Midlife psychological stress and risk of dementia: A 35-year longitudinal population study

Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, 43141 Mölndal, Sweden.
Brain (Impact Factor: 9.2). 08/2010; 133(Pt 8):2217-24. DOI: 10.1093/brain/awq116
Source: PubMed


The number of people with dementia has increased dramatically with global ageing. Nevertheless, the pathogeneses of these diseases are not sufficiently understood. The present study aims to analyse the relationship between psychological stress in midlife and the development of dementia in late-life. A representative sample of females (n = 1462) aged 38-60 years were examined in 1968-69 and re-examined in 1974-75, 1980-81, 1992-93 and 2000-03. Psychological stress was rated according to a standardized question in 1968, 1974 and 1980. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders criteria based on information from neuropsychiatric examinations, informant interviews, hospital records and registry data. During the 35-year follow-up, 161 females developed dementia (105 Alzheimer's disease, 40 vascular dementia and 16 other dementias). We found that the risk of dementia (hazard ratios, 95% confidence intervals) was increased in females reporting frequent/constant stress in 1968 (1.60, 1.10-2.34), in 1974 (1.65, 1.12-2.41) and in 1980 (1.60, 1.01-2.52). Frequent/constant stress reported in 1968 and 1974 was associated with Alzheimer's disease. Reporting stress at one, two or three examinations was related to a sequentially higher dementia risk. Compared to females reporting no stress, hazard ratios (95% confidence intervals) for incident dementia were 1.10 (0.71-1.71) for females reporting frequent/constant stress at one examination, 1.73 (1.01-2.95) for those reporting stress at two examinations and 2.51 (1.33-4.77) at three examinations. To conclude, we found an association between psychological stress in middle-aged women and development of dementia, especially Alzheimer's disease. More studies are needed to confirm our findings and to study potential neurobiological mechanisms of these associations.

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    • "In rodents, both experimental stress and glucocorticoid administration cause a reduced dendritic branching in the frontal cortex and the hippocampus, with corresponding impairments in cognitive function [8] [9] [10]. In humans, analogous reductions of hippocampal volume, cognitive deficiencies and increased dementia risk occur after prolonged stress exposure and in association to elevated glucocorticoid levels [11] [12]. DNA damage from oxidation is considered to be a key event in aging per se [13] [14], as well as an early pathogenic event in many neurodegenerative disorders, including Alzheimer's disease [15] [16]. "
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    ABSTRACT: Neuronal genotoxic insults from oxidative stress constitute a putative molecular link between stress and depression on the one hand, and cognitive dysfunction and dementia risk on the other. Oxidative modifications to DNA are repaired by specific enzymes; a process that plays a critical role for maintaining genomic integrity. The aim of the present study was to characterize the pattern of cerebral DNA repair enzyme regulation after stress through the quantification of a targeted range of gene products involved in different types of DNA repair. 72 male Sprague-Dawley rats were subjected to either restraint stress (6h/day) or daily handling (controls), and sacrificed after 1, 7 or 21 stress sessions. The mRNA expression of seven genes (Ogg1, Ape1, Ung1, Neil1, Xrcc1, Ercc1, Nudt1) involved in the repair of oxidatively damaged DNA was determined by quantitative real time polymerase chain reaction in the prefrontal cortex (PFC) and hippocampus (HC). DNA repair gene expression in PFC exhibited a general trend towards an induction after acute stress and a decrease after subchronic exposure compared to control animals. After chronic stress, a normalization towards control levels was observed. A similar pattern was seen in HC, but with overall smaller effects and without the induction after acute stress. Nuclear DNA damage from oxidation as measured by the comet assay was unaffected by stress in both regions. We conclude that psychological stress have a dynamic influence on brain DNA repair gene expression; however, since we were unable to identify concurrent changes in DNA damage from oxidation, the down-stream consequences of this regulation, if any, remains unclear. Copyright © 2014 Elsevier B.V. All rights reserved.
    Mutation Research/Genetic Toxicology and Environmental Mutagenesis 01/2015; 778. DOI:10.1016/j.mrgentox.2014.12.003 · 2.42 Impact Factor
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    • "Depression. In our review, depression increased the risk of cognitive decline or dementia in 19 out of 21 studies (Boyle et al., 2010; Dotson et al., 2010; Greendale et al., 2010; Johansson et al., 2010; Peters et al., 2010; Ritchie et al., 2010; Rosenberg et al., 2010; Saczynski et al., 2010; Sander et al., 2010; Bielak et al., 2011; Goveas et al., 2011; Kim et al., 2011b; Köhler et al., 2011; Lenoir et al., 2011; Li et al., 2011; Mejia-Arango and Gutierrez, 2011; Potvin et al., 2011; Unverzagt et al., 2011b; Royall et al., 2012). Two studies found no association (90% consistency; Chodosh et al., 2010; Jajodia and Borders, 2011). "
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    ABSTRACT: Objective Dementia has a multifactorial etiology, but the importance of individual health and lifestyle related risk factors is often uncertain or based on few studies. The goal of this paper is to identify the major modifiable risk factors for dementia as a first step in developing an effective preventive strategy and promoting healthy late life cognitive functioning.MethodsA mixed-method approach combined findings from a systematic literature review and a Delphi consensus study. The literature search was conducted in PubMed and updated an earlier review by the United States National Institutes of Health from 2010. We reviewed the available evidence from observational epidemiological studies. The online Delphi study asked eight international experts to rank and weigh each risk factor for its importance for dementia prevention.ResultsOut of 3127 abstracts, 291 were included in the review. There was good agreement between modifiable risk factors identified in the literature review and risk factors named spontaneously by experts. After triangulation of both methods and re-weighting by experts, strongest support was found for depression, (midlife) hypertension, physical inactivity, diabetes, (midlife) obesity, hyperlipidemia, and smoking, while more research is needed for coronary heart disease, renal dysfunction, diet, and cognitive activity.Conclusions Findings provide good support for several somatic and lifestyle factors and will be used to inform the design of a new multicenter trial into dementia prevention. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 11/2014; 30(3). DOI:10.1002/gps.4245 · 2.87 Impact Factor
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    • "Subjects who reported frequent/contrast stress in two of three prior assessments had an elevated risk of AD compared with those reporting no periods of stress. Subjects reporting high stress at one, two, and three earlier periods had escalating risks of dementia (HR 5 1.1, 1.7, and 2.7, respectively) [8]. This latter finding points to a doseresponse curve for the effect of stress exposure. "
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    ABSTRACT: The physiological consequences of acute and chronic stress on a range of organ systems have been well documented after the pioneering work of Hans Selye more than 70 years ago. More recently, an association between exposure to stressful life events and the development of later-life cognitive dysfunction has been proposed. Several plausible neurohormonal pathways and genetic mechanisms exist to support such an association. However, many logistical and methodological barriers must be overcome before a defined causal linkage can be firmly established. Here the authors review recent studies of the long-term cognitive consequences of exposures to cumulative ordinary life stressors as well as extraordinary traumatic events leading to posttraumatic stress disorder. Suggestive effects have been demonstrated for the role of life stress in general, and posttraumatic stress disorder in particular, on a range of negative cognitive outcomes, including worse than normal changes with aging, Alzheimer's disease, and vascular dementia. However, given the magnitude of the issue, well-controlled studies are relatively few in number, and the effects they have revealed are modest in size. Moreover, the effects have typically only been demonstrated on a selective subset of measures and outcomes. Potentially confounding factors abound and complicate causal relationships despite efforts to contain them. More well-controlled, carefully executed longitudinal studies are needed to confirm the apparent association between stress and dementia, clarify causal relationships, develop reliable antemortem markers, and delineate distinct patterns of risk in subsets of individuals.
    Alzheimer's and Dementia 06/2014; 10(3):S155–S165. DOI:10.1016/j.jalz.2014.04.008 · 12.41 Impact Factor
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