March 1998

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IN THIS ISSUE

APOLIPOPROTEIN E AND
ALZHEIMER'S DISEASE

  • Meta-analysis of the association between apoE and Alzheimer's disease
  • ApoE4 and responsiveness to pharmacotherapy

PHARMACOTHERAPY OF
ALZHEIMER'S DISEASE

  • Update on primary drug therapies
  • Pivotal 24-week study of donepezil
  • Placebo-controlled study of Ginkgo biloba

LONG-TERM OUTCOMES IN THE TREATMENT OF ALZHEIMER'S DISEASE

  • Tacrine delays nursing home placement
  • Donepezil shows sustained benefit for 98 weeks

EDITORIAL FOREWORD APOLIPOPROTEIN E AND ALZHEIMER'S DISEASE

Many publications have dealt with the association between apoE4 and Alzheimer's disease since the landmark report by Poirier et al in Lancet 1993;342:697-699. A meta-analysis involving practically all the researchers involving practically all the researchers in this field has been performed and released in JAMA (Farrer et al). Another landmark article by Poirier et al, reproduced in this issue of International Abstracts, raised the possibility that patients' apoE genotypes could determine their clinical responses to symptomatic therapy. When multiple drugs are available for the treatment of AD, knowledge of which patients will benefit the most from a given drug or most likely a class of drug will become an important component of clinical practice and may facilitate decisions by formulary bodies struggling with the important issue of reimbursing drugs that will show pharmaco-economic benefit in the long term.

Effects of age, sex, and ethnicity on the association between
apolipoprotein E genotype and Alzheimer disease: a meta-analysis

(J AM MED ASSOC 1997;278:1349-1356)
LINDSAY A. FARRER,
L. ADRIENNE CUPPLES,
JONATHAN L. HAINES,
BRADLEY HYMAN,
ET AL,
FOR THE APOE AND ALZHEIMER DISEASE META-ANALYSIS CONSORTIUM,
BOSTON, MA,
SEATTLE, WA,
DURHAM, NC,
ROTTERDAM, THE NETHERLANDS

To view abstract in
PubMed

Apolipoprotein E4 alleles as a predictor of cholinergic
deficits and treatment outcome in Alzheimer disease

(PROC NATL ACAD SCI 1995;92:12260-12264)
JUDES POIRIER,
MARIE-CLAUDE DELISLE,
RÉMI QUIRION,
ISABELLE AUBERT,
ET AL,
MONTREAL, QC
INDIANAPOLIS, IN

To view abstract in
PubMed

PHARMACOTHERAPY OF
ALZHEIMER'S DISEASE

EDITORIAL COMMENT The update by Knopman and Morris offers a detailed review of drugs currently approved or under development for the symptomatic treatment of AD, including cholinesterase inhibitors and muscarinic agonists. They also discuss the potential benefit from antioxidants and other noncholinergic agents. The pivotal 24-week study of donepezil has been published in great detail by Rogers et al, allowing interested readers and prescribers an opportunity for full review of the efficacy and safety of this medication. The first large scale study of Ginkgo Biloba using a 52-week placebo-controlled design with traditional outcome variables (ADAS-cog and CGIC) offers encouraging results (Le Bars et al); careful attention to factors such as age of onset, duration of symptoms and apoE genotype will be required in future studies looking at disease stabilization.

An update on primary drug therapies for Alzheimer disease

(ARCH NEUROL 1997;54:1406-1409)
DAVID S. KNOPMAN, MD,
JOHN C. MORRIS, MD,
VARIOUS CENTRES, USA

To view abstract in
PubMed

A 24-week, double-blind, placebo-controlled trial of
donepezil in patients with Alzheimer's disease

(NEUROLOGY 1998;50:136-145)
S.L. ROGERS, PHD,
M.R. FARLOW, MD,
R.S. DOODY, MD, PHD,
R. MOHS, PHD,
L.T. FRIEDHOFF, MD, PHD,
AND THE DONEPEZIL STUDY GROUP

To view abstract in
PubMed

A placebo-controlled, double-blind, randomized
trial of an extract of Ginkgo biloba for dementia

(J AM MED ASSOC 1997;278:1327-1332)
PIERRE L. LE BARS, MD, PHD,
MARTIN M. KATZ, PHD,
NANCY BERMAN, PHD,
TURAN M. ITIL, MD,
ET AL
FOR THE NORTH AMERICAN EGB STUDY GROUP,
NEW YORK, NY
TORRANCE, AND STANFORD, CA,
BOSTON, MA

To view abstract in
PubMed

LONG-TERM OUTCOMES IN THE
TREATMENT OF ALZHEIMER'S DISEASE

EDITORIAL COMMENT The long-term effectiveness of drugs such as tacrine and donepezil requires long-term follow-up in order to establish if the symptomatic benefit of these drugs is of sufficient magnitude to delay important disease milestones such as loss of autonomy and institutionalization. Data from Knopman et al suggest that patients who tolerate tacrine at therapeutic doses and take it long enough are less likely to enter a nursing home than patients on lower doses. Rogers and Friedhoff have published data from an open-label extension of donepezil demonstrating a sustained treatment benefit over 98 weeks. Prospective studies with appropriate control groups are needed to further evaluate the full impact of these encouraging observations.

Long-term tacrine (Cognex) treatment:
effects on nursing home placement and mortality

(NEUROLOGY 1996;47:166-177)
D. KNOPMAN, MD,
L. SCHNEIDER, MD,
K. DAVIS, MD,
S. TALWALKER, PHD,
ET AL,
MINNEAPOLIS, MN,
NEW YORK, NY,
LOS ANGELES, CA

To view abstract in
PubMed

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 NEUROPSYCHOPHARMACOLOGY 1998:67-75)
S.L. ROGERS,
L.T. FRIEDHOFF,
TANNACK, NJ

To view abstract in
PubMed