Prednisone and Memory
ABSTRACT & COMMENTARY
Source: Keenan PA, et al. The effect on memory of chronic prednisone treatment in patients with systemic disease. Neurology 1996;47:1396-1402.
Sapolsky and a number of coworkers have for more than a decade emphasized that mammals receiving sustained doses of glucocorticoids suffer hippocampal cell loss and memory impairment. Early studies by Sapolsky and Pulsinelli (Science 1985;229:1397-1400) demonstrated that giving such steroids to rats undergoing an experimental stroke-inducing model greatly increased the size of the infarct compared to controls. In clinical circumstances, administering glucocorticoids carries an acute risk of inducing confusion or delirium in patents with autoimmune disorders or more trivial illnesses, and confusion is well-known in patients with Cushing’s disease (Starkman and Schteingart. Arch Intern Med 1981;141:215-219). In this setting, Keenan et al examined the possible effect of glucocorticoids on hippocampal-type explicit memory compared to non-hippocampal implicit memory. The authors controlled for changes in attention, affect, global decline in cognitive capacities, or disease severity.
All patients had rheumatologic or autoimmune disorders; none had CNS disease. Twenty-five experimental subjects had received glucocorticoids in doses of 5 mg or more daily for at least one year. The controls had not received such drugs. Subjects in both groups were tested before and after the medication period for explicit and implicit memory as well as for other cognitive and psychiatric performance. Mean age of the experimental group was 51 years, compared with 50 years for the controls. Both experimental and control groups contained 24 women and one man. Apparently, all subjects completed the one-year study. After one year, the treats showed a significantly greater loss of information and recognition memory over the initial tests than did the controls; implicit memory results, however, remained similar between the two groups. Among patients taking corticosteroids for three years or less, the deterioration of memory was greatest in the older patients. By contrast, in patients continuously taking corticosteroids for four years or more, the deterioration in event memory affected every age group similarly.
A second study was carried out on 14 other experimental/control matched subjects, none of whom had received corticosteroids for the previous six months. Prednisone dosage among the seven treats ranged from 5 mg to 80 mg daily. Paragraph recall (explicit memory) and word stem priming (implicit memory) tests were applied at baseline. Seven days later and 12 weeks later, paragraph recall among treats was significantly worse than controls after 12 weeks of treatment. Possibly different results were identified after one week.
COMMENTARY
These results appear to endorse Sapolsky’s repeated emphasis that either short- or long-term exposure of corticosteroid drugs can impair memory mechanisms. Regrettably, however, the authors failed to compare memory mechanisms in the experimental group with controls at intervals after discontinuing the steroids. Such data must be obtained before corticosteroid treatment can be considered to damage the human brain permanently. It is a truism that in the absence of iron-clad, strongly controlled warning studies, doctors prefer to give patients drugs that show no evidence of benefit against severe cerebral trauma, degeneration, or even strokes. The Keenan report suggests that steroid therapy lasting as little as 12 weeks may impair event memory. What remains to be seen is whether the reduction reflects merely a temporary blunting of hippocampal function or, instead, reflects permanent damage to the structure and its expressed memory capacities. Neurologists should be aware that carefully conducted, repeatedly validated experimental studies in mammals including primates indicate that excess systemic glucocorticoids can produce permanent hippocampal damage.
Having directly observed some of the experiments referred to, your editor favors minimizing or withholding corticosteroid medication except for illnesses in which they have a strong, permanent benefit for which no other safe agent can substitute. fp
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