Association of Midlife Diet With Subsequent Risk for Dementia.

Importance: Observational studies suggest that diet is linked to cognitive health. However, the duration of follow-up in many studies is not sufficient to take into account the long preclinical phase of dementia, and the evidence from interventional studies is not conclusive. Objective: To examine whether midlife diet is associated with subsequent risk for dementia. Design, Setting, and Participants: Population-based cohort study established in 1985-1988 that had dietary intake assessed in 1991-1993, 1997-1999, and 2002-2004 and follow-up for incident dementia until March 31, 2017. Exposures: Food frequency questionnaire to derive the Alternate Healthy Eating Index (AHEI), an 11-component diet quality score (score range, 0-110), with higher scores indicating a healthier diet. Main Outcome and Measures: Incident dementia ascertained through linkage to electronic health records. Results: Among 8225 participants without dementia in 1991-1993 (mean age, 50.2 years [SD, 6.1 years]; 5686 [69.1%] were men), a total of 344 cases of incident dementia were recorded during a median follow-up of 24.8 years (interquartile range, 24.2-25.1 years). No significant difference in the incidence rate for dementia was observed in tertiles of AHEI exposure during 1991-1993, 1997-1999 (median follow-up, 19.1 years), and 2002-2004 (median follow-up, 13.5 years). Compared with an incidence rate for dementia of 1.76 (95% CI, 1.47-2.12) per 1000 person-years in the worst tertile of AHEI (lowest tertile of diet quality) in 1991-1993, the absolute rate difference for the intermediate tertile was 0.03 (95% CI, -0.43 to 0.49) per 1000 person-years and for the best tertile was 0.04 (95% CI, -0.42 to 0.51) per 1000 person-years. Compared with the worst AHEI tertile in 1997-1999 (incidence rate for dementia, 2.06 [95% CI, 1.62 to 2.61] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was 0.14 (95% CI, -0.58 to 0.86) per 1000 person-years and for the best AHEI tertile was 0.14 (95% CI, -0.58 to 0.85) per 1000 person-years. Compared with the worst AHEI tertile in 2002-2004 (incidence rate for dementia, 3.12 [95% CI, 2.49 to 3.92] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was -0.61 (95% CI, -1.56 to 0.33) per 1000 person-years and for the best AHEI tertile was -0.73 (95% CI, -1.67 to 0.22) per 1000 person-years. In the multivariable analysis, the adjusted hazard ratios (HRs) for dementia per 1-SD (10-point) AHEI increment were not significant as assessed in 1991-1993 (adjusted HR, 0.97 [95% CI, 0.87 to 1.08]), in 1997-1999 (adjusted HR, 0.97 [95% CI, 0.83 to 1.12]), or in 2002-2004 (adjusted HR, 0.87 [95% CI, 0.75 to 1.00]). Conclusions and Relevance: In this long-term prospective cohort study, diet quality assessed during midlife was not significantly associated with subsequent risk for dementia.

Working memory performance is related to intrinsic resting state functional connectivity changes in community-dwelling elderly cohort.

Characterization of normal age-related changes in resting state brain networks associated with working memory performance is a major prerequisite for studying neurodegenerative diseases. The aim of this study was to investigate the relationship between performing a working memory task (under MRI) and resting-state brain networks in a large cohort of healthy elderly subjects (n=337). Functional connectivity and interactions between networks were assessed within the default mode (DMN), salience (SN), and right and left central executive (CEN) networks in two groups of subjects classed by their performance (low and high). The low performance group showed lower functional connectivity in both the DMN and SN, and higher functional connectivity in the right and left CEN compared to the high performance group. Overall the functional connectivity within the DMN and the CEN were correlated. The lower functional connectivity within the DMN and SN in the low performance group is suggestive of altered attentional and memory processes and/or altered motivation. The higher functional connectivity within the CEN could be related to compensatory mechanisms, without which the subjects would have even lower performances. The correlation between the DMN and CEN suggests a modulation between the lower functional connectivity within the DMN and the higher functional connectivity within the CEN when performance is reduced. Finally, this study suggests that performance modifications in healthy elderly subjects are associated with reorganization of functional connectivity within the DMN, SN, and CEN.

Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study.

AIMS/HYPOTHESIS: South Asian individuals have an increased prevalence of type 2 diabetes, but little is known about the development of glycaemic traits in this ethnic group. We compared age-related changes in glycaemic traits between non-diabetic South Asian and white participants. METHODS: In a prospective British occupational cohort with 5-yearly clinical examinations (n = 230/5,749 South Asian/white participants, age 39-79 years at baseline), age-related trajectories of fasting glucose (FG) and 2 h post-load glucose (PLG), log-transformed fasting insulin (FINS) and 2 h post-load insulin (PLINS), HOMA insulin sensitivity (HOMA2-%S) and HOMA insulin secretion (HOMA2-%B) were fitted for South Asian and white individuals who remained free of diabetes between 1991 and 2009. RESULTS: In sex-adjusted multilevel models, FG was stable in white participants but increased with age in South Asians (0.12 [SE = 0.04] mmol/l per decade). PLG, FINS and PLINS levels were lower among white participants (by 0.271 [SE = 0.092] mmol/l, 0.306 [SE = 0.046] log pmol/l, 0.707 [SE = 0.059] log pmol/l at age 50, respectively) compared with South Asians, although their age-related trajectories were parallel. HOMA2-%S was higher (0.226 [SE = 0.038] at age 50) and HOMA2-%B lower (by 0.189 [SE = 0.026] at age 50) among white than South Asian participants. The age-related decline in HOMA2-%S was similar in these groups, but the age-related increase in HOMA2-%B was greater in white participants (0.04 [SE = 0.02] per decade). This difference was explained by obesity, lifestyle and social status. CONCLUSIONS/INTERPRETATION: Findings from a diabetes-free population suggest an inadequate pancreatic beta cell reserve in South Asians, as a significantly steeper age-related increase in FG was observed in this ethnic group compared with white individuals.

Working memory activation of neural networks in the elderly as a function of information processing phase and task complexity.

Changes in working memory are sensitive indicators of both normal and pathological brain aging and associated disability. The present study aims to further understanding of working memory in normal aging using a large cohort of healthy elderly in order to examine three separate phases of information processing in relation to changes in task load activation. Using covariance analysis, increasing and decreasing neural activation was observed on fMRI in response to a delayed item recognition task in 337 cognitively healthy elderly persons as part of the CRESCENDO (Cognitive REServe and Clinical ENDOphenotypes) study. During three phases of the task (stimulation, retention, probe), increased activation was observed with increasing task load in bilateral regions of the prefrontal cortex, parietal lobule, cingulate gyrus, insula and in deep gray matter nuclei, suggesting an involvement of central executive and salience networks. Decreased activation associated with increasing task load was observed during the stimulation phase, in bilateral temporal cortex, parietal lobule, cingulate gyrus and prefrontal cortex. This spatial distribution of decreased activation is suggestive of the default mode network. These findings support the hypothesis of an increased activation in salience and central executive networks and a decreased activation in default mode network concomitant to increasing task load.

Sleep complaints and metabolic syndrome in an elderly population: the Three-City Study.

OBJECTIVES: To assess whether sleep complaints (rather than clinically defined sleep disturbances) were associated with the metabolic syndrome (MetS) and each of its components in an elderly population. METHODS: Cross-sectional analyses of data from the French Three City Study, a large multicenter cohort of elderly community-dwellers. PARTICIPANTS: 6,354 participants (56.4% women, median age 73; range: 65-97 years). MEASUREMENTS: Frequency of insomnia complaints (difficulty in initiating sleep, difficulty in maintaining sleep [DMS], and early morning awakening) and excessive daytime sleepiness (EDS) were self-reported. MetS was assessed using National Cholesterol Education program Adult Treatment Panel III criteria. RESULTS: A total of 977 participants had MetS. After adjustment for a large range of potential confounders, we report an association between the number of insomnia complaints and MetS. Among insomnia complaints only DMS was consistently associated with MetS (OR: 1.23, 95% CI: 1.06 to 1.43). Our results showed that EDS independently increased the risk of MetS (OR: 1.46, 95% CI: 1.18 to 1.81 for "frequently"; OR: 1.99, 95% CI: 1.49 to 1.67 for "often"). The EDS-MetS association was independent of past-history of cardiovascular disease, insomnia complaints, and obesity and loud snoring. CONCLUSION: We report significant independent associations between frequent sleep complaints (EDS and to a lesser extent DMS) and MetS in the elderly with potential implications in terms of management and cardiovascular prevention in general geriatric practice. Prospective studies are required to clarify the direction of the association between sleep complaints and MetS.

Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia.

OBJECTIVES: Conflicting results have been reported regarding the association between white matter lesions (WML) and cognitive impairment. We hypothesized that education, a marker of cognitive reserve (CR), could modulate the effects of WML on the risk of mild cognitive impairment (MCI) or dementia. METHODS: We followed 500 healthy subjects from a cohort of community-dwelling persons aged 65 years and over (ESPRIT Project). At baseline, WML volume was measured using a semi-automatic method on T2-weighted MRI. Standardized cognitive and neurological evaluations were repeated after 2, 4, and 7 years. The sample was dichotomized according to education level into low (≤8 years) and high (>8 years) education groups. Cox proportional hazard models were constructed to study the association between WML and risk of MCI/dementia. RESULTS: The interaction between education level and WML volume reached significance (p = 0.017). After adjustment for potential confounders, the association between severe WML and increased MCI/dementia risk was significant in the low education group (≤8 years) (p = 0.02, hazard ratio [HR]: 3.77 [1.29-10.99]), but not in the high education group (>8 years) (p = 0.82, HR: 1.07 [0.61-1.87]). CONCLUSIONS: Severe WML significantly increases the risk of developing MCI/dementia over a 7-year period in low educated participants. Subjects with higher education levels were seen to be more likely to be resilient to the deleterious effects of severe WML. The CR hypothesis suggests several avenues for dementia prevention.

APOE ε4 and risk for Alzheimer's disease: do regionally distributed white matter hyperintensities play a role?

BACKGROUND: We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE ε4) have increased parietal WMH volume. METHODS: Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE ε4 was examined separately in each group and then in a combined analysis. RESULTS: In WHICAP, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE ε4 status; those with the ε4 were more likely to have dementia if they also had increased parietal WMH. CONCLUSIONS: APOE ε4 is associated with increased parietal lobe WMH.

Associations between change in sleep duration and inflammation: findings on C-reactive protein and interleukin 6 in the Whitehall II Study.

Cross-sectional evidence suggests associations between sleep duration and levels of the inflammatory markers, C-reactive protein and interleukin-6. This longitudinal study uses data from the London-based Whitehall II study to examine whether changes in sleep duration are associated with average levels of inflammation from 2 measures 5 years apart. Sleep duration (≤5, 6, 7, 8, ≥9 hours on an average week night) was assessed in 5,003 middle-aged women and men in 1991/1994 and 1997/1999. Fasting levels of C-reactive protein and interleukin-6 were measured in 1997/1999 and 2002/2004. Cross-sectional analyses indicated that shorter sleep is associated with higher levels of inflammatory markers. Longitudinal analyses showed that each hour per night decrease in sleep duration between 1991/1994 and 1997/1999 was associated with higher levels of C-reactive protein (8.1%) and interleukin-6 (4.5%) averaged across measures in 1997/1999 and 2002/2004. Adjustment for longstanding illness and major cardiometabolic risk factors indicated that disease processes may partially underlie these associations. An increase in sleep duration was not associated with average levels of inflammatory markers. These results suggest that both short sleep and reductions in sleep are associated with average levels of inflammation over a 5-year period.

Chronic inflammation as a determinant of future aging phenotypes.

BACKGROUND: The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women. METHODS: We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study's baseline (1997-1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007-2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants). RESULTS: Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38-0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15-2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58-3.80). INTERPRETATION: Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic inflammation by repeat measurement of interleukin-6 has the potential to guide clinical practice.

Metabolic syndrome and localization of white matter hyperintensities in the elderly population.

BACKGROUND: Metabolic syndrome (MetS) is defined as a clustering of metabolic disorders: abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Although specific components of MetS have been associated with white matter hyperintensities (WMH), less is known about the association between MetS as a whole and WMH, especially in normal aging. We aimed to: (1) investigate this association in a cohort of healthy elderly individuals, and (2) examine the relationship between MetS and the regional distribution of WMH, to further understanding of the relationship between MetS and structural brain changes. METHODS: Analyses were carried out on 308 participants (48.1% men, age: 71.0 ± 3.9 years) from the French longitudinal ESPRIT (Enquête de Santé Psychologique--Risques, Incidence et Traitement) study, who were free of cerebrovascular disease cognitive and functional impairment. Logistic regression models were used to examine the cross-sectional association between MetS (defined using the National Cholesterol Education Program-Adult Treatment Panel III criteria) and (1) WMH volumes, and (2) WMH volumes according to their localization in insulofrontal and temporoparietal regions. RESULTS: After adjusting for potential confounders, participants with MetS had a twofold increased chance of presenting with high levels of WMH volume compared with those without (odds ratio [OR] = 2.74, 95% confidence interval [CI]: 1.25-6.03). MetS was specifically associated with an increase of temporoparietal WMH volumes, but no association was found between MetS and WMH localized in the insulofrontal region. CONCLUSION: Our findings suggest that effective management of MetS may reduce WMH accumulation in brain areas already vulnerable to the aging process.

Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study.

BACKGROUND: Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes. We aimed to characterise trajectories of fasting and postload glucose, insulin sensitivity, and insulin secretion in individuals who develop type 2 diabetes. METHODS: We analysed data from our prospective occupational cohort study (Whitehall II study) of 6538 (71% male and 91% white) British civil servants without diabetes mellitus at baseline. During a median follow-up period of 9.7 years, 505 diabetes cases were diagnosed (49.1% on the basis of oral glucose tolerance test). We assessed retrospective trajectories of fasting and 2-h postload glucose, homoeostasis model assessment (HOMA) insulin sensitivity, and HOMA beta-cell function from up to 13 years before diabetes diagnosis (diabetic group) or at the end of follow-up (non-diabetics). FINDINGS: Multilevel models adjusted for age, sex, and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics (10,989 measurements), except for insulin secretion that did not change during follow-up. In the diabetic group (801 measurements), a linear increase in fasting glucose was followed by a steep quadratic increase (from 5.79 mmol/L to 7.40 mmol/L) starting 3 years before diagnosis of diabetes. 2-h postload glucose showed a rapid increase starting 3 years before diagnosis (from 7.60 mmol/L to 11.90 mmol/L), and HOMA insulin sensitivity decreased steeply during the 5 years before diagnosis (to 86.7%). HOMA beta-cell function increased between years 4 and 3 before diagnosis (from 85.0% to 92.6%) and then decreased until diagnosis (to 62.4%). INTERPRETATION: In this study, we show changes in glucose concentrations, insulin sensitivity, and insulin secretion as much as 3-6 years before diagnosis of diabetes. The description of biomarker trajectories leading to diabetes diagnosis could contribute to more-accurate risk prediction models that use repeated measures available for patients through regular check-ups. FUNDING: Medical Research Council (UK); Economic and Social Research Council (UK); British Heart Foundation (UK); Health and Safety Executive (UK); Department of Health (UK); National Institute of Health (USA); Agency for Health Care Policy Research (USA); the John D and Catherine T MacArthur Foundation (USA); and Academy of Finland (Finland).

Dietary pattern and depressive symptoms in middle age.

BACKGROUND: Studies of diet and depression have focused primarily on individual nutrients. AIMS: To examine the association between dietary patterns and depression using an overall diet approach. METHOD: Analyses were carried on data from 3486 participants (26.2% women, mean age 55.6 years) from the Whitehall II prospective cohort, in which two dietary patterns were identified: 'whole food' (heavily loaded by vegetables, fruits and fish) and 'processed food' (heavily loaded by sweetened desserts, fried food, processed meat, refined grains and high-fat dairy products). Self-reported depression was assessed 5 years later using the Center for Epidemiologic Studies - Depression (CES-D) scale. RESULTS: After adjusting for potential confounders, participants in the highest tertile of the whole food pattern had lower odds of CES-D depression (OR = 0.74, 95% CI 0.56-0.99) than those in the lowest tertile. In contrast, high consumption of processed food was associated with an increased odds of CES-D depression (OR = 1.58, 95% CI 1.11-2.23). CONCLUSIONS: In middle-aged participants, a processed food dietary pattern is a risk factor for CES-D depression 5 years later, whereas a whole food pattern is protective.

Association between common mental disorder and obesity over the adult life course.

BACKGROUND: Prospective data on the association between common mental disorders and obesity are scarce, and the impact of ageing on this association is poorly understood. AIMS: To examine the association between common mental disorders and obesity (body mass index > or = 30 kg/m(2)) across the adult life course. METHOD: The participants, 6820 men and 3346 women, aged 35-55 were screened four times during a 19-year follow-up (the Whitehall II study). Each screening included measurements of mental disorders (the General Health Questionnaire), weight and height. RESULTS: The excess risk of obesity in the presence of mental disorders increased with age (P = 0.004). The estimated proportion of people who were obese was 5.7% at age 40 both in the presence and absence of mental disorders, but the corresponding figures were 34.6% and 27.1% at age 70. The excess risk did not vary by gender or according to ethnic group or socioeconomic position. CONCLUSIONS: The association between common mental disorders and obesity becomes stronger at older ages.

Education attenuates the association between dietary patterns and cognition.

BACKGROUND/AIMS: Various foods have been shown to be associated with cognitive outcomes. As individual food items are not consumed in isolation, we examined the association between dietary patterns and cognitive function, with special attention to the role of education in this association. METHODS: Analyses were carried out on 4,693 stroke-free white European participants of the Whitehall II study. Two dietary patterns were determined using principal component analysis: a 'whole food' and a 'processed food' pattern. Cognitive function was assessed using a battery of 5 tests. RESULTS: After adjustment for demographic, behavioral and health measures, higher intake of 'whole food' diet was associated with lower and high consumption of 'processed food' with higher odds of cognitive deficit. However, adjustment for education significantly attenuated most of these associations. CONCLUSIONS: Education, through its role as a powerful confounder, shapes the relationship between dietary patterns and cognitive deficit in a healthy middle-aged UK cohort.

Olive oil and cognition: results from the three-city study.

BACKGROUND: Olive oil is a major component of the Mediterranean diet suggested to be beneficial to counteract Alzheimer's disease. AIM OF THE STUDY: Our objective was to examine the association between olive oil use, cognitive deficit and cognitive decline in a large elderly population. METHODS: We followed 6,947 subjects with a brief baseline food frequency questionnaire and repeated cognitive tests. Olive oil intake was categorized as none (22.7%), moderate (use for cooking or dressing, 39.9%) and intensive (use for both cooking and dressing, 37.4%). Associations between olive oil and cognitive outcomes were examined taking into account socio-economic factors, health behaviors, health measures and other dietary intakes. RESULTS: Participants with moderate or intensive use of olive oil compared to those who never used olive oil showed lower odds of cognitive deficit for verbal fluency and visual memory. For cognitive decline during the 4-year follow-up, the association with intensive use was significant for visual memory (adjusted OR = 0.83, 95% CI: 0.69-0.99) but not for verbal fluency (OR = 0.85, 95% CI: 0.70-1.03) in multivariate analysis. CONCLUSIONS: This olive oil-cognition association needs to be confirmed by further studies. However, our findings already shed light on the potential importance of olive oil in the Mediterranean diet and on its beneficial effects on health.

Total plasma carotenoids and mortality in the elderly: results of the Epidemiology of Vascular Ageing (EVA) study.

Carotenoids are pigments found in fruits and vegetables. While high intakes of fruits and vegetables have been found to be associated with lower mortality, our objective is to investigate if total plasma carotenoids, via their antioxidant properties, are associated with mortality risk in a free-living elderly population. The 'Epidemiology of Vascular Ageing' (EVA) study (n 1389; 59-71 years) is a 9-year longitudinal study with six waves of follow-up. The association between baseline total plasma carotenoids and mortality was determined by Cox proportional hazards regression analyses. Low total plasma carotenoid level was significantly associated with all-cause mortality in men but not in women. After controlling for potential confounding factors, mortality risk increased significantly in men (P = 0.03) with plasma carotenoids in the lowest quintile compared with men with plasma carotenoids in the highest (relative risk 2.94 (95% CI 1.21, 7.17)). A significant association between mortality by cancer and low plasma carotenoid level variable was also found in men (unit = 1 micromol/l; relative risk 1.72 (95% CI 1.02, 2.86); P = 0.01). Associations between total plasma carotenoids and mortality risk remained statistically significant after taking into account: (1) plasma Se level, which previously was found associated with mortality in this population and (2) thiobarbituric acid-reactive substances level considered as an indicator of oxidative stress. By showing, prospectively, in a general healthy elderly population, that total plasma carotenoid levels were independently associated with mortality risk in men, the present study suggests that total plasma carotenoid levels could be a health indicator in elderly populations.

Association of 10-Year C-Reactive Protein Trajectories With Markers of Healthy Aging: Findings From the English Longitudinal Study of Aging.

Background: Elevated systematic inflammation is a hallmark of aging, but the association of long-term inflammation trajectories with subsequent aging phenotypes has been little examined. We assessed inflammatory marker C-reactive protein (CRP) repeatedly over time and examined whether long-term changes predicted aging outcomes. Methods: A total of 2,437 men and women aged 47-87 years at baseline (1998-2001) who were participants in the English Longitudinal Study of Ageing had CRP measured on two or three occasions between 1998 and 2009. Inflammation trajectories were computed using latent-class growth mixture modeling and were related to aging outcomes measured in 2012/2013: physical functioning, cardiometabolic, respiratory, mental health, and a composite "healthy aging" outcome. Results: Four CRP trajectories were identified as follows: "stable-low" (71 per cent of the sample) with baseline mean 1.33 mg/L remaining <3 mg/L; "medium-to-high" (14 per cent) with baseline 2.7 mg/L rising to 5.3 mg/L; "high-to-medium" (10 per cent) with baseline 6.6 mg/L decreasing to 2.4 mg/L; and "stable-high" (5 per cent) with levels from 5.7 to 7.5 mg/L. Relative to the stable-low trajectory, individuals in the medium-to-high had a higher risk of limitations in basic activities of daily living (ADL, odds ratio; 95% confidence interval: 2.09; 1.51, 2.88), instrumental ADL (1.62; 1.15, 2.30), impaired balance (1.59; 1.20, 2.11) and walking speed (1.61; 1.15, 2.24), arthritis (1.55; 1.16, 2.06), hypertension (1.57; 1.21, 2.04), obesity (1.95; 1.36, 2.80), poor respiratory function (1.84; 1.36, 2.50), and depression (1.55; 1.13, 2.12). A lower odds of healthy aging was observed in people in the medium-to-high (0.57; 0.40, 0.79) and stable-high (0.50; 0.27, 0.91) trajectories. Conclusions: Older people who displayed an elevation in CRP levels over a decade experienced an increased risk of adverse aging outcomes.

Socio-demographic influences on trends of fish consumption during later adult life in the Whitehall II study.

Our aim was to investigate how socio-demographic factors influence trends and age-related trajectories of fish consumption. We examined consumption of total, fried and recommended fish (white and oily fish, and shellfish) in the Whitehall II study over 11 years in participants aged 39-59 years at phase 3. The cohort included 8358 British civil servants who completed a FFQ at phase 3 (1991-3), phase 5 (1997-9, n 5430) and phase 7 (2002-4, n 5692). Occupational grade, ethnicity, marital and retirement status were collected at each phase. To analyse changes in age-related trends of fish intake over time according to socio-demographic characteristics, we applied a random mixed-effect model. Over the follow-up a significant increase in consumption of 'recommended' (mean: 1.85 to 2.22 portions/week) and total fish (mean: 2.32 to 2.65 portions/week) and a decreasing trend in fried-fish intake (mean: 0.47 to 0.43 portions/week) was observed. Recommended, fried and total fish consumption differed by occupational status, ethnicity, marital status and sex. The trend of age-related fish intake diverged significantly by ethnicity. In South Asian participants (n 432), slope of recommended-fish consumption was significantly higher compared with white participants (0.077 v. 0.025 portions/week per year). For black participants (n 275) slope of fried-fish intake was significantly higher compared with white participants (0.0052 v. - 0.0025 portions/week per year). In terms of public health, our descriptive and analytical work allows detailed understanding of the impact of socio-demographic factors on fish intake and its age-related trends. Such information is valuable for food policies that seek to promote health equity.

Anxiety and 10-Year Risk of Incident Dementia-An Association Shaped by Depressive Symptoms: Results of the Prospective Three-City Study.

Background: Anxiety is common in patients with cognitive impairment and dementia. However, whether anxiety is a risk factor for dementia is still not known. We aimed to examine the association between trait anxiety at baseline and the 10-year risk of incident dementia to determine to which extent depressive symptoms influence this relationship in the general population. Methods: Data came from 5,234 community-dwelling participants from the Three-City prospective cohort study, aged 65 years at baseline and followed over 10 years. At baseline, anxiety trait was assessed using the Spielberger State-Trait Anxiety Inventory (STAI), and depressive symptoms using Center for Epidemiologic Studies-Depression Scale (CESD). Use of anxiolytic drugs was also considered. Diagnoses of dementia were made at baseline and every 2 years. To examine the relationship between anxiety exposures and risk of incident dementia, Cox proportional hazard regression models were performed. Results: Taking anxiolytic drugs or having high trait anxiety (STAI score ≥ 44) increased the risk of dementia assessed over 10 years of follow-up [Hazard Ratio (HR) = 1.39, 95%CI: 1.08-1.80, p = 0.01 and HR = 1.26, 95%CI: 1.01-1.57, p = 0.04, respectively], independently of a large panel of socio-demographic variables, health behaviors, cardio-metabolic disorders, and additional age-related disorders such as cardiovascular diseases, activity limitations, and cognitive deficit. However, the associations were substantially attenuated after further adjustment for depressive symptoms. Conclusion: Our findings suggest that depressive symptoms shape the association between anxiety trait and dementia. Further research is needed to replicate our findings and extrapolate our results to anxiety disorders.

Factors associated with longitudinal plasma selenium decline in the elderly: the EVA study.

Selenium status decreases in elderly populations. Cardiovascular diseases are the primary cause of death in the French elderly, and selenium may protect against cardiovascular diseases. The present work aims to evaluate the relationships between cardiovascular-related risk factors and plasma selenium variability in an elderly population during a 9-year period. Seven hundred fifty-one subjects from the EVA ("Etude du Vieillissement Artériel") study, aged 59 to 71 at baseline, were followed for 9 years. Clinical examinations and lifestyle questionnaires were repeated every 2 years. Plasma selenium determinations were performed at baseline and at the end of the study. The association between the 9-year plasma selenium variability and studied risk factors at baseline or occurring during the follow-up was evaluated by using multivariate linear regression models. After controlling all potential associated factors, age of subjects (P<.01), obesity (P=.02) and occurrence of cardiovascular disease during follow-up (P=.03) increased the longitudinal decline in plasma selenium, whereas gender, education, smoking, alcohol intakes, dyslipidemia, diabetes, hypertension had no effect (P>.05). It may be postulated that obesity and occurrence of cardiovascular events are the main factors associated with plasma selenium fall during ageing. The respective roles played by nutritional and metabolism changes in the mechanism of these associations still need to be explored.