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Background: Depression has been associated with an increased risk of Alzheimer's disease (AD), but the biological mechanisms are still not fully understood. Plasma biomarkers, such as amyloid‐beta, tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), have been associated with AD pathophysiology. However, the relationship with depression is unclear. Assessing these biomarkers in the blood allows for the opportunity to assess if AD pathology is related to depressive symptoms on a large‐scale. We hypothesized if depression is part of the AD process, then these markers will be associated with depressive symptoms. Method: A two‐stage IPD meta‐analysis was performed based on eight cohorts of individuals without dementia as part of the Netherlands Consortium of Dementia Cohorts (NCDC). We examined the cross‐sectional association between each plasma marker for AD (amyloid‐beta42/40 ratio, p‐tau181, NfL, and GFAP) with depressive symptoms (the GDS‐15, PHQ‐9, CES‐D, and SF‐36). Plasma markers were assessed using Single Molecular Array (Simoa; Quanterix) assays. Both plasma markers and depressive symptoms were standardized. We estimated the effect per plasma marker with depressive symptoms using linear regressions, correcting for age, sex, education, and APOE e4 allele presence, in each cohort. The effect estimates were entered into a random‐effects meta‐analysis. We also performed subgroup analyses assessing sex differences and between those with and without an APOE e4 allele. Result: This study involved 7210 participants with an age range of 38 to 102 years. Based on clinical cut‐offs per questionnaire, high depressive symptomology ranged from one to 22% per cohort. None of the plasma markers were associated with depressive symptoms in the meta‐analysis. However, subgroup analyses found an association with NfL and depressive symptoms in women (beta 0.07; 95% CI: 0.03‐0.10, p < 0.001) and in those with an APOE e4 allele (beta 0.11; 95% CI: 0.05‐0.17, p = 0.001). Conclusion: AD pathology did not show an overall relationship with depressive symptoms. However, in women and in those with a genetic risk for AD, NfL showed an association. As NfL is a marker of overall neurodegeneration, this pathology in plasma may be specific to depressive symptoms in certain subgroups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Several modifiable risk factors for cognitive decline have been identified, but whether differences by gender and educational level exist is unclear.Objective: The present study aims to clarify this by prospectively investigating the relationship between health and lifestyle factors and cognitive functioning in different subgroups defined by gender and educational level.Methods: 2,347 cognitive healthy individuals (mean age = 54.8, SD = 6.8, range: 41-71; 51.8% female; 26.2% low education) from the Doetinchem Cohort Study were examined for cognitive function at baseline, and at 5- and 10-year follow-up. Health- and lifestyle factors were captured by a poly-environmental risk score labelled 'LIfestyle for BRAin Health' (LIBRA). This score consists of 12 modifiable risk and protective factors for cognitive decline and dementia, with higher scores indicating greater risk (range: -2.7 to +12.7). Heterogeneity in associations between LIBRA and decline in verbal memory, cognitive flexibility, and mental speed between males and females and individuals with different levels of education were assessed in linear mixed models.Results: Overall, higher LIBRA scores predicted faster decline in verbal memory, cognitive flexibility, and mental speed over 10 years. Higher LIBRA scores were further associated with increased risk for incident cognitive impairment (one-point increase in LIBRA: HR = 1.09, 1.04-1.14, p = 0.001). In general, these effects were similar across gender and educational level.Conclusion: A composite risk score comprising unhealthy lifestyle and relatively poor health in midlife is significantly associated with a worse course of cognition 10 years later. These associations were for the most part unrelated to gender or educational differences. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To assess the relationship between dietary intake of antioxidants (vitamin C, vitamin E, β-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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Background: A recent meta-analysis showed that a Mediterranean style diet may protect against cardiovascular diseases (CVD). Studies on disease-specific associations are limited. We evaluated the Mediterranean Diet Score (MDS) in relation to incidence of total and specific CVDs. Methods: The EPIC-NL Study is a cohort of 40,011 men and women aged 20-70 years, examined between 1993 and 1997, with 10-15 years of follow-up. Diet was assessed with a validated food frequency questionnaire and the MDS was based on the daily intakes of vegetables, fruits, legumes and nuts, grains, fish, fatty acids, meat, dairy, and alcohol. Cardiovascular morbidity and mortality were ascertained through linkage with national registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) adjusted for age, sex, cohort, smoking, physical activity, total energy intake, and educational level. Results: In 34,708 participants free of CVD at baseline, 4881 CVD events occurred, and 487 persons died from CVD. A two unit increment in MDS (range 0-9) was inversely associated with fatal CVD (HR: 0.78; 95%CI: 0.69-0.88), total CVD (HR: 0.95 (0.91-0.98)), myocardial infarction (HR: 0.86 (0.79-0.93)), stroke (HR: 0.88 (0.78-1.00)), and pulmonary embolism (HR: 0.74 (0.59-0.92)). The MDS was not related to incident angina pectoris, transient ischemic attack and peripheral arterial disease. Conclusion: Better adherence to a Mediterranean style diet was more strongly associated with fatal CVD than with total CVD. Disease specific associations were strongest for incident myocardial infarction, stroke and pulmonary embolism. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]