in men. Caffeine consumption did not reduce dementia risk over 4 years., Conclusions: The psychostimulant properties of caffeine appear to reduce cognitive decline in women without dementia, especially at higher ages. Although no impact is observed on dementia incidence, further studies are required to ascertain whether caffeine may nonetheless be of potential use in prolonging the period of mild cognitive impairment in women prior to a diagnosis of dementia.