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LETTER TO THE EDITOR |
Department of Internal Medicine and Clinical Gerontology University of Toulouse France
Address correspondence to Sophie Gillette-Guyonnet, PhD, Service de Médecine Interne et de Gérontologie Clinique, Pavillon J. P. Junod, Centre Hospitalier Universitaire La Grave-Casselardit, 170 avenue de Cassalardit, TSA40031, 31059 Toulouse cedex 9, France. E-mail: gillette.s{at}chu-toulouse.fr or sophie.gillette{at}free.fr
To the Editor:
Since cholinesterase inhibitors (CEIs) were approved for use in mild-to-moderate Alzheimer's disease (AD), the therapeutic efficacy of this class of medications has largely centered on the demonstration of short-term improvement in cognition and global function. Later, evidence suggested that the beneficial effects of CEIs might be sustainable for at least 3 years (1). Mortality is an important outcome that is now considered in analyses of CEIs. As pointed out by Garcia and colleagues (2), results on mortality and CEIs are variable from one study to another. In addition to studies presented by Garcia and colleagues, two studies published in 2005 and 2006 concerned individuals living in nursing homes. In their recent paper, Winblad and colleagues (3) showed that donepezil improved cognition and preserved function in individuals with severe AD (Mini-Mental State Examination [MMSE] score <10) living in nursing homes 6 months after the initiation of treatment. The rate of mortality was not decreased in the treated group. Previously, Gasper and colleagues (4) performed a retrospective matched cohort study using the systematic assessment of geriatric drug use via an epidemiology database that contained data collected with the minimum dataset on a cross-section of 915,469 nursing home residents aged older than 65 years between 1998 and 2000 in six U.S. states. A total of 5423 users and 5423 nonusers of donepezil were identified. Donepezil users showed a lower mortality rate than nonusers over the 2-year study period (Cox proportional hazards models, hazard rate ratio = 0.89; 95% confidence interval [CI] = 0.83–0.92). This survival advantage remained after adjustment on confounding factors (sociodemographic variables, dementia severity, number of medications, major comorbid illnesses). In our article "Outcome of Alzheimer's Disease: Potential Impact of Cholinesterase Inhibitors" (4), we found that the risk of rapid deterioration of cognitive function, institutionalization, and weight loss was significantly decreased after a year's use of CEIs. The patients studied were initially living at home with mild-to-moderate dementia (MMSE score of 10–26 at baseline). Preliminary survival analysis over the 2-year study period showed a rate of mortality significantly lower among patients who had 3 and 4 consecutive exposures compared with untreated patients (4.41% and 3.68% compared to 12.28%). The hazard rate ratio was, respectively, 0.36 (95% CI: 0.15–0.88, p = 0250) and 0.29 (95% CI: 0.11–0.76, p =.0118). A similar relation was found for institutionalization. We must now test these associations by adjusting on confounding variables. These observations have implications for the socioeconomic impact of CEIs in patients with advanced dementia and for quality of life issues in the nursing home, and further studies are needed to conclude about the potential benefit of CEI use on mortality in AD patients. The treatment of the disease remains complex, and pharmacological methods must be associated with management of the complications to improve the outcome of AD patients.
References
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