Pharmacologic Management of Alzheimer Disease Part III: Nonsteroidal Antiinflammatory Drugs

Abstract

Spanish

French

OBJECTIVE:

To provide information about research evaluating the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the prevention, or delay in the onset of, Alzheimer disease (AD).

DATA SOURCES:

Studies, review articles, and editorials identified from MEDLINE searches (January 1990–December 1996) and bibliographies of identified articles. The addendum lists articles from 1996 to June 1999.

STUDY SELECTION:

Studies, review articles, and editorials addressing NSAIDs and AD pharmacotherapy research.

DATA EXTRACTION:

Pertinent information was selected and the data synthesized into a review format.

DATA SYNTHESIS:

AD is a complex disorder and there are numerous factors involved in the process. The pathology of AD is characterized by the development of amyloid plaques and neurofibrillary tangles. In addition, more than 40 immunoprotective proteins that are not unique to AD are found at autopsy that are normally absent, or present in very low concentrations, in normal brain. These findings suggest that AD may involve an inflammatory process. Preliminary results from studies investigating the incidence and onset of AD in patients with arthritis who have taken NSAIDs suggest that NSAIDs may have a protective effect. Studies evaluating the possible association between arthritis, NSAIDs, and AD are reviewed.

CONCLUSIONS:

Preliminary evidence suggests that NSAIDs may have a protective effect against the development of AD. Further prospective, double-blind, placebo-controlled studies are needed to determine the role of NSAIDs in AD. These dose-finding studies should focus on specific agents and identify the dosage and duration of therapy necessary for a protective or therapeutic effect. Additionally, not all elderly patients are candidates for NSAIDs. Determining the definitive mechanism of action of NSAIDs in AD may suggest alternative agents that have similar pharmacologic activity, but are associated with fewer adverse effects.

Keywords

nonsteroidal antiinflammatory drugs Alzheimer disease

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References

Wilcock

Harrold

. Treatment of Alzheimer's disease: Future directions. Acta Neurol Scand Suppl 1996;165 (suppl):S128–36.

McGeer

. The inflammatory response system of brain: Implications of therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 1995;21: 195–218.

McGeer

. Anti-inflammatory drugs in the fight against Alzheimer's disease. Ann N Y Acad Sci 1996;777: 213–20.

McGeer

Schulzer

McGeer

. Arthritis and anti-inflammatory agents as possible protective factor for Alzheimer's disease: A review of 17 epidemiologic studies. Neurology 1996;47: 425–32.

Haruda

. Nonsteroidal anti-inflammatory drugs in Alzheimer's disease (letter). Neurology 1995;45:2116.

McEvoy

, ed. AHFS drug information 96. Bethesda, MD: American Society of Hospital Pharmacists, 1996:1387,1408,1417,1430,1457.

Heyman

Wilkinson

Stafford

Helms

Sigmon

Weinberg

. Alzheimer's disease: A study of epidemiological aspects. Ann Neurol 1984;15: 335–41.

Folstein

McHugh

. “Mini-Mental State”: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12: 189–98.

Wechsler

. Manual for the Wechsler Adult Intelligence Scale. New York: Psychological Corporation, 1955.

10.

French

Schuman

Mortimer

Hutton

Boatman

Christians

. A case-control study of dementia of the Alzheimer's type. Am J Epidemiol 1985;121: 414–21.

11.

Hutton

. Results of clinical assessment for the dementia syndrome: Implications for epidemiologic studies. In: Mortimer

Schuman

, eds. The epidemiology of dementia. New York: Oxford University Press, 1981: 62–9.

12.

Graves

White

Koepsell

Reifler

van Belle

Larson

A case—control study of Alzheimer's disease. Ann Neurol 1990;28:766–74.

13.

Diagnostic and statistical manual of mental disorders. 3rd ed., revised. Washington, DC: American Psychiatric Association, 1987.

14.

McKhann

Drachman

Folstein

Katzman

Price

Stadlan

. 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 of Alzheimer's Disease. Neurology 1984;34: 939–44.

15.

Broe

Henderson

Creasey

McCusker

Korten

Jorm

A case—control study of Alzheimer's disease in Australia. Neurology 1990;40:1698–707.

16.

Wechsler

. A standardized memory scale for clinical use. J Psychol 1945;19: 87–95.

17.

Goldstein

Sheerer

. Tests of abstract and concrete behavior. In: Weider

, ed. Contributions to medical psychology, Vol 2. New York: Ronald Press, 1953.

18.

Benton

Hamsher

. Multilingual aphasia examination. Iowa City, IA: University of Iowa, 1976.

19.

Shen

Chen

Zhau

Silverman

. A case—control study of Alzheimer's disease in China. Neurology 1992;42: 1481–8.

20.

Differential Diagnosis of Dementia Scale. Geneva: World Health Organization, Division of Mental Health.

21.

Rogers

Kirby

Hempelman

Berry

McGeer

Kaszniak

. Clinical trial of indomethacin in Alzheimer's disease. Neurology 1993;43: 1609–11.

22.

Rosen

Mohs

Davis

. A new rating scale for Alzheimer's disease. Am J Psychiatry 1984;141: 1356–64.

23.

Kaplan

Goodglass

Weintraub

. The Boston Naming Test. Boston: E Kaplan & H Goodglass, 1978.

24.

Varney

Spreen

. Contributions to neuropsychological assessment. In: Benton

Hamsher

, eds. New York: Psychological Corporation, 1981.

25.

The Canadian Study of Health and Aging: Risk factors for Alzheimer's disease in Canada. Neurology 1994;44: 2073–80.

26.

Teng

Chui

. The Modified Mini-Mental State (3MS) Examination. J Clin Psychiatry 1987;48: 314–8.

27.

Breitner

JCS

Gau

Welsh

Plassman

McDonald

Helms

Inverse association of anti-inflammatory treatments and Alzheimer's disease: Initial results of a co-twin control study. Neurology 1994;44:227–32.

28.

Brandt

Spencer

Folstein

. The telephone interview for cognitive status. Neuropsychiatry Neuropsychol Behav Neurol 1988;1: 111–7.

29.

Silverman

Breitner

JCS

Mohs

Davis

. Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias. Am J Psychiatry 1986;143: 1279–82.

30.

Rich

Rasmusson

Folstein

Carson

Kawas

Brandt

. Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology 1995;45: 51–5.

31.

Gollin

. Developmental studies of visual recognition of incomplete objects. Percept Mot Skills 1960;11: 289–98.

32.

Moss

Albert

Butters

Payne

. Differential patterns of memory loss among patients with Alzheimer's disease, Huntington's disease and alcoholic Korsakoff's syndrome. Arch Neurol 1986;43: 239–46.

33.

De Renzi

Vignolo

. The Token Test: A sensitive test to detect disturbances in aphasia. Brain 1962;85: 665–78.

34.

Breitner

JCS

Welsh

Helms

Gaskell

Gau

Roses

Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H_₂ blocking drugs. Neurobiol Aging 1995;16:523–30.

35.

Andersen

Launer

Ott

Hoes

Breteler

MMB

Hofman

. Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? The Rotterdam Study. Neurology 1995;45: 1441–5.

36.

Copeland

JRM

Kellerer

Kellett

Gourlay

Gurland

Fleiss

A semi-structured clinical interview for the assessment and diagnosis of mental state in the elderly: The Geriatric Mental State Schedule. Psychol Med 1976;6:439–49.

37.

Berg

. Clinical Dementia Rating (CDR). Psychopharmacol Bull 1988;25: 637–9.

38.

Roth

Tym

Mountjoy

Huppert

Hendrie

Verma

CAMDEX: A standardised instrument for the diagnosis of mental disorders in the elderly with special reference to the early detection of dementia. Br J Psychiatry 1986;149:698–709.

39.

Stewart

Kawas

Corrada

Metter

. Risk of Alzheimer's disease and duration of NSAID use. Neurology 1997;48: 626–32.

40.

Shock

Greulich

Andres

Arenberg

Costa

Jr Lakatta

Normal human aging: the Baltimore Longitudinal Study of Aging (NIH Pub. No. 84–2450). Washington, DC: US Government Printing Office, 1984.

41.

Blessed

Tomlinson

Roth

. The association between quantitative measures of dementia and of senile changes in the cerebral gray matter of elderly subjects. Br J Psychiatry 1968;114: 797–811.

42.

Grober

Buschke

. Genuine memory deficits in dementia. Dev Neuropsychol 1987;3: 13–6.

43.

Army Individual Test Battery. Manual of directions and scoring. Washington, DC: War Department, Adjuvant General's Office, 1944.

44.

Rouleau

Salmon

Butters

Kennedy

McGuire

. Quantitative and qualitative analyses of clock drawings in Alzheimer's and Hunting-ton's disease. Brain Cogn 1992;18: 70–87.

45.

Benton

. Differential behavioral effects in frontal lobe disease. Neuropsychologia 1968;6: 53–60.

46.

Pfeffer

Kurosaki

Harrah

Chance

Filos

. Measurement of functional activities in older adults in the community. J Gerontol 1982;37: 328–9.

47.

Radloff

. The CES-D scale: A self-report depression scale for research in the general population. Appl Psychol Meas 1977;1: 385–401.

48.

Nelson

O'Connell

. Dementia: The estimation of pre-morbid intelligence using the New Adult Reading Test. Cortex 1978;14: 234–44.

49.

Wilkinson

Graham-White

. Psychogeriatric Dependency Rating Scales (PGDRS): A method of assessment for use by nurses. Br J Psychiatry 1980;137: 558–65.

50.

Kukull

Larson

Stergachis

McCormick

Bowen

Teri

nonsteroidal anti-inflammatory drug use and risk of Alzheimer's disease (abstract). Neurology 1994;44 (suppl 2):A237.

51.

Saag

Rubenstein

Chrischilles

Wallace

. Nonsteroidal antiinflammatory drugs and cognitive decline in the elderly. J Rheumatol 1995;22: 2142–7.

52.

Coroni-Huntley

Brock

Ostfeld

Taylor

Wallace

, eds. National Institute of Aging. Established Populations for Epidemiologic Studies of the Elderly: resource data book. Bethesda, MD: National Institutes of Health, 1986.

53.

Pfeifer

. A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J Am Geriatr Soc 1975;23: 433–41.

54.

Rozzini

Ferrucci

Losonczy

Havlik

Guralnik

. Protective effect of chronic NSAID use on cognitive decline in older persons. J Am Geriatr Soc 1996;44: 1025–9.

55.

Hanlon

Schmader

Landerman

Horner

Fillenbaum

Pieper

Relation of prescription nonsteroidal antiinflammatory drug use to cognitive function among community-dwelling elderly. Ann Epidemiol 1997;7:87–94.

56.

May

Moore

Stewart

Hale

. Lack of association of nonsteroidal anti-inflammatory drug use and cognitive function in elderly patients. Gerontology 1992;38: 275–9.

57.

Wysenbeek

Klein

Nakar

Mane

. Assessment of cognitive function in elderly patients treated with naproxen. A prospective study. Clin Exp Rheumatol 1988;6: 399–400.

58.

Bruce-Jones

PNE

Crome

Kalra

. Indomethacin and cognitive function in elderly volunteers. Br J Clin Pharmacol 1994;38: 45–51.

59.

Fourrier

Letenneur

Be'gaud

Dartigues

. Nonsteroidal antiinflammatory drug use and cognitive function in the elderly: Inconclusive results from a population-based cohort study. J Clin Epidemiol 1996;49: 1201.

60.

Johnson

Quinn

Day

. nonsteroidal anti-inflammatory drugs: Prescribing for the elderly. Med J Aust 1995;163: 155–8.

61.

Polisson

. Nonsteroidal anti-inflammatory drugs: Practical and theoretical considerations in their selection. Am J Med 1996;100 (suppl 2A):31S–6S.

62.

F-D-C Reports. SB Relafen promotion on COX-2 selectivity withdrawn following DDMAC letter. Feb. 24, 1997; vol. 59, issue 8.

63.

Bjorkman

. Nonsteroidal anti-inflammatory drug-induced gastrointestinal injury. Am J Med 1996;101 (suppl 1A):25S–32S.

64.

Roth

. NSAID gastropathy: A new understanding. Arch Intern Med 1996;156: 1623–8.

65.

Stucki

Johannesson

Liang

. Use of misoprostol in the elderly. Drugs Aging 1996;2: 84–8.

66.

Schimmer

Parker

. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman

Limbird

Molinoff

Ruddon

Gilman

, eds. Goodman and Gilman's the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996: 1459–85.

67.

Lewis

Smith

. Steroid-induced psychiatric syndromes. J Affect Disord 1983;5: 319–32.

68.

Mallet

Kuyumjian

. Indomethacin-induced behavioral changes in an elderly patient with dementia. Ann Pharmacother 1998;32: 201–3.

69.

Beard

Waring

O'Brien

Kurland

Kokmen

. Nonsteroidal anti-inflammatory drug use and Alzheimer's disease: A case—control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc 1998;73: 951–5.

70.

Pennisi

. Building a better aspirin. Science 1998;280: 1191–2.

71.

Alzheimer's and antiinflammatories. Harv Womens Health Watch 1998;5(8):7.

72.

Mackenzie

Munoz

. Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 1998;50: 986–90.

73.

O'Banion

Chang

Coleman

. Decreased expression of prostaglandin G/H synthase-2 (PGHS-2) in Alzheimer's disease brain. Adv Exp Med Biol 1997;407: 171–7.

74.

Jorm

. Alzheimer's disease: Risk and protection. Med J Aust 1997;167: 443–6.

75.

Scherder

Bouma

. Is decreased use of analgesics in Alzheimer disease due to a change in the affective component of pain? Alzheimer Dis Assoc Disord 1997;11: 171–4.

76.

Zhang

Johnson

Bjornsson

. Pharmacologic inhibition of transglutaminase-induced cross-linking of Alzheimer's amyloid beta-peptide. Life Sci 1997;60 (25): 2323–32.

77.

Doraiswamy

Bieber

Kaiser

Krishnan

Reuning-Scherer

Gulanski

. The Alzheimer's Disease Assessment Scale: Patterns and predictors of baseline cognitive performance in multicenter Alzheimer's disease trials. Neurology 1997;48: 1511–7.

78.

Tocco

Freire-Moar

Schreiber

Sakhi

Aisen

Pasinetti

. Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: Implications for Alzheimer's disease. Exp Neurol 1997;144: 339–49.

79.

Lieb

Fiebich

Hull

Berger

Bauer

. Potent inhibition of interleukin-6 expression in a human astrocytoma cell line by tenidap. Cell Tissue Res 1997;228: 251–7.

Pharmacologic Management of Alzheimer Disease Part III: Nonsteroidal Antiinflammatory Drugs — Emerging Protective Evidence?

Abstract

OBJECTIVE:

DATA SOURCES:

STUDY SELECTION:

DATA EXTRACTION:

DATA SYNTHESIS:

CONCLUSIONS:

Keywords

Get full access to this article

References