Background. To better understand the contribution of frailty to health-related outcomes in elderly persons, it seems valuable to explore data from cohort studies across the world in an attempt to ...establish a comprehensive definition. The purpose of this report is to show the characteristics of frailty and observe its prognosis in a large sample of French community-dwelling elderly persons. Methods. We used data from 6078 persons 65 years old or older participating in the Three-City Study (3C). Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low activity. Principal outcomes were incident disability, hospitalization, and death. Multiple covariates were used to test the predictive validity of frailty on these outcomes. Results. Four hundred twenty-six individuals (7%) met frailty criteria. Participants classified as frail were significantly older, more likely to be female, and less educated and reported more chronic diseases, lower income, and poorer self-reported health status in comparison to nonfrail participants. In multivariate analysis, frailty was significantly associated with 4-year incidence of disability in activities of daily living (ADL) and instrumental ADL. However, frailty was marginally associated with incident hospitalization and was not a statistically significant predictor of incident mobility disability or mortality adjusting for potential confounding factors. Conclusions. Frailty is not specific to a subgroup or region of the world. The construct proposed by Fried and colleagues confirms its predictive validity for adverse-health outcomes, particularly for certain components of disability, thus suggesting that it may be useful in population screening and predicting service needs.
Multiple system atrophy (MSA) is a rare neurodegenerative disease, with limited understanding of disease progression and prognostic factors. We leveraged the data of a large prospective cohort of MSA ...to study both clinical progression and survival and assess their determinants. All consecutive patients seen at the French Reference Centre for MSA since 2007 were included in a prospective cohort with an annual follow-up including the Unified MSA Rating Scale (UMSARS). We used joint models to evaluate the risk of death, the mean trajectory of each UMSARS subscale and to determine the potential factors. Investigated factors included gender, age at baseline, MSA subtype, diagnosis certainty, type of first symptoms and the duration between symptom onset and the first visit. Among the 261 MSA patients included in our cohort, the median duration of clinical follow-up was 2.1 years (up to 10.3 years) and the median survival was 4.0 years since the first visit. Main factors for poor survival were the progression over time of UMSARS score (I + II and IV) and the severity of orthostatic hypotension. MSA subtype had no effect on progression or survival. The UMSARS I + II score progressed faster over time in subjects with autonomic dysfunction as the initial feature and in women. Despite a faster progression, women and men had similar survival. From this large MSA cohort, we confirm the rapid progression and poor prognosis of MSA. We provide additional evidence for a negative impact of early autonomic dysfunction and the severity of orthostatic hypotension on both disease progression and survival.
•Median survival was 4 years since first visit and 9.3 years since symptom onset.•UMSARS I + II progression and severity of orthostatic hypotension were main factors for poor survival.•UMSARS I + II scores progressed faster in subjects with early dysautonomia and women.
To assess the correlation between macular pigment optical density and plasma levels of lutein, zeaxanthin, and fatty acids, especially omega-3 polyunsaturated fatty acids (PUFAs).
The PIMAVOSA study ...is an observational study of 107 healthy volunteers, aged 20 to 60 years and born in southwest France, without histories of ocular disease. Macular pigment optical density (MPOD) was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma measurements (lutein, zeaxanthin, and fatty acids) were performed from fasting blood samples collected on the day of the eye examination.
MPOD within 6° correlated with plasma levels of lutein and zeaxanthin (r = 0.35, P < 0.001, and r = 0.30, P < 0.005, respectively). MPOD also significantly correlated with total plasma omega-3 PUFAs (r = 0.22, P < 0.05). Among the different omega-3 PUFAs, docosapentaenoic acid (DPA) had the highest correlation with MPOD (r = 0.31, P < 0.001), whereas correlation with eicosapentaenoic acid (EPA) was moderate (r = 0.21, P < 0.05) and did not reach statistical significance for docosahexaenoic acid (r = 0.14, P = 0.14).
In the present study, macular pigment density was associated not only with plasma lutein and zeaxanthin but also with omega-3 long-chain PUFAs, particularly with EPA and DPA. Further studies will be needed to confirm these findings and to identify the underlying mechanisms.
Objective
This study aimed to develop a deep learning (DL) model, named ‘DeepAlienorNet’, to automatically extract clinical signs of age‐related macular degeneration (AMD) from colour fundus ...photography (CFP).
Methods and Analysis
The ALIENOR Study is a cohort of French individuals 77 years of age or older. A multi‐label DL model was developed to grade the presence of 7 clinical signs: large soft drusen (>125 μm), intermediate soft (63–125 μm), large area of soft drusen (total area >500 μm), presence of central soft drusen (large or intermediate), hyperpigmentation, hypopigmentation, and advanced AMD (defined as neovascular or atrophic AMD). Prediction performances were evaluated using cross‐validation and the expert human interpretation of the clinical signs as the ground truth.
Results
A total of 1178 images were included in the study. Averaging the 7 clinical signs' detection performances, DeepAlienorNet achieved an overall sensitivity, specificity, and AUROC of 0.77, 0.83, and 0.87, respectively. The model demonstrated particularly strong performance in predicting advanced AMD and large areas of soft drusen. It can also generate heatmaps, highlighting the relevant image areas for interpretation.
Conclusion
DeepAlienorNet demonstrates promising performance in automatically identifying clinical signs of AMD from CFP, offering several notable advantages. Its high interpretability reduces the black box effect, addressing ethical concerns. Additionally, the model can be easily integrated to automate well‐established and validated AMD progression scores, and the user‐friendly interface further enhances its usability. The main value of DeepAlienorNet lies in its ability to assist in precise severity scoring for further adapted AMD management, all while preserving interpretability.
Purpose
To test the hypothesis that central drusen location is strongly linked with known Age‐related Macular Degeneration (AMD) risk factors and risk of incident late AMD.
Methods
The Alienor study ...is a prospective population‐based cohort study of residents of Bordeaux, France, followed from 2009 to 2017. On retinal photographs, we defined central drusen as at least one soft drusen (>63 μm) within 500 μm from fovea and pericentral drusen as at least one drusen 500–3000 μm from fovea, in the absence of any central drusen. Late AMD (atrophic and/or neovascular) was diagnosed using multimodal imaging. In total, 481 eyes were included in the analysis: 160 central and 321 pericentral. We investigated associations with systemic (age, sex, smoking, medical prescriptions, plasma concentrations of lipids and nutrients, UV exposure, blood pressure), ocular (retinal thickness, cataract extraction) and genetic risk scores (GRS).
Results
In multivariate logistic regression central drusen were associated with smoking (OR, 2.95 for smoking more than 20 pack‐years, p = 0.02), HDL‐cholesterol (OR, 1.57 for 1 standard deviation (SD) increase, p = 0.0048), pulse pressure (OR, 0.77 for 1 SD increase, p = 0.04), Age‐Related Maculopathy Susceptibility 2 (ARMS2) GRS (OR, 1.42; 95% CI, 1.11–1.83) and complement GRS (OR, 1.55; 95% CI, 1.15–2.10). In Cox modelling, the central location of drusen (at baseline or during the follow‐up) was associated with a 4.41‐fold increased risk (95% CI,1.98–9.81) for an incident late AMD.
Conclusion
Central drusen were strongly associated with AMD risk factors and incident late AMD, suggesting that it represents a key marker for AMD progression.
Objective
Whereas cognitive deficits are known to be detectable long before the typical symptoms of Alzheimer's disease (AD) are evident, previous studies have failed to determine when cognitive ...functioning actually begins to decline before dementia. Utilizing the long follow‐up of the PAQUID study, we examined the emergence of the first clinical symptoms over a 14‐year period of follow‐up before the dementia phase of AD.
Methods
This study relies on a case–control sample selected from the PAQUID cohort. Of the 3,777 initial subjects of the cohort, 350 subjects experienced development of AD during the 14 years of follow‐up. The cases were matched to 350 elderly control subjects. The evolution of scores on cognitive, functional, and depression scales was described throughout the 14‐year follow‐up using a semiparametric extension of the mixed‐effects linear model.
Results
The first decline in cognitive performances appeared as early as 12 years before dementia in measures of semantic memory and conceptual formation. Then, more global deficits appeared that were concomitant with an increase in memory complaints and depressive symptoms. About 2 years later, as a consequence of cognitive dysfunction, the subjects started to become slightly dependent in their activities of daily living. In the last 3 years, the impairment significantly worsened until the subjects reached the dementia phase.
Interpretation
This approach, describing the 14 years preceding dementia, provides a clear illustration of the particularly long and progressive prodromal phase of AD, and shows the successive emergence of cognitive deficits, depressive symptoms, and functional impairment during this phase. Ann Neurol 2008;64:492–498
We conducted a meta-analysis of randomized controlled trials to assess the effectiveness of disease-management programs for improving glycemic control in adults with diabetes mellitus and to study ...which components of programs are associated with their effectiveness.
We searched several databases for studies published up to December 2009. We included randomized controlled trials involving adults with type 1 or 2 diabetes that evaluated the effect of disease-management programs on glycated hemoglobin (hemoglobin A₁(C)) concentrations. We performed a meta-regression analysis to determine the effective components of the programs.
We included 41 randomized controlled trials in our review. Across these trials, disease-management programs resulted in a significant reduction in hemoglobin A₁(C) levels (pooled standardized mean difference between intervention and control groups -0.38 95% confidence interval -0.47 to -0.29, which corresponds to an absolute mean difference of 0.51%). The finding was robust in the sensitivity analyses based on quality assessment. Programs in which the disease manager was able to start or modify treatment with or without prior approval from the primary care physician resulted in a greater improvement in hemoglobin A₁(C) levels (standardized mean difference -0.60 v. -0.28 in trials with no approval to do so; p < 0.001). Programs with a moderate or high frequency of contact reported a significant reduction in hemoglobin A₁(C) levels compared with usual care; nevertheless, only programs with a high frequency of contact led to a significantly greater reduction compared with low-frequency contact programs (standardized mean difference -0.56 v. -0.30, p = 0.03).
Disease-management programs had a clinically moderate but significant impact on hemoglobin A₁(C) levels among adults with diabetes. Effective components of programs were a high frequency of patient contact and the ability for disease managers to adjust treatment with or without prior physician approval.
While exposure to ultraviolet radiation (UVR) is a recognized risk factor for cataract, its association is more controversial with age-related macular degeneration (AMD). We report the associations ...of lifetime exposure to ambient UVR with cataract extraction and AMD.
The Alienor Study is a population-based study of 963 residents of Bordeaux (France), aged 73 years or more. Lifetime exposure to ambient UVR was estimated from residential history and Eurosun satellite-based estimations of ground UVR. It was divided in three groups (lower quartile, intermediate quartiles, upper quartile), using the intermediate quartiles as the reference. Early and late AMD was classified from retinal color photographs. Cataract extraction was defined as absence of the natural lens at slit-lamp.
After multivariate adjustment, subjects in the upper quartile of lifetime ambient UVR exposure were at increased risk for cataract extraction (odds ratio OR = 1.53; 95% confidence interval CI, 1.04-2.26; P = 0.03) and for early AMD (OR = 1.59; 95% CI, 1.04-2.44; P = 0.03), by comparison with subjects in the intermediate quartiles. Subjects in the lower quartile of UVR exposure also were at increased risk for early AMD (OR = 1.69; 95% CI, 1.06-2.69; P = 0.03), by comparison with those with medium exposure. Associations of late AMD with UVR exposure was not statistically significant.
This study further confirms the increased risk for cataract extraction in subjects exposed to high ambient UVR. Moreover, it suggests that risk for early AMD is increased in subjects exposed to high UVR, but also to low UVR, by comparison with medium exposures.
Olive oil provides a mixture of lipids and antioxidant nutrients which may help preventing age-related diseases such as age-related macular degeneration (AMD). However, little is known about the ...associations between olive oil consumption and the risk of AMD.
To examine associations between olive oil use and AMD prevalence in elderly subjects.
Alienor (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) is a population-based study on eye diseases performed in elderly residents of Bordeaux (France). In 1999-2000, frequencies of consumption of main categories of dietary fats used were collected. In 2006-2088, AMD was graded from non mydriatic retinal photographs into three exclusive stages: no AMD, early AMD, and late AMD. Two categories of preferred dietary fat used (olive oil, n-3 rich oils, n-6 rich oils, mixed oils, butter and margarine) were defined: "no use" and "regular use" (using fat for spreading and/or cooking and/or dressing). Associations of AMD with each fat use were estimated using Generalized Estimating Equation logistic regressions models.
Our study included 654 subjects (1269 eyes) with complete data (n = 268 eyes with early AMD and n = 56 with late AMD). After adjustment for potential confounders, regular use of olive oil was significantly associated with a decreased risk of late AMD (odds ratio OR = 0.44, 95% confidence interval CI: 0.21;0.91). In contrast, regular use of olive oil was not significantly associated with early AMD (OR = 0.84, 95%CI: 0.59;1.21). No associations were found between regular consumption of n-3 rich oils, n-6 rich oils, mixed oils, butter and margarine and AMD, whatever the stage.
This study suggests a protective effect of olive oil consumption for late AMD in this elderly community-dwelling population. Characterization of the mediating nutrients deserves further research.
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