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Background: Individuals with depression often experience widespread and persistent cognitive deficits, which might be due to brain atrophy and cerebral small vessel disease (CSVD). We therefore studied the associations between depression, markers of brain atrophy and CSVD, and cognitive functioning. Methods: We used cross-sectional data from the population-based Maastricht study (n = 4734; mean age 59.1 ± 8.6 years, 50.2% women), which focuses on type 2 diabetes. A current episode of major depressive disorder (MDD, n = 151) was assessed by the Mini-International Neuropsychiatric Interview. Volumes of cerebral spinal fluid, white matter, gray matter and white matter hyperintensities, presence of lacunar infarcts and cerebral microbleeds, and total CSVD burden were assessed by 3 T magnetic resonance imaging. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning in memory, information processing speed, and executive functioning & attention, and presence of cognitive impairment. Structural equation modeling was used to test mediation. Results: In fully adjusted models, MDD was associated with lower scores in information processing speed [mean difference = −0.18(−0.28;−0.08)], executive functioning & attention [mean difference = −0.13(−0.25;−0.02)], and with higher odds of cognitive impairment [odds ratio (OR) = 1.60(1.06;2.40)]. MDD was associated with CSVD in participants without type 2 diabetes [OR = 1.65(1.06;2.56)], but CSVD or other markers of brain atrophy or CSVD did not mediate the association with cognitive functioning. Conclusions: MDD is associated with more impaired information processing speed and executive functioning & attention, and overall cognitive impairment. Furthermore, MDD was associated with CSVD in participants without type 2 diabetes, but this association did not explain an impaired cognitive profile. [ABSTRACT FROM AUTHOR]

Background: Individuals with depression often show an adverse cardiometabolic risk profile and might represent a distinct depression subtype. The aim of this study was to investigate whether a cardiometabolic depression subtype could be identified and to investigate its association with demographics and clinical characteristics (severity, symptomatology, anti-depressant use, persistence and cognitive functioning).Methods: We used data from The Maastricht Study, a population-based cohort in the southern part of The Netherlands. A total of 248 participants with major depressive disorder were included (mean [SD] age, 58.8 ± 8.5 years; 121 [48.8 %] were men). Major depressive disorder was assessed at baseline by the Mini-International Neuropsychiatric Interview. Cardiometabolic risk factors were defined as indicators of the metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. We measured severity and persistence of depressive symptoms by use of the 9-item Patient Health Questionnaire.Results: Latent class analysis resulted in two subtypes, one with cardiometabolic depression (n = 145) and another with non-cardiometabolic depression (n = 103). The cardiometabolic depression subtype was characterized by being male, low education, more severe depressive symptoms, less symptoms of depressed mood and more symptoms of loss of energy, more use of antidepressant medication and lower cognitive functioning.Limitations: No conclusions can be made about causality.Conclusions: Latent class analysis suggested a distinct cardiometabolic depression subtype. Participants with cardiometabolic depression differed from participants with non-cardiometabolic depression in terms of demographics and clinical characteristics. The existence of a cardiometabolic depression subtype may indicate the need for prevention and treatment targeting cardiometabolic risk management. [ABSTRACT FROM AUTHOR]

Microvascular dysfunction (MVD) is a common pathophysiological change that occurs in various diseases, such as type 2 diabetes mellitus (T2DM), heart failure, dementia, and depression. Recent technical advances have enabled noninvasive measurement and quantification of microvascular changes in humans. In this paper, we describe the protocols of the microvascular measurements applied in the Maastricht Study, an ongoing prospective, population-based cohort study of persons aged 40–75 years being carried out in the southern part of the Netherlands (baseline data assessment, November 2010–January 2020). The study includes a variety of noninvasive measurements in skin, retina, brain, and sublingual tissue, as well as plasma and urine biomarker assessments. Following this, we summarize our main findings involving these microvascular measurements through the end of 2018. Finally, we provide a brief perspective on future microvascular investigations within the framework of the Maastricht Study. [ABSTRACT FROM AUTHOR]

Objective: Prediabetes and type 2 diabetes are associated with structural brain abnormalities, often observed in cognitive disorders. Besides visible lesions, (pre)diabetes might also be associated with alterations of the intrinsic organization of the white matter. In this population-based cohort study, the association of prediabetes and type 2 diabetes with white matter network organization was assessed.Research Design and Methods: In the Maastricht Study, a type 2 diabetes-enriched population-based cohort study (1,361 subjects with normal glucose metabolism, 348 with prediabetes, and 510 with type 2 diabetes assessed by oral glucose tolerance test; 52% men; aged 59 ± 8 years), 3 Tesla structural and diffusion MRI was performed. Whole-brain white matter tractography was used to assess the number of connections (node degree) between 94 brain regions and the topology (graph measures). Multivariable linear regression analyses were used to investigate the associations of glucose metabolism status with network measures. Associations were adjusted for age, sex, education, and cardiovascular risk factors.Results: Prediabetes and type 2 diabetes were associated with lower node degree after full adjustment (standardized [st]βPrediabetes = -0.055 [95% CI -0.172, 0.062], stβType2diabetes = -0.256 [-0.379, -0.133], Ptrend < 0.001). Prediabetes was associated with lower local efficiency (stβ = -0.084 [95% CI -0.159, -0.008], P = 0.033) and lower clustering coefficient (stβ = -0.097 [95% CI -0.189, -0.005], P = 0.049), whereas type 2 diabetes was not. Type 2 diabetes was associated with higher communicability (stβ = 0.148 [95% CI 0.042, 0.253], P = 0.008).Conclusions: These findings indicate that prediabetes and type 2 diabetes are associated with fewer white matter connections and weaker organization of white matter networks. Type 2 diabetes was associated with higher communicability, which was not yet observed in prediabetes and may reflect the use of alternative white matter connections. [ABSTRACT FROM AUTHOR]

Background The pathogenesis of depression may involve low-grade inflammation and endothelial dysfunction. We aimed to evaluate the independent associations of inflammation and endothelial dysfunction with depressive symptoms and depressive disorder, and the role of lifestyle factors in this association. Methods In The Maastricht Study, a population-based cohort study (n = 852, 55% men, m = 59.8 ± 8.5 years), depressive symptoms were assessed with the Patient Health Questionnaire-9 and (major and minor) depressive disorder with the Mini-International Neuropsychiatric Interview. Plasma biomarkers of inflammation (hsCRP, SAA, sICAM-1, IL-6, IL-8, TNF-α) and endothelial dysfunction (sVCAM-1, sICAM-1, sE-selectin, vWF) were measured with sandwich immunoassays and combined into two standardized sum scores. Results Biomarkers of inflammation (hsCRP, TNF-α, SAA, sICAM-1) and endothelial dysfunction (sICAM-1, sE-Selectin) were univariately associated with depressive symptoms and depressive disorder. The sum scores of inflammation and endothelial dysfunction were associated with depressive disorder after adjustment for age, sex, type 2 diabetes, kidney function and prior cardiovascular disease (OR 1.54, p = 0.001 and 1.40, p = 0.006). Both sum scores remained significantly associated with depressive disorder after additional adjustment for lifestyle factors smoking, alcohol consumption and body mass index. The sum score of inflammation was also independently associated with depressive symptoms, while the sum score of endothelial dysfunction was not. Conclusions Inflammation and endothelial dysfunction are both associated with depressive disorder, independent of lifestyle factors. Our results might suggest that inflammation and endothelial dysfunction are involved in depression. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to investigate the association of local and segmental arterial stiffness with incident cardiovascular events and all-cause mortality. Background: The association of different stiffness indices, in particular of carotid, brachial, and femoral stiffness, with cardiovascular disease and mortality is currently unknown. Methods: In a population-based cohort (n = 579, mean age 67 years, 50% women, 23% with type 2 diabetes [by design]), we assessed local stiffness of carotid, femoral, and brachial arteries (by ultrasonography), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index, and systemic arterial compliance. Results: After a median follow-up of 7.6 years, 130 participants had a cardiovascular event and 96 had died. The hazard ratios (HRs) (95% confidence intervals [CIs]) per 1 SD for cardiovascular events and all-cause mortality, respectively, were HR: 1.22 (95% CI: 0.95 to 1.56) and 1.51 (95% CI: 1.11 to 2.06) for lower carotid distensibility; HR: 1.19 (95% CI: 1.00 to 1.41) and 1.28 (95% CI: 1.07 to 1.53) for higher carotid elastic modulus; HR: 1.08 (95% CI: 0.88 to 1.31) and 1.43 (95% CI: 1.10 to 1.86) for lower carotid compliance; HR: 1.39 (95% CI: 1.06 to 1.83) and 1.27 (95% CI: 0.90 to 1.79) for lower femoral distensibility; HR: 1.25 (95% CI: 0.96 to 1.63) and 1.47 (95% CI: 1.01 to 2.13) for lower femoral compliance; and HR: 1.56 (95% CI: 1.23 to 1.98) and 1.13 (95% CI: 0.83 to 1.54) for higher cfPWV. These results were adjusted for age, sex, mean arterial pressure, and cardiovascular risk factors. Mutual adjustments for each of the other stiffness indices did not materially change these results. Brachial stiffness, augmentation index, and systemic arterial compliance were not associated with cardiovascular events or mortality. Conclusions: Carotid and femoral stiffness indices are independently associated with incident cardiovascular events and all-cause mortality. The strength of these associations with events may differ per stiffness parameter. [Copyright &y& Elsevier]

Background Advanced glycation endproducts (AGEs) may play a role in the development of coronary artery calcification (CAC) in type 1 diabetes (T1DM). We studied plasma AGEs in association with T1DM and CAC, and whether or not the latter association could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods We studied 165 individuals with and 169 without T1DM. CAC was quantified in a CAC score based on CT-scanning. Plasma levels of protein-bound pentosidine, Nε- (carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) were measured with HPLC/UPLC with fluorescence detection or tandem-mass spectrometry. Tetrahydropyrimidine (THP) was measured with ELISA, as were HsCRP, and sVCAM-1 and vWF, as markers for LGI and ED, respectively. Associations were analyzed with ANCOVA and adjusted for age, sex, BMI, waist-to-hip ratio, smoking, blood pressure, lipid profile, eGFR and T1DM. Results Individuals with T1DM had higher plasma levels of pentosidine, CML and THP compared with controls; means (95%CI) were 0.69 (0.65-0.73) vs. 0.51 (0.48-0.54) nmol/mmol LYS, p < 0.001; 105 (102-107) vs. 93 (90-95) nmol/mmol LYS, p < 0.001; and 126 (118-134) vs. 113 (106-120) U/mL, p = 0.03, respectively. Levels of pentosidine were higher in individuals with T1DM with a moderate to high compared with a low CAC score, means (95%CI) were 0.81 (0.70-0.93) vs. 0.67 (0.63-0.71) nmol/mmol LYS, p = 0.03, respectively. This difference was not attenuated by adjustment for LGI or ED. Conclusions We found a positive association between pentosidine and CAC in T1DM. These results may indicate that AGEs are possibly involved in the development of CAC in individuals with T1DM. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes is associated with considerable comorbidity and severe complications, which reduce quality of life of the patients and require high levels of healthcare. The Diabetes Pearl is a large cohort of patients diagnosed with type 2 diabetes, covering different geographical areas in the Netherlands. The aim of the study is to create a research infrastructure that will allow the study of risk factors, including biomarkers and genetic determinants for severe diabetes complications. Methods/design: Baseline examinations began November 2009 and will continue through 2012. By the end of 2012, it is expected that 7000 patients with type 2 diabetes will be included in the Diabetes Pearl cohort. To ensure quality of the data collected, standard operation procedures were developed and used in all 8 recruitment centers. From all patients who provide informed consent, the following information is collected: personal information, medication use, physical examination (antropometry, blood pressure, electrocardiography (ECG), retina photographs, ankle-brachial index, peripheral vibration perception), self-report questionnaire (socio-economic status, lifestyle, (family) history of disease, and psychosocial well-being), laboratory measurements (glucose, A1c, lipid profile, kidney function), biobank material (storage of urine and blood samples and isolated DNA). All gathered clinical data and biobank information is uploaded to a database for storage on a national level. Biobanks are maintained locally at all recruitment centers. Discussion: The Diabetes Pearl is large-scale cohort of type 2 diabetes patients in the Netherlands aiming to study risk factors, including biomarkers and genetic markers, for disease deterioration and the development of severe diabetes complications. As a result of the well-designed research design and the national coverage, the Diabetes Pearl data can be of great value to national and international researchers with an interest in diabetes related research. [ABSTRACT FROM AUTHOR]

Background: Ethnic minorities living in Western societies may have a higher prevalence of diabetes. We investigated whether the prevalence of diabetes among Turkish and Moroccan migrants differs from the indigenous urban population in the Netherlands, and whether these differences can be explained by differences in risk factors. Methods: In 2004 a general health survey, stratified by ethnicity and age, was carried out among the population of Amsterdam. The current study included 375 Turkish, 314 Moroccan and 417 Dutch individuals aged 18–70 years. Participants underwent a physical examination and a health interview. Diabetes was based on self-report, the use of anti-diabetic medicine, blood glucose levels and HbA1c. Results: The prevalence of diabetes in the Amsterdam population was significantly higher in Turkish (5.6%) and Moroccan (8.0%), compared to Dutch individuals (3.1%). These differences, which were much larger after adjustment for age, were only partly explained by the lower socioeconomic status and higher frequency of obesity among ethnic minorities. The difference between Dutch and Moroccan individuals remained significant even after adjustments for multiple risk factors. The typical age of onset of diabetes in both Turks and Moroccans is respectively one and two decades younger than in the indigenous population. Conclusion: Diabetes is more prevalent among Turkish and Moroccan migrants as compared to the indigenous population. Only part of this difference can be explained by differences in demographic and lifestyle risk factors. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: The aim of the study was to investigate how settings and registry characteristics affect the prevalence and nature of multimorbidity in elderly individuals. Study Design and Setting: We used data from three population-based studies, two general practitioner registries, one hospital discharge register, and one nursing home registry to estimate the prevalence of multimorbidity. Individuals aged 55 years and over were included. Results: Multimorbidity was most prevalent in nursing homes (82%), followed by the general population and general practitioner registries (56%–72%) and the hospital setting (22%). There were large differences in the nature of multimorbidity between settings. Combinations of hypertension, heart disease, and osteoarthritis were dominant in the population-based setting, whereas hypertension in combination with osteoarthritis, obesity, disorders of lipid metabolism, and diabetes dominated in the general practitioner setting. In the hospital setting, combinations of heart diseases had the highest prevalence. Combinations of dementia, hypertension, and stroke were dominant within the nursing home setting. Conclusion: This study shows that setting and registry characteristics have an important influence on the outcome of multimorbidity studies. We recommend provision of at least information about the setting, the (list of) conditions included, the data collection method, and the time frame used, when reporting about the size and nature of multimorbidity. [Copyright &y& Elsevier]

OBJECTIVES: To determine whether serum calcium is associated with cognitive function in elderly individuals in the general population. DESIGN: Prospective follow-up study of two independent, population-based cohorts. SETTING: The Rotterdam Study (median follow-up 11 years) and the Leiden 85-plus Study (median follow-up 5 years). PARTICIPANTS: Three thousand nine hundred ninety-four individuals, mean age 71, from the Rotterdam Study and 560 individuals, all aged 85, from the Leiden 85-plus Study. MEASUREMENTS: Global cognitive function was assessed in both cohorts using the Mini-Mental State Examination; attention, psychomotor speed, and memory function were assessed in the Leiden 85-plus Study only. Linear regression and linear mixed models were used for statistical analyses. RESULTS: In the Rotterdam Study, high serum calcium was associated with worse global cognitive function at baseline ( P<.05) and a faster rate of decline in cognitive function during follow-up ( P=.005) in individuals aged 75 and older but not in younger individuals. In the Leiden 85-plus Study, high serum calcium was associated with worse global cognitive function from age 85 through 90 ( P<.001). This observation also held for the specific cognitive domains tested (all P<.01). These results did not change when individuals with serum calcium levels greater than normal (>2.55 mmol/L) were excluded from the analyses. CONCLUSION: In the general population, high serum calcium levels are associated with faster decline in cognitive function over the age of 75. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate whether higher circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and α1-antichymotrypsin (ACT) are associated with worse cognitive function and decline in old age. DESIGN: Two independent population-based cohort studies. SETTING: The Rotterdam Study (mean follow-up 4.6 years) and the Leiden 85-plus Study (maximal follow-up 5 years). PARTICIPANTS: Three thousand eight hundred seventy-four individuals, mean age 72, from the Rotterdam Study, and 491 individuals, all aged 85, from the Leiden 85-plus Study. MEASUREMENTS: Both studies assessed global cognition, executive function, and memory. Linear regression analyses were used in the current study to investigate the associations between inflammatory markers and cognitive function and decline. RESULTS: In the Rotterdam Study, higher levels of CRP and IL-6 were cross-sectionally associated with worse global cognition and executive function ( P<.05). ACT was not associated with cognitive function. In the Leiden 85-plus Study, estimates were similar for CRP, although not statistically significant. Higher IL-6 levels were related to a steeper annual decline in memory function in the longitudinal analysis in the Leiden 85-plus Study ( P<.05). The effect of higher IL-6 levels on global and memory function decline was stronger in apolipoprotein E (APOE) ℇ4 carriers ( P-interaction=.01) than in those who were not ( P-interaction=.05). In the Rotterdam Study, higher IL-6 levels were related to a steeper annual decline in global cognition in APOE ℇ4 carriers only. CONCLUSION: Systemic markers of inflammation are only moderately associated with cognitive function and decline and tend to be stronger in carriers of the APOE ℇ4 allele. Systemic markers of inflammation are not suitable for risk stratification. [ABSTRACT FROM AUTHOR]

This randomised double-blind, placebo-controlled, clinical trial investigated the effect of 3 months of treatment with calcium dobesilate on endothelium-dependent vasodilation, markers of endothelial function, blood pressure, and markers of oxidation in obese, male smokers. Vascular effects may depend on the type of vessel and we, therefore, investigated both smaller arteries, i.e. resistance arteries and small arterioles, and large conduit arteries. Vascular function was measured by acetylcholine- and sodium-nitroprusside-mediated vasodilation, and capillary recruitment, in the skin microcirculation; by forearm blood flow (FBF) responses to several agonists and to N-G-monomethyl l-arginine (l-NMMA) in the forearm vascular bed; by flow-mediated vasodilation in the brachial artery; and by determination of soluble levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin. Twenty-eight individuals received dobesilate and 24 placebo. No effect of calcium dobesilate on endothelial function, blood pressure or markers of oxidation was observed compared with placebo. The difference in acetylcholine-mediated vasodilation in the microcirculation was −52.1%-point (95% confidence interval −132.8 to 28.1); in sodium-nitroprusside-mediated vasodilation in the microcirculation, 2.6%-point (−95.1 to 100.2); in capillary recruitment, 2.5%-point (−6.8 to 11.7); in acetylcholine-induced increases in FBF (n=28), 23%-point (−173 to 126); in l-NMMA-induced reduction of basal FBF, −2.8%-point (−29.3 to 23.8); in flow-mediated vasodilation of the brachial artery, 0.3%-points (−2.7 to 3.3); in 24-h systolic blood pressure, 2.1 mmHg (−1.3 to 5.5); in soluble VCAM-1, 54 ng/ml (−8 to 115); in soluble ICAM-1, 9 ng/ml (−49 to 67); in sE-selectin, −17 ng/ml (−44 to 11); in ketocholesterol 5 nM (−17 to 26); and in oxidised LDL −1.6 U/l (−6.7 to 3.5). We have shown that endothelial function, blood pressure, and markers of oxidation were not affected by 3 months of treatment with calcium dobesilate in mildly obese, smoking men. Thus, our data provide no evidence of an effect on vascular function of calcium dobesilate in humans. [Copyright &y& Elsevier]

Objective: Inflammatory activity is increased in type 1 diabetes and may predispose to vascular disease. Its origin is not clear. We therefore investigated determinants of inflammation in type 1 diabetes.Research Design and Methods: We performed a nested case-control study from the EURODIAB Prospective Complications Study of 543 European individuals having type 1 diabetes (278 men), diagnosed at <36 years of age. Case subjects (n = 348) were those with one or more complications of diabetes; control subjects (n = 195) were all those with no evidence of any complication. We determined levels of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha, combined them in a "general score of inflammatory markers," and investigated their associations with vascular risk factors and markers of endothelial dysfunction by use of multiple linear regression analysis.Results: Measures of inflammation were associated with sex, diabetes duration, glycemic control, the advanced glycation end product pentosidine, BMI, HDL cholesterol, triglycerides, and systolic blood pressure (standardized betas with the general score of inflammatory markers 0.15 [P = 0.002], 0.15 [P = 0.006], 0.18 [P < 0.0001], 0.12 [P = 0.005], 0.10 [P = 0.057], -0.15 [P = 0.001], 0.16 [P < 0.0001], and 0.09 [P = 0.042], respectively). In addition, measures of inflammation were strongly associated with markers of endothelial dysfunction, soluble vascular cell adhesion molecule-1, and soluble E-selectin (standardized betas with the general score of inflammatory markers 0.28 [P < 0.0001] and 0.19 [P < 0.0001]).Conclusions: We have shown that conventional risk factors for vascular disease and endothelial adhesion molecules are important determinants of inflammation in type 1 diabetic individuals, suggesting that strategies to decrease inflammatory activity in type 1 diabetes should focus not only on control of conventional risk factors, but also on improvement of endothelial function. [ABSTRACT FROM AUTHOR]

Estimates hemorrhage rates during initial unfractionated heparin treatment of patients with deep venous thrombosis and pulmonary embolism in the Netherlands. Percentage values of major bleeding events on initial treatment; Exclusion of patients with high risk of bleeding; Details on the occurrence of hemorrhaging and recurrence of venous thromboembolism.

In population-based cohort studies, magnetic resonance imaging (MRI) is vital for examining brain structure and function. Advanced MRI techniques, such as diffusion-weighted MRI (dMRI) and resting-state functional MRI (rs-fMRI), provide insights into brain connectivity. However, biases in MRI data acquisition and processing can impact brain connectivity measures and their associations with demographic and clinical variables. This study, conducted with 5110 participants from The Maastricht Study, explored the relationship between brain connectivity and various image quality metrics (e.g., signal-to-noise ratio, head motion, and atlas–template mismatches) that were obtained from dMRI and rs-fMRI scans. Results revealed that in particular increased head motion (R2 up to 0.169, p < 0.001) and reduced signal-to-noise ratio (R2 up to 0.013, p < 0.001) negatively impacted structural and functional brain connectivity, respectively. These image quality metrics significantly affected associations of overall brain connectivity with age (up to −59%), sex (up to −25%), and body mass index (BMI) (up to +14%). Associations with diabetes status, educational level, history of cardiovascular disease, and white matter hyperintensities were generally less affected. This emphasizes the potential confounding effects of image quality in large population-based neuroimaging studies on brain connectivity and underscores the importance of accounting for it. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is a common chronic disease that disproportionally affects disadvantaged groups. People with a low socioeconomic position (SEP) have increased risk of T2DM and people with a low SEP and T2DM have higher HbA1c-levels compared to people with T2DM and high SEP. The aim of this study is to analyze longitudinal socioeconomic differences in health-related functioning in people with T2DM. Methods: Longitudinal data from 1,537 participants of The Maastricht Study with T2DM were used (32.6% female, mean (SD) age 62.9 (7.7) years). SEP was determined by baseline measures of education, occupation and income. Health-related functioning (physical, mental and social) was measured with the Short-Form Health Survey and the Impact on Participation and Autonomy survey (all scored from 0 to 100). Associations of SEP and health-related functioning were studied annually over a 10-year period (median (IQR) 7.0 (5.0) years, baseline 2010–2018) using linear mixed methods adjusting for demographics, HbA1c-levels and lifestyle factors. Results: Participants with a low SEP had significantly worse health-related functioning compared to those with a high SEP. For example, participants with low income had lower scores for physical (-4.49[CI -5.77;-3.21]), mental (-2.61[-3.78,-1.44]) and social functioning (-9.76[-12.30;-7.23]) compared to participants with high income on a scale from 0 to 100. In addition, participants with a low education significantly declined more over time in mental (score for interaction education with time − 0.23[-0.37;-0.09]) and social functioning (-0.44[-0.77;-0.11]) compared to participants with high education. Participants with low and intermediate incomes significantly declined more over time in physical functioning (-0.17 [-0.34, -0.01 and − 0.18 [-0.36, 0.00]) compared to participants with high income. Conclusions: Among people with T2DM, those with a lower SEP had worse health-related functioning in general than people with a higher SEP. Additionally, people with T2DM and low education developed poorer mental and social functioning over time compared to people with T2DM and high education. People with T2DM and low or intermediate income declined more in physical functioning over time than those with high incomes. In addition to HbA1c-levels and lifestyle patterns, more attention is needed for socioeconomic differences in health-related functioning for people living with T2DM. [ABSTRACT FROM AUTHOR]

Background: We investigated the association of neighborhood walkability with accelerometer‐measured physical activity (PA) and sedentary behavior (SB) and examined whether objective and subjective measures of walkability resulted in similar findings. Methods: PA and SB from the first 7689 Maastricht Study participants ages 40–75 from 2010 to 2017 were measured using accelerometers for 7 days. Mean daily step count, light‐intensity PA, moderate‐ to vigorous‐ intensity PA (MVPA), and SB were calculated. Objective walkability was measured by the 7‐component Dutch Walkability Index within 500 m Euclidean buffers around residential addresses of participants. Subjective walkability was obtained from the Abbreviated Neighborhood Environment Walkability Scale. Linear regression models analyzed the associations of walkability with PA and SB, controlling for potential confounders. Results: Objective walkability was negatively associated with light intensity PA in the most walkable quartile (b = −14.58, 95% CI = −20.94, −8.23). Compared to participants living in the least walkable neighborhoods, those in the most walkable quartile had statistically significantly higher SB levels (b = 11.64, 95% CI = 4.95, 18.32). For subjective walkability, mean daily step count was significantly higher in the most walkable quartile (b = 509.60, 95% CI = 243.38, 775.81). Higher subjective walkability was positively associated with MVPA (b = 4.40, 95% CI = 2.56, 6.23). Conclusion: Living in a neighborhood with higher objective walkability was associated with lower levels of PA and higher SB levels while higher subjective walkability was associated with higher levels of PA. These results show discordant findings and thus, the effect of walkability on participant PA and SB within our sample is to be determined. [ABSTRACT FROM AUTHOR]

Background: Most infections are spread through social networks (detrimental effect). However, social networks may also lower infection acquisition (beneficial effect). This study aimed to examine associations between social network parameters and prevalence of self-reported upper and lower respiratory, gastrointestinal and urinary tract infections in a population aged 40-75.Methods: In this population-based cross-sectional cohort study (N = 3004, mean age 60.0 ± 8.2 years, 49% women), infections within the past two months were assessed by self-administered questionnaires. Social network parameters were assessed using a name generator questionnaire. To examine the associated beneficial and detrimental network parameters, univariable and multivariable logistic regression was used.Results: Participants reported an average of 10 people (alters) with whom they had 231 contacts per half year. Prevalences were 31.1% for upper respiratory, 11.5% for lower respiratory, 12.5% for gastrointestinal, and 5.7% for urinary tract infections. Larger network size, and a higher percentage of alters that were friends or acquaintances were associated with higher odds of upper respiratory, lower respiratory and/or gastrointestinal infections (detrimental). A higher total number of contacts, higher percentages of alters of the same age, and higher percentages of family members/acquaintances were associated with lower odds of upper respiratory, lower respiratory and/or gastrointestinal infections (beneficial).Conclusion: We identified both detrimental and beneficial associations of social network parameters with the prevalence of infections. Our findings can be used to complement mathematical models on infection spread, as well as to optimize current infectious disease control. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the associations between personality, general and diabetes-specific well-being and self-efficacy, and weight management indicators, among adults with type 2 diabetes. In addition, to examine whether personality provides incremental explanation of variance in weight management indicators. Australian adults with type 2 diabetes (N = 270; 56% women; age: 61±12 years) were recruited via the national diabetes registry. An online survey included measures of: personality (HEXACO-PI-R), weight management indicators (physical activity, healthy diet, body mass index [BMI]), general well-being (WHO-5), general self-efficacy (GSE), diabetes distress (DDS) and diabetes self-efficacy (DMSES). Analyses included bivariate correlations and linear regression, adjusted for demographic, clinical, and psychological variables. All six personality domains showed significant correlation with at least one weight management indicator: physical activity with extraversion (r =.28), conscientiousness (r =.18) and openness (r =.19); healthy diet with honesty-humility (r =.19), extraversion (r =.24), and agreeableness (r =.14); and BMI with emotionality (r =.20) and extraversion (r = -.20). The strongest associations with general and diabetes-specific well-being and self-efficacy were apparent for extraversion, emotionality and conscientiousness (range: r = -.47-.66). Beyond covariates, personality domains explained additional variance for physical activity (Adjusted R2 =.31, R2 difference =.03, p =.03; openness: β =.16, p =.02, emotionality: β =.15, p =.04) and healthy diet (Adjusted R2 =.19, R2 difference =.03, p =.02; honesty-humility: β =.20, p =.002, extraversion: β =.19, p =.04) but not BMI. This study shows that personality is associated with weight management indicators and psychological factors among adults with type 2 diabetes. Further research is needed, including objective measurement of weight management indictors, to examine how personality influences the experience of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Individuals with depression have an increased dementia risk, which might be due to modifiable risk factors for dementia. This study investigated the extent to which the increased risk for dementia in depression is explained by modifiable dementia risk factors. Methods: We used data from the English Longitudinal Study of Ageing (2008–2009 to 2018–2019), a prospective cohort study. A total of 7460 individuals were included [mean(standard deviation) age, 65.7 ± 9.4 years; 3915(54.7%) were women]. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale-8 (score ≥3) or self-reported doctor's diagnosis. Ten modifiable risk factors for dementia were combined in the 'LIfestyle for BRAin health' (LIBRA) score. Dementia was determined by physician diagnosis, self-reported Alzheimer's disease or the shortened version of the Informant Questionnaire on Cognitive Decline in the Elderly (average score ≥3.38). Structural equation modelling was used to test mediation of LIBRA score. Results: During 61 311 person-years, 306 individuals (4.1%) developed dementia. Participants aged 50–70 years with depressive symptoms had higher LIBRA scores [difference(s.e.) = 1.15(0.10)] and a 3.59 times increased dementia risk [HR(95% CI) = 3.59(2.20–5.84)], adjusted for age, sex, education, wealth and clustering at the household level. In total, 10.4% of the dementia risk was mediated by differences in LIBRA score [indirect effect: HR = 1.14(1.03–1.26)], while 89.6% was attributed to a direct effect of depressive symptoms on dementia risk [direct effect: HR = 3.14(2.20–5.84)]. Conclusions: Modifiable dementia risk factors can be important targets for the prevention of dementia in individuals with depressive symptoms during midlife. Yet, effect sizes are small and other aetiological pathways likely exist. [ABSTRACT FROM AUTHOR]

Background: Altered white matter brain connectivity has been linked to depression. The aim of this study was to investigate the association of markers of white matter connectivity with prevalence, incidence and course of depressive symptoms. Methods: Markers of white matter connectivity (node degree, clustering coefficient, local efficiency, characteristic path length, and global efficiency) were assessed at baseline by 3 T MRI in the population-based Maastricht Study (n = 4866; mean ± standard deviation age 59.6 ± 8.5 years, 49.0% women; 17 406 person-years of follow-up). Depressive symptoms (9-item Patient Health Questionnaire; PHQ-9) were assessed at baseline and annually over seven years of follow-up. Major depressive disorder (MDD) was assessed with the Mini-International Neuropsychiatric Interview at baseline only. We used negative binominal, logistic and Cox regression analyses, and adjusted for demographic, cardiovascular, and lifestyle risk factors. Results: A lower global average node degree at baseline was associated with the prevalence and persistence of clinically relevant depressive symptoms [PHQ-9 ⩾ 10; OR (95% confidence interval) per standard deviation = 1.21 (1.05–1.39) and OR = 1.21 (1.02–1.44), respectively], after full adjustment. On the contrary, no associations were found of global average node degree with the MDD at baseline [OR 1.12 (0.94–1.32) nor incidence or remission of clinically relevant depressive symptoms [HR = 1.05 (0.95–1.17) and OR 1.08 (0.83–1.41), respectively]. Other connectivity measures of white matter organization were not associated with depression. Conclusions: Our findings suggest that fewer white matter connections may contribute to prevalent depressive symptoms and its persistence but not to incident depression. Future studies are needed to replicate our findings. [ABSTRACT FROM AUTHOR]

Background and aims Arterial remodelling aims at normalising circumferential wall stress (CWS). Greater CWS in the carotid artery has previously been associated with the prevalence and severity of cerebral small vessel disease, a major cause of ageing-related cognitive decline. Here we test the hypothesis that greater carotid CWS is associated with poorer cognitive performance. Methods We studied 722 individuals (60 ± 8 years, 55% men, 42.5% highly educated, blood pressure 137 ± 19/77 ± 11 mmHg, n = 197 with type 2 diabetes) who completed a neuropsychological assessment and underwent vascular ultrasound to measure the intima-media thickness (IMT) and interadventitial diameter (IAD) of the left common carotid artery at a plaque-free site. From IMT and IAD, lumen diameter (LD) was calculated. These structural measures were then combined with local carotid pulse pressure and brachial mean arterial pressure to obtain a measure of pulsatile (CWS pulsatile ) and average (CWS mean ) mechanical load on the vessel wall. Cognitive domains assessed were memory, executive function and attention, and processing speed. Results After adjustment for age, sex, and education, regression analyses showed that neither CWS pulsatile nor CWS mean were associated with measures of cognitive performance (p-values ≥0.31). This null association did not differ by age or educational level, and was observed in both individuals with and without carotid plaque, diabetes and/or hypertension. In addition, none of the individual measures of carotid structure (i.e. IMT, IAD, and LD) was related to cognitive performance. Conclusions The present cross-sectional study shows that carotid CWS is not associated with cognitive performance, at least not among relatively highly educated individuals in late middle age with adequately controlled cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Computational models of human glucose homeostasis can provide insight into the physiological processes underlying the observed inter-individual variability in glucose regulation. Modelling approaches ranging from "bottom-up" mechanistic models to "top-down" data-driven techniques have been applied to untangle the complex interactions underlying progressive disturbances in glucose homeostasis. While both approaches offer distinct benefits, a combined approach taking the best of both worlds has yet to be explored. Here, we propose a sequential combination of a mechanistic and a data-driven modeling approach to quantify individuals' glucose and insulin responses to an oral glucose tolerance test, using cross sectional data from 2968 individuals from a large observational prospective population-based cohort, the Maastricht Study. The best predictive performance, measured by R2 and mean squared error of prediction, was achieved with personalized mechanistic models alone. The addition of a data-driven model did not improve predictive performance. The personalized mechanistic models consistently outperformed the data-driven and the combined model approaches, demonstrating the strength and suitability of bottom-up mechanistic models in describing the dynamic glucose and insulin response to oral glucose tolerance tests. [ABSTRACT FROM AUTHOR]

Aims: There are sex differences in the excess risk of diabetes‐associated cardiovascular disease. However, it is not clear whether these sex differences exist with regard to other complications like mental health aspects. Therefore, we investigated sex differences in the association of prediabetes and type 2 diabetes (T2D) with cognitive function, depression, and quality of life (QoL). Materials and Methods: In a population‐based cross‐sectional cohort study (n = 7639; age 40–75 years, 50% women, 25% T2D), we estimated sex‐specific associations, and differences therein, of prediabetes and T2D (reference: normal glucose metabolism) with measures of cognitive function, depression, and physical and mental QoL. Sex differences were analysed using multiple regression models with interaction terms. Results: In general, T2D, but not prediabetes, was associated with higher odds of cognitive impairment, major depressive disorder, and poorer QoL. The odds ratio (OR) of cognitive impairment associated with T2D was 1.29 (95% CI: 0.96–1.72) for women and 1.39 (1.10–1.75) for men. The OR of major depressive disorder associated with T2D was 1.19 (0.69–2.04) for women and 1.68 (1.02–2.75) for men. The mean difference of the physical QoL score (ranging from 0 to 100, with 100 indicating the best possible QoL) associated with T2D was −2.09 (−2.92 to −1.25) for women and −1.81 (−2.48 to −1.13) for men. The mean difference of the mental QoL score associated with T2D was −0.90 (−1.79 to −0.02) for women and −0.52 (−1.23 to 0.20) for men. There was no clear pattern of sex differences in the associations of either prediabetes or T2D with measures of cognitive function, depression, or QoL. Conclusions: In general, T2D was associated with worse cognitive function, depression, and poorer QoL. The strength of these associations was similar among women and men. [ABSTRACT FROM AUTHOR]

Background: If retinal indices of neurodegeneration are to be biomarkers for the monitoring of cerebral neurodegeneration, it is important to establish whether potentially modifiable risk factors for dementia are associated with retinal neurodegenerative changes. Objective: To study associations of dementia risk factors with retinal sensitivity, an index of retinal neural function, and retinal nerve fiber layer (RNFL) thickness, an index of retinal neural structure. Methods: We used cross-sectional data from The Maastricht Study (up to 5,666 participants, 50.5% men, mean age 59.7), and investigated associations with regression analyses (adjusted for potential confounders). Results: Most risk factors under study (i.e., hyperglycemia, unhealthy diet, lower cardiorespiratory fitness, smoking, alcohol consumption, and hypertension) were significantly associated with lower retinal sensitivity and lower RNFL thickness. Conclusion: Findings of this population-based study support the concept that retinal neural indices may be biomarkers for the monitoring of therapeutic strategies that aim to prevent early-stage cerebral neurodegeneration and, ultimately, dementia. [ABSTRACT FROM AUTHOR]

Objective: We investigated, using population-based data, whether worse autonomic function, estimated from lower 24-hour heart rate variability (HRV), was associated with beta cell function, assessed from beta cell response during an oral glucose tolerance test (OGTT). Research design and methods: We used cross-sectional data from The Maastricht Study, a population-based cohort study (N = 2,007; age, mean ± SD:60 ± 8 years; 52% men; and 24% with type 2 diabetes). We used linear regression analyses with adjustment for potential confounders (demographic, cardiovascular, and lifestyle factors) to study the associations of time- and frequency-domain HRV (composite scores) with overall beta cell response (estimated from a composite score calculated from: C-peptidogenic index, overall insulin secretion, beta cell glucose sensitivity, beta cell potentiation factor, and beta cell rate sensitivity). In addition, we tested for interaction by sex and glucose metabolism status. Results: After full adjustment, lower time- and frequency-domain HRV was significantly associated with lower overall beta cell response composite score (standardized beta, -0.055 [-0.098; -0.011] and − 0.051 [-0.095; -0.007], respectively). These associations were not modified by sex and there was no consistent pattern of interaction by glucose metabolism status. Conclusion: The present etiological study found that worse autonomic function, estimated from lower HRV, was associated with worse beta cell function, estimated from a composite score in a population-based sample which covered the entire spectrum of glucose metabolism. Hence, autonomic dysfunction may contribute to beta cell dysfunction and, ultimately, to the alteration of glucose metabolism status from normal glucose metabolism to prediabetes and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Context Depression is the most common causes of disease burden worldwide (GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1789–1858). Objective An umbrella review has been performed to assess the strength and validity of the available observational and trial evidence for the association between a variety of dietary patterns and depression. Data Sources MEDLINE/PubMed, Scopus, Web of Science, EMBASE, PsycINFO, and Cochrane Database were searched. Data Extraction The Joanna Briggs Institute Umbrella Review Methodology was used. Data Analysis The review included 19 articles, covering a relatively wide range of dietary patterns: healthy dietary patterns (n = 8), Mediterranean diet (MedDiet) (n = 6), Dietary Inflammatory Index (DII) (n = 5), Western diet (n = 4), Dietary Approaches to Stop Hypertension (DASH) (n = 2), vegetarian diets (n = 4), and other dietary interventions (n = 2). The methodological quality of the included meta-analyses was generally low or critically low. The strength of the evidence was generally weak, although convincing or suggestive evidence was found for an inverse relationship between MedDiet/DII and depression. Higher adherence to the MedDiet and lower DII score were significantly associated with lower risk of depression. Conclusion Considering the generally high heterogeneity and low quality of the available evidence, further studies adopting more coherent and uniform methodologies are needed. Systematic Review Registration PROSPERO registration no. CRD42020223376. [ABSTRACT FROM AUTHOR]

Aims Type 2 diabetes, hyperinsulinemia, and insulin resistance are associated with cognitive impairment. Experimental studies indicate that insulin signaling in the brain is related to cognitive performance. Here we evaluated whether insulin-related variables contribute to the variance in cognitive performance among individuals with type 2 diabetes. Methods A total of 806 individuals with type 2 diabetes (mean age 62 ± 8 years, HbA1c 6.9 ± 1.1%) completed a neuropsychological test battery. Insulin-related variables evaluated were: fasting plasma insulin, C-peptide, and the Homeostasis Model Assessment (HOMA2-IR; in individuals without insulin treatment; n = 641). The unadjusted coefficient of determination (R 2 ), obtained from multiple linear regression analyses, was used to estimate the proportion of variance in cognition explained by insulin-related variables. Results Sex, age, and educational level together explained 18.0% (R 2 ) of the variance in memory function, 26.5% in information processing speed, and 22.8% in executive function and attention. Fasting insulin, C-peptide, or HOMA2-IR did not increase the explained variance (maximum ΔR 2 0.3%, P ≥ 0.14). Similar results were obtained when insulin-related variables were added to models that additionally included glycemic control, cardiovascular risk factors, and depression. Conclusions Our results show that measures of peripheral insulin resistance are unrelated to cognitive performance among individuals with adequately controlled type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Using cross-sectional data from The Maastricht Study, we examined the association of socioeconomic conditions in early life with prediabetes and T2DM in adulthood. We also examined potential mediating pathways via both adulthood socioeconomic conditions and adult BMI and health behaviours. Methods: Of the 3263 participants (aged 40-75 years), 493 had prediabetes and 906 were diagnosed with T2DM. By using logistic regression analyses, the associations and possible mediating pathways were examined. Results: Participants with low early life socioeconomic conditions had a 1.56 times higher odds of prediabetes (95% confidence interval (CI) = 1.21-2.02) and a 1.61 times higher odds of T2DM (95% CI = 1.31-1.99). The relation between low early life socioeconomic conditions and prediabetes was independent of current socioeconomic conditions (OR = 1.38, 95% CI = 1.05-1.80), whereas the relation with T2DM was not independent of current socioeconomic conditions (OR = 1.10, 95% CI = 0.87-1.37). BMI party mediated the association between early life socioeconomic conditions and prediabetes. Conclusions: Socioeconomic inequalities starting in early life were associated with diabetes-related outcomes in adulthood and suggest the usefulness of early life interventions aimed at tackling these inequalities. [ABSTRACT FROM AUTHOR]

Background and aims There is increasing evidence linking arterial (mainly aortic) stiffness and type 2 diabetes, a risk factor for arterial stiffness, to cognitive impairment and dementia. However, data on carotid stiffness, which may be especially relevant for cognitive performance, are scarce, and few studies have addressed the interplay between arterial stiffness, type 2 diabetes, and cognitive performance. Methods We studied individuals with (n = 197) and without (n = 528) type 2 diabetes, who completed a neuropsychological test battery and underwent applanation tonometry and vascular ultrasound to evaluate aortic (i.e. carotid-to-femoral pulse wave velocity) and carotid stiffness (i.e. distensibility, compliance and Young's elastic modulus). Linear regression analyses were performed and adjusted for demographics, vascular risk factors, and depression. Results Overall, our results showed that carotid, but not aortic, stiffness was associated with worse cognitive performance, primarily in the domains of processing speed (standardized regression coefficient for distensibility −0.083, p = 0.040; compliance −0.077, p = 0.032) and executive function and attention (distensibility −0.133, p = 0.001; compliance −0.090, p = 0.015; Young's elastic modulus −0.081, p = 0.027). These associations did not differ by diabetes status. The differences in cognitive performance between individuals with and without type 2 diabetes (mean difference in domain scores relative to those without diabetes for free recall memory −0.23, processing speed −0.19, executive function and attention −0.23; all p ≤ 0.009 and adjusted for demographics, traditional vascular risk factors, and depression) were not substantially altered after additional adjustment for carotid stiffness. Conclusions Our findings suggest that carotid stiffness is associated with cognitive performance in both individuals with and without diabetes, but does not mediate the relationship between type 2 diabetes and cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background: Higher anxiety levels in older adults are associated with worse executive functioning and an increased risk for dementia. In this study individual anxiety disorders and clinically relevant generalized anxiety symptoms are studied in relation to multiple cognitive domains.Method: This cross-sectional study includes 7344 community-dwelling participants of The Maastricht Study aged 40-75 years and oversampling of type 2 diabetes. Panic disorder with and without agoraphobia, agoraphobia and lifetime panic disorder were measured with the Mini International Neuropsychiatric Interview. Generalized anxiety symptoms were measured with the Generalized Anxiety Disorder 7-item scale (GAD-7). Multiple cognitive domains (executive functioning, memory and processing speed) and cognitive impairment were assessed. Multivariable linear and logistic regression analyses were used with adjustment for potential confounders. Interaction analyses were performed to test the moderation of age, sex and type 2 diabetes (due to oversampling).Results: Agoraphobia was associated with worse scores on all cognitive domains (range B = -0.12 to -0.10; range 95%CI = -0.20 to -0.04) and with higher odds of cognitive impairment (OR = 1.51, 95%CI = 1.18-1.93). High scores on the GAD-7 were associated with worse scores on processing speed (B = -0.11, 95%CI = -0.20 to -0.03) and higher odds of cognitive impairment (OR = 1.42, 95%CI = 1.02-1.97). Panic disorder was significantly associated with worse scores on memory tasks (B = -0.25, 95%CI = -0.48 to -0.02). Associations were stronger in the younger participants and for agoraphobia and GAD-7 scores also in those with type 2 diabetes.Conclusion: Multiple anxiety disorders and generalized anxiety symptoms were associated with worse cognitive functioning on several cognitive domains. [ABSTRACT FROM AUTHOR]

This study aims to compare the accelerometer‐measured daily patterns of PA and sedentary behavior among participants with and without prevalent/incident depressive symptoms. We used data from 5582 individuals in The Maastricht Study (59.9 ± 8.6 years, 50.3% women). Daily patterns of sedentary time, light‐intensity physical activity (LiPA), moderate‐to‐vigorous physical activity (MVPA), and sit‐to‐stand transitions were objectively measured at baseline with the activPAL3 activity monitor. Depressive symptoms were assessed using the 9‐item Patient Health Questionnaire, both at baseline and annually (median follow‐up: 5.1 years). General linear models were used to compare patterns of physical activity and sedentary behavior between those with and without prevalent/incident depressive symptoms. Participants with prevalent depressive symptoms had significantly more sedentary time (18.6 min/day) and lower LiPA (26.8 min/day) and MVPA (4.8 min/day) than participants without depressive symptoms. Considering the daily patterns, participants with prevalent depressive symptoms had significantly more sedentary time early in the afternoon (12:00–18:00), early evening (18:00–21:00), and during the night (00:00–03:00), less time in LiPA in all periods between 09:00–21.00 and less MVPA in the morning (09:00:12:00), early afternoon (12:00–15:00), and evening (18:00–21:00), than those without. Similar differences in activity and sedentary behavior patterns between those and without incident depressive symptoms were observed albeit the differences were smaller. Overall, we did not find specific time slots particularly associated with both prevalent and incident depressive symptoms. These findings may indicate that less sedentary time and more intense PA can be important targets for the prevention of depression irrespective of the timing of the day. [ABSTRACT FROM AUTHOR]

The easily accessible retinal vessels provide a unique opportunity to study a proxy for cerebral small vessels. Associations between retinal vessel diameters and macrostructural brain white matter changes have already been demonstrated. Alterations in microvascular function, likely precede these structural abnormalities. We examined whether retinal microvascular function is related to cerebral microvascular properties, assessed by the intravoxel incoherent motion (IVIM) effect in brain MRI. Seventy participants (age 60 ± 8 years, 41% women) from the population-based Maastricht Study underwent brain IVIM diffusion imaging (3 Tesla) to determine the microvascular measures f (perfusion volume fraction) and D* (pseudo-diffusion of circulating blood). The retinal arteriolar and venular dilation response to flicker light stimulation were measured by a dynamic vessel analyzer. Linear regression analysis was used to investigate associations between retinal vasoreactivity and IVIM measures in white matter hyperintensities (WMH), normal-appearing white matter (NAWM) and cortical gray matter (CGM). More retinal arteriolar dilation was significantly associated with stronger pseudo-diffusion (D*) in the NAWM and CGM (β 0.280 [95% CI 0.084–0.475], and β 0.310 [95% CI 0.091–0.528], respectively), but not with the cerebral blood volume fraction (f). No associations were observed between retinal venular dilation response and cerebrovascular IVIM measures. Variations in retinal arteriolar microvascular function and microcirculatory properties in the brain are linked. The retina could serve as a proxy for early detection of brain microvascular dysfunction. • A dynamic vessel analyzer can detect early microvascular dysfunction in the retina. • Altered intravoxel incoherent motion imaging measures are a sign of early microvascular dysfunction in the brain. • Retinal arteriolar microvascular function is associated with the pseudo-diffusion D* in the brain. • The retina could serve as a proxy for early detection of brain microvascular dysfunction. [ABSTRACT FROM AUTHOR]

Retinopathy and neuropathy in type 2 diabetes are preceded by retinal nerve fibre layer (RNFL) thinning, an index of neurodegeneration. We investigated whether glucose metabolism status (GMS), measures of glycaemia, and daily glucose variability (GV) are associated with RNFL thickness over the entire range of glucose tolerance. We used cross-sectional data from The Maastricht Study (up to 5455 participants, 48.9% men, mean age 59.5 years and 22.7% with type 2 diabetes) to investigate the associations of GMS, measures of glycaemia (fasting plasma glucose [FPG], 2-h post-load glucose [2-h PG], HbA1c, advanced glycation endproducts [AGEs] assessed as skin autofluorescence [SAF]) and indices of daily GV (incremental glucose peak [IGP] and continuous glucose monitoring [CGM]-assessed standard deviation [SD]) with mean RNFL thickness. We used linear regression analyses and, for GMS, P for trend analyses. We adjusted associations for demographic, cardiovascular risk and lifestyle factors, and, only for measures of GV, for indices of mean glycaemia. After full adjustment, type 2 diabetes and prediabetes (versus normal glucose metabolism) were associated with lower RNFL thickness (standardized beta [95% CI], respectively − 0.16 [− 0.25; − 0.08]; − 0.05 [− 0.13; 0.03]; Ptrend = 0.001). Greater FPG, 2-h PG, HbA1c, SAF, IGP, but not CGM-assessed SD, were also associated with lower RNFL thickness (per SD, respectively − 0.05 [− 0.08; − 0.01]; − 0.06 [− 0.09; − 0.02]; − 0.05 [− 0.08; − 0.02]; − 0.04 [− 0.07; − 0.01]; − 0.06 [− 0.12; − 0.01]; and − 0.07 [− 0.21; 0.07]). In this population-based study, a more adverse GMS and, over the entire range of glucose tolerance, greater glycaemia and daily GV were associated with lower RNFL thickness. Hence, early identification of individuals with hyperglycaemia, early glucose-lowering treatment, and early monitoring of daily GV may contribute to the prevention of RNFL thinning, an index of neurodegeneration and precursor of retinopathy and neuropathy. [ABSTRACT FROM AUTHOR]

Background: This study examined the associations between accelerometer-derived sedentary time (ST), lower intensity physical activity (LPA), higher intensity physical activity (HPA) and the incidence of depressive symptoms over 4 years of follow-up. Methods: We included 2082 participants from The Maastricht Study (mean ± s.d. age 60.1 ± 8.0 years; 51.2% men) without depressive symptoms at baseline. ST, LPA and HPA were measured with the ActivPAL3 activity monitor. Depressive symptoms were measured annually over 4 years of follow-up with the 9-item Patient Health Questionnaire (PHQ-9). Cox regression analysis was performed to examine the associations between ST, LPA, HPA and incident depressive symptoms (PHQ-9 ⩾ 10). Analyses were adjusted for total waking time per day, age, sex, education level, type 2 diabetes mellitus, body mass index, total energy intake, smoking status and alcohol use. Results: During 7812.81 person-years of follow-up, 203 (9.8%) participants developed incident depressive symptoms. No significant associations [Hazard Ratio (95% confidence interval)] were found between sex-specific tertiles of ST (lowest v. highest tertile) [1.13 (0.76–1.66], or HPA (highest v. lowest tertile) [1.14 (0.78–1.69)] and incident depressive symptoms. LPA (highest v. lowest tertile) was statistically significantly associated with incident depressive symptoms in women [1.98 (1.19–3.29)], but not in men (p -interaction <0.01). Conclusions: We did not observe an association between ST or HPA and incident depressive symptoms. Lower levels of daily LPA were associated with an increased risk of incident depressive symptoms in women. Future research is needed to investigate accelerometer-derived measured physical activity and ST with incident depressive symptoms, preferably stratified by sex. [ABSTRACT FROM AUTHOR]

We aim to investigate the relationship between social cohesion and sedentary behavior (SB), total physical activity (PA), moderate-to-vigorous PA (MVPA), and dietary quality. Additionally, we assess whether these associations are independent of neighborhood walkability and the food environment. A total of 7641 participants from The Maastricht Study in the Netherlands between the ages of 40 and 75 years were analyzed. Neighborhood social cohesion was obtained by participant questionnaire completed at baseline and measured by the Dutch Livability meter. Home addresses were linked to geographic information system (GIS) data from the Geoscience and Health Cohort Consortium (GECCO) to create neighborhood exposures of walkability and food environment. A thigh worn accelerometer collected data to measure sedentary time, total daily PA, and MVPA. Dietary quality was measured with a food frequency questionnaire. Multivariate linear regression analyses were adjusted for age, sex, socioeconomic position, neighborhood walkability, and food environment. Those living in the highest quartile area of perceived social cohesion had statistically significant lower levels of SB (Q4 B: -13.04; 95% CI = −20.23, −5.85), higher total PA (Q4 B: 4.39; 95% CI = 1.69, 7.10), and higher MVPA (Q4 B: 2.57; 95% CI = 0.83, 4.31) and better diet quality (Q4 B: 1.12; 95% CI = 0.24, 2.01) compared to the lowest quartile independent of walkability and food environment. Similar results were found using the Livability meter. We discovered neighborhood social cohesion as an important obesogenic determinant that should be considered in policymaking to encourage higher levels of PA and higher diet quality. • Social cohesion can encourage positive health behaviors through social engagement. • Higher social cohesion was associated with more physical activity and better diet. • Policymakers should target social cohesion in addition to the built environment. [ABSTRACT FROM AUTHOR]

Mortality in type 2 diabetes, is determined not only by classical complications, but also by comorbidities, and is linked to hyperglycaemia and apparent even in prediabetes. We aimed to comprehensively investigate, in a population-based cohort, health burden defined as the presence of comorbidities in addition to classical complications and cardiometabolic risk factors, in not only type 2 diabetes but also prediabetes. Such population-based study has not been performed previously. Extensive phenotyping was performed in 3,410 participants of the population-based Maastricht Study (15.0% prediabetes and 28.6% type 2 diabetes) to assess presence of 17 comorbidities, six classical complications, and ten cardiometabolic risk factors. These were added up into individual and combined sum scores and categorized. Group differences were studied with multinomial regression analyses adjusted for age and sex. Individuals with type 2 diabetes and prediabetes, as compared to normal glucose metabolism (NGM), had greater comorbidities, classical complications, cardiometabolic risk factors and combined sum scores (comorbidities sum score ≥ 3: frequencies (95% CI) 61.5% (57.6;65.4) and 41.2% (36.5;45.9) vs. 25.4% (23.5;27.4), p-trend < 0.001; classical complications ≥ 2 (26.6% (23.1;30.1; P < 0.001 vs. NGM) and 10.1% (7.8;12.7; P = 0.065 vs NGM) vs. 8.0% (6.9;9.3)); cardiometabolic risk factors ≥ 6 (39.7% (35.9;43.4) and 28.5% (24.5;32.6) vs. 14.0% (12.5;15.6); p-trend < 0.001); combined ≥ 8 (66.6% (62.7;70.5) and 48.4% (43.7;53.1) vs. 26.0%(24.1;28.0), p-trend < 0.001). Type 2 diabetes and prediabetes health burden was comparable to respectively 32 and 14 years of ageing. Our population-based study shows, independently of age and sex, a considerable health burden in both type 2 diabetes and prediabetes, which to a substantial extent can be attributed to comorbidities in addition to classical complications and cardiometabolic risk factors. Our findings emphasize the necessity of comorbidities’ awareness in (pre)diabetes and for determining the exact role of hyperglycaemia in the occurrence of comorbidities. [ABSTRACT FROM AUTHOR]

Objective: Epidemiological evidence regarding the relationship between fructose intake and intrahepatic lipid (IHL) content is inconclusive. We, therefore, assessed the relationship between different sources of fructose and IHL at the population level.Research Design and Methods: We used cross-sectional data from The Maastricht Study, a population-based cohort study (n = 3,981; mean ± SD age: 60 ± 9 years; 50% women). We assessed the relationship between fructose intake (assessed with a food-frequency questionnaire)-total and derived from fruit, fruit juice, and sugar-sweetened beverages (SSB)-and IHL (quantified with 3T Dixon MRI) with adjustment for age, sex, type 2 diabetes, education, smoking status, physical activity, and intakes of total energy, alcohol, saturated fat, protein, vitamin E, and dietary fiber.Results: Energy-adjusted total fructose intake and energy-adjusted fructose from fruit were not associated with IHL in the fully adjusted models (P = 0.647 and P = 0.767). In contrast, energy-adjusted intake of fructose from fruit juice and SSB was associated with higher IHL in the fully adjusted models (P = 0.019 and P = 0.009). Individuals in the highest tertile of energy-adjusted intake of fructose from fruit juice and SSB had a 1.04-fold (95% CI 0.99; 1.11) and 1.09-fold (95% CI 1.03; 1.16) higher IHL, respectively, in comparison with the lowest tertile in the fully adjusted models. Finally, the association for fructose from fruit juice was stronger in individuals with type 2 diabetes (P for interaction = 0.071).Conclusions: Fructose from fruit juice and SSB is independently associated with higher IHL. These cross-sectional findings contribute to current knowledge in support of measures to reduce the intake of fructose-containing beverages as a means to prevent nonalcoholic fatty liver disease at the population level. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether there is a bidirectional longitudinal association of depression with HbA1c. Methods: We conducted a systematic literature search in PubMed, PsycINFO, CINAHL and EMBASE for observational, longitudinal studies published from January 2000 to September 2020, assessing the association between depression and HbA1c in adults. We assessed study quality with the Newcastle‐Ottawa‐Scale. Pooled effect estimates were reported as partial correlation coefficients (rp) or odds ratios (OR). Results: We retrieved 1642 studies; 26 studies were included in the systematic review and eleven in the meta‐analysis. Most studies (16/26) focused on type 2 diabetes. Study quality was rated as good (n = 19), fair (n = 2) and poor (n = 5). Of the meta‐analysed studies, six investigated the longitudinal association between self‐reported depressive symptoms and HbA1c and five the reverse longitudinal association, with a combined sample size of n = 48,793 and a mean follow‐up of 2 years. Higher levels of baseline depressive symptoms were associated with subsequent higher levels of HbA1c (partial r = 0.07; [95% CI 0.03, 0.12]; I238%). Higher baseline HbA1c values were also associated with 18% increased risk of (probable) depression (OR = 1.18; [95% CI 1.12,1.25]; I20.0%). Conclusions: Our findings support a bidirectional longitudinal association between depressive symptoms and HbA1c. However, the observed effect sizes were small and future research in large‐scale longitudinal studies is needed to confirm this association. Future studies should investigate the role of type of diabetes and depression, diabetes distress and diabetes self‐management behaviours. Our results may have clinical implications, as depressive symptoms and HbA1c levels could be targeted concurrently in the prevention and treatment of diabetes and depression. Registration: PROSPERO ID CRD42019147551. [ABSTRACT FROM AUTHOR]

Objective: Type 2 diabetes is associated with increased risks of cognitive dysfunction and brain abnormalities. The extent to which risk factor modification can mitigate these risks is unclear. We investigated the associations between incident dementia, cognitive performance, and brain abnormalities among individuals with type 2 diabetes, according to the number of risk factors on target, compared with control subjects without diabetes.Research Design and Methods: Prospective data were from UK Biobank of 87,856 individuals (n = 10,663 diabetes, n = 77,193 control subjects; baseline 2006-2010), with dementia follow-up until February 2018. Individuals with diabetes were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking; guideline-recommended levels of glycated hemoglobin, blood pressure, BMI, albuminuria, physical activity, and diet). Outcomes were incident dementia, domain-specific cognitive performance, white matter hyperintensities, and total brain volume.Results: After a mean follow-up of 9.0 years, 147 individuals (1.4%) with diabetes and 412 control subjects (0.5%) had incident dementia. Among individuals with diabetes, excess dementia risk decreased stepwise for a higher number of risk factors on target. Compared with control subjects (incidence rate per 1,000 person-years 0.62 [95% CI 0.56; 0.68]), individuals with diabetes who had five to seven risk factors on target had no significant excess dementia risk (absolute rate difference per 1,000 person-years 0.20 [-0.11; 0.52]; hazard ratio 1.32 [0.89; 1.95]). Similarly, differences in processing speed, executive function, and brain volumes were progressively smaller for a higher number of risk factors on target. These results were replicated in the Maastricht Study.Conclusions: Among individuals with diabetes, excess dementia risk, lower cognitive performance, and brain abnormalities decreased stepwise for a higher number of risk factors on target. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between depression and all-cause and cardiovascular mortality in people with diabetes by systematically reviewing the literature and carrying out a meta-analysis of relevant longitudinal studies. Research Design and Methods: PUBMED and PSYCINFO were searched for articles assessing mortality risk associated with depression in diabetes up until August 16, 2012. The pooled hazard ratios were calculated using random-effects models. Results: Sixteen studies met the inclusion criteria, which were pooled in an overall all-cause mortality estimate, and five in a cardiovascular mortality estimate. After adjustment for demographic variables and micro- and macrovascular complications, depression was associated with an increased risk of all-cause mortality (HR = 1.46, 95% CI = 1.29–1.66), and cardiovascular mortality (HR = 1.39, 95% CI = 1.11–1.73). Heterogeneity across studies was high for all-cause mortality and relatively low for cardiovascular mortality, with an I-squared of respectively 78.6% and 39.6%. Subgroup analyses showed that the association between depression and mortality not significantly change when excluding three articles presenting odds ratios, yet this decreased heterogeneity substantially (HR = 1.49, 95% CI = 1.39–1.61, I-squared = 15.1%). A comparison between type 1 and type 2 diabetes could not be undertaken, as only one study reported on type 1 diabetes specifically. Conclusions: Depression is associated with an almost 1.5-fold increased risk of mortality in people with diabetes. Research should focus on both cardiovascular and non-cardiovascular causes of death associated with depression, and determine the underlying behavioral and physiological mechanisms that may explain this association. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the prospective relationship between blood pressure (BP) and cognitive function across a wide age range. DESIGN: Prospective population-based cohort study. SETTING: The Rotterdam Study and the Leiden 85-plus Study. PARTICIPANTS: Three thousand seventy-eight men and women, initial age 55 to 84 from the Rotterdam Study and 276 men and women, initial age 85, from the Leiden 85-plus Study. MEASUREMENTS: Systolic BP (SBP) and diastolic BP (DBP) were measured at baseline, cognitive function was assessed at the end of follow-up using a dedicated neuropsychological test battery. The association between baseline BP levels and cognitive function later in life was assessed in 10-year age groups in the Rotterdam Study and in 85-year-olds of the Leiden 85-plus Study. RESULTS: In the youngest participants (<65), SBP and DBP were not associated with cognitive function 11 years later. For persons aged 65 to 74, higher baseline SBP and DBP were related to worse cognitive function 11 years later. In contrast, in older age (≥75), higher SBP and DBP seemed to be related to better cognitive function at the end of follow-up. This effect appeared strongest in the highest age group (aged 85). CONCLUSION: High BP was associated with greater risk of cognitive impairment in persons younger than 75 but with better cognitive function in older persons. Age-specific guidelines for BP management are needed, because the current directive that “lower is better” may not apply to BP levels in the very old. [ABSTRACT FROM AUTHOR]

Aims: Social network characteristics may provide a novel non-pharmaceutical target for the prevention of depression. We investigated the temporal association of a broad range of structural and functional social network characteristics with incident depressive symptoms over 5 years of follow-up.Methods: We used data from The Maastricht Study, a population-based prospective cohort study (n=2,465, mean age 59.8±8.1 years, 49.1% women, 11,585 person-years of follow-up). Social network characteristics were assessed through a name generator questionnaire. Clinically relevant depressive symptoms (9-item Patient Health Questionnaire score≥10) were assessed at baseline and annually. We used multivariable logistic and Cox regression analyses, adjusted for sociodemographic, lifestyle and cardiovascular risk factors.Results: In cross-sectional analyses less emotional support for discomfort and with important decisions, and less informational support were associated with prevalent depressive symptoms (OR[95%CI] 1.19 [1.01-1.40]; 1.22 [1.05-1.43], and 1.20 [1.04-1.39], respectively). Every fewer 10% of family members was associated with prevalent depressive symptoms (1.11 [1.01-1.23]). In longitudinal analyses, less emotional support on important decisions was also associated with higher risk of incident depressive symptoms (HR[95%CI] 1.13 [1.03-1.25]). In addition, every fewer 10% of the network that was a family member was associated with a higher hazard of incident depressive symptoms (1.07 [1.01-1.13]).Conclusions: This study shows that less emotional support and fewer family members in the network were associated with higher risk of both prevalent and incident depression. The importance of emotional support and the role that family plays should be considered in treatment and prevention of depression. [ABSTRACT FROM AUTHOR]

• LGI and ED were both associated with incident depressive symptoms. • The association of ED was substantially mediated by LGI. • ED was associated with a persistent course of depressive symptoms. • LGI was not associated with a persistent course of depressive symptoms. • This suggests a temporal, vascular contribution of LGI and ED to the etiology and chronicity of depressive symptoms. Low-grade inflammation (LGI) and endothelial dysfunction (ED) might play a key role in the development of depression. We investigated the associations and mediation of LGI and ED with four-year incidence and course of depressive symptoms (remitted, recurrent or persistent). In this prospective cohort study (mean age 59.6 ± 8.2 years, 48.9% women, 26.6% diabetes by design), Cox and multinomial regression analyses, adjusted for age, sex, educational level and diabetes status were used to investigate the associations of LGI and ED with onset and course of depressive symptoms as assessed by the PHQ-9 questionnaire. During 10,847 person-years of follow-up, 264 participants developed incident depression. Higher levels of LGI (OR [95%CI] per SD 1.32[1.16–1.49], p < 0.001) and ED (1.26[1.11–1.43], p < 0.001) were associated with incident depressive symptoms. In mediation analysis, 60% of the total effect of ED with incident depressive symptoms could be attributed to LGI. 76 out of 2637 participants had a persistent course of depressive symptoms. Higher levels of LGI (1.75[1.40–2.19], p < 0.001) and ED (1.33[1.04–1.71], p = 0.021) were associated with a persistent course of depressive symptoms. Higher ED was more strongly associated with persistent depressive symptoms (1.33[1.04–1.71], p = 0.021), while LGI was associated with remission of depression symptoms. LGI and ED were both associated with incident depressive symptoms, where the latter association was substantially mediated by LGI. ED was further associated with a persistent course of depressive symptoms, while LGI was not. These results suggest a temporal, vascular contribution of both LGI and ED to the etiology and chronicity of depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (CSVD) and neurodegeneration may be involved in the development and persistence of late-life depressive symptoms, but longitudinal evidence is scarce. We investigated the longitudinal associations of markers of CSVD and brain atrophy with incident depressive symptoms and the course of depressive symptoms, above and below 60 years of age.Methods: White matter hyperintensity volumes (WMH), presence of lacunar infarcts and cerebral microbleeds, and white matter, grey matter, and cerebral spinal fluid volumes were assessed at baseline by 3T MRI in The Maastricht Study (mean age 59.5±8.5 years, 49.6% women, n=4,347; 16,535 person-years of follow-up). Clinically relevant depressive symptoms (9-item Patient Health Questionnaire≥10) were assessed at baseline and annually over seven years. We used Cox regression and multinomial logistic regression analyses adjusted for demographic, cardiovascular, and lifestyle risk factors.Results: Above 60 years of age, larger WMH volumes were associated with an increased risk for incident depressive symptoms (HR[95%CI]:1.24[1.04;1.48] per SD) and a persistent course of depressive symptoms (OR:1.44[1.04;2.00] per SD). Total CSVD burden was associated with persistent depressive symptoms irrespective of age (adjusted OR:1.58[1.03;2.43]), while no associations were found for general markers of brain atrophy.Limitationss: Our findings need replication in other large-scale population-based studies.Conclusions: Our findings may suggest a temporal association of larger WMH volume with the incidence and persistence of late-life depression in the general population and may provide a potential target for the prevention of chronic late-life depression. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether higher blood pressure and greater arterial stiffness are associated with the presence of macular cysts and whether this association is already present in the absence of micro‐aneurysms in individuals with and without type 2 diabetes. Methods: Using spectral domain optical coherence tomography (OCT), we performed a macular volume scan in 2647 individuals (mean age 60 ± 8 years, 50% men, 27% type 2 diabetes). The association between macular cysts and 24‐hour systolic and diastolic blood pressure, pulse pressure, mean arterial blood pressure, carotid‐femoral pulse wave velocity and carotid distensibility was assessed by use of logistic regression. Results: Twenty‐four hours systolic blood pressure was associated with the presence of macular cysts [OR = 1.03 (95% CI 1.00–1.05) per 1 mmHg, p = 0.03]. 24 hr pulse pressure [OR = 1.61 (95% CI 1.11–2.34) per 10 mmHg, p = 0.01] and carotid‐femoral pulse wave velocity [OR = 1.16 (95% CI 1.02–1.32) per 1 m/s, p = 0.02] were associated with macular cysts, while carotid distensibility was not [OR = 1.03 (95% CI 0.96–1.11) per 1.0*10−3/kPa, p = 0.45]. Associations were similar in individuals with and without type 2 diabetes and were already present in the absence of micro‐aneurysms. Conclusion: Twenty‐four hours systolic blood pressure, 24 hr pulse pressure and carotid‐femoral pulse wave velocity are associated with the presence of OCT‐detected macular cysts in individuals with and without type 2 diabetes, even in the absence of micro‐aneurysms. Therefore, blood pressure and aortic stiffness are potential factors contributing to macular cysts. [ABSTRACT FROM AUTHOR]

Objective: This study investigated whether arterial stiffening is a determinant of subtle retinal microvascular changes that precede diabetic retinopathy. Research design and methods: This study used cross‐sectional data from the Maastricht Study, a type 2 diabetes‐enriched population‐based cohort study. We used multivariable linear regression analysis to investigate, in individuals without and with type 2 diabetes, the associations of carotid distensibility coefficient and carotid‐femoral pulse wave velocity with retinal microvascular diameters and flicker light‐induced dilation and adjusted for cardiovascular and lifestyle risk factors. Results: The retinal microvascular diameter study population consisted of N = 2434 participants (51.4% men, mean ± SD age 59.8 ± 8.1 years, and 28.1% type 2 diabetes). No measures of arterial stiffness were significantly associated with microvascular diameters. Greater carotid distensibility coefficient (i.e., lower carotid stiffness) was significantly associated with greater retinal arteriolar flicker light‐induced dilation (per standard deviation, standardized beta [95% CI] 0.06 [0.00; 0.12]) and non‐significantly, but directionally similarly, associated with greater retinal venular flicker light‐induced dilation (0.04 [−0.02; 0.10]). Carotid‐femoral pulse wave velocity (i.e., aortic stiffness) was not associated with retinal microvascular flicker light‐induced dilation. The associations between carotid distensibility coefficient and retinal arteriolar and venular flicker light‐induced dilation were two‐ to threefold stronger in individuals with type 2 diabetes than in those without. Conclusion: In this population‐based study greater carotid, but not aortic, stiffness was associated with worse retinal flicker light‐induced dilation and this association was stronger in individuals with type 2 diabetes. Hence, carotid stiffness may be a determinant of retinal microvascular dysfunction. [ABSTRACT FROM AUTHOR]