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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    • "Similarly, mid-life psychological stress is related to development of dementia later in life (Johansson et al., 2010;Johansson et al., 2013). The risk of dementia was found to increase cumulatively with the number of stressful periods in life (Johansson et al., 2010), suggesting that prolonged periods of stress are deleterious while shorter periods are not. Interestingly, permanent memory and learning impairments in healthy individuals have been associated with chronic elevation of stress steroids (Lupien et al., 2005). "
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    ABSTRACT: Chronic stress in various forms increases the risk for cognitive dysfunction, dementia and Alzheimer's disease. While the pathogenesis behind these findings is unknown, growing evidence suggests that chronic increase in neurosteroid levels, such as allopregnanolone, is part of the mechanism. We treated wild-type C57BL/6J mice with allopregnanolone for 5months, using osmotic pumps. This treatment led to moderately increased levels of allopregnanolone, equivalent to that of mild chronic stress. After an interval of no treatment for 1month, female mice showed impaired learning and memory function in the Morris water maze (MWM) in combination with diminished hippocampus weight and increased cerebellum weight, both correlating to MWM performance. Male mice showed a minor reduction in memory function and no differences in brain structure. We conclude that chronic allopregnanolone elevation can lead to cognitive dysfunction and negative brain alterations. We suggest that allopregnanolone could play a key role in the pathogenesis of stress-induced cognitive disturbances and perhaps dementia.
    Full-text · Article · Oct 2015 · Hormones and Behavior
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    • "Long-term population studies have also provided considerable evidence to suggest that late-life Alzheimer's dementia may be linked to exposures occurring in early and midlife. From the prospective population study of women in Gothenburg , which started in 1968 with last follow-up in 2010, it has been reported that higher blood pressure [22], the personality factor neuroticism [23], psychosocial stress [24], number of stressful events [25], poorer lung function [26], oral health [27], diabetes [28], obesity [28], low physical activity [28], larger waist-hip ratio [29], and consumption of spirits [30] in midlife are related to late-life Alzheimer's dementia occurring more than three decades later. In contrast, wine drinking reduced the risk [30]. "
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    ABSTRACT: Introduction Increasing evidence suggests that Alzheimer's disease (AD) may begin decades before evidence of dementia, indicating that it may be a disorder of midlife rather than old age. Methods In the absence of long-term prospective studies from early adulthood specifically designed to address this question, a group of international experts examined evidence presently available from previous clinical and population studies to provide an evidence-based opinion as to whether such a change in conceptualization may be justified. Results Although still lacking confirmation from dedicated prospective biomarker studies, there is already considerable evidence to suggest both risk factor exposure and brain changes may be already present in midlife. Discussion Current evidence suggests (1) that a change in clinical approach notably involving promotion of cardiovascular health in persons with a family history of AD may considerably reduce disease risk and (2) that the development of biomarkers at this early stage will lead to the possibility of clinical trials at a much earlier stage.
    Full-text · Article · Jul 2015
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    • "Foruten aldring og arv påvirker også livsstilen risikoen for demens (Alexopoulos, 2005; Fratiglioni, Paillard-Borg & Winblad, 2004). For eksempel er langvarig stress (Johansson et al., 2010), høyt blodtrykk over lengre tid ( Kennelly, Lawlor & Kenny, 2009), og diabetes vist å øke risikoen for demens ( Westwood et al., 2014). Videre er det også vist at ensomhet gir økt risiko for demens (Holwerda et al., 2012). "

    Full-text · Article · May 2015
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