Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-22T18:28:57.208Z Has data issue: false hasContentIssue false
  • English
  • Français

The effect of cholinesterase inhibitors on decline in multiple functional domains in Alzheimer's disease: a two-year observational study in the Sunnybrook dementia cohort

Published online by Cambridge University Press:  08 July 2008

Pearl Behl ,
Krista L. Lanctôt ,
David L. Streiner  and
Sandra E. Black
Pearl Behl
Affiliation:
Linda C. Campbell Cognitive Neurology Research Unit, University of Toronto, Canada Faculty of Medicine, University of Toronto, Canada
Krista L. Lanctôt
Affiliation:
Sunnybrook Health Sciences Center, University of Toronto, Canada Faculty of Medicine, University of Toronto, Canada Department of Psychiatry, University of Toronto, Canada Neuroscience Research Program, Sunnybrook Research Institute, University of Toronto, Canada
David L. Streiner
Affiliation:
Faculty of Medicine, University of Toronto, Canada Department of Psychiatry, University of Toronto, Canada Kunin-Lunenfeld Applied Research Unit, Baycrest Centre, University of Toronto, Canada
Sandra E. Black*
Affiliation:
Linda C. Campbell Cognitive Neurology Research Unit, University of Toronto, Canada Sunnybrook Health Sciences Center, University of Toronto, Canada Department of Medicine (Neurology), University of Toronto, Canada Faculty of Medicine, University of Toronto, Canada Neuroscience Research Program, Sunnybrook Research Institute, University of Toronto, Canada Kunin-Lunenfeld Applied Research Unit, Baycrest Centre, University of Toronto, Canada Rotman Research Institute, University of Toronto, Canada
*
Correspondence should be addressed to: Dr. Sandra E. Black, Brill Chair of Neurology (Medicine), Sunnybrook Health Sciences Centre, Room A421, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada, Tel: +1 416 480 4551, Fax: +1 416 480 4552. Email: [email protected].
Get access

Abstract

Background: Despite widespread use of second-generation cholinesterase inhibitors (CHEIs) for the symptomatic treatment of Alzheimer's disease (AD), little is known about possible long-term effects in different functional domains. This study seeks to assess change in activities of daily living (ADLs) over two years in AD patients treated with CHEIs matched to untreated patients in the same longitudinal cohort study.

Methods: This study is based on the two-year prospective cohort study at the Memory Clinic in Sunnybrook Health Sciences Centre, University of Toronto. Probable AD patients (N = 130: untreated = 65, treated = 65) underwent standardized neuropsychological assessments including the Disability Assessment for Dementia Scale (DAD), at baseline, one-year and two-year follow-up. Groups received a careful evaluation of comorbid illnesses, concomitant medication use, and vascular risk factors.

Results: At baseline, there were no significant differences in demographics and characteristics. Treated patients showed less decline in overall function and in instrumental and basic ADLs. Furthermore, less decline was seen in the overall scores for initiation and planning over two years with moderate to large effect sizes.

Conclusion: These findings have clinical relevance since functional ability has been increasingly recognized as a key outcome variable in AD treatment. It is also of note that the subscores reflecting executive functioning appear to drive these beneficial differences.

Keywords

functional declineinstrumental ADLbasic ADLDisability Assessment for Dementia Scale (DAD)executive functionAlzheimer's disease
Type
Research Article
Information
International Psychogeriatrics , Volume 20 , Issue 6 , December 2008 , pp. 1141 - 1159
Copyright
Copyright © International Psychogeriatric Association 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th edn. Washington DC: American Psychiatric Association.Google Scholar
Behl, P., Lanctot, K. L., Streiner, D. L., Guimont, I. and Black, S. E. (2006). Cholinesterase inhibitors slow decline in executive functions, rather than memory, in Alzheimer's disease: a 1-year observational study in the Sunnybrook dementia cohort. Current Alzheimer Research, 3, 147–156.CrossRefGoogle ScholarPubMed
Boyle, P. A. (2004). Assessing and predicting functional impairment in Alzheimer's disease: the emerging role of frontal system dysfunction. Current Psychiatry Reports, 6, 20–24.CrossRefGoogle ScholarPubMed
Boyle, P. A., Malloy, P. F., Salloway, S., Cahn-Weiner, D. A., Cohen, R. and Cummings, J. L. (2003). Executive dysfunction and apathy predict functional impairment in Alzheimer disease. American Journal of Geriatric Psychiatry, 11, 214–221.CrossRefGoogle ScholarPubMed
Courtney, C. et al. (2004). Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. Lancet, 363, 2105–2115.Google ScholarPubMed
Feldman, H., Gauthier, S., Hecker, J., Vellas, B., Emir, B., Mastey, V. and Subbiah, P. (2003). Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden. Journal of the American Geriatrics Society, 51, 737–744.CrossRefGoogle ScholarPubMed
Feldman, H., Gauthier, S., Hecker, J., Vellas, B., Subbiah, P. and Whalen, E. (2001). A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease. Neurology, 57, 613–620.CrossRefGoogle ScholarPubMed
Geldmacher, D. S., Provenzano, G., McRae, T., Mastey, V. and Ieni, J. R. (2003). Donepezil is associated with delayed nursing home placement in patients with Alzheimer's disease. Journal of the American Geriatrics Society, 51, 937–944.CrossRefGoogle ScholarPubMed
Gelinas, I., Gauthier, L., McIntyre, M. and Gauthier, S. (1999). Development of a functional measure for persons with Alzheimer's disease: the disability assessment for dementia. American Journal of Occupational Therapy, 53, 471–481.CrossRefGoogle ScholarPubMed
Gelinas, I., Gauthier, S. and Cyrus, P. A. (2000). Metrifonate enhances the ability of Alzheimer's disease patients to initiate, organize, and execute instrumental and basic activities of daily living. Journal of Geriatric Psychiatry and Neurology, 13, 9–16.CrossRefGoogle ScholarPubMed
Glosser, G., Gallo, J., Duda, N., de Vries, J. J., Clark, C. M. and Grossman, M. (2002). Visual perceptual functions predict instrumental activities of daily living in patients with dementia. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 15, 198–206.Google ScholarPubMed
Holland, B. S. and Copenhaver, M. D. (1988). Improved Bonferroni-type multiple testing procedures. Psychological Bulletin, 104, 145–149.CrossRefGoogle Scholar
Karaman, Y., Erdogan, F., Koseoglu, E., Turan, T. and Ersoy, A. O. (2005). A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 19, 51–56.CrossRefGoogle ScholarPubMed
Khang, P., Weintraub, N. and Espinoza, R. T. (2004). The use, benefits, and costs of cholinesterase inhibitors for Alzheimer's dementia in long-term care: are the data relevant and available? Journal of the American Medical Directors Association, 5, 249–255.CrossRefGoogle ScholarPubMed
Lanctôt, K. L. et al. (2003). Efficacy and safety of cholinesterase inhibitors in Alzheimer's disease: a meta-analysis. Canadian Medical Association Journal, 169, 557–564.Google ScholarPubMed
Lingler, J. H., Martire, L. M. and Schulz, R. (2005). Caregiver-specific outcomes in antidementia clinical drug trials: a systematic review and meta-analysis. Journal of the American Geriatrics Society, 53, 983–990.CrossRefGoogle ScholarPubMed
Lopez, O. L., Becker, J. T., Saxton, J., Sweet, R. A., Klunk, W. and DeKosky, S. T. (2005). Alteration of a clinically meaningful outcome in the natural history of Alzheimer's disease by cholinesterase inhibition. Journal of the American Geriatrics Society, 53, 83–87.CrossRefGoogle ScholarPubMed
Lopez, O. L., Becker, J. T., Wisniewski, S., Saxton, J., Kaufer, D. I. and DeKosky, S. T. (2002). Cholinesterase inhibitor treatment alters the natural history of Alzheimer's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 72, 310–314.CrossRefGoogle ScholarPubMed
Marshall, G. A., Fairbanks, L. A., Tekin, S., Vinters, H. V. and Cummings, J. L. (2006). Neuropathologic correlates of activities of daily living in Alzheimer disease. Alzheimer Disease and Associated Disorders, 20, 56–59.CrossRefGoogle ScholarPubMed
Mattis, S. (1976). Mental status examination for organic mental syndrome in the elderly patient. In Bellak and, L. Karasu, T.B. (eds.), Lezak Neuropsychological Assessment (pp. 739–740). New York: Grune & Stratton.Google Scholar
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.CrossRefGoogle ScholarPubMed
Mesulam, M. (2004). The cholinergic lesion of Alzheimer's disease: pivotal factor or side show? Learning and Memory, 11, 43–49.CrossRefGoogle ScholarPubMed
Mohr, E., Feldman, H. and Gauthier, S. (1995). Canadian guidelines for the development of antidementia therapies: a conceptual summary. Canadian Journal of Neurological Sciences, 22, 62–71.CrossRefGoogle ScholarPubMed
Mohs, R. C. et al. (2001). A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology, 57, 481–488.CrossRefGoogle ScholarPubMed
Perry, R. J. and Hodges, J. R. (1999). Attention and executive deficits in Alzheimer's disease: a critical review. Brain, 122, 383–404.CrossRefGoogle ScholarPubMed
Perry, R. J. and Hodges, J. R. (2000). Relationship between functional and neuropsychological performance in early Alzheimer disease. Alzheimer Disease and Associated Disorders, 14, 1–10.CrossRefGoogle ScholarPubMed
Raskind, M. A., Peskind, E. R., Truyen, L., Kershaw, P. and Damaraju, C. V. (2004). The cognitive benefits of galantamine are sustained for at least 36 months: a long-term extension trial. Archives of Neurology, 61, 252–256.CrossRefGoogle ScholarPubMed
Severson, M. A. et al. (1994). Patterns and predictors of institutionalization in community-based dementia patients. Journal of the American Geriatrics Society, 42, 181–185.Google ScholarPubMed
Tariot, P. N., Solomon, P. R., Morris, J. C., Kershaw, P., Lilienfeld, S. and Ding, C. (2000). A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology, 54, 2269–2276.CrossRefGoogle ScholarPubMed
Teri, L., Borson, S., Kiyak, H. A. and Yamagishi, M. (1989). Behavioral disturbance, cognitive dysfunction, and functional skill. Prevalence and relationship in Alzheimer's disease. Journal of the American Geriatrics Society, 37, 109–116.Google ScholarPubMed
Winblad, B. et al. (2001). A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology, 57, 489–495.CrossRefGoogle ScholarPubMed