Body composition and plasma total-tau, neurofilament light chain, and amyloid-ß: A population-based study.

A higher body mass at older age has been linked to a lower risk of dementia. This unexpected trend may be explained by age-related lean mass depletion, or methodological issues such as the long preclinical phase of dementia or competing risks. Focusing on preclinical markers of dementia may overcome these issues. Between 2002 and 2005, body composition and plasma total-tau, neurofilament light chain (NfL), amyloid-ß40, and amyloid-ß42 were measured in 3408 dementia-free participants from the population-based Rotterdam Study. The cross-sectional associations between body composition and plasma markers were determined using linear regression models. Whole body and fat mass, but not lean mass, were positively associated with total-tau, while all these measures were inversely associated with NfL. Apart from an inverse association between lean mass and amyloid-ß40, body composition measures were not associated with plasma amyloid-ß. Our findings suggest distinct effects of body composition on neurodegeneration.

The inflammatory potential of diet is associated with the risk of age-related eye diseases.

BACKGROUND & AIMS: Inflammation is involved in the pathogenesis of cataract, age-related macular degeneration (AMD), and possibly open-angle glaucoma (OAG). We assessed whether the inflammatory potential of diet (quantified using the dietary inflammatory index; DII) affects the incidence of these common blinding age-related eye diseases. Serum inflammation markers were investigated as possible mediators. METHODS: Participants aged >45 years were selected from the prospective, population-based Rotterdam Study. From 1991 onwards, every 4-5 years, participants underwent extensive eye examinations. At baseline, blood samples and dietary data (using food frequency questionnaires) were collected. The DII was adapted based on the data available. Of the 7436 participants free of eye diseases at baseline, 4036 developed incident eye diseases during follow-up (cataract = 2895, early-intermediate AMD = 891, late AMD = 81, OAG = 169). RESULTS: The adapted DII (aDII) ranged from -4.26 (i.e., anti-inflammatory) to 4.53 (i.e., pro-inflammatory). A higher aDII was significantly associated with increased inflammation. A higher neutrophil-lymphocyte ratio (NLR) was associated with an increased risk of cataract and AMD. Additionally, complement component 3c (C3c) and systemic immune-inflammation index (SII) were associated with increased risks of cataract and late AMD, respectively. Every point increase in the aDII was associated with a 9% increased risk of cataract (Odds ratio [95% confidence interval]: 1.09 [1.04-1.14]). The NLR and C3c partly mediated this association. We also identified associations of the aDII with risk of AMD (early-intermediate AMD, OR [95% CI]: 1.11 [1.03-1.19]; late AMD, OR [95% CI]: 1.24 [1.02-1.53]). The NLR partly mediated these associations. The aDII was not associated with OAG. CONCLUSIONS: A pro-inflammatory diet was associated with increased risks of cataract and AMD. Particularly the NLR, a marker of subclinical inflammation, appears to be implicated. These findings are relevant for patients with AMD and substantiate the current recommendations to strive for a healthy lifestyle to prevent blindness.

Plant-based dietary patterns and the risk of dementia: a population-based study.

BACKGROUND: Plant-based dietary patterns are increasingly popular in western countries and are supported by many governments and health organisations for their potential beneficial role in the prevention of chronic diseases. Yet, the potential role of plant-based dietary patterns in the development of dementia remains unclear. OBJECTIVE: To evaluate the association between plant-based dietary patterns and the risk of dementia. METHODS: Dietary intake was measured at baseline in 9,543 dementia-free participants (mean age 64 years, birth years 1897-1960, 58% women) of the prospective population-based Rotterdam Study, using food frequency questionnaires. Based on these questionnaires, we calculated an overall plant-based dietary index (PDI), healthy PDI (hPDI) and unhealthy PDI (uPDI), with higher scores reflecting higher consumption of (any, healthy and unhealthy, respectively) plant-based foods and lower consumption of animal-based foods. We analysed the association of the PDIs with incident dementia using Cox proportional hazard models. RESULTS: During a mean follow-up of 14.5 years, 1,472 participants developed dementia. Overall, the PDIs were not associated with the risk of dementia (hazard ratio [95% confidence interval] per 10-point increase: 0.99 [0.91-1.08] for PDI, 0.93 [0.86-1.01] for hPDI, 1.02 [0.94-1.10] for uPDI). However, among men and APOE ε4 carriers, a higher hPDI was linearly associated with a lower risk of dementia (0.86 [0.75-0.99] and 0.83 [0.73-0.95], respectively), while this association was U-shaped among APOE ε4 non-carriers (P value for non-linearity = 0.01). CONCLUSIONS: We found no strong evidence for an overall association between plant-based eating and the risk of dementia. Our findings in stratified analyses warranted further investigation.

Dietary nitrate intake in relation to the risk of dementia and imaging markers of vascular brain health: a population-based study.

BACKGROUND: Nitric oxide is a free radical that can be produced from dietary nitrate and positively affects cardiovascular health. With cardiovascular health playing an important role in the etiology of dementia, we hypothesized a link between dietary nitrate intake and the risk of dementia. OBJECTIVES: This study aimed to find the association of total, vegetable, and nonvegetable dietary nitrate intake with the risk of dementia and imaging markers of vascular brain health, such as total brain volume, global cerebral perfusion, white matter hyperintensity volume, microbleeds, and lacunar infarcts. METHODS: Between 1990 and 2009, dietary intake was assessed using food-frequency questionnaires in 9543 dementia-free participants (mean age, 64 y; 58% female) from the prospective population-based Rotterdam Study. Participants were followed up for incidence dementia until January 2020. We used Cox models to determine the association between dietary nitrate intake and incident dementia. Using linear mixed models and logistic regression models, we assessed the association of dietary nitrate intake with changes in imaging markers across 3 consecutive examination rounds (mean interval between images 4.6 y). RESULTS: Participants median dietary nitrate consumption was 85 mg/d (interquartile range, 55 mg/d), derived on average for 81% from vegetable sources. During a mean follow-up of 14.5 y, 1472 participants developed dementia. A higher intake of total and vegetable dietary nitrate was associated with a lower risk of dementia per 50-mg/d increase [hazard ratio (HR): 0.92; 95% confidence interval (CI): 0.87, 0.98; and HR: 0.92; 95% CI: 0.86, 0.97, respectively] but not with changes in neuroimaging markers. No association between nonvegetable dietary nitrate intake and the risk of dementia (HR: 1.15; 95% CI: 0.64, 2.07) or changes in neuroimaging markers were observed. CONCLUSIONS: A higher dietary nitrate intake from vegetable sources was associated with a lower risk of dementia. We found no evidence that this association was driven by vascular brain health.

Adiposity in the older population and the risk of dementia: The Rotterdam Study.

INTRODUCTION: We determined associations of total and regional adiposity with incident dementia among older adults. METHODS: Within the population-based Rotterdam Study, adiposity was measured as total, android, and gynoid fat mass using dual-energy X-ray absorptiometry in 3408 men and 4563 women, every 3 to 6 years between 2002 and 2016. Incident dementia was recorded until 2020. RESULTS: Higher adiposity measures were associated with a decreased risk of dementia in both sexes. After excluding the first 5 years of follow-up, only the association of gynoid fat among women remained significant (hazard ratio 0.85 [95% confidence interval 0.75-0.97] per standard deviation increase). No major differences in trajectories of adiposity measures were observed between dementia cases and dementia-free controls. DISCUSSION: Higher total and regional fat mass related to a decreased risk of dementia. These results may be explained by reverse causality, although a protective effect of adiposity cannot be excluded. HIGHLIGHTS: Total and regional adiposity were assessed using dual-energy X-ray absorptiometry scans in 7971 older adults. All adiposity measures were associated with a decreased risk of dementia. The results suggest a beneficial effect of gynoid fat on the risk of dementia in women. Reverse causation and competing risk may explain these inverse associations.

Air Pollution and the Risk of Dementia: The Rotterdam Study.

BACKGROUND: Exposure to air pollution has been suggested to increase the risk of dementia, but studies on this link often lack a detailed screening for dementia and data on important confounders. OBJECTIVE: To determine the association of exposure to air pollution with the risk of dementia and cognitive decline in the population-based Rotterdam Study. METHODS: Between 2009 and 2010, we determined air pollutant concentrations at participants residential addresses using land use regression models. Determined air pollutants include particulate matter <10µm (PM10) and <2.5µm (PM2.5), a proxy of elemental carbon (PM2.5 absorbance), nitrogen oxide (NOx), and nitrogen dioxide (NO2). As the individual air pollutant levels were highly correlated (r = 0.71-0.98), we computed a general marker covering all air pollutants based on a principal component analysis. We followed participants up for dementia until 2018 and determined cognitive performance during two subsequent examination rounds. Using Cox and linear mixed models, we related air pollution to dementia and cognitive decline. RESULTS: Of the 7,511 non-demented participants at baseline, 545 developed dementia during a median follow-up of 7 years. The general marker of all air pollutants was not associated with the risk of dementia (hazard ratio [95% confidence interval]: 1.04 [0.95-1.15]), neither were the individual air pollutants. Also, the general marker of all air pollutants or the individual air pollutant levels were not associated with cognitive decline. CONCLUSION: In this study, we found no clear evidence for an association between exposure to air pollution and the risk of dementia or cognitive decline.

MIND diet lowers risk of open-angle glaucoma: the Rotterdam Study.

PURPOSE: To assess the association between the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and the incidence of open-angle glaucoma (iOAG), as well as the association between iOAG and two other well-established diets in the Netherlands, i.e., the Mediterranean diet and Dutch dietary guidelines. METHODS: In the Rotterdam Study, participants were followed for iOAG since 1991, with intervals of approximately 5 years. A total of 170 participants developed iOAG during follow-up. Participants with iOAG were matched with healthy controls on age and sex in a case:control ratio of 1:5. The associations between food frequency questionnaire-derived diet adherences (baseline) and iOAG were analyzed using multivariable conditional logistic regression analyses. The associations between the diet adherences and intraocular pressure (IOP; a risk factor for OAG) were assessed using multivariable linear regression analyses. RESULTS: Greater adherence to the MIND diet was associated with a decreased iOAG risk (odds ratio [95% confidence interval]: 0.80 [0.66 to 0.96], for each 10-percent increase in adherence). Food component analyses showed that, in particular a higher intake of green leafy vegetables, berries and fish tended to be protective for iOAG. No significant associations were observed between adherence to the Mediterranean diet or Dutch dietary guidelines and iOAG. Moreover, none of the three examined diets were associated with IOP. CONCLUSION: Adherence to the MIND diet was significantly associated with a lower incidence of OAG in contrast to adherence to the Mediterranean diet or the Dutch dietary guidelines. As this association was IOP-independent, the MIND diet may be particularly relevant for the prevention of neurodegeneration in the eye.

Dietary Nitrate Intake Is Associated with Decreased Incidence of Open-Angle Glaucoma: The Rotterdam Study.

Previous studies suggest that nitric oxide is involved in the regulation of the intraocular pressure (IOP) and in the pathophysiology of open-angle glaucoma (OAG). However, prospective studies investigating the association between dietary nitrate intake, a source of nitric oxide, and incident (i)OAG risk are limited. We aimed to determine the association between dietary nitrate intake and iOAG, and to evaluate the association between dietary nitrate intake and IOP. From 1991 onwards, participants were followed each five years for iOAG in the Rotterdam Study. A total of 173 participants developed iOAG during follow-up. Cases and controls were matched on age (mean ± standard deviation: 65.7 ± 6.9) and sex (%female: 53.2) in a case:control ratio of 1:5. After adjustment for potential confounders, total dietary nitrate intake was associated with a lower iOAG risk (odds ratio (OR) with corresponding 95% confidence interval (95% CI): 0.95 (0.91-0.98) for each 10 mg/day higher intake). Both nitrate intake from vegetables (OR (95% CI): 0.95 (0.91-0.98) for each 10 mg/day higher intake) and nitrate intake from non-vegetable food sources (OR (95% CI): 0.63 (0.41-0.96) for each 10 mg/day higher intake) were associated with a lower iOAG risk. Dietary nitrate intake was not associated with IOP. In conclusion, dietary nitrate intake was associated with a reduced risk of iOAG. IOP-independent mechanisms may underlie the association with OAG.

MIND diet and the risk of dementia: a population-based study.

BACKGROUND: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been linked to a decreased risk of dementia, but reverse causality and residual confounding by lifestyle may partly account for this link. We aimed to address these issues by studying the associations over cumulative time periods, which may provide insight into possible reverse causality, and by using both historical and more contemporary dietary data as this could give insight into confounding since historical data may be less affected by lifestyle factors. METHODS: In the population-based Rotterdam Study, dietary intake was assessed using validated food frequency questionnaires in 5375 participants between 1989 and 1993 (baseline I) and in a largely non-overlapping sample in 2861 participants between 2009 and 2013 (baseline II). We calculated the MIND diet score and studied its association with the risk of all-cause dementia, using Cox models. Incident all-cause dementia was recorded until 2018. RESULTS: During a mean follow-up of 15.6 years from baseline I, 1188 participants developed dementia. A higher MIND diet score at baseline I was associated with a lower risk of dementia over the first 7 years of follow-up (hazard ratio (HR) [95% confidence interval (CI)] per standard deviation (SD) increase, 0.85 [0.74, 0.98]), but associations disappeared over longer follow-up intervals. The mean follow-up from baseline II was 5.9 years during which 248 participants developed dementia. A higher MIND diet score at baseline II was associated with a lower risk of dementia over every follow-up interval, but associations slightly attenuated over time (HR [95% CI] for 7 years follow-up per SD increase, 0.76 [0.66, 0.87]). The MIND diet score at baseline II was more strongly associated with the risk of dementia than the MIND diet score at baseline I. CONCLUSION: Better adherence to the MIND diet is associated with a decreased risk of dementia within the first years of follow-up, but this may in part be explained by reverse causality and residual confounding by lifestyle. Further research is needed to unravel to which extent the MIND diet may affect the risk of dementia.

Trajectories and Determinants of Physical Activity during COVID-19 Pandemic: A Population-Based Study of Middle-Aged and Elderly Individuals in The Netherlands.

Physical inactivity is a major public health problem, and there are concerns this might have increased during the COVID-19 pandemic. We aimed to identify distinct trajectories of physical activity over a 6-week period after the first restrictive measures and to explore determinants of these trajectories in a population-based cohort of middle-aged and elderly in the Netherlands (n = 5777). We observed that at least 59% of participants did not meet the World Health Organization recommendations for physical activity. Using latent class trajectory analyses over three time points, we identified five distinct trajectories, including four steady trajectories at different levels (very low, low, medium and high) and one increasing trajectory. Using multinomial logistic regression analyses, we observed that, compared to the 'steadily high' trajectory, participants in the 'steadily very low' trajectory were more often older, lower educated, reporting poorer physical health, more depressive symptoms, consuming a less healthy diet, smoking, and lower alcohol use, and were less often retired. A similar pattern of determinants was seen for those in the increasing trajectory, albeit with smaller effect sizes. Concluding, we observed low levels of physical activity that generally remained during the pandemic. The determinants we described can help identify groups that require additional preventive interventions.