No abstract

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer's disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., withingroup meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a transdiagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.

Background Several risk factors contribute to dementia, but the role of obesity remains unclear. This study investigated whether increased body weight or central obesity were associated with a higher risk of developing dementia in a representative sample of older English adults. Methods We studied 6582 participants from the English Longitudinal Study of Ageing (ELSA) who were aged ≥50 years and were dementia-free at baseline, that being either wave 1 (2002–2003) for study members who started at wave 1, or at either wave 2 (2004–2005) or 4 (2008–2009) for those who began the study as refreshment samples. Body mass index (BMI) was measured at baseline and categorized into normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥30 kg/m2). Central obesity was defined as a waist circumference (WC) >88 cm for women and >102 cm for men. Cumulative incidence of dementia was ascertained based on physician-diagnosed dementia, an overall score >3.38 on the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Hospital Episodes Statistics (HES) data at every ELSA wave from baseline until wave 8 (2016–2017). Cox proportional hazards models were used to assess the association between baseline BMI levels or abdominal obesity in relation to dementia incidence during the mean follow-up period of 11 years. Results From the overall sample, 6.9% (n = 453) of participants developed dementia during the follow-up period of maximum 15 years (2002–2017). Compared with participants with normal weight, those who were obese at baseline had an elevated risk of dementia incidence [hazard ratio (HR) = 1.34, 95% confidence interval (CI) 1.07–1.61] independent of sex, baseline age, apolipoprotein E-ε4 (APOE-ε4), education, physical activity, smoking and marital status. The relationship was slightly accentuated after additionally controlling for hypertension and diabetes (HR = 1.31, 95% CI 1.03–1.59). Women with central obesity had a 39% greater risk of dementia compared with non-central obese women (HR = 1.39, 95% CI 1.12–1.66). When compared with a normal BMI and WC group, the obese and high WC group had 28% (HR = 1.28, 95% CI 1.03–1.53) higher risk of dementia. Conclusions Our results suggest that having an increased body weight or abdominal obesity are associated with increased dementia incidence. These findings have significant implications for dementia prevention and overall public health.