Skip to main content
NCBI home page
Canadian Family Physician logoLink to Canadian Family Physician
. 1999 Apr;45:945–952.

Diagnosis of dementia and treatment of Alzheimer's disease. Pharmacologic management of disease progression and cognitive impairment.

R van Reekum 1, M Simard 1, K Farcnik 1
PMCID: PMC2328342  PMID: 10216793

Abstract

OBJECTIVE: To highlight the importance of family physicians in the management of Alzheimer's disease (AD) and related dementias. To provide an update on the diagnostic workup of people with suspected dementia and on the pharmacologic management of cognitive impairment and disease progression in AD. QUALITY OF EVIDENCE: MEDLINE and Psychological Abstracts were searched using the terms "cognitive enhancers" or a specific drug name and "dementia (exp)." Evidence is generally limited but promising. Methodologic flaws in existing research likely to affect clinicians are briefly reviewed. MAIN MESSAGE: Increasing evidence suggests that early intervention can delay the progression of AD and improve the symptoms and function of those affected. Available treatments have modest but important effects on the outcome of patients with AD; some patients respond dramatically. Most currently available treatments are relatively safe in carefully selected cases. CONCLUSIONS: The diagnostic workup of most cases of dementia can at least be initiated in family physicians' offices. Beginning the workup is important because, for treating AD, the earlier you start, the better. Donepezil, vitamin E, and, in the near future, propentofylline are the main pharmacologic choices for improving cognition and slowing disease progression.

Full text

PDF
945

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albert M. L., Feldman R. G., Willis A. L. The 'subcortical dementia' of progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 1974 Feb;37(2):121–130. doi: 10.1136/jnnp.37.2.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burke W. J., Ranno A. E., Roccaforte W. H., Wengel S. P., Bayer B. L., Willcockson N. K. L-deprenyl in the treatment of mild dementia of the Alzheimer type: preliminary results. J Am Geriatr Soc. 1993 Apr;41(4):367–370. doi: 10.1111/j.1532-5415.1993.tb06942.x. [DOI] [PubMed] [Google Scholar]
  3. Caine E. D. Pseudodementia. Current concepts and future directions. Arch Gen Psychiatry. 1981 Dec;38(12):1359–1364. doi: 10.1001/archpsyc.1981.01780370061008. [DOI] [PubMed] [Google Scholar]
  4. Cummings J. L., Benson D. F. Subcortical dementia. Review of an emerging concept. Arch Neurol. 1984 Aug;41(8):874–879. doi: 10.1001/archneur.1984.04050190080019. [DOI] [PubMed] [Google Scholar]
  5. Finali G., Piccirilli M., Piccinin G. L. Neuropsychological correlates of L-deprenyl therapy in idiopathic parkinsonism. Prog Neuropsychopharmacol Biol Psychiatry. 1994 Jan;18(1):115–128. doi: 10.1016/0278-5846(94)90028-0. [DOI] [PubMed] [Google Scholar]
  6. Folstein M. F., Folstein S. E., McHugh P. R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar]
  7. Giacobini E. Therapy of Alzheimer disease: symptomatic or neuroprotective? J Neural Transm Suppl. 1994;43:211–217. [PubMed] [Google Scholar]
  8. Hachinski V. C., Iliff L. D., Zilhka E., Du Boulay G. H., McAllister V. L., Marshall J., Russell R. W., Symon L. Cerebral blood flow in dementia. Arch Neurol. 1975 Sep;32(9):632–637. doi: 10.1001/archneur.1975.00490510088009. [DOI] [PubMed] [Google Scholar]
  9. Herrmann N., Lanctôt K. L. From transmitters to treatment: the pharmacotherapy of behavioural disturbances in dementia. Can J Psychiatry. 1997 Jun;42 (Suppl 1):51S–64S. [PubMed] [Google Scholar]
  10. Kertesz A., Clydesdale S. Neuropsychological deficits in vascular dementia vs Alzheimer's disease. Frontal lobe deficits prominent in vascular dementia. Arch Neurol. 1994 Dec;51(12):1226–1231. doi: 10.1001/archneur.1994.00540240070018. [DOI] [PubMed] [Google Scholar]
  11. Kertesz A., Hudson L., Mackenzie I. R., Munoz D. G. The pathology and nosology of primary progressive aphasia. Neurology. 1994 Nov;44(11):2065–2072. doi: 10.1212/wnl.44.11.2065. [DOI] [PubMed] [Google Scholar]
  12. Khachaturian Z. S. Diagnosis of Alzheimer's disease. Arch Neurol. 1985 Nov;42(11):1097–1105. doi: 10.1001/archneur.1985.04060100083029. [DOI] [PubMed] [Google Scholar]
  13. Lantos P. L., Papp M. I. Cellular pathology of multiple system atrophy: a review. J Neurol Neurosurg Psychiatry. 1994 Feb;57(2):129–133. doi: 10.1136/jnnp.57.2.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Le Bars P. L., Katz M. M., Berman N., Itil T. M., Freedman A. M., Schatzberg A. F. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. 1997 Oct 22;278(16):1327–1332. doi: 10.1001/jama.278.16.1327. [DOI] [PubMed] [Google Scholar]
  15. Marcusson J., Rother M., Kittner B., Rössner M., Smith R. J., Babic T., Folnegovic-Smalc V., Möller H. J., Labs K. H. A 12-month, randomized, placebo-controlled trial of propentofylline (HWA 285) in patients with dementia according to DSM III-R. The European Propentofylline Study Group. Dement Geriatr Cogn Disord. 1997 Sep-Oct;8(5):320–328. doi: 10.1159/000106650. [DOI] [PubMed] [Google Scholar]
  16. Marin D. B., Bierer L. M., Lawlor B. A., Ryan T. M., Jacobson R., Schmeidler J., Mohs R. C., Davis K. L. L-deprenyl and physostigmine for the treatment of Alzheimer's disease. Psychiatry Res. 1995 Oct 16;58(3):181–189. doi: 10.1016/0165-1781(95)02714-8. [DOI] [PubMed] [Google Scholar]
  17. McGeer P. L., Schulzer M., McGeer E. G. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology. 1996 Aug;47(2):425–432. doi: 10.1212/wnl.47.2.425. [DOI] [PubMed] [Google Scholar]
  18. McKeith I. G., Fairbairn A. F., Bothwell R. A., Moore P. B., Ferrier I. N., Thompson P., Perry R. H. An evaluation of the predictive validity and inter-rater reliability of clinical diagnostic criteria for senile dementia of Lewy body type. Neurology. 1994 May;44(5):872–877. doi: 10.1212/wnl.44.5.872. [DOI] [PubMed] [Google Scholar]
  19. McKeith I. G., Galasko D., Kosaka K., Perry E. K., Dickson D. W., Hansen L. A., Salmon D. P., Lowe J., Mirra S. S., Byrne E. J. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996 Nov;47(5):1113–1124. doi: 10.1212/wnl.47.5.1113. [DOI] [PubMed] [Google Scholar]
  20. McKeith I. G., Perry R. H., Fairbairn A. F., Jabeen S., Perry E. K. Operational criteria for senile dementia of Lewy body type (SDLT). Psychol Med. 1992 Nov;22(4):911–922. doi: 10.1017/s0033291700038484. [DOI] [PubMed] [Google Scholar]
  21. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. 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. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  22. Miller B. L., Ikonte C., Ponton M., Levy M., Boone K., Darby A., Berman N., Mena I., Cummings J. L. A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations. Neurology. 1997 Apr;48(4):937–942. doi: 10.1212/wnl.48.4.937. [DOI] [PubMed] [Google Scholar]
  23. Neary D., Snowden J. Fronto-temporal dementia: nosology, neuropsychology, and neuropathology. Brain Cogn. 1996 Jul;31(2):176–187. doi: 10.1006/brcg.1996.0041. [DOI] [PubMed] [Google Scholar]
  24. Padovani A., Di Piero V., Bragoni M., Iacoboni M., Gualdi G. F., Lenzi G. L. Patterns of neuropsychological impairment in mild dementia: a comparison between Alzheimer's disease and multi-infarct dementia. Acta Neurol Scand. 1995 Dec;92(6):433–442. doi: 10.1111/j.1600-0404.1995.tb00477.x. [DOI] [PubMed] [Google Scholar]
  25. Papp M. I., Kahn J. E., Lantos P. L. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. 1989 Dec;94(1-3):79–100. doi: 10.1016/0022-510x(89)90219-0. [DOI] [PubMed] [Google Scholar]
  26. Piccinin G. L., Finali G., Piccirilli M. Neuropsychological effects of L-deprenyl in Alzheimer's type dementia. Clin Neuropharmacol. 1990 Apr;13(2):147–163. doi: 10.1097/00002826-199004000-00004. [DOI] [PubMed] [Google Scholar]
  27. Pillon B., Deweer B., Michon A., Malapani C., Agid Y., Dubois B. Are explicit memory disorders of progressive supranuclear palsy related to damage to striatofrontal circuits? Comparison with Alzheimer's, Parkinson's, and Huntington's diseases. Neurology. 1994 Jul;44(7):1264–1270. doi: 10.1212/wnl.44.7.1264. [DOI] [PubMed] [Google Scholar]
  28. Pillon B., Dubois B., Ploska A., Agid Y. Severity and specificity of cognitive impairment in Alzheimer's, Huntington's, and Parkinson's diseases and progressive supranuclear palsy. Neurology. 1991 May;41(5):634–643. doi: 10.1212/wnl.41.5.634. [DOI] [PubMed] [Google Scholar]
  29. Prince M., Rabe-Hesketh S., Brennan P. Do antiarthritic drugs decrease the risk for cognitive decline? An analysis based on data from the MRC treatment trial of hypertension in older adults. Neurology. 1998 Feb;50(2):374–379. doi: 10.1212/wnl.50.2.374. [DOI] [PubMed] [Google Scholar]
  30. Rogers J., Kirby L. C., Hempelman S. R., Berry D. L., McGeer P. L., Kaszniak A. W., Zalinski J., Cofield M., Mansukhani L., Willson P. Clinical trial of indomethacin in Alzheimer's disease. Neurology. 1993 Aug;43(8):1609–1611. doi: 10.1212/wnl.43.8.1609. [DOI] [PubMed] [Google Scholar]
  31. Rogers S. L., Friedhoff L. T. Long-term efficacy and safety of donepezil in the treatment of Alzheimer's disease: an interim analysis of the results of a US multicentre open label extension study. Eur Neuropsychopharmacol. 1998 Feb;8(1):67–75. doi: 10.1016/s0924-977x(97)00079-5. [DOI] [PubMed] [Google Scholar]
  32. Rogers S. L., Friedhoff L. T. The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. The Donepezil Study Group. Dementia. 1996 Nov-Dec;7(6):293–303. doi: 10.1159/000106895. [DOI] [PubMed] [Google Scholar]
  33. Román G. C., Tatemichi T. K., Erkinjuntti T., Cummings J. L., Masdeu J. C., Garcia J. H., Amaducci L., Orgogozo J. M., Brun A., Hofman A. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993 Feb;43(2):250–260. doi: 10.1212/wnl.43.2.250. [DOI] [PubMed] [Google Scholar]
  34. Rosen W. G., Terry R. D., Fuld P. A., Katzman R., Peck A. Pathological verification of ischemic score in differentiation of dementias. Ann Neurol. 1980 May;7(5):486–488. doi: 10.1002/ana.410070516. [DOI] [PubMed] [Google Scholar]
  35. Sahgal A., Galloway P. H., McKeith I. G., Lloyd S., Cook J. H., Ferrier I. N., Edwardson J. A. Matching-to-sample deficits in patients with senile dementias of the Alzheimer and Lewy body types. Arch Neurol. 1992 Oct;49(10):1043–1046. doi: 10.1001/archneur.1992.00530340059019. [DOI] [PubMed] [Google Scholar]
  36. Sahgal A., McKeith I. G., Galloway P. H., Tasker N., Steckler T. Do differences in visuospatial ability between senile dementias of the Alzheimer and Lewy body types reflect differences solely in mnemonic function? J Clin Exp Neuropsychol. 1995 Feb;17(1):35–43. doi: 10.1080/13803399508406579. [DOI] [PubMed] [Google Scholar]
  37. Sano M., Ernesto C., Thomas R. G., Klauber M. R., Schafer K., Grundman M., Woodbury P., Growdon J., Cotman C. W., Pfeiffer E. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997 Apr 24;336(17):1216–1222. doi: 10.1056/NEJM199704243361704. [DOI] [PubMed] [Google Scholar]
  38. Schneider L. S., Farlow M. R., Henderson V. W., Pogoda J. M. Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer's disease. Neurology. 1996 Jun;46(6):1580–1584. doi: 10.1212/wnl.46.6.1580. [DOI] [PubMed] [Google Scholar]
  39. Schneider L. S., Olin J. T. Overview of clinical trials of hydergine in dementia. Arch Neurol. 1994 Aug;51(8):787–798. doi: 10.1001/archneur.1994.00540200063018. [DOI] [PubMed] [Google Scholar]
  40. Schneider L. S., Tariot P. N. Emerging drugs for Alzheimer's disease. Mechanisms of action and prospects for cognitive enhancing medications. Med Clin North Am. 1994 Jul;78(4):911–934. doi: 10.1016/s0025-7125(16)30142-0. [DOI] [PubMed] [Google Scholar]
  41. Tariot P. N., Weingartner H. A psychobiologic analysis of cognitive failures. Structure and mechanisms. Arch Gen Psychiatry. 1986 Dec;43(12):1183–1188. doi: 10.1001/archpsyc.1986.01800120069014. [DOI] [PubMed] [Google Scholar]
  42. Villardita C. Alzheimer's disease compared with cerebrovascular dementia. Neuropsychological similarities and differences. Acta Neurol Scand. 1993 Apr;87(4):299–308. doi: 10.1111/j.1600-0404.1993.tb05512.x. [DOI] [PubMed] [Google Scholar]
  43. van Reekum R., Black S. E., Conn D., Clarke D. Cognition-enhancing drugs in dementia: a guide to the near future. Can J Psychiatry. 1997 Jun;42 (Suppl 1):35S–50S. [PubMed] [Google Scholar]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada

RESOURCES