Alzheimer's disease and related disorders annual. / 2001

225 Pages·2004·2.39 MB·English

by  Serge Gauthier

Alzheimer’s Disease and Related Disorders
Annual 2001

Alzheimer’s Disease
and Related Disorders
Annual 2001
Edited by
Serge Gauthier
MD FRCPC
Professor and Director
Alzheimer’s Disease Research Unit
The McGill Center for Studies in Aging
Douglas Hospital
Verdun PQ
Canada
Jeffrey L Cummings
MD
Director, UCLA Alzheimer’s Disease Center
Augustus S Rose Professor of Neurology
Professor of Psychiatry and Biobehavioural Sciences
UCLA School of Medicine
Los Angeles CA
USA
Martin Dunitz
© Martin Dunitz Ltd 2001
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Contents
Contributors vii
Preface viii
1 Amyloid processing in Alzheimer’s disease brain 1
Greg M Cole
2 Cerebral amyloid (congophilic) angiopathy 23
Harry V Vinters
3 Clinical use of neuroimaging in the evaluation 47
of dementia
Philip Scheltens
4 Clinical trials in mild cognitive impairment 69
Yonas Endale Geda and Ronald C Petersen
5 Muscarinic agonists in Alzheimer’s disease 85
Serge Gauthier
6 Depression in dementia 97
Davangere P Devanand
7 Depression in neurodegenerative disorders and 123
related conditions
Anand Kumar and Jeffrey L Cummings
8 Use of antipsychotic drugs in dementia 143
Jeremy A Sable and Dilip V Jeste
9 Assessing competency in Alzheimer’s disease: 165
treatment consent capacity and financial capacity
Daniel C Marson and Susan D Briggs
vi Contents
10 Management of late stage dementia 193
Ladislav Volicer
Index 211
Contributors
Susan M Briggs PhD Dilip V Jeste MD
Neuropsychology Fellow, Department VA San Diego Healthcare System, San
of Neurology, The University of Diego CA, USA
Alabama at Birmingham, Birmingham
AL, USA Anand Kumar MD
Professor of Psychiatry,
Neuropsychiatric Institute, UCLA
Greg M Cole MD
School of Medicine, Los Angeles CA,
Sepulveda VA GRECC, Sepulveda CA,
USA
USA
Daniel C Marson JD PhD
Jeffrey L Cummings MD Neuropsychology Fellow, Department
Director, UCLA Alzheimer’s Disease of Neurology, The University of
Center, Augustus S Rose Professor of Alabama at Birmingham, Birmingham
Neurology, Professor of Psychiatry and AL, USA
Biobehavioral Sciences, UCLA School
of Medicine, Los Angeles CA, USA Ronald C Petersen MD
The Mayo Clinic, Rochester MN, USA
Davangere P Devanand MD Jeremy A Sable MD
Professor of Clinical Psychiatry, Department of Psychiatry, University of
College of Physicians and Surgeons, California, San Diego CA
Columbia University, Co-Director, USA
Memory Disorders Center, New York
State Psychiatric Institute, New York, Philip Scheltens Ph MD PhD
USA Department of Neurology, Academisch
Ziekenhuis, Vrije Universiteit,
Amsterdam, The Netherlands
Serge Gauthier MD FRCPC
Professor and Director, Alzheimer’s
Harry V Vinters MD
Disease Research Unit, The McGill
UCLA Center for the Health Sciences,
Center for Studies in Aging, Douglas
Los Angeles CA, USA
Hospital, Verdun PQ, Canada
Ladislav Volicer MD PhD
Yonas Endale Geda MD Geriatric Research Education Clinical
Fellow, Behavioural Neurology, The Center, EN Rogers Memorial Veterans
Mayo Clinic, Rochester MN, USA Hospital, Bedford MA, USA
Preface
As achieved in last year’s Alzheimer’s Disease and Related Disorders
Annual, we attempt to bridge basic sciences and clinical practice in the
realm of dementia. Special emphasis is placed on amyloid processing
and amyloid angiopathy, considering the interest in modifying amyloid
deposition using immunotherapy and selective secretase inhibitors. The
advances on brain imaging in diagnosing the different types of demen-
tias are summarized, and are relevant to the study of mild cognitive
impairment where whole brain volumetry has become a surrogate out-
come variable. The disappointing results observed with muscarinic ago-
nists as symptomatic drugs for Alzheimer’s disease are reviewed in
detail. The very common issues of depression and psychosis associated
with Alzheimer’s and other dementias are discussed in depth. A novel
and systematic approach to competency assessment is presented and
management of late stage dementia deserves special attention with
regard to the patient’s vulnerability.
We believe that these reviews of timely topics will prove useful to
researchers and clinicians who share the common goal of better quality
of life for so many patients and their caregivers.
Serge Gauthier
Jeffrey L Cummings
June 2001
1
Amyloid processing in Alzheimer’s disease
brain
Greg M Cole
This chapter will focus on what amyloid peptides do after they are made
and how they may be cleared, rather than how they are produced.
Amyloid precursor processing to (cid:1)-amyloid as a cause of
Alzheimer’s disease
Alzheimer’s Disease (AD) is characterized by a slow accumulation of aggre-
gated central nervous system (CNS) (cid:1)-amyloid peptide, deposited extracellu-
larly as amyloid fibrils in the neuropil as plaques, and in many cases, also in
the vasculature. (cid:1)-amyloid (A(cid:1)) peptides of 40–43 amino acids in length
(A(cid:1)40, A(cid:1)42 or A(cid:1)43) are a normal product derived by proteolytic processing
from a larger (695–770kD) amyloid precursor protein (APP) by almost all cells,
but in young individuals and many normal elderly, the peptides are success-
fully cleared since they fail to accumulate. A(cid:1)is produced by cleavage of the
(cid:1)-APP with the N-terminal and C-terminal cuts by (cid:1)- and gamma-secretases,
respectively. Alternatively, A(cid:1) production can be prevented by another
endopeptidase, alpha-secretase, which cleaves within the A(cid:1)domain.1
The strongest argument that the peptide causes the disease comes from
observations that the mutations in early onset familial AD (fAD) all cause
increased production of the rapidly aggregating A(cid:1)1–42.2,3However, in most
cases of AD, there is A(cid:1) accumulation without evidence of genetically
increased A(cid:1)production. Other post-APP processing aspects of A(cid:1)metab-
olism appear to be important. For example, the increased risk and earlier
onset of AD from the apolipoprotein (Apo) E4 allele which is strongest
between 65 and 80 years of age is not associated with increased A(cid:1) pro-
duction, but instead with reduced A(cid:1)clearance or enhanced amyloid forma-
tion. Some of the reasons why A(cid:1)is believed by most to be causal are that
(a) the fAD mutations presenilin (PS) 1, PS2 and APP are associated with
overproduction of A(cid:1)42;3–8
(b) the major risk factor ApoE4 is associated with overaccumulation of
A(cid:1)40;9,10
1