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Journal of Clinical Oncology, Vol 22, No 5 (March 1), 2004: pp. 966-967 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.290
The Measurement of Cognitive Functioning in Low-Grade Glioma Patients After RadiotherapyDepartments of Medical Psychology and Neurology, VU University Medical Center, Amsterdam, the Netherlands To the Editor: We read with great interest the study of Brown et al [1] in the July 1, 2003 issue of the Journal of Clinical Oncology, in which they report on the impact of radiotherapy on cognitive functioning of low-grade glioma (LGG) patients. From this well-performed prospective study the authors conclude that most LGG patients maintained a stable cognitive status after focal radiotherapy as measured by Folstein's Mini-Mental State Examination (MMSE) [2], which probably is the most widely used standardized cognitive screening test. Although we think that studies into the cognitive effects of treatment of these patients with a dismal prognosis should be strongly encouraged, we also would like to caution against the overuse of short cognitive screening batteries, including the MMSE. The MMSE was intended to assist psychiatric residents in the cognitive part of the mental status exam and was not meant to be used for the diagnosis of dementia [2], nor was it designed to measure cognitive deterioration in neurologic patients. Even though the MMSE appears to be less useful in patients with little formal education and those with severe language problems [3], Brown et al do not report whether there were differences in educational level or in the incidence of aphasia between MMSE groups, or, at least, they do not correct for these factors in their statistical analyses. Conversely, patients who are highly educated may get the maximum score of 30 even though clinically they are severely affected. The MMSE furthermore contains some items that assess neurologic function as well as cognition (eg, language and visuospatial abilities). This is particularly problematic in the Brown et al study because at each key evaluation, patients were classified as progressors or nonprogressors according to their neurologic status. Predictably, Brown et al (Table 2) reported the worst neurologic status in patients with abnormal MMSE scores. In fact, this was the only patient characteristic that exhibited a statistically significant difference between the two groups. Brown et al found evidence for cognitive deterioration after radiotherapy in only a small percentage of patients. Given its limited sensitivity, their documented declines on the MMSE may be underestimates of the proportion of patients with true declines: potential subtle negative effects of radiotherapy on cognition, if present at all, may have been missed. Radiotherapy in glioma patients may give rise to subcortical white matter changes [4,5], which are associated with behavioral slowing [6]. The fact that none of the MMSE items have time constraints might also have contributed to the lack of demonstration of a clear trend toward cognitive worsening after radiotherapy in a significant proportion of patients or might have led to an underestimation of the actual radiation effects. Unfortunately, Brown et al did not specifically examine the effect of the used fraction dose in a multivariate model. In our recent study [7] on the mid- to long-term effects of radiotherapy in LGG patients, by using an extensive cognitive test battery, we found that the tumor appears to be the main cause of cognitive deficits. Multivariate logistic regression analysis was evidential for cognitive disability only in LGG patients who received fraction doses exceeding 2 Gy. We suggest that these results argue against using MMSE scores in future studies, given that an instrument that may identify cognitive functioning after radiotherapy, and call for the need to use more sophisticated and discriminating neurocognitive assessment tools. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Brown PD, Buckner JC, O'Fallon JR, et al: Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the Folstein mini-mental state examination. J Clin Oncol 21:2519–2524, 2003 2. Folstein MF, Folstein SE, McHugh PR: "Mini-mental state": A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198, 1975[CrossRef][Medline]
3. Vertesi A, Lever JA, Molloy DW, et al: Standardized Mini-Mental State Examination: Use and interpretation. Can Fam Physician 47:2018–2023, 2001
4. Postma TJ, Klein M, Verstappen CC, et al: Radiotherapy-induced cerebral abnormalities in patients with low-grade glioma. Neurology 59:121–123, 2002 5. Virta A, Patronas N, Raman R, et al: Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients. Magn Reson Imaging 18:851–857, 2000[CrossRef][Medline]
6. Ylikoski R, Ylikoski A, Erkinjuntti T, et al: White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol 50:818–824, 1993 7. Klein M, Heimans JJ, Aaronson NK, et al: Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: A comparative study. Lancet 360:1361–1368, 2002[CrossRef][Medline]
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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