Apolipoprotein E Genotype, Cortisol, and Cognitive Function in Community-Dwelling Older Adults

Abstract

Background Elevated cortisol may be a risk factor for cognitive decline in aging. Genetic factors may influence individual vulnerability to the adverse effects of stress on cognitive function in aging. Methods We investigated whether gene-environment interaction by apolipoprotein E genotype and cortisol predicted cognitive performance in an urban population of older adults. A cross-sectional analysis of data was conducted from a population-based sample of 50–70 year old men and women. Cognitive performance, salivary cortisol levels, and APOE genotype was assessed in 967 subjects. Performance on 20 standard cognitive tests was assessed and combined to form seven summary domain scores (language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory and learning, visuoconstruction). Results In adjusted models, while higher levels of cortisol were associated with worse cognitive scores, the slopes of the adverse relations were steeper in persons with at least one ε4 allele. Effect sizes were large: for example, the effect of having one ε4 allele and cortisol area under curve > 75th percentile was equivalent to a decrease in language score expected from an increase in 8.0 (95% CI: 1.7, 14.4) years of age, while having two ε4 alleles and cortisol area under curve > 75th percentile was equivalent to an increase of 33.4 (14.8, 52.0) years of age. Conclusion These data indicate that APOE genotype may modify relations of cortisol with cognitive functioning, and suggest that the ε4 allele increases vulnerability of the aging brain to the adverse effects of stress.

ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations

“…However, the effects of APOE on cortisol levels in humans (Fiocco et al, 2008;Peskind et al, 2001) and mice (Raber et al, 2000;Reverte et al, 2014;Robertson et al, 2005;Thorngate et al, 2002) are less clear. Additionally, several studies have shown varying results when examining the relationship between APOE and cortisol on stress and cognitive function (Beluche et al, 2010;Gallagher-Thompson et al, 2001;Gerritsen et al, 2011;Lee et al, 2008). Looking beyond basal levels of cortisol, Yehuda et al (2005) showed that the normal circadian rhythm of cortisol levels is flattened in Holocaust survivors with PTSD compared with non-exposed subjects.…”

Lower morning to evening cortisol ratio is associated with cognitive impairment in men but not women: An analysis of 733 older subjects of the cross-sectional KORA-Age study

“…This may be a limitation because previous studies have suggested the modifying role of APOE-4 on the association between cortisol levels and cognition (Gerritsen et al, 2011;Lee et al, 2008). However, recent evidence does not support the modifying role of APOE-4 in this relationship (Fiocco et al, 2008;Lara et al, 2013).…”

“…Furthermore, there are other clinical studies that examined these relationships but yielded mixed findings with most studies reporting higher morning cortisol levels. In addition, some studies focused on specific study populations, for example, among APOE-4 carriers and non-carriers (Gerritsen et al, 2011;Lara et al, 2013;Lee et al, 2008), MCI subjects (Lind et al, 2007;Venero et al, 2013), and diabetic patients (Reynolds et al, 2010). Thus, these previously mentioned studies were not generalizable to the older general population.…”

Stress, race, and APOE: understanding the interplay of risk factors for changes in cognitive functioning

“…Although previous studies have demonstrated the potentiating effects of environmental stressors, such as problems meeting basic needs, on the relationship between APOE e4 and CD (Comijs, Van Den Kommer, Minnaar, Penninx, & Deeg, 2011;Lee et al, 2008;Lee, Glass, James, Bandeen-Roche, & Schwartz, 2011;SachsEricsson, Corsentino, Collins, Sawyer, & Blazer, 2010), few have examined these effects based on race. According to the 'Weathering' hypothesis suggested by Geronimus, Hicken, Keene, and Bound (2006), older African-Americans may have experienced consistently higher stress throughout their lives, causing them to be more vulnerable to later insults.…”