A long-term follow-up assessment of mood, cognition, and in two cases, structural MRI in a group of patients on long-term prednisone therapy and controls was conducted. The main finding was that cognition was relatively stable over time in both groups, and that the prednisone-treated group tended to continue to have higher scores on psychiatric symptom scales and poorer performance on the RAVLT than controls.
The findings of our original study suggested higher levels of depression and poorer performance on the RAVLT and Stroop in patients who had received prednisone therapy at a mean dose of approximately 16 mg/day for a mean duration of 92 months than in controls. The present study suggests that these differences in mood and cognition, with the exception of the HRSD, had not increased substantially over time. Prednisone may initially induce changes in memory over a period of time. However, these changes then appear to remain stable over time. Cognition did not improve but neither did it worsen compared to the controls suggesting that an ongoing neurodegenerative process is not occurring.
Even brief exposure to exogenous corticosteroids is associated with a decline in declarative memory performance (Brown et al., 2006
; Brunner et al., 2005
; Newcomer et al., 1999
). However, changes in hippocampal volume may take much longer to emerge. Hajek et al. (2006)
reported a decline in declarative memory performance but no change in hippocampal volume after a mean of 73 and 173 days of prescription corticosteroid therapy. In our earlier report we found poorer performance on a declarative memory task and smaller hippocampal volumes in patients receiving a mean of 92 months of prednisone therapy as compared to controls. Our present findings suggest that declarative memory changed little over time. Thus, the effects of corticosteroids on memory appear to be an acute effect that does not increase over time.
Scores on the HRSD increased from baseline to follow-up in the corticosteroid treated group. Whether this increase is secondary to life events, life with a chronic illness, the cumulative effects of prednisone or other factors cannot be determined. The reason for the decline in YMRS scores in the control group is unclear. However, neither the baseline nor follow-up values suggest clinically significant manic symptomatology.
The one participant who completely discontinued prednisone therapy between the initial and follow-up assessments showed substantial improvement in psychiatric symptoms and some cognitive measures. These findings are potentially consistent with improvement in mood and cognition in patients who discontinue long-term prednisone therapy. Unfortunately, we were not able to find more participants who discontinued prednisone therapy.
As repeat hippocampal volumes were only available for two participants, the findings must be interpreted with great caution. Changes in volume did not show a consistent pattern and the overall change was small. Raz et al. (2004)
reported healthy adult controls showed a decrease in hippocampal volume of 0.86%/year over a 5 year follow-up period. In contrast, Hashimoto et al. (2005)
reported a mean decrease in hippocampal volume of 5.04% after 1 year in placebo-treated patients with Alzheimer’s disease. As with the cognitive data, the imaging data in these patients do not clearly suggest a neurodegenerative process of the magnitude seen in Alzheimer’s disease.
The study has limitations. First, the two groups showed differences in education and age. The differences were not found in the original sample (Brown et al., 2004
). However, the controls who were identified and agreed to participate in the follow-up study were 11 years older than the prednisone-treated patients. However, the use of normative scores for the cognitive measures adjusts for age. Additionally, our primary aim was to examine within-group changes over time not between-group differences. Second, our sample size was small. The original study did not have a planned long-term follow-up assessment. Thus, we did not remain in contact with former study participants over the years limiting ability to enroll them in the follow-up study. The strength of this study is that it is the first, to our knowledge, to longitudinally examine the effects of long-term corticosteroid therapy on mood and memory.
In conclusion, at reassessment, a mean of 4 years after the original assessment, corticosteroid-treated patients and controls showed little change in declarative memory performance. The results suggest that long-term corticosteroid-therapy is associated with initial deficits in declarative memory that remains relatively stable over time. One participant discontinued corticosteroid therapy between the assessments and showed improvement on some memory measures. Additional research is needed to confirm these preliminary observations and determine if memory changes associated with long-term corticosteroid therapy are reversible with corticosteroid discontinuation.