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ARTICLES: J. Olazarán, R. Muñiz, B. Reisberg, J. Peña-Casanova, T. del Ser, A. J. Cruz-Jentoft, P. Serrano, E. Navarro, M. L. García de la Rocha, A. Frank, M. Galiano, Y. Fernández-Bullido, J. A. Serra, M. T. González-Salvador, and C. Sevilla Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease Neurology 2004; 63: 2348-2353 [Abstract] [Full text] [PDF]

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Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease

Harish C. Kavirajan   (8 March 2005)

Reply to Kavirajan

Javier Olazarán, Ruben Muñiz   (8 March 2005)

Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease 8 March 2005
Harish C. Kavirajan, UCLA Geffen School of Medicine 950 South Coast Drive, Suite 202, Costa Mesa, CA 92626 Send Correspondence to journal: Re: Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease hkaviraj{at}yahoo.com Harish C. Kavirajan	We read the article by Olazaran et al with interest. [1] There are several problems with study design and data analysis: 1. The quality of the blinding is questionable. Most patients had MCI or mild dementia, and therefore presumably fair recall of recent events/activities. The patients themselves, not only caregivers, could have divulged group assignment to the blinded evaluators. 2. The control group lacked a social stimulation intervention so the modest benefits of CMI could be ascribed to nonspecific social stimulation effects, rather than specific properties of the CMI. 3. The CMI group was responsible for paying for treatment and attending frequent training sessions. Accordingly, differences in financial or psychosocial resources may have impacted differences in outcome. 4. “Mood responders” were defined as patients who maintain or improve their baseline GDS score. However, GDS depression scores were low in both groups, with means well below the cutoff for even mild depression. Lack of change or improvement in such subjects would not qualify as a response. 5. Instead using of a more conventional paired t-test, the authors treated data from each group at different points in time as though from different groups, suggesting that large within-subject variance may have reduced statistical significance with analysis of within-subject change. The unreliability of the MMSE for measuring short-term change is well known. [2] 6. Failure to adjust for multiple statistical analyses increased the probability of a type I error. The only justification offered is that such a correction would have increased the probability of a type II error. 7. The conclusions regarding behavioral benefits were based on comparisons of the mean scores on the ADRQL and NPI only at study endpoint, without controlling for baseline data. Hence, the differences between groups at endpoint may simply have reflected baseline differences in the two groups. 8. The authors failed to describe CMI program attendance. Besides demonstrating tolerability of the intervention, such data might suggest a dose-effect of treatment, which would bolster the case for an effect of CMI. 9. The explanation of the negative effect of education is not clear. The logic of the cognitive reserve hypothesis is inconsistent with the notion that higher levels of education could explain poorer performance on cognitive measures. References 1. Olazaran J, Muniz R, Reisberg, B, et al. Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer’s disease. Neurology 2004;63:2348-2353. 2. Clark, CM, Sheppard L, Fillenbaum GG, et al. Variability in Annual Mini-Mental State Examinations Score in Patients With Probable Alzheimer Disease. Arch Neurol. 1999;56:857-62.
Reply to Kavirajan 8 March 2005
Javier Olazarán, Fundación Maria Wolff Montesa 11, E-28006 Madrid, Spain, Ruben Muñiz Send Correspondence to journal: Re: Reply to Kavirajan javier{at}mariawolff.es Javier Olazarán, et al.	As Dr. Kavirajan states, our paper has some methodological limitations which are already discussed in our article. Program attendance and lack of a dose effect are described in the Results (‘Safety and Compliance’ and last paragraph) whereas statistical and other limitations regarding study design are discussed in the final paragraph. A completely blind assessment in non-pharmacological interventions is very difficult, if not impossible. Ideally, a mock intervention should have been designed and implemented but, even under those circumstances, the quality of blinding is questionable. [3] Kavirajan mentions that patients and caregivers could have mentioned issues related to cognitive-motor intervention during assessments. It is unlikely that a systematic bias could have been introduced because our evaluators were blind not only to patient group, but also to study design. Since Alzheimer disease (AD) is a progressive and irreversible condition, lack of deterioration is gaining acceptance as a way of determining response in long-term trials. [4,5] As long as affective disturbances increase from mild cognitive impairment to more advanced dementia stages, defining response should also be adequate for the affective domain. [6] The cognitive reserve concept does not predict a poorer cognitive performance in patients with higher educational attainment. Rather, cognitive reserve would allow better coping with AD pathology. For that reason, given a level of clinical severity, the underlying AD pathology would be more advanced in patients with more cognitive reserve. [7] These patients would be at their limit of compensating capacity and therefore would hardly benefit from the strategies given at the cognitive-motor sessions. References 3. Davis RN, Massman PJ, Doody RS. Cognitive intervention in Alzheimer disease: a randomized placebo-controlled study. Alzheimer Dis Assoc Disord 2001;15:1-9. 4. Farlow M, Anand R, Mesina J, Hartman R, Veach J. A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol 2000; 44: 236-241. 5. Wilcock G, Howe I, Coles H, Lilienfeld S, Truyen L, Zhu Y, et al. A long-term comparison of galantamine and donepezil in the treatment of Alzheimer’s disease. Drugs Aging 2003; 20: 777-789. 6. Eastwood R, Reisberg B. Abnormal behaviour in Alzheimer’s disease. In: Gauthier S, editor. Clinical diagnosis and management of Alzheimer’s disease. Second edition revised. London: Martin Dunitz 2001; 197-212. 7. Scarmeas N, Stern Y. Cognitive reserve and lifestyle. J Clin Exp Neuropsychol 2003; 25: 625-633.