Patient Care Neurology & Psychiatry - November 2007 - (Page 15)

Dementia I anti-apoptotic protein Bcl-2.29 Donepezil has been shown not only to protect cortical neurons against glutamate neurotoxicity but also to prevent apoptotic neuronal death.30 N-methyl-D-aspartate receptor antagonists Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate leads to a neuronal calcium overload that is implicated in the neuronal death characteristic of AD.31 Because physiologic activation of the NMDA receptor is necessary for normal cognitive function, only compounds that finely modulate NMDA receptor activity can protect cholinergic neurons while permitting normal cognitive function.32 Research studies have also suggested that galantamine and donepezil inhibit glutamate-induced excitotoxicity associated with overstimulation of the NMDA receptor by glutamate.28,29 Memantine (Namenda), a low-moderate affinity, uncompetitive (channel blocking) NMDA-receptor antagonist, appears to block pathologic neural toxicity associated with prolonged glutamate release but not physiologic activation of the NMDA receptor.33 The combiREFERENCES 1. Lynch PD, Pocinki KM (eds). 2003 Progress Report on Alzheimer’s Disease (NIH Publication Number: 04-5570). Silver Spring, MD: Alzheimer’s Disease Education and Referral (ADEAR) Center; 2004. 2. Maurer K, Volk S, Gerbaldo H. Auguste D and Alzheimer’s disease. Lancet. 1997;349(9064):1546-1549. 3. Hebert LE, Scherr PA, Bienias JL, et al. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60(8):1119-1122. 4. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998;88(9):1337-1342. 5. Cummings JL, Cole G. Alzheimer disease. JAMA. 2002;287(18):23352338. 6. Schulz R, Mendelsohn AB, Haley WE, et al; Resources for Enhancing Alzheimer’s Caregiver Health (REACH) Investigators. End-of-life care and the effects of bereavement on family caregivers of persons with dementia. N Engl J Med. 2003;349(20):1936-1942. 7. Boustani M, Peterson B, Hanson L, et al. Screening for dementia in primary care: a Summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003;138:927-937. 8. Knopman DS, Dekosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56:1143. 9. Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method of grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198. 10. Freidl W, Schmidt R, Stronegger WJ, et al. Mini-mental state examination: influence of sociodemographic, environmental and behavioral factors and vascular risk factors. J Clin Epidemiol. 1996;49:73-78. nation of memantine and donepezil has been shown to have greater clinical efficacy than either drug alone and is better tolerated than monotherapy.34 Memantine has been shown to improve symptoms and reduce the rate of clinical deterioration in moderate to severe AD. This drug has demonstrated the ability to delay cognitive and functional deterioration and was not associated with a significant frequency of adverse events.35,36 Donepezil has been demonstrated to improve cognition and preserves function in severe AD.37 This has led to FDA approval for donepezil for severe AD as well as for the mild and moderate stages. Statistically significant improvements in higher-level functions were noted in patients receiving memantine compared with placebo in patients with moderate to severe AD receiving stable donepezil treatment.38 The combination of donepezil and memantine may favorably impact overall functional levels and some of the cognitive processing underlying ADL performance in severe AD patients. Memantine is not a substitute for ChEIs but rather is a useful addition. Continued on page 18 11. Borson S, Scanlan J, Brush M, et al. The mini-cog: a cognitive ‘vital signs’ measure for dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry. 2000;15:1021-1027. 12. Sunderland T, Hill JL, Mellow AM, et al. Clock drawing in Alzheimer’s disease: a novel measure of dementia severity. J Am Geriatr Soc. 1998; 37:725-729. 13. Wolf-Klein GP, Silverstone FA, Levy AP, et al. Screening for Alzheimer’s disease by clock drawing. J Am Geriatr Soc. 1989;37:730-734. 14. Nishiwaki Y, Breeze E, Smeeth L, et al. Validity of the clock drawing test as a screening tool for cognitive impairment in the elderly. Am J Epidemiol. 2004;160:797-807. 15. Hansson O, Zetterberg H, Buchhave P, et al. Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5(3):228-234. 16. Hansson O, Zetterberg H, Buchhave P, et al. Prediction of Alzheimer’s disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment. Dement Geriatr Cogn Disord. 2007;23(5):316-320. 17. Burke WJ, Roccaforte WH, Wengel SP. The short form of the Geriatric Depression Scale: a comparison with the 30-item form. J Geriatr Psychiatry Neurol. 1991;4:173-178. 18. Andresen EM, Malgren JA, Carter WB, et al. Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale). Am J Prev Med. 1994;10:77-84. 19. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatr. 1960;23:56-62. 20. Forsell Y, Winblad B. Major depression in a population of demented and nondemented older people: prevalence and correlates. J Am Geriatr Soc. 1998;46:27-30. 21. Standridge JB. Pharmacotherapeutic approaches to the treatment of Alzheimer’s disease. Clin Ther. 2004;26(5):615-630. Continued on page 18 NOVEMBER 2007 PATIENT CARE NEUROLOGY & PSYCHIATRY 15

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Patient Care Neurology & Psychiatry - November 2007 Contents Research Digest Medicine in the News The 15-Minute Visit Dementia workup and treatment: Do the drugs really work? Help for Your Patients Who Suffer from Specific Phobias Clinical Clips Case & Comment The Science of Healing Classified Advertising

Patient Care Neurology & Psychiatry - November 2007

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