Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies.

BACKGROUND: Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aß) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia. METHODS: A two-stage meta-analysis was performed on 2 clinic-based and 6 population-based cohorts (N = 7210) as part of the Netherlands Consortium of Dementia Cohorts. Plasma markers (Aß42/40, p-tau181, NfL, and GFAP) were measured using Single Molecular Array (Simoa; Quanterix) assays. Depressive symptoms were measured with validated questionnaires. We estimated the cross-sectional association of each standardized plasma marker (determinants) with standardized depressive symptoms (outcome) using linear regressions, correcting for age, sex, education, and APOE ε4 allele presence, as well as subgrouping by sex and APOE ε4 allele. Effect estimates were entered into a random-effects meta-analysis. RESULTS: Mean age of participants was 71 years. The prevalence of clinically relevant depressive symptoms ranged from 1% to 22%. None of the plasma markers were associated with depressive symptoms in the meta-analyses. However, NfL was associated with depressive symptoms only in APOE ε4 carriers (ß 0.11; 95% CI: 0.05-0.17). CONCLUSIONS: Late-life depressive symptoms did not show an association to plasma biomarkers of AD pathology. However, in APOE ε4 allele carriers, a more profound role of neurodegeneration was suggested with depressive symptoms.

Biomarkers of endothelial dysfunction and cognition: A two-step IPD meta-analysis.

INTRODUCTION: This study assessed the association of plasma biomarkers of endothelial dysfunction with cognitive performance and decline. METHODS: Data from 9414 individuals from eight Dutch cohorts were included (Ø  age-range: 57-93 years). Plasma biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin) were combined into a standardized composite score. Cognitive outcomes included executive function, processing speed, immediate and delayed memory, attention, and language. Linear regressions and linear mixed models were run in the individual cohorts and standardized coefficients were subsequently pooled using random-effects meta-analyses. RESULTS: A higher endothelial dysfunction composite score was cross-sectionally associated with worse performance on executive function, processing speed, delayed memory, and attention, but not immediate memory or language (pooled ß-range: -0.04, -0.02). We found no association with change in cognition over time. DISCUSSION: This comprehensive two-step, individual participant data (IPD) meta-analysis showed a small, consistent cross-sectional association between endothelial dysfunction and worse cognitive performance across multiple domains but no support for a longitudinal association. HIGHLIGHTS: Prior evidence on endothelial dysfunction (ED) biomarkers and cognition is conflicting. This two-step, individual participant data (IPD) meta-analysis used data from eight Dutch cohorts. ED was consistently associated with concurrent cognition. ED was not associated with a change in cognition over time. The association of ED with current cognition may be generic.

Sex Differences in Cognitive Functioning with Aging in the Netherlands.

INTRODUCTION: Dementia prevalence in older women is higher than that in men. The purpose of the present study was to investigate whether there is a female disadvantage in cognitive functioning at adult age and/or whether a female disadvantage develops with age. METHODS: Data of 5,135 women and 4,756 men from the Longitudinal Aging Study Amsterdam (LASA) and the Doetinchem Cohort Study (DCS) were used. In the LASA, memory, processing speed, fluid intelligence, and global cognitive function were measured every 3-4 years since 1992 in persons aged 55+ years for up to 23 years. In the DCS, memory, processing speed, cognitive flexibility, and global cognitive function were measured every 5 years since 1995 in persons aged 45+ years for up to 20 years. Sex differences in cognitive aging were analyzed using linear mixed models and also examined by the 10-year birth cohort or level of education. RESULTS: Women had a better memory, processing speed, flexibility, and, in the DCS only, global cognitive function than men (p's < 0.01). However, women showed up to 10% faster decline in these cognitive domains, except for flexibility, where women showed 9% slower decline. In the LASA, women scored poorer on fluid intelligence (p < 0.01), but their decline was 10% slower than that in men. Female advantage was larger in later born cohorts; adjustment for the educational level increased the female advantage. CONCLUSION: Women have better memory and processing speed than men at middle age. This female advantage becomes smaller with aging and has increased in more recent birth cohorts.

Fish consumption, intake of fats and cognitive decline at middle and older age: the Doetinchem Cohort Study.

PURPOSE: To get insight in the impact of fish and fat intake in the prevention of accelerated cognitive decline with ageing, we tested associations between fish and different fat intakes and 5-year change in cognitive functions. METHODS: In 2612 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline, dietary intake (including fish consumption) and cognitive function were assessed at baseline and at 5-year follow-up. Average fish consumption (frequency) and intakes (as energy percentages) of total fat, saturated, mono unsaturated, and polyunsaturated fatty acids (PUFA), linoleic, docosahexaenoic, eicosapentaenoic, and a-linolenic acid (ALA), and cholesterol were averaged over baseline and follow-up. Intakes were studied in relation to 5-year change in global cognitive function, memory, information processing speed, and cognitive flexibility, using ANCOVA and multivariate linear regression analyses. RESULTS: No consistent association between (fatty) fish consumption and cognitive decline was observed. Higher cholesterol intake was associated with faster cognitive decline (p < 0.05). Higher n-3 PUFA (especially ALA) intake was associated with slower decline in global cognitive function and memory (p < 0.01). Intakes of other fatty acids were not associated with cognitive decline. CONCLUSIONS: Higher cholesterol intake was detrimental, while higher ALA intake was beneficial for maintaining cognitive function with ageing, already at middle age.

Health literacy among older adults is associated with their 10-years' cognitive functioning and decline - the Doetinchem Cohort Study.

BACKGROUND: Many older adults have low levels of health literacy which affects their ability to participate optimally in healthcare. It is unclear how cognitive decline contributes to health literacy. To study this, longitudinal data are needed. The aim of this study was therefore to assess the associations of cognitive functioning and 10-years' cognitive decline with health literacy in older adults. METHODS: Data from 988 participants (mean age = 65.3) of the Doetinchem Cohort Study were analyzed. Health literacy was measured by the Brief Health Literacy Screening. Memory, mental flexibility, information processing speed, and global cognitive functioning were assessed at the same time as health literacy and also 10 years earlier. Logistic regression analyses were performed, adjusted for age, gender, and educational level. RESULTS: Higher scores on tests in all cognitive domains were associated with a lower likelihood of having low health literacy after adjustment for confounders (all ORs < 0.70, p-values<.001). Similar associations were found for past cognitive functioning (all ORs < 0.75, p-values<.05). Before adjustment, stronger cognitive decline was associated with a greater likelihood of having low health literacy (all ORs > 1.37, p-values<.05). These associations lost significance after adjustment for educational level, except for the association of memory decline (OR = 1.40, p = .023, 95% CI: 1.05 to 1.88). CONCLUSION: Older adults with poorer cognitive functioning and stronger cognitive decline are at risk for having low health literacy, which can affect their abilities to promote health and self-manage disease. Low health literacy and declining cognitive functioning might be a barrier for person-centered care, even in relatively young older adults.

Dementia incidence trend over 1992-2014 in the Netherlands: Analysis of primary care data.

BACKGROUND: Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary care records from a large population in the Netherlands. METHODS AND FINDINGS: A dynamic cohort representative of the Dutch population was composed using primary care records from general practice registration networks (GPRNs) across the country. Data regarding dementia incidence were obtained using general-practitioner-recorded diagnosis of dementia within the electronic health records. Age-specific dementia incidence rates were calculated for all persons aged 60 y and over; negative binomial regression analysis was used to estimate the time trend. Nine out of eleven GPRNs provided data on more than 800,000 older people for the years 1992 to 2014, corresponding to over 4 million person-years and 23,186 incident dementia cases. The annual growth in dementia incidence rate was estimated to be 2.1% (95% CI 0.5% to 3.8%), and incidence rates were 1.08 (95% CI 1.04 to 1.13) times higher for women compared to men. Despite their relatively low numbers of person-years, the highest age groups contributed most to the increasing trend. There was no significant overall change in incidence rates since the start of a national dementia program in 2003 (-0.025; 95% CI -0.062 to 0.011). Increased awareness of dementia by patients and doctors in more recent years may have influenced dementia diagnosis by general practitioners in electronic health records, and needs to be taken into account when interpreting the data. CONCLUSIONS: Within the clinical records of a large, representative sample of the Dutch population, we found no evidence for a declining incidence trend of dementia in the Netherlands. This could indicate true stability in incidence rates, or a balance between increased detection and a true reduction. Irrespective of the exact rates and mechanisms underlying these findings, they illustrate that the burden of work for physicians and nurses in general practice associated with newly diagnosed dementia has not been subject to substantial change in the past two decades. Hence, with the ageing of Western societies, we still need to anticipate a dramatic absolute increase in dementia occurrence over the years to come.

Diet and cognitive decline at middle age: the role of antioxidants.

To assess the relationship between dietary intake of antioxidants (vitamin C, vitamin E, ß-carotene, lutein, flavonoids and lignans) and cognitive decline at middle age, analyses were performed on data from the population based Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice with a 5-year interval in 2613 persons aged 43-70 year at baseline (1995-2002). Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive function was assessed with a neuropsychological test battery, consisting of the 15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter Digit Substitution Test. Scores on global cognitive function, memory, processing speed, and cognitive flexibility were calculated. In regression analyses, quintiles of antioxidant intake were associated with change in cognitive domain scores. Results showed that higher lignan intake was linearly associated with less decline in global cognitive function (P= 0.01), memory (P< 0.01) and processing speed (P= 0.04), with about two times less declines in the highest v. the lowest quintile. In the lowest quintile of vitamin E intake, decline in memory was twice as fast as in all higher quintiles (P< 0.01). Global cognitive decline in the highest lutein intake group was greater than in the lowest intake group (P< 0.05). Higher flavonoid intake was associated with greater decline in cognitive flexibility (P for trend = 0.04). Intakes of other antioxidants were not associated with cognitive decline. We conclude that within the range of a habitual dietary intake, higher intake of lignans is associated with less cognitive decline at middle age.

Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.

Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline. The aim of the present study was to evaluate the associations between the total consumption of alcoholic beverages and different types of alcoholic beverages and cognitive decline at middle age. In 2613 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline (1995-2002), cognitive function (global cognitive function and the domains memory, speed and flexibility) was assessed twice, with a 5-year time interval. In linear regression analyses, the consumption of different types of alcoholic beverages was analysed in relation to cognitive decline, adjusting for confounders. We observed that, in women, the total consumption of alcoholic beverages was inversely associated with the decline in global cognitive function over a 5-year period (P for trend = 0·02), while no association was observed in men. Regarding the consumption of different types of alcoholic beverages in men and women together, red wine consumption was inversely associated with the decline in global cognitive function (P for trend < 0·01) as well as memory (P for trend < 0·01) and flexibility (P for trend = 0·03). Smallest declines were observed at a consumption of about 1·5 glasses of red wine per d. No other types of alcoholic beverages were associated with cognitive decline. In conclusion, only (moderate) red wine consumption was consistently associated with less strong cognitive decline. Therefore, it is most likely that non-alcoholic substances in red wine are responsible for any cognition-preserving effects.

The APOE locus is linked to decline in general cognitive function: 20-years follow-up in the Doetinchem Cohort Study.

Cognitive decline is part of the normal aging process. However, some people experience a more rapid decline than others due to environmental and genetic factors. Numerous single nucleotide polymorphisms (SNPs) have been linked to cognitive function, but only a few to cognitive decline. To understand whether cognitive function and cognitive decline are driven by the same mechanisms, we investigated whether 433 SNPs previously linked to cognitive function and 2 SNPs previously linked to cognitive decline are associated with both general cognitive functioning at baseline and general cognitive decline up to 20-years follow-up in the Doetinchem Cohort Study (DCS). The DCS is a longitudinal population-based study that enrolled men and women aged 20-59 years between 1987-1991, with follow-up examinations every 5 years. We used data of rounds 2-6 (1993-2017, n = 2559). General cognitive function was assessed using four cognition tests measuring memory, speed, fluency and flexibility. With these test scores, standardized residuals (adjusted for sex, age and examination round) were calculated for each cognition test at each round and subsequently combined into one general cognitive function measure using principal component analyses. None of the 435 previously identified variants were associated with baseline general cognitive function in the DCS. But rs429358-C, a coding apolipoprotein E (APOE) SNP and one of the variants previously associated with cognitive decline, was associated with general cognitive decline in our study as well (p-value = 1 × 10-5, Beta = -0.013). These findings suggest that decline of general cognitive function is influenced by other mechanisms than those that are involved in the regulation of general cognitive function.

Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study.

To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43-70 years at baseline (1995-2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P = 0·02) and worse cognitive flexibility (P = 0·03) at baseline, but with smaller decline in information processing speed (P < 0·01) and global cognitive function (P = 0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.

Adherence to dietary guidelines and cognitive decline from middle age: the Doetinchem Cohort Study.

BACKGROUND: Diet, in particular the Mediterranean diet, has been associated with better cognitive function and less cognitive decline in older populations. OBJECTIVES: To quantify associations of a healthy diet, defined by adherence to either the Mediterranean diet, the WHO guidelines, or Dutch Health Council dietary guidelines, with cognitive function and cognitive decline from middle age into old age. METHODS: From the Doetinchem Cohort Study, a large population-based longitudinal study, 3644 participants (51% females) aged 45-75 y at baseline, were included. Global cognitive function, memory, processing speed, and cognitive flexibility were assessed at 5-y time intervals up to 20-y follow-up. Adherence to the Mediterranean diet was measured with the modified Mediterranean Diet Score (mMDS), adherence to the WHO dietary guidelines with the Healthy Diet Indicator (HDI), and adherence to the Dutch Health Council dietary guidelines 2015 with the modified Dutch Healthy Diet 2015 index (mDHD15-index). The scores on the dietary indices were classified in tertiles (low, medium, high adherence). Linear mixed models were used to model level and change in cognitive function by adherence to healthy diets. RESULTS: The highest tertiles of the mMDS, HDI, and mDHD15-index were associated with better cognitive function compared with the lowest tertiles (P values <0.01), for instance at age 65 y equal to being 2 y cognitively younger in global cognition. In addition, compared with the lowest tertiles, the highest tertiles of the mMDS, HDI, and mDHD15-index were statistically significantly associated with 6-7% slower global cognitive decline from age 55 to 75 y, but also slower decline in processing speed (for mMDS: 10%; 95% CI: 2, 18%; for mDHD15: 12%; 95% CI: 6, 21%) and cognitive flexibility (for mDHD15: 10%; 95% CI: 4, 18%). CONCLUSIONS: Healthier dietary habits, determined by higher adherence to dietary guidelines, are associated with better cognitive function and slower cognitive decline with aging from middle age onwards.

Macronutrient distribution over a period of 23 years in relation to energy intake and body fatness.

The distribution of the four macronutrients is associated with energy intake and body fatness according to short-term interventions. The present study involves macronutrient distribution in relation to energy intake and body fatness over a period of 23 years in individuals who have ad libitum access to food. Eight follow-up measurements have been performed in 168 men and 182 women who participate in the Amsterdam Growth and Health Longitudinal Study. From the age of 13 years onwards, dietary intake, physical activity and the thickness of four skinfolds have been assessed. Body fatness was assessed using dual-energy X-ray absorptiometry at the age of 36 years. Generalised estimating equation regression analyses showed that energy percentages (En%) from protein and (in men) carbohydrates were inversely related to energy intake, while the En% from fat was positively related with energy intake. The men and women with high body fatness at the age of 36 years had a 1 En% higher protein intake, and the women with high body fatness had a 2 En% lower alcohol intake at the age of 32 and 36 years. The apparent inconsistent relationships between protein and energy intake and protein and body fatness can in women be explained by reverse causation and underreporting, as in women, low energy intake could not be explained by low physical activity. In conclusion, high intake of protein and (in men) carbohydrate, and low intake of fat are inversely related to total energy intake. High body fatness at the age of 36 years is related to a higher protein intake and, in women, to a lower alcohol intake.

Age, period and cohort effects on body weight and body mass index in adults: The Doetinchem Cohort Study.

OBJECTIVE: To study the development of body weight with ageing, in a general adult population, taking into account possible period and cohort effects. DESIGN: A prospective cohort study with 11 years of follow-up. At baseline and after 6 and 11 years, body weight and height were measured. SETTING: The Doetinchem Cohort Study, consisting of inhabitants of Doetinchem, a town in a rural area of The Netherlands. SUBJECTS: In total, 4070 healthy men and women aged 20-59 years at baseline. RESULTS: Increase in BMI with ageing was less profound based on cross-sectional data than based on longitudinal data. More recent-born cohorts had a higher BMI at a given age than cohorts who were born earlier. Increase in mean BMI with ageing was observed in all age groups and was similar for groups with a different educational level. Highest increase in BMI over 11 years was observed in the youngest group, aged 20-29 years at baseline (2.2 [95 % CL 2.0, 2.3] kg/m2), and lowest increase in the oldest group, aged 50-59 years at baseline (1.1 [1.0, 1.3] kg/m2). CONCLUSIONS: Findings of the present study using longitudinal data suggest that increase in BMI with ageing is underestimated in all age groups by studying cross-sectional data only. Further, weight gain is present in all educational levels and does not stop at middle age.

Trajectories of (Bio)markers During the Development of Cognitive Frailty in the Doetinchem Cohort Study.

Background: Long-term changes in (bio)markers for cognitive frailty are not well characterized. Therefore, our aim is to explore (bio)marker trajectories in adults who became cognitively frail compared to age- and sex-matched controls who did not become cognitively frail over a 15 year follow-up. We hypothesize that those who become cognitively frail have more unfavorable trajectories of (bio)markers compared to controls. Methods: The Doetinchem Cohort Study is a longitudinal population-based study that started in 1987-1991 in men and women aged 20-59 years, with follow-up examinations every 5 years. For the current analyses, we used data of 17 potentially relevant (bio)markers (e.g., body mass index (BMI), urea) from rounds 2 to 5 (1993-2012). A global cognitive functioning score (based on memory, speed, and flexibility) was calculated for each round and transformed into education and examination round-adjusted z-scores. The z-score that corresponded to the 10th percentile in round 5 (z-score = -0.77) was applied as cut-off point for incident cognitive frailty in rounds 2-5. In total, 455 incident cognitively frail cases were identified retrospectively and were compared with 910 age- and sex-matched controls. Trajectories up to 15 years before and 10 years after incident cognitive frailty were analyzed using generalized estimating equations with stratification for sex and adjustment for age and, if appropriate, medication use. Results were further adjusted for level of education, depressive symptoms, BMI, and lifestyle factors. Results: In men, (bio)marker trajectories did not differ as they ran parallel and the difference in levels was not statistically significant between those who became cognitively frail compared to controls. In women, total cholesterol trajectories first increased and thereafter decreased in cognitively frail women and steadily increased in controls, gamma-glutamyltransferase trajectories were more or less stable in cognitively frail women and increased in controls, and urea trajectories increased in cognitively frail women and remained more or less stable in controls. Results were similar after additional adjustment for potential confounders. Conclusions: Out of the 17 (bio)markers included in this explorative study, differential trajectories for three biomarkers were observed in women. We do not yet consider any of the studied (bio)markers as promising biomarkers for cognitive frailty.

Sex differences in physical performance by age, educational level, ethnic groups and birth cohort: The Longitudinal Aging Study Amsterdam.

BACKGROUND: Older women perform consistently poorer on physical performance tests compared to men. Risk groups for this "female disadvantage" in physical performance and it's development over successive birth cohorts are unknown. This is important information for preventive strategies aimed to enhance healthy aging in all older women. This study aims to longitudinal investigate whether there are risk groups for a more apparent female disadvantage and study its trend over successive birth cohorts. METHODS: Data of the Longitudinal Aging Study Amsterdam (LASA) were used. All participants were aged 55-65 years at baseline. Longitudinal data of two birth cohorts with baseline measurements in 1992/1993 (n = 966, 24 year follow-up) and 2002/2003 (n = 1002, 12 year follow-up) were included. Follow-up measurements were repeated every three/four years. Cross-sectional data of two additional cohorts were included to compare ethnic groups: a Dutch cohort (2012/2013, n = 1023) and a Migration cohort (2013/2014, n = 478) consisting of migrants with a Turkish/Moroccan ethnicity. RESULTS: Mixed model analysis showed that women aged 55 years and older had a lower age- and height-adjusted gait speed (-0.03 m/s; -0.063-0.001), chair stand speed (-0.05 stand/s; -0.071--0.033), handgrip strength (-14,8 kg; -15.69--13.84) and balance (OR = 0.71; 0.547-0.916) compared to men. The sex difference in handgrip strength diminished with increasing age, but remained stable for gait speed, chair stand speed and balance. In general, results were consistent across different, educational levels and Turkish/Moroccan ethnic groups and birth cohorts. CONCLUSIONS: There is a consistent "female disadvantage" in physical performance among older adults, which remains stable with increasing age (except for handgrip strength) and is consistent across different educational levels, ethnic groups and successive birth cohorts. So, no specific risk groups for the female disadvantage in physical performance were identified. Preventive strategies aimed to enhance healthy aging in older women are needed and should target all older women.

Smoking and cognitive decline among middle-aged men and women: the Doetinchem Cohort Study.

OBJECTIVES: We studied the effect of smoking on cognitive decline over a 5-year period at middle age (43 to 70 years). METHODS: In the Doetinchem Cohort Study, 1964 men and women in the Netherlands were examined for cognitive function at baseline and 5 years later. The association between smoking status and memory function, speed of cognitive processes, cognitive flexibility, and global cognitive function were assessed. RESULTS: At baseline, smokers scored lower than never smokers in global cognitive function, speed, and flexibility. At 5-year follow-up, decline among smokers was 1.9 times greater for memory function, 2.4 times greater for cognitive flexibility, and 1.7 times greater for global cognitive function than among never smokers. Among ever smokers, the declines in all cognitive domains were larger with increasing number of pack-years smoked. CONCLUSIONS: Interventions to prevent or stop people from smoking may postpone cognitive decline in middle-aged persons.

Long sleep duration is associated with lower cognitive function among middle-age adults - the Doetinchem Cohort Study.

OBJECTIVES: In older adults, both short and long sleep duration are associated with lower cognitive function, suggesting an inverted U-shaped association between sleep duration and cognitive outcomes. This study examined whether sleep duration is associated with (changes in) cognitive function in a middle-aged population. METHODS: In the Doetinchem Cohort Study, the cognitive function of 2970 men and women aged 41-75 years at baseline (1995-2007) was examined 2-3 times, with 5-year time intervals. Global cognitive function and the domains memory, information processing speed, and cognitive flexibility were assessed. In multivariable linear regression models, (change in) self-reported sleep duration was studied in association with the level and change in cognitive function. In a subsample of the population (n = 2587), the association of sleep duration and feeling rested with cognitive function was studied. RESULTS: Sleep duration of 9 h and more was statistically significantly associated with lower global cognitive function (p < 0.01), memory (p = 0.02), and flexibility (p = 0.03), compared to a sleep duration of 7 or 8 h. Among adults feeling frequently not well rested, both short and long sleep duration were associated with a lower speed of cognitive function. An inverted U-shaped association between sleep duration and cognitive function was observed for speed, flexibility, and global cognitive function. Sleep duration was not associated with change in cognitive function. CONCLUSIONS: Middle-age adults with long sleep duration had a lower cognitive function.

Adolescent skinfold thickness is a better predictor of high body fatness in adults than is body mass index: the Amsterdam Growth and Health Longitudinal Study.

BACKGROUND: Body mass index (BMI) during adolescence is predictive of BMI at adult age. However, BMI cannot distinguish between lean and fat body mass. Skinfold thickness may be a better predictor of body fatness. OBJECTIVE: The objective of this study was to evaluate the relations between BMI and skinfold thickness during adolescence and body fatness during adulthood. DESIGN: We included 168 men and 182 women from the Amsterdam Growth and Health Longitudinal Study, a prospective study that conducted 8 measurements of BMI and skinfold thickness between 1976 and 2000. BMI and skinfold thickness during adolescence were analyzed in relation to adult body fatness measured at a mean age of 37 y with dual-energy X-ray absorptiometry. RESULTS: None of the boys and 1.7% of the girls were overweight at baseline, whereas the prevalence of high body fatness during adulthood was 29% in men and 32% in women. At the ages of 12-16 y, skinfold thickness was more strongly associated with adult body fatness than was BMI. Age-specific relative risks for a high level of adult body fatness varied between 2.3 and 4.0 in boys and between 2.1 and 4.3 in girls in the highest versus the lowest tertile of the sum of 4 skinfold thicknesses. For the highest tertile of BMI, the relative risk varied between 0.8 and 2.1 in boys and between 1.3 and 1.8 in girls. CONCLUSION: Skinfold thickness during adolescence is a better predictor of high body fatness during adulthood than is BMI during adolescence.

All-cause mortality risk of metabolically healthy abdominal obese individuals: the EPIC-MORGEN study.

OBJECTIVE: It appears that a certain proportion of obese individuals have a normal metabolic profile despite having excess weight. Whether these so-called "metabolically healthy" obese express lower disease and mortality risks than "metabolically unhealthy" obese is still unclear. The mortality risk of "metabolically healthy" abdominal obese (MHAO) individuals was investigated. DESIGN AND METHODS: Prospective cohort study (EPIC-MORGEN) among 22,654 individuals aged 20-59 years followed for an average of 13.4 years (SD 2.3). MHAO was assessed at baseline (1993-1997) and defined as abdominal obesity (waist circumference ≥102 cm/≥88 cm (men/women)) with normal glucose, blood pressure, and plasma lipids. All-cause mortality risks adjusted for age and sex were estimated using Cox proportional hazards models. RESULTS: Individuals who were "metabolically healthy" nonabdominal obese (MHNAO) comprised the reference group. As compared to MHNAO, mortality risk for MHAO was around 40% higher (Hazard ratio (HR) 1.43; 95% confidence interval (CI): 1.00-2.04) and of the same magnitude as that for "metabolically unhealthy" nonabdominal obese (MUNAO) (HR 1.31; 95% CI: 1.08-1.59). The HR for MUAO was 1.99 (95% CI: 1.62-2.43). CONCLUSIONS: Mortality risk of MHAO individuals was significantly higher than that of MHNAO individuals and lower than, but not statistically significantly different from, that of MUAO individuals.

Today's adult generations are less healthy than their predecessors: generation shifts in metabolic risk factors: the Doetinchem Cohort Study.

BACKGROUND: The health of the elderly of the future is partly determined by their exposure to metabolic risk factors during their life course. Our aim is to study generation shifts in metabolic risk factors. DESIGN: Cohort study. METHODS: We used data of the Doetinchem Cohort Study, that started in 1987-1991 and had follow-up examinations after 6, 11, and 16 years (n = 6,377). The analyses were stratified by sex and generation, i.e. 10-year age groups (20-29, 30-39, 40-49, and 50-59 years) at baseline. Whether a generation had, at a similar age, a different risk profile compared to a generation born 10 years earlier (i.e. generation shift) was tested by means of generalized estimation equations. RESULTS: The prevalence of overweight, obesity, and hypertension increased with age within all generations, but in general more recently born generations had, at a similar age, a higher prevalence of these risk factors than generations born 10 years earlier (p < 0.05). Unfavourable generation shifts were most pronounced for overweight/obesity, present in men between every generation while in women especially present between the most recently born generations. We observed unfavourable generation shifts in diabetes among men but not among women. No generation shifts for hypercholesterolaemia were observed and favourable generation shifts for low high-density lipoprotein cholesterol between the oldest two generations only. In general, the pattern of generation shifts did not differ according to socioeconomic status. CONCLUSIONS: The lifelong exposure to especially obesity will increase. As a consequence, more elderly of the future will develop overweight-related diseases such as diabetes and cardiovascular disease.