Tasnime N. Akbaraly

Metabolic syndrome and cognitive decline in French elders The Three-City Study

Objective: To examine associations between metabolic syndrome (MetS) and its individual components with risk of cognitive decline on specific cognitive functions. Methods: Participants were 4,323 women and 2,764 men aged 65 and over enrolled in the longitudinal Three-City Study. Cognitive decline, defined as being in the worst quintile of the distribution of the difference between baseline score and either 2- or 4-year follow-up, was assessed by the Mini-Mental State Examination (MMSE, global cognitive function), the Isaacs Set Test (IST, verbal fluency), and the Benton Visual Retention Test (BVRT, visual working memory). MetS was defined by National Cholesterol Education Program–Adult Treatment Panel III criteria (at least 3 of 5 cardio-metabolic abnormalities: hypertension, high waist circumference, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, hyperglycemia). Proportional hazards models were adjusted for age, gender, educational level, center, baseline cognitive score, APOE4 genotype, and other potential confounders. Results: MetS at baseline was associated with an increased risk of cognitive decline on MMSE (hazard ratio [HR] = 1.22 [1.08–1.37]; p = 0.001) and BVRT (HR = 1.13 [1.01–1.26]; p = 0.03) but not on IST (HR = 1.11 [0.95–1.29]; p = 0.18). Among MetS components, hypertriglyceridemia and low HDL cholesterol were significantly associated with higher decline on MMSE; diabetes, but not elevated fasting glycemia, was significantly associated with higher decline on BVRT and IST. Conclusions: MetS as a whole and several of its components had a negative impact on global cognitive decline and specific cognitive functions in older persons.

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 Onset of Depressive Symptoms in the Elderly: Findings from the Three-City Study

OBJECTIVE Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and the onset of depressive symptoms according to different age-groups in a large, general elderly population. RESEARCH DESIGN AND METHODS This was a prospective cohort study of 4,446 men and women aged 65–91 years who were free of depression or depressive symptoms at baseline (the Three-City Study, France). MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale score ≥16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups. RESULTS After adjusting for a large range of potential confounders, we observed MetS to be associated with 1.73-fold (95% CI 1.02–2.95) odds for new-onset depressive symptoms in the youngest age-group (65–70 years at baseline), independently of cardiovascular diseases. No such association was seen in older age-groups. CONCLUSIONS Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged people can be extended to older adults but not to the oldest ones. Additional research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65–70 years.

Overall Diet History and Reversibility of the Metabolic Syndrome Over 5 Years: The Whitehall II prospective cohort study

OBJECTIVE We examined the impact of adherence to the Alternative Healthy Eating Index (AHEI), a set of dietary guidelines targeting major chronic diseases, on metabolic syndrome (MetS) reversion in a middle-aged population. RESEARCH DESIGN AND METHODS Analyses were carried out on the 339 participants (28% women, mean age 56.4 years) from the Whitehall II study with MetS as defined by the National Cholesterol Education Program Adult Treatment Panel III criteria. Reversion was defined as not having MetS after 5 years of follow-up (158 case subjects). RESULTS After controlling for potential confounders, adherence to AHEI was associated with MetS reversion (odds ratio 1.88 [95% CI 1.04–3.41]), predominantly in participants with central obesity and in those with high triglyceride. CONCLUSIONS Our findings support the benefit of adherence to AHEI dietary guidelines for individuals with MetS, especially those with central obesity or high triglyceride levels.

Psychological Distress and Incidence of Type 2 Diabetes in High-Risk and Low-Risk Populations: The Whitehall II Cohort Study

OBJECTIVE We examined whether psychological distress predicts incident type 2 diabetes and if the association differs between populations at higher or lower risk of type 2 diabetes. RESEARCH DESIGN AND METHODS This was a prospective cohort of 5,932 diabetes-free adults (4,189 men and 1,743 women, mean age 54.6 years) with three 5-year data cycles (1991–2009): a total of 13,207 person-observations. Participants were classified into four groups according to their prediabetes status and Framingham Offspring Type 2 Diabetes Risk Score: normoglycemia with a risk score of 0–9, normoglycemia with a risk score of 10–19, prediabetes with a risk score of 10–19, and prediabetes with a risk score of >19. Psychological distress was assessed by the General Health Questionnaire. Incident type 2 diabetes was ascertained by 2-h oral glucose tolerance test, doctor diagnosis, or use of antihyperglycemic medication at the 5-year follow-up for each data cycle. Adjustments were made for age, sex, ethnicity, socioeconomic status, antidepressant use, smoking, and physical activity. RESULTS Among participants with normoglycemia and among those with prediabetes combined with a low risk score, psychological distress did not predict type 2 diabetes. Diabetes incidence in these groups varied between 1.6 and 15.6%. Among participants with prediabetes and a high risk score, 40.9% of those with psychological distress compared with 28.5% of those without distress developed diabetes during the follow-up. The corresponding adjusted odds ratio for psychological distress was 2.07 (95% CI 1.19–3.62). CONCLUSIONS These data suggest that psychological distress is associated with an accelerated progression to manifest diabetes in a subpopulation with advanced prediabetes.

Plasma Carotenoids and Onset of Dysglycemia in an Elderly Population: Results of the Epidemiology of Vascular Ageing Study

OBJECTIVE—The hypothesis of carotenoid having a preventive role in diabetes is suggested by their antioxidant properties. In this report, we investigated the relationship between baseline total plasma carotenoid levels and 9-year onset of dysglycemia (impaired fasting glucose or type 2 diabetes) in a healthy elderly population. RESEARCH DESIGN AND METHODS—The Epidemiology of Vascular Ageing Study is a 9-year longitudinal study including 1,389 volunteers aged 59–71 years. Fasting plasma glucose was measured at baseline and at 2, 4, and 9 years after inclusion. The relationship between plasma carotenoid at baseline and incidence of dysglycemia was determined by Cox proportional hazards regression analysis adjusting for potential confounders. RESULTS—At 9 years, 127 incident cases of dysglycemia had occurred. Risk of dysglycemia was significantly lower in participants with plasma carotenoid in the highest quartile (Q4) compared with participants in the lowest quartile (Q1) (Q4 vs. Q1: relative risk 0.26 [95% CI 0.14–0.49], P < 10−4; Q3 vs. Q1: 0.55 [0.34–0.89], P = 0.01; and Q2 vs. Q1: 0.82 [0.51–1.31], P = 0.40). After controlling for sociodemographic variables, lifestyle habits, cardiovascular disease, blood pressure, BMI, and lipid profile, risk of dysglycemia remained significantly lower in participants in the highest quartile of total plasma carotenoid compared with participants in the lowest quartile (Q4 vs. Q1: 0.42 [0.22–0.82], P = 0.01; Q3 vs. Q1: 0.69 [0.41–1.15], P = 0.16; and Q2 vs. Q1: 0.80 [0.48–1.32], P = 0.38). CONCLUSIONS—This study prospectively confirms that plasma carotenoid levels have an independent relationship to onset of dysglycemia.

P4-008: Olive oil and cognition: Results from the three-city study

Conclusions: Our results suggest that FHx of AD has a stronger association with microstructural brain differences, than 4. Presence of 4 alone was not associated with measurable difference, though presence of FHx and 4 resulted in the greatest difference in FA. These results support the conclusion that a greater emphasis be placed on elucidating the contribution of FHx to early brain changes in people at risk for AD. Additionally, our results provide evidence that DTI may be useful for detecting or tracking AD related brain changes, prior to disease onset.

Plasma F2 isoprostanes and dementia : Results from a longitudinal study

ipants underwent yearly neuropsychological testing for up to 7 years (2002-2009), with their cognitive status (presence and type of dementia) adjudicated based on clinical and imaging data. Prevalent cardiovascular disease status was determined at the time of entry into the CHS. Noninvasive vascular studies collected during the course of CHS (19881998) included: Ankle-Arm Index, Coronary calcium (CCa) score, and MRI white matter grade. Slope of the Modified Mini Mental State (3MS) examination assessed yearly from 1988-98 was calculated for each participant. Kaplan Meir survival curves were generated to determine cumulative survival to dementia among different groups. Results: 210 of the 445 participants developed dementia during the observation period. ApoE*4 status (HR 1.3[CI 1.0, 1.8]), age at the baseline visit (> 79, (HR 2.3 [CI 1.3, 4.1]), and the 3MS score at baseline (< 90 (HR 2.1 [1.3, 3.1]) increased the risk of developing dementia during follow up. Dementia (including AD) developed more rapidly as a function of having an AnkleArm Index below 0.9, higher CCa score and steeper slope of decline on 3 MS prior to diagnosis. The presence of hypertension, diabetes, orMRI white matter grade were not related to time to develop dementia or AD. Conclusions: In an elderly cohort, markers of peripheral vascular disease were associated with an accelerated progression to Alzheimer’s dementia and dementia of all causes.

Chronic use of benzodiazepines and cognitive decline

Background: In the elderly, benzodiazepines use concerns 10 to 20% of the population. To date, three prospective studies have investigated the association between chronic use of benzodiazepines and cognitive decline, and gave conflicting results. The interpretation of these studies is limited by a qualitative statistical analysis (decline or not). We aimed to examine whether the long-term use of benzodiazepine is associated with an accelerated decline of cognitive performances by using a recent published statistical model adapted tomultivariate, longitudinal, nonGaussian quantitative outcomes. Thismodel allowed us to study change over time of the latent common cognitive factor underlying several psychometric tests considered simultaneously and measured repeatedly.Methods:Data came from thewell knownmulticentric prospective Three Cities study in which 5,196 participants from three cities in France (Bordeaux, Montpellier and Dijon) aged 65 years or older were followed-up during 7 years. At each examination phase (baseline, 2, 4 and 7 years), the use of benzodiazepine was collected by a face-to-face interview, and cognitive functioningwas assessed by trained neuropsychologists. Cognitive declinewas analyzed using a nonlinearmultivariatemodelwith latent process for longitudinal data. Latent cognitive factor was constructed from five neuropsychological tests outcomes:MMSE, Isaacs Set test, BentonVisual Retention Test, and the Trail Making Test (A and B). Analyses were adjusted for center, gender, education, socio-professional status, depression, insomnia, high blood pressure, hypercholesterolemia, alcohol, tobacco consumption and physical activity.Results: In the present study, 969 chronic users reported taking benzodiazepine during 2, 4 or 7 consecutive years (Cognitive datawere taken into account only for consecutiveyears of use or nouse). The chronic use of benzodiazepines was significantly associated with a low cognitive latent level (ß1⁄4 1,80 SE1⁄4 0,26 p1⁄4< 0,001). No association was found between chronic use and anacceleration of cognitive decline, neitheron latent cognitive factor (ß*(year after 65)21⁄4 0,10 SE1⁄4 0.10 p1⁄4 0,34), nor on specific psychometric tests (figure1).Conclusions: By showing a cross sectional association between use of benzodiazepines and cognition, but no association with accelerated cognitive decline, we evidenced that chronic use of benzodiazepines is not a risk factor of cognitive decline in free-dementia elderly population.