Bonnie Au

C-reactive protein, depressive symptoms, and risk of diabetes: Results from the English Longitudinal Study of Ageing (ELSA)

OBJECTIVES Raised levels of C-reactive protein (CRP), an inflammatory biomarker, and depressive symptoms are both independently linked to risk of diabetes. The purpose of this study was to assess the joint association of CRP and depressive symptomatology with diabetes incidence in a representative sample of English people ≥50 years old. METHOD Data were from the English Longitudinal Study of Ageing, a prospective study of community-dwelling older adults. The sample was comprised of 4955 participants without self-reported doctor-diagnosed diabetes at baseline. High CRP level was dichotomized as >3 mg/L. Elevated depressive symptomatology was defined as ≥4 using the 8-item Center for Epidemiologic Studies Depression Scale. Incident diabetes was determined based on newly self-reported doctor-diagnosed diabetes. Cox proportional hazard regressions were used to examine the association between CRP and depressive symptoms with incidence of type 2 diabetes. RESULTS During approximately 63.2 months of follow-up, 194 participants reported diabetes diagnosis. After adjustment for socio-demographics, lifestyle behaviors, clinical factors, and BMI, the hazard ratio for diabetes was 1.63 (95% CI 0.88-3.01) for people with elevated depressive symptoms only, 1.43 (95% CI 0.99-2.07) for people with high CRP only, and 2.03 (95% CI 1.14-3.61) for people with both high CRP and elevated depressive symptoms. CONCLUSION The presence of both high CRP levels and elevated depressive symptoms was associated with risk of diabetes. Further investigation into this relationship could aid in understanding the mechanisms underlying inflammation, depression, and diabetes.

The longitudinal associations between C‐reactive protein and depressive symptoms: evidence from the English Longitudinal Study of Ageing (ELSA)

The inflammatory marker C‐reactive protein (CRP) is associated with depression. We examined the directional relations between CRP and symptoms of depression among older adults.

The association between C-reactive protein, Interleukin-6 and depression among older adults in the community: a systematic review and meta-analysis

&NA; Previous research indicates there may be an association between inflammation and depression in older adults but results are inconsistent. Therefore, the aim of this review was to determine the cross‐sectional and longitudinal associations of two inflammatory markers C‐reactive protein (CRP) and Interleukin‐6 (IL‐6) with depression in older adults. We searched five databases for cross‐sectional and longitudinal studies reporting an association between CRP or IL‐6 with depression among adults sampled from the community aged 50 or older. We found 32 studies (23 cross‐sectional, 7 longitudinal, and 2 assessing both cross‐sectional and longitudinal associations) that met eligibility criteria. These studies were entered into a random‐effects meta‐analysis to determine the cross‐sectional association and longitudinal direction of association between both IL‐6 and CRP with depression. Results indicated a cross‐sectional and longitudinal association between both CRP and IL‐6 with depression in older adults, with inflammation leading to depression in longitudinal studies rather than depression to inflammation. However, there was notable heterogeneity between studies as results differed based on adjusting for confounders and on how inflammation and depression were measured. These sources of heterogeneity could explain differences in study results. HighlightsThis is the first meta‐analysis to explicitly examine the association between inflammation and depression in older adults.Results indicate a cross‐sectional association between inflammation and depression in older adults.Results from longitudinal analyses indicate that it is inflammation that leads to depression rather than depression to inflammation.Sources of study heterogeneity that could explain differences in findings were identified.

Sex differences in the prevalence and incidence of mild cognitive impairment: A meta-analysis

OBJECTIVE More women have Alzheimers disease (AD) than men. Understanding sex differences in mild cognitive impairment (MCI) may further knowledge of AD etiology and prevention. We conducted a meta-analysis to examine sex differences in the prevalence and incidence of MCI, which included amnestic and non-amnestic subtypes. METHOD Systematic searches were performed in July 2015 using MEDLINE/PubMed, Scopus, and PsycINFO for population-or community-based studies with MCI data for men and women. Random-effects model were used. RESULTS Fifty-six studies were included. There were no statistically significant sex differences in prevalence or incidence of amnestic MCI. There was a significantly higher prevalence (p=0.038), but not incidence, of non-amnestic MCI among women. There were no sex differences in studies that combined both subtypes of MCI. CONCLUSION The only statistically significant finding emerging from this study was that women have a higher prevalence of non-amnestic MCI. To better understand sex differences in the preclinical stages of dementia, studies must better characterize the etiology of the cognitive impairment.

Meta-analysis of Driving Cessation and Dementia: Does Sex Matter?

Objectives The number of drivers with dementia is expected to increase over the coming decades. Because dementia is associated with a higher risk of crashes, driving cessation becomes inevitable as the disease progresses, but many people with dementia resist stopping to drive. This meta-analysis examines whether there are sex differences in the prevalence and incidence of driving cessation among drivers with dementia and compares the pattern of sex differences in drivers with dementia to those without dementia. Method MEDLINE, PsycINFO, Scopus, and CINAHL were searched in July 2015 for observational studies of sex differences in driving cessation. Meta-analyses were performed using a random-effects model. Results Twenty studies provided data on sex differences in driving cessation in older adults with or without dementia. Driving cessation was significantly more prevalent in women with dementia than men (odds ratio [OR] = 2.11, 95% confidence interval [CI] = 1.50-2.98), and the same pattern was found in women without dementia (OR = 2.74, 95% CI = 1.85-4.06). Discussion Our findings suggest that the patterns of driving cessation differ between men and women with dementia, and this may have implications for sex-specific approaches designed to support drivers with dementia both before and after driving cessation.

Sex differences in the prevalence of genetic mutations in FTD and ALS: A meta-analysis.

Objective: To conduct a meta-analysis that investigates sex differences in the prevalence of mutations in the 3 most common genes that cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)—chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT)—in patients clinically diagnosed with these conditions. Methods: MEDLINE, EMBASE, and PsycINFO databases were searched (inception to June 30, 2016). Studies of patients with FTD or ALS that reported the number of men and women with and without mutations of interest were selected. Female to male pooled risk ratios (RR) and 95% confidence intervals (CI) for each mutation were calculated using random-effects models. Results: Thirty-two articles reporting 12,784 patients with ALS (including 1,244 C9orf72 mutation carriers) revealed a higher prevalence of female patients with C9orf72-related ALS (RR 1.16, 95% CI 1.04–1.29). Twenty-three articles reporting 5,320 patients with FTD (including 488 C9orf72 mutation carriers) revealed no sex differences in C9orf72-related FTD (RR 0.95, 95% CI 0.81–1.12). Thirty-six articles reporting 3,857 patients with FTD (including 369 GRN mutation carriers) revealed a higher prevalence of female patients with GRN-related FTD (RR 1.33, 95% CI 1.09–1.62). Finally, 21 articles reporting 2,377 patients with FTD (including 215 MAPT mutation carriers) revealed no sex difference in MAPT-related FTD (RR 1.21, 95% CI 0.95–1.55). Conclusions: Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN-mediated phenotypic expression.

Depressive symptoms, prediabetes, and incident diabetes in older English adults.

The objective of this study was to assess the risk of diabetes in older adults with elevated depressive symptoms, prediabetes, or both.

Risk of diabetes in older adults with co-occurring depressive symptoms and cardiometabolic abnormalities: Prospective analysis from the English longitudinal study of ageing.

High depressive symptoms and cardiometabolic abnormalities are independently associated with an increased risk of diabetes. The purpose of this study was to assess the association of co-occurring depressive symptoms and cardiometabolic abnormalities on risk of diabetes in a representative sample of the English population aged 50 years and older. Data were from the English Longitudinal Study of Ageing. The sample comprised of 4454 participants without diabetes at baseline. High depressive symptoms were based on a score of 4 or more on the 8-item binary Centre for Epidemiologic Studies–Depression scale. Cardiometabolic abnormalities were defined as 3 or more cardiometabolic risk factors (hypertension, impaired glycemic control, systemic inflammation, low high-density lipoprotein cholesterol, high triglycerides, and central obesity). Cox proportional hazards regressions assessed the association between co-occurring depressive symptoms and cardiometabolic abnormalities with incidence of diabetes. Multiple imputation by chained equations was performed to account for missing data. Covariates included age, sex, education, income, smoking status, physical activity, alcohol consumption, and cardiovascular comorbidity. The follow-up period consisted of 106 months, during which 193 participants reported a diagnosis of diabetes. Diabetes incidence rates were compared across the following four groups: 1) no or low depressive symptoms and no cardiometabolic abnormalities (reference group, n = 2717); 2) high depressive symptoms only (n = 338); 3) cardiometabolic abnormalities only (n = 1180); and 4) high depressive symptoms and cardiometabolic abnormalities (n = 219). Compared to the reference group, the hazard ratio for diabetes was 1.29 (95% CI 0.63, 2.64) for those with high depressive symptoms only, 3.88 (95% CI 2.77, 5.44) for those with cardiometabolic abnormalities only, and 5.56 (95% CI 3.45, 8.94) for those with both high depressive symptoms and cardiometabolic abnormalities, after adjusting for socio-demographic, lifestyle and clinical variables. These findings suggest that those with high depressive symptoms and cardiometabolic abnormalities are at a particularly increased risk of type 2 diabetes.

Evaluating lifestyle and health-related characteristics of older adults with co-occurring depressive symptoms and cardiometabolic abnormalities.

Comorbid depression and cardiometabolic abnormalities might represent an important subgroup of depression. The aim of the present study was to evaluate lifestyle and health‐related characteristics of individuals with both depressive symptoms and cardiometabolic abnormalities.

Response to Kawada: C-reactive protein, depressive symptoms and incident diabetes mellitus with special emphasis on physical activity.

Au et al. conducted a 6-year follow-up study to know the effect of serum C-reactive protein and depressive symptom on an incident of diabetes mellitus, and concluded that a combination of these two factors contributed significantly to the incident of diabetes mellitus [1]. The authors selected a physical activity as one of the confounders for the adjustment in their models 3 to 5, and speculated the possible mechanism for the association. I have some concerns on their study. There are several reports of physical activity handling and inactive behavior independently for the risk assessment of diabetes mellitus. Wilmot et al. conducted a systematic review with meta-analysis on the association between sedentary time and diabetes mellitus [2]. Pooled RR (95% confidence interval) of sedentary time by TV viewing for diabetes mellitus from 10 studies was 2.12 (1.61–2.78), and predictive effect by considering heterogeneity in meta-analysis also became significant. Among 10 studies, 7 studies used physical activity as a confounder, and the association between sedentary time and risk of diabetes mellitus was evaluated with adjustment of physical activity. Although Au et al. quoted two references on risk factor of diabetes mellitus [3,4], these refer to the positive effect of reducing systemic inflammation and mental disorders, and no adverse effect of sedentary lifestyle on health. About the combined effect of physical activity and sedentary behavior, Smith and Hamer conducted a 2-year follow-up study to know the effect of physical inactivity and subsequent incident of diabetesmellitus in the elderly [5]. Odds ratio (95% confidence interval) of inactive physical activity plus high television viewing was 1.94 (1.02–3.68) against physically active plus low television viewing, and the author concluded that the incidence of diabetes in the elderly was associated with a physically inactive life with high television viewing time. I suspect that the level of physical activity should not be handled binary but bidirectionally. Wiseman et al. conducted over a 5-year follow-up study to know the effect of change in TV viewing time on the levels of C-reactive protein and insulin resistance [6]. Increasing sedentary behavior over time significantly related to the insulin resistance, and no significancewas observed in Creactive protein. In contrast, Jarvie et al. conducted a 5-year follow-up study to know the effect of physical activity on the levels of inflammation and insulin resistance in outpatients with coronary heart disease [7], and CRP, interleukin-6, glucose and fibrinogen decreased with a stable high activity during the follow-up period by adjusting confounders. Combination of depressive symptom and C-reactive protein has a possibility of an emerging stable study outcome on the association between TV viewing time and C-reactive protein. There is no clear pathway for understanding the risk of diabetes, and further studies are required to confirm the mechanism on the association or causality. Journal of Psychosomatic Research 78 (2015) 407–408