Chronic Psychological Distress and Risk of Alzheimer’s Disease in Old Age

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Ill, USA.
Neuroepidemiology (Impact Factor: 2.56). 02/2006; 27(3):143-53. DOI: 10.1159/000095761
Source: PubMed


Clinical and pathological data from the Rush Memory and Aging Project were used to test the hypothesis that distress proneness is associated with increased risk of Alzheimer's disease (AD). More than 600 older persons without dementia completed a 6-item measure of neuroticism, a stable indicator of proneness to psychological distress. At annual intervals thereafter, they underwent uniform evaluations that included clinical classification of AD and administration of 18 cognitive tests. Those who died underwent brain autopsy from which composite measures of AD pathology were derived. During a mean of about 3 years of follow-up, 55 people were clinically diagnosed with AD. In analyses that controlled for age, sex, and education, persons with a high level of distress proneness (score = 24, 90th percentile) were 2.7 times more likely to develop AD than those not prone to distress (score = 6, 10th percentile). Adjustment for depressive symptomatology or frequency of cognitive, social, and physical activity did not substantially change this effect. Distress proneness was also associated with more rapid cognitive decline. Among 45 participants who died and underwent brain autopsy, distress proneness was unrelated to diverse measures of AD pathology and was inversely related to cognition after controlling for AD pathology. The results support the hypothesis that distress proneness is associated with increased risk of dementia and suggest that neurobiologic mechanisms other than AD pathology may underlie the association.

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    • "The link between distress and the diagnosis of dementia remained after controlling for depression, levels of social and physical activity, and recency of cognitive symptoms. Echoing their prior work, the authors concluded that psychological distress is associated with cognitive decline, but not specifically with AD [6]. Peavy and colleagues performed a 3-year longitudinal study on 52 individuals, who were either cognitively intact or evidencing signs of mild cognitive impairment (MCI). "
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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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    • "The rate of cognitive decline (disease progression) in 329 AD patients (214 from ANM, 87 from ARUK, and 28 from DCR) was calculated based on longitudinal MMSE assessments [26]. For the ANM cohort, MMSE scores were gathered at five visits, in which visits were 3 months apart (1-year follow-up). "
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    Alzheimer's & dementia: the journal of the Alzheimer's Association 04/2014; 10(6). DOI:10.1016/j.jalz.2013.09.016 · 12.41 Impact Factor
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    • "The chronic stress that often characterizes the lives of those with cognitive impairment, as well as their caregivers, has been linked to adverse changes in sleep (30), mood (33, 34), and immunological function (33, 35), and elevated risk for metabolic syndrome, cardiovascular disease (CVD), and mortality (36, 37). Chronic psychological stress can have profound effects on memory and behavior in persons both with and without cognitive impairment, and has been prospectively linked to increased risk for incident MCI and dementia in older adults, and to accelerated cognitive decline (38–40). Chronic stress leads to deleterious neuroendocrine and associated inflammatory changes, to suppression of IGF-1 and other neuroprotective factors, and to impaired synaptic plasticity, suppressed neurogenesis, reduced neuronal survival, and other adverse morphological and functional changes in the hippocampus, prefrontal cortex, and other brain structures; all these changes can profoundly affect mood, sleep, memory, and learning (41–45). "
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