Glucocorticoid Therapy-Induced Memory Deficits: Acute versus Chronic Effects

Abstract

Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits. Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology. However, because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval, it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure. To investigate this issue, we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically (5.3 Ϯ 1.0 years, mean Ϯ SE) with low to moderate doses of prednisone (7.5 Ϯ 0.8 mg, mean Ϯ SE) or without glucocorticoids. In both groups, delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind, placebo-controlled crossover design. Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se, acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall. Thus, these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result, at least in part, from acute and reversible glucocorticoid effects on memory retrieval.

Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis

“…Several mechanisms are potentially involved with cognitive dysfunction in RA, including the chronic inflammatory condition per se as well as long-term GC use. GCs have been linked with cognitive impairment [29,30,31] and GC receptors are particularly involved in the consolidation and retention of learned information [32]. Persistent inflammation may also contribute to cognitive decline [33,34] and systemic inflammation has been observed to increase with advancing age in humans (known as ‘inflammaging') [33].…”

Cognitive Impairment in Rheumatoid Arthritis: A Systematic Review

“…Further, immune activities such as alterations in dehydroepiandrosterone metabolism also appear to be associated with cognitive impairment, particularly in relation to attention and learning, even when controlling for depression and in sample with mild disease activity (35,40). Medication may also affect cognitive function temporarily at single and accumulative dose levels (22,23,30,31). Finally, pain, fatigue, poor sleep, and depression may be attentional distractions, and in turn affect cognition (23,33,37).…”

“…A commonly prescribed medication for RA is methotrexate (MTX), which is highly effective (19) but which might be associated with cognitive impairment (20), mood changes, and confusion (21). Glucocorticoid therapy has been associated with an immediate impact on memory (22) and a possible cumulative influence on hippocampal function (23). While there seems to be an association between glucocorticoid medication and cognitive impairment in RA (24), the nature of that association has not been determined.…”

Medications and Cognition in Older Adults

“…Severe psychiatric symptoms, such as affective and psychotic conditions, may occur in upward of 5% of patients treated with corticosteroids [ 148 ] . Acute corticosteroid treatment, but not chronic treatment, seemed to induce memory impairment in patients with rheumatoid arthritis [ 149 ] . Steroid use has likewise been associated with reversible dementia [ 150,151 ] .…”