Lifetime posttraumatic stress disorder as a predictor of mortality: a systematic review and meta-analysis.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) could potentially increase the risk of mortality, and there is a need for a meta-analysis to quantify this association. This study aims to determine the extent to which PTSD is a predictor of mortality. METHODS: EMBASE, MEDLINE, and PsycINFO were searched systematically on 12th February 2020, with updated searches conducted in July 2021, and December 2022 (PROSPERO CRD42019142971). Studies involving community-dwelling participants with a diagnosis of PTSD or PTSD symptoms, and a comparator group of individuals without PTSD, and which assessed mortality risk, were included. A random-effects meta-analysis was conducted on studies reporting Odds Ratio (OR), Hazard Ratio (HR), and Risk Ratio (RR), and subgroup analysis was also performed by age, sex, type of trauma experienced, PTSD diagnosis, and cause of death. RESULTS: A total of 30 eligible studies of mostly good methodological quality were identified, with a total of more than 2.1 million participants with PTSD. The majority of studies involved male-dominated, veteran populations. PTSD was associated with a 47% (95% CI: 1.06-2.04) greater risk of mortality across six studies that reported OR/RR, and a 32% increased risk across 18 studies which reported time to death (HR: 1.32, 95% CI: 1.10-1.59). There was very high study heterogeneity (I2 > 94%) and this was not explained by the prespecified subgroup analysis. CONCLUSION: PTSD is associated with increased mortality risk, however further research is required amongst civilians, involving women, and in individuals from underdeveloped countries.

Factors associated with brain ageing - a systematic review.

BACKGROUND: Brain age is a biomarker that predicts chronological age using neuroimaging features. Deviations of this predicted age from chronological age is considered a sign of age-related brain changes, or commonly referred to as brain ageing. The aim of this systematic review is to identify and synthesize the evidence for an association between lifestyle, health factors and diseases in adult populations, with brain ageing. METHODS: This systematic review was undertaken in accordance with the PRISMA guidelines. A systematic search of Embase and Medline was conducted to identify relevant articles using search terms relating to the prediction of age from neuroimaging data or brain ageing. The tables of two recent review papers on brain ageing were also examined to identify additional articles. Studies were limited to adult humans (aged 18 years and above), from clinical or general populations. Exposures and study design of all types were also considered eligible. RESULTS: A systematic search identified 52 studies, which examined brain ageing in clinical and community dwelling adults (mean age between 21 to 78 years, ~ 37% were female). Most research came from studies of individuals diagnosed with schizophrenia or Alzheimer's disease, or healthy populations that were assessed cognitively. From these studies, psychiatric and neurologic diseases were most commonly associated with accelerated brain ageing, though not all studies drew the same conclusions. Evidence for all other exposures is nascent, and relatively inconsistent. Heterogenous methodologies, or methods of outcome ascertainment, were partly accountable. CONCLUSION: This systematic review summarised the current evidence for an association between genetic, lifestyle, health, or diseases and brain ageing. Overall there is good evidence to suggest schizophrenia and Alzheimer's disease are associated with accelerated brain ageing. Evidence for all other exposures was mixed or limited. This was mostly due to a lack of independent replication, and inconsistency across studies that were primarily cross sectional in nature. Future research efforts should focus on replicating current findings, using prospective datasets. TRIAL REGISTRATION: A copy of the review protocol can be accessed through PROSPERO, registration number CRD42020142817 .

Adverse events in older adults and the risk of dementia and cognitive decline.

Background: Increasing evidence suggests that stress could be a risk factor for dementia but this might vary by gender. This study investigated whether adverse life events were associated with cognitive decline and dementia in later-life, separately in men and women. Methods: Participants were 12,789 community-dwelling Australians aged ≥ 70 years. Ten common adverse events in later-life were self-reported. Cognitive decline was defined as a 1.5 SD decline from participants' baseline score in tests of global cognition, psychomotor speed, episodic memory, and executive functioning, which were assessed regularly over a maximum of 10.3 years. Dementia was diagnosed according to DSM-IV criteria. Results: An increased risk of dementia was observed in participants who experienced the death of a spouse/partner (HR: 1.72, 95% CI: 1.17 - 2.52) and for individuals who experienced major financial problems (HR: 1.53, 95% CI: 1.05 - 2.23). The latter also increased the risk of cognitive decline in men specifically (HR: 1.43, 95% CI: 1.10 - 1.86). In contrast, some events for women were associated with a reduced risk of dementia (e.g. close family or friends lost their job/retired (HR: 0.62, 95% CI: 0.40-0.95)). Limitations: Events including major money problems may result from prodromal dementia symptoms, thus reverse causation needs to be considered. Conclusions: Adverse life events may influence dementia risk in older adults, but associations vary depending on the nature of the event, and across genders. These findings support the need for early interventions in older people who have experienced adversities, particularly for the death of a loved one.

The association between adverse events in later life and mortality in older individuals.

Background: Stress can have adverse impacts on health, particularly when it is chronic or resulting from major adverse events. Our study investigated whether relatively common adverse events in older individuals were associated with an increased risk of death, as well as cause-specific death and potential gender differences. Methods: Participants were 12896 community-dwelling Australians aged ≥70 years at enrolment into the ASPREE (ASPirin in Reducing Events in the Elderly) study and without known life-limiting disease. A questionnaire administered in the year after enrolment, collected information on ten adverse events experienced in the past year. Mortality status was verified by multiple sources including health records and the National Death Index across a maximum of 10 years. Underlying causes of death were determined using clinical information by two adjudicators. Cox-proportional hazards regression models were used to estimate mortality risk. Results: Two of the ten adverse events were associated with an increased risk of mortality in fully adjusted models. A 69% increased risk of mortality was observed in participants who reported their spouse/partner had recently died (95% CI: 1.19-2.39, P < 0.01). Cancer-related but not cardiovascular deaths also increased. Participants with a seriously ill spouse/partner also had a 23% increased risk of mortality (HR: 1.23, 95% CI: 1.02-1.48, P = 0.03). There was a tendency for these associations to be stronger among men than women. Limitations: Perceived stress and cortisol were not measured, thus limiting our understanding of the psychological and physiological impacts of adverse events. Conclusions: Experiencing adverse events in later-life, especially the death of a spouse/partner, may be a risk factor for earlier mortality. These findings may increase public health awareness and better inform initiatives for particular groups, including bereaved men.

The association between adverse childhood events and later-life cognitive function and dementia risk.

BACKGROUND: Considerable work exists in the literature to describe the negative impacts of early-life stress exposures on health in adulthood. This study investigated whether the accumulation of adverse childhood events is associated with later-life cognitive function and incident dementia. METHODS: Participants were 1562 community-dwelling older adults, who were enrolled in the ESPRIT cohort in France. Adverse childhood events were measured using a modified version of the Childhood Trauma Questionnaire. Cognition was measured using tests of global cognition, visual memory, verbal fluency, psychomotor speed and executive function. Fourteen-year incident dementia was diagnosed using DSM-IV criteria. RESULTS: In comparison to participants with two or less adverse childhood events, increased risk of poor psychomotor speed at baseline was observed in individuals with multiple adverse childhood events (3-4 events OR: 1.39, 95% CI: 1.00-1.93); ≥5 events (OR: 1.52, 95% CI: 1.07-2.17), particularly in women but not in men. Worse verbal fluency was also observed in individuals who experienced between three and four adverse childhood events (OR: 1.34, 95% CI: 1.00-1.78). Amongst the individual factors investigated, early-life abuse/maltreatment (OR: 1.47, 95% CI: 1.02-2.14) and poverty/financial difficulties (OR: 1.53, 95% CI: 1.12-2.08) was associated with worse psychomotor speed. No associations were observed with incident dementia. LIMITATIONS: Participants most at risk (those with baseline dementia) were excluded. CONCLUSION: Multiple adverse childhood events are associated with worse psychomotor speed, and verbal fluency in later-life, however further research is needed to determine the mechanisms underlying this association and whether it results from unmeasured confounding, including social disadvantage.

The long-term consequences of trauma and posttraumatic stress disorder symptoms on later life cognitive function and dementia risk.

Stress may be a risk factor for dementia, however it is unknown whether post-traumatic stress disorder (PTSD) symptoms are associated with incident dementia in community-dwelling older individuals. The aim was to determine whether lifetime major trauma with and without re-experiencing of PTSD symptoms is associated with later-life cognition and dementia risk. Participants were 1,700 community-dwelling older adults (65+) in the longitudinal ESPRIT study followed over 14 years. Lifetime major traumatic exposure and PTSD were assessed using Watson's PTSD Inventory. Cognitive tests assessed global cognition, visual memory, verbal fluency, psychomotor speed and executive function. Incident dementia was diagnosed according to DSM-IV criteria. Lifetime major trauma (versus no trauma) was associated with significantly increased executive function and increased global function in men, however women with lifetime trauma and re-experiencing symptoms had a significantly increased risk of low global cognition. Over 14 years, lifetime trauma without re-experiencing symptoms was associated with a significantly decreased risk of incident dementia, particularly for women. Lifetime major trauma without re-experiencing symptoms (but not with) may be protective for later life cognitive function. However, the mechanisms and moderating factors underlying these association requires further investigation.