Introduction:The locus coeruleus (LC) undergoes extensive neurodegeneration in early Alzheimer's disease (AD). The LC is implicated in regulating the sleep-wake cycle, modulating cognitive function, and AD progression.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Evidence strongly suggests that being overweight or obese at midlife confers significantly higher risk for Alzheimer's disease (AD) and greater brain atrophy later in life. Few studies, however, examine associations between longitudinal changes in adiposity during early adulthood and later brain morphometry. Measures of body mass index (BMI) were collected in 373 men from the Vietnam Era Twin Study of Aging at average age 20, 40, 56, and 62 years, yielding two BMI trajectories. We then examined associations between BMI phenotypes (trajectories, continuous BMI, obese/non-obese), cortical thickness, and white matter measures from structural magnetic resonance imaging at mean age 62 (Time 4, range 56-66). Those on the obesity trajectory (N=171) had thinner cortex compared with the normal/lean trajectory (N=202) in multiple frontal and temporal lobe bilateral regions of interest: superior, inferior, middle temporal gyri, temporal pole, fusiform gyrus, banks of the superior temporal sulcus, frontal pole, pars triangularis, caudal and rostral middle frontal gyri (all p<0.05 FDR corrected). Frontal lobe thinness tended to occur mainly in the right hemisphere. Results were similar for obese versus non-obese adults at age 62.

Background Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems. Methods The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)]. Results Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60). Conclusions A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.

Background and aims Smoking is associated with increased risk for brain aging/atrophy and dementia. Few studies have examined early associations with brain aging. This study aimed to measure whether adult men with a history of heavier smoking in early mid‐life would have older than predicted brain age 16–28 years later. Design Prospective cohort observational study, utilizing smoking pack years data from average age 40 (early mid‐life) predicting predicted brain age difference scores (PBAD) at average ages 56, 62 (later mid‐life) and 68 years (early old age). Early mid‐life alcohol use was also evaluated. Setting Population‐based United States sample. Participants/cases Participants were male twins of predominantly European ancestry who served in the United States military between 1965 and 1975. Structural magnetic resonance imaging (MRI) began at average age 56. Subsequent study waves included most baseline participants; attrition replacement subjects were added at later waves. Measurements Self‐reported smoking information was used to calculate pack years smoked at ages 40, 56, 62, and 68. MRIs were processed with the Brain‐Age Regression Analysis and Computation Utility software (BARACUS) program to create PBAD scores (chronological age—predicted brain age) acquired at average ages 56 (n = 493; 2002–08), 62 (n = 408; 2009–14) and 68 (n = 499; 2016–19). Findings In structural equation modeling, age 40 pack years predicted more advanced age 56 PBAD [β = −0.144, P = 0.012, 95% confidence interval (CI) = –0.257, −0.032]. Age 40 pack years did not additionally predict PBAD at later ages. Age 40 alcohol consumption, but not a smoking × alcohol interaction, predicted more advanced PBAD at age 56 (β = −0.166, P = 0.001, 95% CI = –0.261, –0.070) with additional influences at age 62 (β = −0.115, P = 0.005, 95% CI = –0.195, –0.036). Age 40 alcohol did not predict age 68 PBAD. Within‐twin‐pair analyses suggested some genetic mechanism partially underlying effects of alcohol, but not smoking, on PBAD. Conclusions Heavier smoking and alcohol consumption by age 40 appears to predict advanced brain aging by age 56 in men.