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.
"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   . 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  . DNA damage from oxidation is considered to be a key event in aging per se  , as well as an early pathogenic event in many neurodegenerative disorders, including Alzheimer's disease  . "
"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). "
"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) . This latter finding points to a doseresponse curve for the effect of stress exposure. "
[Show abstract][Hide abstract] 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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