May 2002

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IN THIS
ISSUE

NEW PROTECTIVE FACTOR FOR ALZHEIMER'S DISEASE

  • Statin use was associated with lower dementia risk
  • Plasma cholesterol may contribute to AD development
  • Lipid-lowering agents decreased dementia development in those over 50

TREATMENT WITH CHOLINESTERASE INHIBITORS

  • Cholinesterase inhibitors show long-term benefit in AD patients
  • Patient compliance with donepezil needs improvement

NEW RISK FACTOR FOR ALZHEIMER'S DISEASE

  • Higher plasma homocysteine levels is a risk factor for dementia and AD

COMPARISON OF AN ANTIPSYCHOTIC AND SSRI

  • Citalopram was superior to placebo in demented patients

ISLINGTON STUDY DEMENTIA SUBTYPES

  • DLB and FTD are the most common forms of dementia in the elderly

ADVERSE EFFECTS OF IPHENHYDRAMINE

  • Diphenhydramine increases cognitive decline in hospitalized older patients

COGNITIVELY STIMULATING ACTIVITIES AND AD RISK

  • Frequent participation in cognitively stimulating activities reduces AD risk

DEPRESSIVE SYMPTOMS IN ALZHEIMER'S DISEASE

  • Depression in dementia is related to functional decline

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EDITORIAL
COMMENT

NEW PROTECTIVE FACTOR FOR AD
There are recent studies suggesting that statins may be protective against Alzheimer's disease (AD). For example, an analysis of data from the Canadian Study of Health and Aging has demonstrated that lipid-lowering-agent use is associated with a lower risk of AD, at least in persons younger than 80 years of age (Rockwood et al, 2002). Converging evidence is that a strong linear association has been found between increasing HDL-cholesterol plasma levels and neuritic plaques in the brain (Launer et al, 2002). One of the most impressive presentations at the 7th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy, April 3-6, 2002, was made by David Drachman, highlighting the protective effects of statins through microvascular and endothelial effects, in addition to their lipid-lowering effects. A number of randomized clinical trials are starting soon in Canada and elsewhere to test this important treatment hypothesis.

Use of lipid-lowering agents, indications bias, and the risk
of dementia in community-dwelling elderly people

(ARCH NEUROL 2002;59:223-227)


KENNETH ROCKWOOD, MD, FRCPC,
SUSAN KIRKLAND, PHD,
DAVID B. HOGAN, MD, FRCPC,
CHRIS MACKNIGHT, MD, MSC, FRCPC,
ET AL,
VARIOUS CENTRES, CANADA

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PubMed

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Cholesterol and neuropathologic markers of AD:
a population-based autopsy study

(NEUROLOGY 2001;57:1447-1452)


L.J. LAUNER, PHD,
L.R. WHITE, MD,
H. PETROVITCH, MD,
G.W. ROSS, MD,
ET AL,
BETHESDA, MD,
HONOLULU, HI

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Do statins reduce the risk of dementia?

(7th INT'l GENEVA/SPRINGFIELD SYMPOSIUM ABSTRACT P.51)


D.A. DRACHMAN,
H. JICK,
S. JICK,
S. SUSHADRI,
WORCHESTER, BOSTON, MA		 Sorry, this abstract is not available


DURATION OF TREATMENT WITH CHOLINESTERASE INHIBITORS

EDITORIAL
COMMENT

Although there is an academic consensus that cholinesterase inhibitors (CI) should be used over at least one year if well tolerated, aiming at slowing the progression of symptoms in the cognitive, functional and behavioural domains (Winblad et al, 2001), the evidence from pharmacy claims data for the most widely used CI donepezil suggest early dropout for many patients (Roe et al, 2002). The Canadian Consensus Conference on Dementia (C3D) will reconvene in 2003 in order to develop evidence-based guidelines on how best to use the CIs over time, including whether switching from one to the other is useful. Furthermore, the clinical state of Mild Cognitive Impairment (MCI), as well as treatment of severe Alzheimer's disease, will be incorporated into the treatment guidelines.

Pharmacotherapy of Alzheimer's disease:
is there a need to redefine treatment success?

(INT J GERIATR PSYCHIATRY 2001;16:653-666)


BENGT WINBLAD,
HENRY BRODATY,
SERGE GAUTHIER,
JOHN C. MORRIS,
ET AL,
VARIOUS INT''L CENTRES

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How many patients complete an adequate trial of donepezil?

(ALZHEIMER DIS 2002;16[1]:49-51)


CATHERINE M. ROE,
MICHAEL J. ANDERSON,
BARNEY SPIVACK,
STAMFORD, CN,
MARYLAND HEIGHTS, MO

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NEW RISK FACTOR FOR ALZHEIMER'S DISEASE

EDITORIAL
COMMENT

An analysis from the Framingham Study has revealed that elevated plasma levels of homocysteine is a significant risk factor for Alzheimer's disease (Seshadri et al, 2002). The accompanying editorial by Joseph Loscalzo (N Engl J Med 346, 466-8, 2002) highlights the plausibility of this risk factor acting through a cerebral angiopathy, endothelial dysfunction and oxidative stress, as well as enhancement of beta-amyloid neurotoxicity. A reduction in homocysteine levels is possible using supplements of B vitamins and/or folic acid. Randomized clinical trials are required to test this therapeutic hypothesis.

Plasma homocysteine as a risk factor for dementia and Alzheimer's disease

(NEJM 2002;346[7]:476-483)


SUDHA SESHADRI, MD,
ALEXA BEISER, PHD,
JACOB SELHUB, PHD,
PAUL F. JACQUES,
ET AL,
BOSTON, MA

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COMPARISON OF AN ANTIPSYCHOTIC AND SSRI IN DEMENTIA

EDITORIAL
COMMENT

Research continues to focus on alternatives to the antipsychotics for treatment of behavioural disturbances in dementia. In the first double-blind placebo-controlled trial of an SSRI in a seriously disturbed patient group, citalopram was found to be more efficacious than placebo and on some measures superior to perphenazine in this short-term, well designed study by Pollock et al.

Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients

AM J PSYCHIATRY 2002;159:460-465)


BURCE G. POLLOCK, MD, PHD,
BENOIT H. MULSANT, MD,
JULES ROSEN, MD,
ROBERT A.SWEET, MD,
ET AL,
PITTSBURGH, PA

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PubMed

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ISLINGTON STUDY OF DEMENTIA SUBTYPES

EDITORIAL
COMMENT

Few studies have ever examined the community prevalence of subtypes of dementia. In a careful epidemiological study, Stevens et al, 2002, applied standardized diagnostic criteria to patients with dementia in a north London suburb. While AD was the most common cause of dementia, followed by VaD, the prevalence of dementia with Lewy bodies (11%) and frontal lobe dementia (8%) was also significant.

Islington study of dementia subtypes in the community

(BR J PSYCHIATRY 2002;180:270-276)


TIM STEVENS,
GILL LIVINGSTON,
GINNETTE KITCHEN,
MONICA MANELA,
ET AL,
UK

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ADVERSE EFFECTS OF DIPHENHYDRAMINE

EDITORIAL
COMMENT

Cognitive impairment and delirium caused by anticholinergic medications is well recognized. In a prospective observational study by Agostini et al, the effect of diphenhydramine, a commonly used over-the-counter antihistamine, was assessed in elderly hospitalized patients. Diphenhydramine increased the risk of delirious symptoms, urinary catheterization and length of stay significantly, leading the investigators to recommend caution when using this drug in the elderly.

Cognitive and other adverse effects of
diphenhydramine use in hospitalized older patients

(ARCH INTERN MED 2001;161:2091-2097)


JOSEPH V. AGOSTINI, MD,
LINDA S. LEO-SUMMERS, MPH,
SHARON K. INOUYE, MD, MPH,
NEW HAVEN, CN

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PubMed

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COGNITIVELY STIMULATING ACTIVITIES AND AD RISK

EDITORIAL
COMMENT 		While "keeping busy mentally and physically" is frequently recommended to patients with dementia, little research has actually demonstrated the effectiveness of these suggestions. In a longitudinal study, Wilson et al, assessed "cognitive activity" in a group of Catholic nuns, priests and brothers followed for an average 4.5 years. Frequent participation in cognitively stimulating activities (e.g. reading, playing cards, crosswords, etc.) significantly reduced the risk of developing AD.

Participation in cognitively stimulating activities
and risk of incident Alzheimer disease

(JAMA 2002;287[6]:742-748)


ROBERT S. WILSON, PHD,
CARLOS F. MENDES DE LEON, PHD,
LISA L. BARNES, PHD,
JULIE A. SCHNEIDER, MD,
ET AL,
CHICAGO, IL

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PubMed

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DEPRESSIVE SYMPTOMS IN ALZHEIMER'S DISEASE

EDITORIAL
COMMENT 		A study by D. Espiritu et al, not only emphasizes the fact that depressive symptoms contribute to functional impairment in AD above and beyond cognitive scores, but also suggests that AD patients' self-report of depressive symptoms is valid and important.

Depression, cognitive impairment and function in Alzheimer's disease

(INT J GERIATR PSYCHIATRY 2001;16:1098-1103)


DOREE ANN V. ESPIRITU,
HARUN RASHID,
BENJAMIN T. MAST,
JOE FITZGERALD,
ET AL,
DETROIT, MI

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