Anxiety and Vulnerability to Stress – Dementia
In a recent American Journal of Geriatric Psychiatry study, Robert Wilson and colleagues from the Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL examined the relation of different facets of neuroticism to risk of developing AD.
Emerging research implicates a consistent reciprocal relationship between late-life anxiety and cognition, and that severe anxiety may predict future cognitive decline.
Recent population-based prospective study indicates that anxiety is a risk factor for cognitive impairment not dementia (CIND) and dementia, although the extent to which the association is independent of depression remains unidentified (Gallacher et al., Psychosomatic Medicine 2009, 71:659).
Anxiety has also been implicated in the progression from mild cognitive impairment to Alzheimer’s disease (AD). In addition, high level of chronic psychological distress is associated with increased incidence of mild cognitive impairment, and proneness to experience psychological distress is a risk factor for dementia or AD.
In old age, anxiety is often part of a more complex personality trait such as neuroticism, which includes anxiety, depression, self-consciousness and impulsiveness. High levels of neuroticism has been associated with lower level of cognitive function, more rapid cognitive decline, and increased risk of developing mild cognitive impairment and dementia. It is unclear; however, which components of neuroticism are primarily responsible for its association with late-life dementia.
The American Journal of Geriatric Psychiatry study used data are from the Rush Memory and Aging Project, a longitudinal clinical pathologic study of risk factors for common chronic conditions of old age.
In this prospective study of more than 700 old persons the authors demonstrate that neuroticism’s association with AD risk primarily reﬂects two components: vulnerability to stress and anxiety. The association of perceived vulnerability to stress with AD risk is consistent with previous data linking stressful life events and reactivity to stress with late-life dementia or cognitive decline.
The authors discuss that high perceived stress and anxiety has been associated with reduced hippocampal volume and decreased density of dendrites and spines in the CA3 region of the hippocampus. Thus, according to the authors, their observations suggest that perceived stress and anxiety in humans may eventually damage selective circuits supporting stress-related behavior, thereby contributing to cognitive impairment and dementia.
SOURCE: Am J Geriatr Psychiatry 2011, 19:327.
A 2013 prospective longitudinal population study by Lena Johansson et al. examined whether common psychosocial stressors in midlife were related to distress, late-life dementia and Alzheimer’s disease (AD) in 800 women, systematically selected for a psychiatric examination in 1968. During the 37 years of follow-up, 153 women developed dementia. The study suggests that common psychosocial stressors may have severe and long-standing physiological and psychological consequences. Specifically, it indicates that stress in middle-age women is associated with increased risk of dementia and AD decades later in life. This is perhaps the first population study on the relationship between midlife stressors and increased risk of dementia in late life.
A 2016 report published in Alzheimer Disease and Associated Disorders is based on the Einstein Aging Study (EAS) of older adults. This is a longitudinal study of a community cohort of adults aged 70 years or older who were systematically recruited from Bronx County, NY beginning in 1993. As stress is a potentially risk factor for amnestic Mild Cognitive Impairment (aMCI), the objective of this study was to determine whether perceived stress predicts incident aMCI and to determine the influence of stress on aMCI.
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. Thus, this study demonstrates that perceived stress is an independent predictor of aMCI, the preclinical stage of AD. The authors conclude that 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.
A 2017 systematic review concluded that clinically significant anxiety in midlife was associated with an increased risk of dementia over an interval of at least 10 years. Of note, this systematic review found four high-quality studies that all showed a positive association between clinically significant anxiety and risk of late-onset dementia over a mean interval of at least 10 years from anxiety assessment to dementia diagnosis, even after accounting for potential confounders.
Thus, as per Gimson and colleagues, anxiety may be an independent risk factor for late-onset dementia, excluding the anxiety that might represent the initial symptoms of dementia. The link between anxiety and dementia may be explained by the excessive stress response triggered by the mental health condition.
Interestingly, the investigators discussed that benzodiazepines, commonly used in the treatment of anxiety, have been shown to increase risk of mortality in some groups and therefore cannot be considered a measure to reduce dementia. In addition, they suggest that given the high prevalence of anxiety seen in primary care, the general practitioners could consider anxiety alongside depression as an indicator of risk for dementia.
A 2020 meta-analysis included nine prospective cohorts from eight studies, representing 29,608 participants. This analysis concluded that anxiety is significantly associated with an increased risk of all-cause dementia.
Thus, this meta-analysis indicates a positive association between anxiety and risk of all-cause dementia. Of note, participants with prevalent anxiety at baseline show 24% higher risk of developing dementia during the follow-up. Despite this being considered a low effect size, with an average of 20% of people with anxiety, the proportion of incident dementia attributable to anxiety is estimated to be 4%. This is also comparable to the proportion attributable to other modifiable risk factors such as diabetes or hypertension.
A 2022 prospective cohort study, published in the Lancet, used data from a nationally provided psychological intervention service in England from 2012 to 2019, Improving Access to Psychological Therapies (IAPT).
This study demonstrates that reliable improvement in anxiety symptoms following psychological intervention is associated with reduced incidence of all-cause dementia, Alzheimer’s disease, and vascular dementia. The findings were consistent when using alternative metrics of intervention outcome (reliable recovery and GAD-7 scale), after accounting for service-level variation, and after excluding cases in which dementia was diagnosed within 2 years of the end of the intervention. Results also showed that completing a course of treatment in IAPT was significantly associated with reduced dementia incidence, compared with assessment only.
As per the authors of this study, overall, it suggests that improving anxiety symptoms in psychological therapies is associated with a reduced incidence of all-cause dementia, Alzheimer’s disease, and vascular dementia in older people, with a follow-up period of up to 8 years.