The Einstein Aging Study: Stress and the Risk of Developing Dementia
According to a recent report published in the journal Alzheimer Disease & Associated Disorders stress may increase up to 30% the risk of developing amnestic mild cognitive impairment (aMCI) or dementia.
Cognitive impairment and dementia are major causes of morbidity and mortality and contribute substantially to health-care expenditures for older adults worldwide. As the population ages, the prevalence of Alzheimer’s dementia (AD) and the pre-dementia states which precede it, such as amnestic mild cognitive impairment (aMCI), are expected to rise.
Mild cognitive impairment is a significant risk factor for the development of dementia and Alzheimer’s disease. Moreover, among all MCI subtypes, patients with amnestic MCI are at greatest risk (A Levey et al., Clin Ther, 2006, 28:991).
Of note, MCI is now considered an intermediate clinical and neuropathological state between the cognitive changes of aging and the very earliest features of Alzheimer’s disease (Ronald C. Petersen, Curr Alzheimer Res, 2009, 6: 324).
Previous research indicates that stress is linked to the pathogenesis of Alzheimer’s disease and that a higher number of psychosocial stressors, particularly in middle-aged women are associated with increased risk of dementia and Alzheimer’s.
Work in animal models have demonstrated that chronic stress plays an important role in Alzheimer’s related neuropathology, including hippocampal vulnerability, accumulation and sustained elevations in tau phosphorylation. This implies that stress measures reflecting chronic influences will exhibit stronger relationships with cognitive outcomes than measures which reflect the frequency of stressful events which may be transient.
In the Alzheimer Disease & Associated Disorders study, a research group from the Albert Einstein College of Medicine, NY and the Pennsylvania State University, PA assessed 507 participants (≥ 70 yrs old) enrolled in the Einstein Aging Study (EAS). All subjects were free of aMCI and dementia at baseline. Stress was assessed using the Perceived Stress Scale (PSS).
The authors used the Perceived Stress Scale (PSS) to measure global life stress during a 30 day period. The PSS was an instrument designed to be sensitive to chronic stress resulting from ongoing life circumstances, possible future events, as well as events not typically listed on event check-lists.
The PSS is a widely used index of psychological stress that is robustly associated with a broad range of biological outcomes hypothesized to be influenced by chronic stress, such as compromised immune function and dysregulated endocrine function.
The authors report that the stress level correlated with the participants’ risk for developing aMCI. Subjects in the highest-stress quintile had an almost 2.5-times greater risk of developing aMCI as compared to those in the remaining four quintiles combined.
Interestingly, the study’s participants in the high-stress group were more likely to be female with higher levels of depression, but depression did not appear to interfere with the effect of stress on aMCI.
The results suggest that the effects of PSS on aMCI onset are independent of demographic features, depression and APOE ε4 allele status.
The magnitude of the hazard ratios, the consistency of results after adjusting for multiple covariates and the stability of results when perceived stress is modeled as either a categorical or continuous variable suggests that these findings are robust.
There have been few longitudinal, community-based studies that have focused on perceived stress as a risk factor for incident aMCI or dementia. None have examined perceived stress in relation to the incidence of aMCI.
As a modifiable risk factor, perceived stress should be considered to be targeted in preventive interventions including mindfulness-based stress reduction, cognitive–behavioral therapies, and pharmacologic interventions that aim to reduce cognitive decline.
Effect of stress on cognition may be mediated through multiple physiological pathways involving the central nervous, neuroendocrine, immune and cardiovascular systems. Neuroendocrine effects are thought to be primarily mediated through the activation of the HPA axis, marked by increased levels of corticotrophin releasing factor (CRF), adrenocorticotropic hormone (ACTH) and glucocorticoids.
These neuroendocrine changes lead to alteration of brain structure and function in the prefrontal cortex and hippocampus, among other brain regions.
Source: Alzheimer Dis Assoc Disord. 2015 Dec 10.
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