The Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults

doi:10.1016/j.biopsych.2007.03.013

Biological Psychiatry

Volume 62, Issue 5, 1 September 2007, Pages 472-478

https://doi.org/10.1016/j.biopsych.2007.03.013 Get rights and content

Background

Chronic elevations in cortisol associated with prolonged stress have been associated with memory loss, as has the apolipoprotein E gene (APOE-ε4) genotype. Combined effects of stress and APOE status on memory and cortisol in humans have not been studied.

Methods

A semistructured interview with standardized scoring was used to measure stress level and univariate analysis of variance to assess effects of stress and APOE-ε4 status on memory and salivary cortisol in 91 nondemented subjects (mean age 78.8 years).

Results

Low-stress subjects performed better than high-stress subjects on delayed recall of stories (p = .04), word lists (p = .02), and visual designs (p = .04). APOE-ε4-negative subjects obtained better scores than ε4-positive subjects on immediate (p = < .01) and delayed (p < .01) recall of visual designs. Significant stress by APOE-ε4 interaction effects on memory (p = .03) and cortisol (p < .01) resulted from consistently worse memory and higher cortisol concentrations in the high stress, ε4-positive group.

Conclusions

These findings are consistent with a model in which prolonged exposure of older, nondemented individuals to stress in the presence of an ε4 allele leads to memory decline. Further studies will assess whether stress and APOE-ε4 interact to increase the risk of developing Alzheimer’s disease.

Section snippets

Subjects

Participants—volunteers over age 65 and living independently—were recruited from the University of California, San Diego (UCSD) Shiley-Marcos Alzheimer’s Disease Research Center (ADRC) and the UCSD Memory Screening Clinic. Potential subjects were excluded if at baseline they were found to have a significant medical (e.g., end-stage cancer) or psychiatric (e.g., psychosis) condition that would affect cognition. Individuals with moderate to severe depression, those with posttraumatic stress

Results

Table 1 shows means and standard deviations for demographic and cognitive variables for groups based on level of stress (high, low) and APOE status (ε4-pos, ε4-neg). The groups did not differ significantly in years of education or global cognitive functioning on the Mattis DRS. A Stress × APOE status ANOVA on age showed a significant main effect of APOE status, indicating that those with at least one ε4 allele were younger [F(1,83) = 5.9; p = .02] than those with no ε4 allele. The main effect

Discussion

Elderly individuals with high stress due to the impact of recent “real-life” events and difficulties had worse memory performance than those with low stress. This finding is consistent with the results of studies assessing memory in humans exposed to stress in laboratory settings (6, 10, 11) and extends the results to more naturalistic causes of stress. In addition, elderly individuals with at least one APOE-ε4 allele performed worse than those without an ε4 allele on several memory measures,

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Original ArticleThe Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Biol Psychiatry

Life Sci

Psychoneuroendocrinology

Curr Opin Neurobiol

Behav Brain Res

Neurosci Lett

Brain Res Bull

Brain Res

Neurobiol Learn Mem

Neuroscience

Brain Research

J Psychiatr Res

Lancet

Role of genes and environments for explaining Alzheimer disease

Arch Gen Psychiatry

Differential genetic influence for components of memory in aging adult twins

Arch Neurol

The epidemiology of dementia and Alzheimer’s disease

Cortisol levels during human aging predict hippocampal atrophy and memory deficits

Nat Neurosci

Basal cortisol levels and cognitive deficits in human aging

J Neurosci

Impaired memory retrieval after psychosocial stress in healthy young men

J Neurosci

Stress-induced declarative memory impairment in healthy elderly subjects: relationship to cortisol reactivity

J Clin Endocrinol Metab

Apolipoprotein E and cognitive performance: A meta-analysis

Psychol Aging

Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer’s disease

Psychol Aging

Episodic memory changes are associated with the APOE-epsilon 4 allele in nondemented older adults

Neurology

Impact of APOE in mild cognitive impairment

Neurology

Original Article
The Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults