Enhanced Effects of Cortisol Administration on Episodic and Working Memory in Aging Veterans with PTSD

Abstract

Though both glucocorticoid alterations and memory impairments have been noted in posttraumatic stress disorder (PTSD), it is not clear if these phenomena are causally linked. As there is emerging evidence that these domains become further altered in PTSD with increasing age, it is of interest to examine these relationships in an older cohort. Aging (mean age, 62.778.9; range, 52-81) combat veterans with (n ¼ 13) and without (n ¼ 17) PTSD received an intravenous bolus of 17.5 mg hydrocortisone (cortisol), a naturally occurring glucocorticoid, or placebo in a randomized, double-blind manner, on two mornings approximately 1-2 weeks apart. Neuropsychological testing to evaluate episodic and working memory performance was performed 75 min later. Cortisol enhanced episodic memory performance in both groups of subjects, but enhanced elements of working memory performance only in the PTSD + group. The preferential effect of cortisol administration on working memory in PTSD may be related to the superimposition of PTSD and age, as cortisol had impairing effects on this task in a previously studied, younger cohort. The findings suggest that there may be opportunities for developing therapeutic strategies using glucocorticoids in the treatment of aging combat veterans.

Acute stress and working memory in older people

“…Using pharmacological approaches, previous findings showed no cortisol effects on WM in older men (Porter et al, 2002;Wolf et al, 2001;Yehuda et al, 2007). These results coincide with the idea that older people may be less sensitive to acute effects of cortisol on memory due to a loss and/or dysfunction of corticoid receptors in the aging brain (Giordano et al, 2005;Heffelfinger & Newcomer, 2001;Perlman et al, 2007;Porter et al, 2002).…”

“…Using a task designed to assess declarative memory, we found that stress improved memory span and impaired retroactive interference (a PFC-dependent executive ability) in women from 54 to Correspondence 1 Previous studies that investigated the effect of acute stress and/or cortisol increases on memory in older people have included samples with a mean age of older than 60 years and an age range from 52 to 83 years old (e.g. an age range from 54 to 72 in Almela et al (2011a); from 52 to 81 in Yehuda et al (2007); and from 59 to 76 in Wolf et al (2001)). To be consistent with the terms used in most of these studies, in this article, we refer to the participants as older people; however, it should be noted that in the present study and previous studies some participants are in the second half of the age range called middle-aged people (from 50 to 60 years old); therefore, the results and conclusions should also be applicable to them.…”

Hydrocortisone reduces emotional distracter interference in working memory

“…Given the present results, it could be hypothesized that GC administration enhances suppression of intrusions by decreasing distraction by emotional stimuli directly, or indirectly by improving WM. In a recent study, GC administration showed to enhance WM performance in elderly PTSD patients (Yehuda et al, 2007). It would thus be interesting to see whether cortisol-induced WM enhancements in PTSD patients are related to enhanced distracter suppression.…”

Blunted Corticosterone Response to Acute Predator Stress Results in Long-Term Spatial Memory Impairment

“…It is not exactly clear why a blunted HPA axis response to stress would exacerbate its effects on cognitive performance. Clinical research has shown that the administration of glucocorticoids can enhance learning and memory in people with PTSD, while impairing those processes in healthy controls [31][32]. In addition, several studies have reported that the administration of glucocorticoids either shortly after the trauma or after the development of PTSD can prevent / ameliorate the onset / maintenance of PTSD symptoms [33][34][35][36][37].…”