Summary
Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable ...quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta‐analysis. Compared with body mass index–defined lower‐normal weight (18.5‐22.4 kg/m2), the risk of all‐cause dementia was higher among underweight individuals but lower among those with upper‐normal (22.5‐24.9 kg/m2) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all‐cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non‐linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.
Introduction
Numerous results suggest the implication of infectious agents in the onset of Alzheimer's disease (AD).
Methods
In the Bordeaux‐3C prospective cohort, we assessed the impact of herpes ...simplex virus type 1 (HSV‐1) infection on the incidence of AD according to apolipoprotein E (APOE) status, a genetic susceptibility factor. Cox models were performed to estimate the 10‐year risk of AD associated with anti‐HSV antibodies in 1037 participants according to APOE4 status.
Results
Among APOE4 carriers, subjects for whom the frequency of HSV‐1 reactivation is supposed to be high, that is, immunoglobulin M (IgM) positive or elevated levels of IgG, had an increased risk of AD with adjusted hazard ratios (HRs) of 3.68 (1.08–12.55) and 3.28 (1.19–9.03), respectively. No significant association was found in APOE4‐negative subjects.
Discussion
These results, in accordance with a solid pathophysiological rationale, suggest a role for HSV‐1 in AD development among subjects with a genetic susceptibility factor, the APOE4 allele.
To assess diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) to discriminate glaucoma and control subjects in an elderly population.
The antioxidants, essential lipids, ...nutrition and ocular maladies study (ALIENOR: "Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires") is a population-based study. From 2009 to 2010, a total of 624 subjects, aged 74 years or older underwent a complete eye examination, including optic disc color photography and SD-OCT examination of the macula and the optic nerve head. Glaucoma diagnosis was made using retinophotography of the optic nerve head and International Society for Epidemiologic and Geographical Ophthalmology criteria. Average and sectorial peripapillary retinal nerve fiber layer thicknesses (RNFLT) were compared between glaucoma and control subjects using area under the receiver operating characteristic curves (AUC), positive and negative likelihood ratios (LR+/LR-), and diagnostic odds ratios (DOR).
A total of 532 subjects had complete data, 492 were classified as controls and 40 were classified as glaucoma. Mean age was 82.1 ± 4.2 years and average RNFLT was significantly different between both groups (controls: 88.7 ± 12.2 μm, glaucoma: 65.4 ± 14.4 μm, P < 0.001). Highest AUC values were observed for average (0.895), temporal-inferior (0.874), and temporal-superior (0.868) RNFLT. Temporal-superior RNFLT had the highest DOR (25.31; LR+, 4.65; LR-, 0.18), followed by average RNFLT (DOR: 24.80; LR+, 6.36; LR-, 0.26). When using the normative database provided by the machine, DOR increased to 31.03 (LR+, 1.75; LR-, 0.06) if at least one parameter was considered abnormal (at P < 0.05).
Parameters of SD-OCT RNFL may provide valuable information in a screening strategy to improve glaucoma detection in a general population of elderly people.
The authors examined associations between exposure to aluminum or silica from drinking water and risk of cognitive decline, dementia, and Alzheimer's disease among elderly subjects followed for 15 ...years (1988–2003). They actively searched for incident cases of dementia among persons aged 65 years or over living in 91 civil drinking-water areas in southern France. Two measures of exposure to aluminum were assessed: geographic exposure and individual exposure, taking into account daily consumption of tap water and bottled water. A total of 1,925 subjects who were free of dementia at baseline and had reliable water assessment data were analyzed. Using random-effects models, the authors found that cognitive decline with time was greater in subjects with a higher daily intake of aluminum from drinking water (≥0.1 mg/day, P = 0.005) or higher geographic exposure to aluminum. Using a Cox model, a high daily intake of aluminum was significantly associated with increased risk of dementia. Conversely, an increase of 10 mg/day in silica intake was associated with a reduced risk of dementia (adjusted relative risk = 0.89, P = 0.036). However, geographic exposure to aluminum or silica from tap water was not associated with dementia. High consumption of aluminum from drinking water may be a risk factor for Alzheimer's disease.
To determine changes in the incidence of dementia between 1988 and 2015.
This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the ...United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex.
Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval CI, 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% 95% CI 14%-32% vs 8% 0%-15%).
The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations.
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Purpose: To describe dry eye disease in French elderly subjects.
Methods: The Alienor Study is a population‐based study on age‐related eye disease in 963 residents of Bordeaux (France), aged 73 ...years or more. Self‐reported dry eye disease and use of artificial tears were documented through face‐to‐face interview. Dry eye symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire and tear film stability by tear break‐up time measurements (TBUT). Definite dry eye disease was defined as self‐reported dry eye, confirmed by use of artificial tears and/or OSDI greater or equal to 22.
Results: Nine hundred and fifteen subjects, with mean age of 80 ± 4 years, returned the OSDI questionnaire. Of these, 271 (29.6%) subjects reported a dry eye disease and 135 (14.7%) were using artificial tears. An OSDI score > 22 was found in 359 (39.2%) subjects and a TBUT < 5 seconds in 335/746 (44.9%) subjects. Overall, definite dry eye affected 21.9% of subjects and was more frequent in women (27.1%) than in men (13.6%). After multivariate adjustment, dry eye disease was also significantly less frequent in subjects with high educational level (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.31–0.78 for long secondary school) and more frequent in subjects with ocular hypertension (OR = 1.61, 95% CI: 1.02–2.57) and those using anxiolytics (OR = 1.53, 95% CI: 1.02–2.29).
Conclusions: This large observational study confirmed the high prevalence of dry eye symptoms among elderly subjects and confirmed some of the previously identified risk factors (in particular female gender and use of anxiolytics).
Lipid metabolism and particularly high-density lipoprotein (HDL) may be involved in the pathogenic mechanism of age-related macular degeneration (AMD). However, conflicting results have been reported ...in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD.
The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France). AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes); large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247); late AMD (n = 40, 61). Associations of AMD with plasma lipids (HDL, total cholesterol (TC), Low-density lipoprotein (LDL), and triglycerides (TG)) were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data.
After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261), higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95%CI: 1.54-3.90; P = 0.0002) and any AMD (OR = 2.29, 95%CI: 1.46-3.59; P = 0.0003). Association with late AMD was far from statistical significance (OR = 1.58, 95%CI: 0.48-5.17; p = 0.45). No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use.
This study suggests that elderly patients with high HDL concentration may be at increased risk for AMD and, further, that HDL dysfunction might be implicated in AMD pathogenesis.
Hypovitaminosis D has been associated with several chronic conditions; yet, its association with cognitive decline and the risk of dementia and Alzheimer's disease (AD) has been inconsistent.
The ...study population consisted of 916 participants from the Three-City Bordeaux cohort aged 65+, nondemented at baseline, with assessment of vitamin D status and who were followed for up to 12 years.
In multivariate analysis, compared with individuals with 25(OH)D sufficiency (n = 151), participants with 25(OH)D deficiency (n = 218) exhibited a faster cognitive decline. A total of 177 dementia cases (124 AD) occurred: 25(OH)D deficiency was associated with a nearly three-fold increased risk of AD (hazard ratio = 2.85, 95% confidence interval 1.37–5.97).
This large prospective study of French older adults suggests that maintaining adequate vitamin D status in older age could contribute to slow down cognitive decline and to delay or prevent the onset of dementia, especially of AD etiology.
Thanks to the growing interest in personalized medicine, joint modeling of longitudinal marker and time‐to‐event data has recently started to be used to derive dynamic individual risk predictions. ...Individual predictions are called dynamic because they are updated when information on the subject's health profile grows with time. We focus in this work on statistical methods for quantifying and comparing dynamic predictive accuracy of this kind of prognostic models, accounting for right censoring and possibly competing events. Dynamic area under the ROC curve (AUC) and Brier Score (BS) are used to quantify predictive accuracy. Nonparametric inverse probability of censoring weighting is used to estimate dynamic curves of AUC and BS as functions of the time at which predictions are made. Asymptotic results are established and both pointwise confidence intervals and simultaneous confidence bands are derived. Tests are also proposed to compare the dynamic prediction accuracy curves of two prognostic models. The finite sample behavior of the inference procedures is assessed via simulations. We apply the proposed methodology to compare various prediction models using repeated measures of two psychometric tests to predict dementia in the elderly, accounting for the competing risk of death. Models are estimated on the French Paquid cohort and predictive accuracies are evaluated and compared on the French Three‐City cohort.
Aging has been clearly associated with decline in visual and physical performance. Alteration of visual function is associated with negative health outcomes including physical frailty. We assessed ...the relationship between Visual Impairment (VI) and sarcopenia in older persons in Cameroon. In a cross-sectional survey conducted in Douala in 2019, sarcopenia was assessed using the SPPB (Short Physical Performance Battery) test scored from 0 to 12. The diagnosis of sarcopenia was based on SPPB test score < 9 while VI was self-reported. Of the 403 participants (50.4% male) with a mean age of 67.1 (± 6.2) years, 356 (88.3%) reported a VI while the prevalence of sarcopenia was 47.9% 95% CI 43.0-52.7. After adjusting for several factors, VI was significantly associated with sarcopenia (OR 2.66 95% CI 1.29-5.48). Of the SPPB subtests, only chair stand test was negatively associated with VI (β = - 0.45 95% CI - 0.82 to 0.07). Our study supports an association between VI and sarcopenia. If confirmed by further cohort studies, this result would suggest that VI could be considered as an early indicator of sarcopenia among older people in sub-Saharan Africa.
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