Associations between air pollution and psychiatric symptoms in the normative aging study

Background: Environmental risk factors for psychiatric health are poorly identified. We examined the association between air pollution and psychiatric symptoms, which are often precursors to the development of psychiatric disorders. Methods: This study included 570 participants in the US Veterans Administration (VA) Normative Aging Study and 1,114 visits (defined as an onsite follow-up at the VA with physical examination and questionnaires) from 2000-2014 with information on the Brief Symptom Inventory (BSI) to assess their psychiatric symptom levels. Differences in the three BSI global measures (Global Severity Index – GSI, Positive Symptom Distress Index – PSDI and Positive Symptom Total - PST) were reported per interquartile (IQR) increase of residential address-specific air pollutants levels (fine particulate matter – PM2.5, ozone - O3, nitrogen dioxide – NO2) at averages of 1 week, 4 weeks, 8 weeks and 1 year prior to the visit using generalized additive mixed effects models. We also evaluated modification by neighborhood factors. Results: On average, among the NAS sample (average age, 72.4 yrs. (standard deviation: 6.7 yrs.)), an IQR increase in 1- and 4- week averages of NO2 before visit was associated with a PSDI T score (indicator for psychiatric symptom intensity) increase of 1.60 (95% Confidence Interval (CI): 0.31, 2.89), 1.71 (95% CI: 0.18, 3.23), respectively. Similarly, for each IQR increase in 1- and 4-week averages of ozone before visit, PSDI T-score increased by 1.66 (95% CI: 0.68, 2.65), and 1.36 (95% CI: 0.23, 2.49), respectively. Stronger associations were observed for ozone and PSDI in low house value and low household income areas. No associations were found for PM2.5. Conclusions: Exposure to gaseous air pollutants was associated with higher intensity of psychiatric symptoms among a cohort of older men, particularly in communities with lower socio-economic or housing conditions.

Does HbA1c Influence the Relationship between Stress and Cognition? Findings from the VA Normative Aging Study

Type 2 diabetes has increased in prevalence globally, with potential adverse effects on cognition. Both high levels of hemoglobin A1c (HbA1c) and stressful life events (SLEs) are associated with impaired cognitive performance, but few studies have examined their synergistic effects. The present study examined direct effects of stress and HbA1c on several cognitive outcomes, and whether HbA1c moderated the relationship between SLEs and cognition. Utilizing a sample of 527 older men from the VA Normative Aging Study (Mage = 74.3, SD = 6.5), stress was inversely related to MMSE, verbal fluency, and pattern recognition; HbA1c was only inversely associated with MMSE. The moderation model was supported only for pattern recognition (𝛽 = 1.64, p < .05), with stress having worse effects in those high in HbA1c. Stratifying analyses by age group (<75, 75+) showed that stress predicted cognition only in the young-old, while HbA1c was inversely related to cognition only in old-old participants. Further, these age-group analyses yielded different effects of demographics on cognition. In the young-old, age was consistently inversely related to all cognitive outcomes, but in the old-old only with MMSE and word list recall. Among the young-old, education was associated with only word list recall but improved performance for most scales among the old-old. Finally, HbA1c intensified the effect of stress moderation on verbal fluency only in old-old (𝛽 = 2.78, p < .05). In summary, stress was more important for cognition in the young-old, while education and health status were more important in the old-old.

Metabolomic differences in lung function metrics: evidence from two cohorts

RationaleThe biochemical mechanisms underlying lung function are incompletely understood.ObjectivesTo identify and validate the plasma metabolome of lung function using two independent adult cohorts: discovery—the European Prospective Investigation into Cancer–Norfolk (EPIC-Norfolk, n=10 460) and validation—the VA Normative Aging Study (NAS) metabolomic cohort (n=437).MethodsWe ran linear regression models for 693 metabolites to identify associations with forced expiratory volume in one second (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC), in EPIC-Norfolk then validated significant findings in NAS. Significance in EPIC-Norfolk was denoted using an effective number of tests threshold of 95%; a metabolite was considered validated in NAS if the direction of effect was consistent and p<0.05.Measurements and main resultsOf 156 metabolites that associated with FEV1 in EPIC-Norfolk after adjustment for age, sex, body mass index, height, smoking and asthma status, 34 (21.8%) validated in NAS, including several metabolites involved in oxidative stress. When restricting the discovery sample to men only, a similar percentage, 18 of 79 significant metabolites (22.8%) were validated. A smaller number of metabolites were validated for FEV1/FVC, 6 of 65 (9.2%) when including all EPIC-Norfolk as the discovery population, and 2 of 34 (5.9%) when restricting to men. These metabolites were characterised by involvement in respiratory track secretants. Interestingly, no metabolites were validated for both FEV1 and FEV1/FVC.ConclusionsThe validation of metabolites associated with respiratory function can help to better understand mechanisms of lung health and may assist the development of biomarkers.

A Mixed-Effects Model of Associations between Interleukin-6 and Hippocampal Volume

Previous studies report hippocampal volume loss can help predict conversion from normative aging to mild cognitive impairment (MCI) to dementia. Additionally, a growing literature indicates that stress-related allostatic load may increase disease vulnerability. The current study examined the relationship between stress related cytokines (i.e., interleukin-6 - IL-6), cognition as measured by Mini Mental Status scores (MMSE), and hippocampal volume. Mixed-models were employed to examine both within (across time) and between subjects effects of IL-6 and hippocampal volume on MMSE score among 566 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The within subjects analysis found left hippocampal volume significantly (p= .009) predicted MMSE score. Between subjects analysis found the effect of IL-6 on MMSE was moderated by right hippocampal volume (p = .001). These results replicate previous findings and also extend prior work demonstrating stress-related cytokines may play a role in Alzheimer’s disease (AD) progression.

The Rhesus Macaque as a Translational Model for Neurodegeneration and Alzheimer’s Disease

A major obstacle to progress in understanding the etiology of normative and pathological human brain aging is the availability of suitable animal models for experimentation. The present article will highlight our current knowledge regarding human brain aging and neurodegeneration, specifically in the context of Alzheimer’s disease (AD). Additionally, it will examine the use of the rhesus macaque monkey as a pragmatic translational animal model in which to study underlying causal mechanisms. Specifically, the discussion will focus on behavioral and protein-level brain changes that occur within the central nervous system (CNS) of aged monkeys, and compare them to the changes observed in humans during clinically normative aging and in AD.