Aim: To investigate whether there is a bidirectional longitudinal association of depression with HbA_1c.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 HbA_1c in adults. We assessed study quality with the Newcastle‐Ottawa‐Scale. Pooled effect estimates were reported as partial correlation coefficients (r_p) 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 HbA_1c 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 HbA_1c (partial r = 0.07; [95% CI 0.03, 0.12]; I²38%). Higher baseline HbA_1c 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 HbA_1c. 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 HbA_1c levels could be targeted concurrently in the prevention and treatment of diabetes and depression.Registration: PROSPERO ID CRD42019147551.

Aims/hypothesis: Depression is twice as common in individuals with type 2 diabetes as in the general population. However, it remains unclear whether hyperglycaemia and insulin resistance are directly involved in the aetiology of depression. Therefore, we investigated the association of markers of hyperglycaemia and insulin resistance, measured as continuous variables, with incident depressive symptoms over 4 years of follow-up. Methods: We used data from the longitudinal population-based Maastricht Study (n = 2848; mean age 59.9 ± 8.1 years, 48.8% women, 265 incident depression cases, 10,932 person-years of follow-up). We assessed hyperglycaemia by fasting and 2 h post-load OGTT glucose levels, HbA_1c and skin autofluorescence (reflecting AGEs) at baseline. We used the Matsuda insulin sensitivity index and HOMA-IR to calculate insulin resistance at baseline. Depressive symptoms (nine-item Patient Health Questionnaire score ≥10) were assessed at baseline and annually over 4 years. We used Cox regression analyses, and adjusted for demographic, cardiovascular and lifestyle risk factors. Results: Fasting plasma glucose, 2 h post-load glucose and HbA_1c levels were associated with an increased risk for incident depressive symptoms after full adjustment (HR 1.20 [95% CI 1.08, 1.33]; HR 1.25 [1.08, 1.44]; and HR 1.22 [1.09, 1.37] per SD, respectively), while skin autofluorescence, insulin sensitivity index and HOMA-IR were not (HR 0.99 [0.86, 1.13]; HR 1.02 [0.85, 1.25]; and HR 0.93 [0.81, 1.08], per SD, respectively). Conclusions/interpretation: The observed temporal association between hyperglycaemia and incident depressive symptoms in this study supports the presence of a mechanistic link between hyperglycaemia and the development of depressive symptoms.

Both sex/gender and socioeconomic differences have been reported in the prevalence of modifiable risk factors for dementia. However, it remains unclear whether the associations between modifiable risk factors for dementia and incident dementia differ by sex/gender or socioeconomic status. This study aimed to investigate sex/gender and socioeconomic differences in the associations of modifiable risk factors with incident dementia using a life-course perspective. We used data from the English Longitudinal Study of Ageing (2008/2009 to 2018/2019). A total of 8,941 individuals were included [mean (standard deviation) age, 66.1 ± 9.8 years; 4,935 (55.2%) were women]. No overall sex/gender difference in dementia risk was found. Dementia risk was higher among those who experienced childhood deprivation [hazard ratio (HR) = 1.51 (1.17; 1.96)], lower occupational attainment [HR low versus high = 1.60 (1.23; 2.09) and HR medium versus high = 1.53 (1.15; 2.06)], and low wealth [HR low versus high = 1.63 (1.26; 2.12)]. Though different associations were found among the subgroups, there might be a sex/gender difference in dementia risk only for low cognitive activity, suggesting a higher risk for women [HR = 2.61 (1.89; 3.60)] compared to men [HR = 1.73 (1.20; 2.49)]. No consistent socioeconomic differences in modifiable dementia risk were found. A population-based approach that tackles inequalities in dementia risk profiles directly may be more effective than individual approaches in dementia prevention.

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.

The etiology of late-life depression (LLD) is still poorly understood. Microvascular dysfunction (MVD) has been suggested to play a role in the etiology of LLD, but direct evidence of this association is scarce. The aim of this study was to investigate whether direct and indirect markers of early microvascular dysfunction are associated with prevalent and incident LLD in the population-based Maastricht Study cohort. We measured microvascular dysfunction at baseline by use of flicker light-induced retinal vessel dilation response (Dynamic Vessel Analyzer), heat-induced skin hyperemic response (laser- Doppler flowmetry), and plasma markers of endothelial dysfunction (endothelial dysfunction; sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [Von Willebrand Factor]). Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) at baseline and annually over 4 years of follow-up (n=3029; mean age 59.6±8.2 years, 49.5% were women, n=132 and n=251 with prevalent and incident depressive symptoms [PHQ-9≥10]). We used logistic, negative binominal and Cox regression analyses, and adjusted for demographic, cardiovascular, and lifestyle factors. Retinal venular dilatation and plasma markers of endothelial dysfunction were associated with the more prevalent depressive symptoms after full adjustment (PHQ-9 score, RR, 1.05 [1.00–1.11] and RR 1.06 [1.01–1.11], respectively). Retinal venular dilatation was also associated with prevalent depressive symptoms (PHQ-9≥10; odds ratio, 1.42 [1.09–1.84]), after full adjustment. Retinal arteriolar dilatation and plasma markers of endothelial dysfunction were associated with incident depressive symptoms (PHQ-9≥10; HR, 1.23 [1.04–1.46] and HR, 1.19 [1.05–1.35]), after full adjustment. These findings support the concept that microvascular dysfunction in the retina, and plasma markers of endothelial dysfunction is involved in the etiology of LLD and might help in finding additional targets for the prevention and treatment of LLD.

Breakfast is often considered the most important meal of the day and can benefit adolescent health in several ways. The aims of the present study were (1) to identify adolescents’ socio-demographic (sex, family affluence and family structure) determinants of daily breakfast consumption (DBC) and (2) to describe trends in DBC among adolescents across 23 countries. Cross-sectional surveys of nationally representative samples of adolescents (aged 11, 13, and 15 years) (n = 589,737) participating in the Health Behaviour in School-aged Children (HBSC) survey from 2002 to 2018 were used. Multilevel logistic regression analyses modeled DBC over time, adjusted for family affluence, family structure and year of survey. Four countries showed an increased trend in DBC (the Netherlands, Macedonia, Slovenia, and England). A significant decrease in DBC was observed in 15 countries (Belgium-Fr, France, Germany, Croatia, Portugal, Spain, Hungary, Poland, Russian Federation, Ukraine, Denmark, Finland, Latvia, Lithuania and Sweden). In 4 countries no significant change was observed (Czech Republic, Scotland, Ireland and Norway). In most of the countries (n = 19), DBC was higher among the adolescents from high-affluence homes. In all the countries analysed, the adolescents living in two-parent households report higher DBC use than those in single-parent households. More than half of the countries showed a decrease in DBC. There is a need to implement key interventions by developing different strategies (education, incorporating educational curriculum and counselling programmes) to increase DBC. Comparing DBC patterns across HBSC countries is important for understanding regional and global trends, monitoring strategies, and developing health promotion programmes.