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SUMMARY
Summary
Alzheimer's disease remains a challenge in management. With nearly 8 million
sufferers from this condition in the seven major markets of the world and
anticipated increases in the future. Considerable research is in progress to
understand the pathomechanism of the disease and find a cure. The only drugs
approved currently are acetylcholinesterase inhibitors but they do not correct
the basic pathology of the disease, beta amyloid deposits and neurofibrillary
tangles. Several new approaches emphasize neuroprotection as well.
Early diagnosis of Alzheimer's disease is an important first step in
management. Several biomarkers in cerebrospinal fluid, blood and urine can
detect the disease. They provide a valuable aid to the clinical examination
and neuropsychological testing which are the main diagnostic methods
supplemented by brain imaging. Genotyping, particularly of ApoE gene alleles
is also useful in the evaluation of cases and planning management.
The current management of Alzheimer's disease is reviewed and it involves a
multidisciplinary approach. Acetylcholinesterase inhibitors are mostly a
symptomatic treatment but some claims are made about a neuroprotective effect.
Currently the only approved neuroprotective therapy in is memantine.
Management of these patients also require neuroleptics for aggressive behavior
and antidepressants. There is an emphasis on early detection at the stage of
mild cognitive impairment and early institution of neuroprotective measures.
The value of mental exercise in delaying the onset of Alzheimer's disease is
being recognized.
Research in Alzheimer's disease still aims at elucidating the basic
pathomechanisms. Animal models are important for research, particularly in
testing some of the potential therapeutic approaches. There is considerable
research in progress at the various centers, some of which is funded by the
National Institute of Aging of the National Institutes of Health.
Over 300 different compounds are at various stages of development for the
treatment of Alzheimer's disease. These are classified and described. There
are non-pharmacological approaches such as vagal nerve stimulation and
cerebrospinal fluid shunting, which are in clinical trials. Over 166 clinical
trials are listed, of which 125 are still in progress and 41 were discontinued
for various reasons.
Alzheimer's disease market in the seven major markets is analyzed for the year
2006. Several new therapies are expected to be in the market and the shares of
various types of approaches are estimated for the future up to the year 2017.
As a background to the markets, pharmacoeconomic aspects of care of Alzheimer
disease patients and patterns of practice are reviewed in the seven major
markets.
Profiles of 132 companies involved in developing diagnostics and therapeutics
for Alzheimer's disease are presented along with 100 collaborations. The
bibliography contains over 600 publications that are cited in the report.The
report is supplemented with 42 tables and 14 figures.
TABLE OF CONTENTS
0. Executive Summary 17
1. Clinical Features, Epidemiology and Pathology 19
- Introduction 19
- Historical aspects 19
- Clinical features of Alzheimer disease 20
- Seven stages of Alzheimer disease 22
- Detection of AD in the preclinical phase 23
- Differentiation of AD from other dementias 24
- Differentiation of AD from non-dementing disorders 25
- Cerebral insufficiency and AD 25
- Memory deficits and preclinical AD 26
- Mild cognitive impairment 26
- Diagnostic criteria of AD 28
- Epidemiology 30
- Epidemiology of aging 30
- Epidemiology of dementia 31
- Epidemiology of AD 31
- Prevalence of AD according to age 32
- Mortality in AD 32
- Pathophysiology of AD 32
- Cerebral atrophy and neuronal loss 32
- Neuritic plaques and neurofibrillary tangles 33
- Sp proteins as markers of neuronal death in AD 33
- Role of tau in the pathogenesis of AD 33
- Amyloid precursor protein 35
- Relation of APP mutations to CNS disorders 35
- Relation of APP to Aβ deposits and pathogenesis of AD 35
- Role of secretases in amyloid cascade 37
- Role of exosomal proteins 39
- Role of nicastrin 39
- Neurotixicity of Aβ
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