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      Common psychosocial stressors in middle-aged women related to longstanding distress and increased risk of Alzheimer's disease: a 38-year longitudinal population study

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          Abstract

          Objective

          To study the relation among psychosocial stressors, long-standing distress and incidence of dementia, in a sample of women followed from midlife to late life.

          Design

          Prospective longitudinal population study.

          Setting

          The analyses originate from the prospective population study of women in Gothenburg, Sweden, a representative sample of women examined in 1968 (participation rate 90%) and re-examined in 1974, 1980, 1992, 2000 and 2005.

          Participants

          800 women born in 1914, 1918, 1922 and 1930 who were systematically selected for a psychiatric examination at baseline, in 1968.

          Primary and secondary outcome measures

          18 psychosocial stressors (eg, divorce, widowhood, work problems and illness in relative) were obtained at baseline. Symptoms of distress were measured according to a standardised question at each study wave. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria based on information from neuropsychiatric examinations, informant interviews, hospital records, and registry data, and measured through the whole study period.

          Results

          During the 37 years of follow-up, 153 women developed dementia (104 of those had Alzheimer's disease (AD)). Number of psychosocial stressors in 1968 was associated (HR, 95% CI) with higher incidence of dementia (1.15, 1.04 to 1.27) and AD (1.20, 1.07 to 1.35) between 1968 and 2005, in multivariate Cox regressions. Number of psychosocial stressors in 1968 was also associated (OR, 95% CI) with distress in 1968 (1.48, 1.32 to 1.67), 1974 (1.31, 1.17 to 1.46), 1980 (1.27, 1.11 to 1.45), 2000 (1.39, 1.14 to 1.70) and 2005 (1.35, 1.02 to 1.79), in multivariate logistic regressions. Number of psychosocial stressors (HR 1.17, 95% CI 1.03 to 1.33) and long-standing distress (1968–1974–1980) (HR 1.58, 95% CI 1.03 to 2.45) were independently associated with AD.

          Conclusions

          Our study shows that common psychosocial stressors may have severe and long-standing physiological and psychological consequences. However, more studies are needed to confirm these results and investigate whether more interventions such as stress management and behavioural therapy should be initiated in individuals who have experienced psychosocial stressors.

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          Most cited references31

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          Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

          Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.
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            Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

            To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Convents in the Midwestern, Eastern, and Southern United States. A total of 102 college-educated women aged 76 to 100 years. Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
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              MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder.

              Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder. Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse. The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only. These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2013
                31 August 2013
                : 3
                : 9
                : e003142
                Affiliations
                [1 ]Neuropsychiatric Epidemiology Unit, Institute of Neuroscience and Physiology, Sahlgrenska Academy at Gothenburg University , Mölndal, Sweden
                [2 ]Department of Clinical Neuroscience, Section for Psychiatry/Huddinge, Karolinska Institutet , Stockholm, Sweden
                [3 ]Department of Family Consumer and Human Development and Departments of Psychology, Utah State University , Logan, USA
                [4 ]Sahlgrenska School of Public Health and Community Medicine, Section for Public Health Epidemiology, The Sahlgrenska Academy at University of Gothenburg , Gothenburg, Sweden
                Author notes
                Correspondence to Lena Johansson; lena.johansson@ 123456neuro.gu.se
                Article
                bmjopen-2013-003142
                10.1136/bmjopen-2013-003142
                3787482
                24080094
                1d30c7fe-44ea-4d6c-912b-e28b96fb7b74
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                : 30 April 2013
                : 5 July 2013
                : 8 July 2013
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