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Background Whether cognitive decline is related to a higher risk of death independent of the initial cognitive function is inconclusive. Evidence of the association between cognitive decline and mortality among Chinese older people is limited. We aimed to examine whether cognitive decline, assessed by the rate of decrease in the Mini-Mental State Examination (MMSE) score, was associated with mortality independent of initial cognitive function (baseline MMSE score) among Chinese older people. Methods We established two successive and non-overlapping cohorts of older adults nested within the Chinese Longitudinal Healthy Longevity Survey (CLHLS), an ongoing, open, community-based cohort survey conducted every 2–3 years. Cognitive function was measured using the Chinese version of the MMSE. A total of 11,732 older adults who completed two consecutive cognitive function examinations were included and followed for 3 years. A Cox proportional hazards model was used to examine the association of cognitive decline with mortality after adjusting for sociodemographic characteristics, health behaviours, comorbidities and initial cognitive function. Results The mean age was 82.5 years old, and 44.9% (5264/11732) of participants were men. After adjusting for baseline MMSE scores and other covariates, the rate of change in MMSE scores over 3 years was monotonically and positively associated with subsequent 3-year mortality. Compared to those with stable cognitive function, participants with rapid cognitive decline (decline faster than average, a reduction of MMSE scores > 1.62 points/year) had a 75% higher risk of death (hazard ratio = 1.75, 95% confidence interval 1.57–1.95). The association between cognitive decline and mortality was stronger among relatively younger Chinese older people (aged 65–79 years versus 80 years and over) and those with normal cognitive function at baseline (MMSE scores ≥ 24 versus < 24 points), respectively, but did not differ by cohort and sex. Conclusion Faster cognitive decline was associated with higher mortality independent of initial cognitive function, especially among those aged 65–79 years and those with normal cognitive function at baseline. The association was consistent across two successive cohorts. Our findings indicate the practical significance of monitoring cognitive change in older adults.

The relation between sodium intake and cardiovascular disease is controversial. This study used individual-participant data from six prospective cohorts of healthy adults. Higher sodium and lower potassium intakes, estimated from multiple 24-hour urine samples, were associated in a dose-dependent manner with a higher cardiovascular risk.

Alzheimer's disease is one of the most heritable diseases in elderly people and the most common type of dementia. In addition to the major genetic determinant of Alzheimer's disease, the APOE gene, 23 genetic variants have been associated with the disease. We assessed the effects of these variants and APOE on cumulative risk and age at onset of Alzheimer's disease and all-cause dementia. We studied incident dementia in cognitively healthy participants (aged >45 years) from the community-based Rotterdam Study, an ongoing prospective cohort study based in Rotterdam, the Netherlands, focusing on neurological, cardiovascular, endocrine, and ophthalmological disorders, and other diseases in elderly people. The Rotterdam Study comprises participants in three baseline cohorts (initiated in 1990, 2000, and 2006), who are re-invited to the research centre every 3–4 years, and continuously monitored by records from general practitioners and medical specialists. Cumulative incidence curves up to age 100 years were calculated for Alzheimer's disease and dementia, taking into account mortality as a competing event. These risk curves were stratified by APOE genotypes, tertiles of a weighted genetic risk score (GRS) of 23 Alzheimer's disease-associated genetic variants, and parental history of dementia. 12 255 of 14 926 participants (58·5% women) from the Rotterdam Study were included in this study. During a median follow-up of 11·0 years (IQR 4·9–15·9; 133 123 person years), 1609 participants developed dementia, of whom 1262 (78%) were classified as having Alzheimer's disease; 3310 people died of causes other than dementia. Both APOE and the GRS significantly modified the risks of Alzheimer's disease and dementia. There was evidence for a significant interaction between APOE genotypes and the GRS for the association with Alzheimer's disease (p=0·03) and dementia (p=0·04); the risk for carriers homozygous for APOE ε4 was modified most by the GRS. In carriers homozygous for APOE ε4, the difference between the high-risk tertile and the low-risk tertile by age 85 years was 27·0% for Alzheimer's disease (p=8·5 × 10−3) and 37·2% for dementia (p=2·2 × 10−4), which translates to a 7–10 year difference in age at onset. Comparing the risk extremes, which were carriers homozygous for APOE ε2 or heterozygous with one copy each of the ε2 and ε3 alleles in the low-risk tertile of the GRS versus carriers homozygous for APOE ε4 in the high-risk tertile of the GRS, the difference in risk by age 85 years was 58·6% (4·1% vs 62·7%; p=6·2 × 10−13) for Alzheimer's disease, and 70·3% (7·2% vs 77·5%; p=3·0 × 10−23) for dementia. These risk differences translate into an 18–29 years difference in age at onset for Alzheimer's disease and an 18–23 year difference in age at onset dementia. This difference becomes more pronounced when parental history of dementia is considered (difference in risk 83·8%; p=1·1 × 10−20). Common variants with small individual effects jointly modify the risk and age at onset of Alzheimer's disease and dementia, particularly in APOE ε4 carriers. These findings highlight the potential of common variants in determining Alzheimer's disease risk. None.

Application of biological age as a measure of an individual´s health status offers new perspectives into extension of both lifespan and healthspan. While algorithms predicting mortality and most aging-related morbidities have been reported, the major shortcoming has been an inability to predict dementia. We present a community-based cohort study of 1930 participants with a mean age of 72 years and a follow-up period of over 7 years, using two variants of a phenotypic blood-based algorithm that either excludes (BioAge1) or includes (BioAge2) neurofilament light chain (NfL) as a neurodegenerative marker. BioAge1 and BioAge2 predict dementia equally well, as well as lifespan and healthspan. Each one-year increase in BioAge1/2 was associated with 11% elevated risk (HR 1.11; 95%CI 1.08–1.14) of mortality and 7% elevated risk (HR 1.07; 95%CI 1.05–1.09) of first morbidities. We additionally tested the association of microRNAs with age and identified 263 microRNAs significantly associated with biological and chronological age alike. Top differentially expressed microRNAs based on biological age had a higher significance level than those based on chronological age, suggesting that biological age captures aspects of aging signals at the epigenetic level. We conclude that accelerated biological age for a given age is a predictor of major age-related morbidity, including dementia, among healthy elderly.

COPD is the third leading cause of death in the world and its global burden is predicted to increase further. Even though the prevalence of COPD is well studied, only few studies examined the incidence of COPD in a prospective and standardized manner. In a prospective populationbased cohort study (Rotterdam Study) enrolling subjects aged ≥45, COPD was diagnosed based on a pre-bronchodilator obstructive spirometry (FEV₁/FVC < 0.70). In absence of an interpretable spirometry within the Rotterdam Study, cases were defined as having COPD diagnosed by a physician on the basis of clinical presentation and obstructive lung function measured by the general practitioner or respiratory physician. Incidence rates were calculated by dividing the number of incident cases by the total number of person years of subjects at risk. In this cohort of 14,619 participants, 1993 subjects with COPD were identified of whom 689 as prevalent ones and 1304 cases as incident ones. The overall incidence rate (IR) of COPD was 8.9/1000 person-years (PY); 95 % Confidence Interval (CI) 8.4-9.4. The IR was higher in males and in smokers. The proportion of female COPD participants without a history of smoking was 27.2 %, while this proportion was 7.3 % in males. The prevalence of COPD in the Rotterdam Study is 4.7 % and the overall incidence is approximately 9/1000 PY, with a higher incidence in males and in smokers. The proportion of never-smokers among female COPD cases is substantial.

Structural brain markers are studied extensively in the field of neurodegeneration, but are thought to occur rather late in the process. Functional measures such as functional connectivity are gaining interest as potentially more subtle markers of neurodegeneration. However, brain structure and function are also affected by ‘normal’ brain ageing. More information is needed on how functional connectivity relates to aging, particularly in the absence of overt neurodegenerative disease. We investigated the association of age with resting-state functional connectivity in 2878 non-demented persons between 50 and 95 years of age (54.1% women) from the population-based Rotterdam Study. We obtained nine well-known resting state networks using data-driven methodology. Within the anterior default mode network, ventral attention network, and sensorimotor network, functional connectivity was significantly lower with older age. In contrast, functional connectivity was higher with older age within the visual network. Between resting state networks, we found patterns of both increases and decreases in connectivity in approximate equal proportions. Our results reinforce the notion that the aging brain undergoes a reorganization process, and serves as a solid basis for exploring functional connectivity as a preclinical marker of neurodegenerative disease. •The aging brain undergoes a complex functional reorganization process.•Age is related to decreases in within-network functional connectivity and to widespread increases and decreases in (anti-)correlations between different networks.•This study forms a basis for exploring functional connectivity as a preclinical marker of neurodegenerative disease.

PurposeHigh myopia (≤−6 D) usually has its onset before 10 years of age and can lead to blinding complications later in life. We examined whether differences in myopia prevalences in socioeconomic risk groups could be explained by differences in lifestyle factors.MethodsA total of 5711 six-year-old children participating in the prospective population-based birth cohort study Generation R underwent a stepwise ophthalmic examination, which included visual acuity and objective cycloplegic refraction to identify children with myopia (≤−0.5D). Daily activities, ethnicity, factors representing family socioeconomic status and housing were ascertained by questionnaire. Risk assessments of myopia and mediation analyses were performed using logistic regression; attenuation of risks was calculated by bootstrapping.ResultsPrevalence of myopia was 2.4% (n=137). Myopic children spent more time indoors and less outdoors than non-myopic children (p<0.01), had lower vitamin D (p=0.01), had a higher body mass index and participated less in sports (p=0.03). Children of non-European descent (OR 2.60; 95% CI 1.84 to 3.68), low maternal education (OR 2.27; 95% CI 1.57 to 3.28) and low family income (OR 2.62; 95% CI 1.8 to 3.74) were more often myopic. Lifestyle factors explained the majority of the increased risk for ethnicity (82%; 95% CI 55 to 120), maternal education (69%; 95% CI 45 to 109) and family socioeconomic status (71%; 95% CI 46 to 104).ConclusionThis study found environmental factors to be strong risk factors for myopia already at the age of 6 years. The myopia prevalence differences in socioeconomic groups were greatly determined by differences in distribution of these environmental risk factors, highlighting the importance of lifestyle adjustments in young children developing myopia.

Imaging plays an essential role in research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to elucidate the causes of neurological disease by performing imaging of the brain in a prospective population-based setting. Initially, in 1995 and 1999, random subsamples of participants from the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. Moreover, we describe the imaging protocol, image post-processing techniques, and the main findings to date. Finally, we provide recommendations for future research, which will also be topics of investigation in the Rotterdam Scan Study.

Background The association of thyroid function with risk of type 2 diabetes remains elusive. We aimed to investigate the association of thyroid function with incident diabetes and progression from prediabetes to diabetes in a population-based prospective cohort study. Methods We included 8452 participants (mean age 65 years) with thyroid function measurement, defined by thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and longitudinal assessment of diabetes incidence. Cox-models were used to investigate the association of TSH and FT4 with diabetes and progression from prediabetes to diabetes. Multivariable models were adjusted for age, sex, high-density lipoprotein cholesterol, and glucose at baseline, amongst others. Results During a mean follow-up of 7.9 years, 798 diabetes cases occurred. Higher TSH levels were associated with a higher diabetes risk (hazard ratio [HR] 1.13; 95 % confidence interval [CI], 1.08–1.18, per logTSH), even within the reference range of thyroid function (HR 1.24; 95 % CI, 1.06–1.45). Higher FT4 levels were associated with a lower diabetes risk amongst all participants (HR 0.96; 95 % CI, 0.93–0.99, per 1 pmol/L) and in participants within the reference range of thyroid function (HR 0.96; 95 % CI, 0.92–0.99). The risk of progression from prediabetes to diabetes was higher with low-normal thyroid function (HR 1.32; 95 % CI, 1.06–1.64 for TSH and HR 0.91; 95 % CI, 0.86–0.97 for FT4). Absolute risk of developing diabetes type 2 in participants with prediabetes decreased from 35 % to almost 15 % with higher FT4 levels within the normal range. Conclusions Low and low-normal thyroid function are risk factors for incident diabetes, especially in individuals with prediabetes. Future studies should investigate whether screening for and treatment of (subclinical) hypothyroidism is beneficial in subjects at risk of developing diabetes.

Variation in blood pressure may relate to dementia risk via autonomic disturbance or hemodynamic mechanisms, but the long-term associations are unclear. We aimed to determine whether blood pressure variation over a period of years, considering both magnitude and direction, is associated with the risk of dementia. In a prospective cohort study ongoing since 1989 in the Netherlands, 5,273 dementia-free participants (58.1% women; mean [SD] age, 67.6 [8.0] years) were included. As of 2016, 1,059 dementia cases occurred during a median follow-up of 14.6 years. Absolute variation in systolic blood pressure (SBP) was assessed as the absolute difference in SBP divided by the mean over two sequential visits every 4.2 (median) years, with the first quantile set as the reference level. The direction was the rise or fall in SBP, with the third quantile set as the reference level. We estimated the risk of dementia in relation to SBP variation measured at different time windows (i.e., at least 0, 5, 10, and 15 years) prior to dementia diagnosis, with adjustments for age, sex, education, apolipoprotein E (APOE) genotype, vascular risk factors, and history of cardiovascular disease. We repeated the above analysis for variation in diastolic blood pressure (DBP). A large SBP variation was associated with an increased dementia risk, which became more pronounced with longer intervals between the assessment of SBP variation and the diagnosis of dementia. The hazard ratio (HR) associated with large variation (the highest quintile) increased from 1.08 (95% confidence interval [CI] 0.88-1.34, P = 0.337) for risk within 5 years of SBP variation measurement to 3.13 (95% CI 2.05-4.77; P < 0.001) for risk after at least 15 years since the measurement of SBP variation. The increased long-term risk was associated with both large rises (HR for the highest quintile, 3.31 [95% CI 2.11-5.18], P < 0.001) and large falls in SBP (HR for the lowest quintile, 2.20 [95% CI 1.33-3.63], P = 0.002), whereas the higher short-term risk was only associated with large falls in SBP (HR, 1.21 [95% CI 1.00-1.48], P = 0.017). Similar findings were observed for variation in DBP. Despite our assessment of major confounders, potential residual confounding is possible, and the findings on blood pressure variability over periods of years may not be generalizable to variability over periods of days and other shorter periods. Results of this study showed that a large blood pressure variation over a period of years was associated with an increased long-term risk of dementia. The association between blood pressure variation and dementia appears most pronounced when this variation occurred long before the diagnosis. An elevated long-term risk of dementia was observed with both a large rise and fall in blood pressure.