How-to-Cope-with-Alzheimer-s-Disease-_1998_Neurobiology-of-Aging

How to Cope with Alzheimer’s Disease?

K.HASEGAWA

St.Marianna University School of Medicine,2-16-1,Sugao,Miyamae-Ku,Kawasaki,Kanagawa,216Japan

HASEGAWA,K.How to cope with Alzheimer’s disease?NEUROBIOL AGING 19(1S)S107–S108,1998.—Alzheimer’s disease (AD)is the most common causative brain disease of primary dementia in the elderly.The incidence of AD rises exponentially with age.Many countries,where the aging population is a national problem,have to face how to cope with AD.The main strategies against AD include the estimation of the exact size of the problem,the elucidation of etiology of AD,the development of effective treatment,and the establishment of the caring system for AD sufferers in the community.A recent fruit of the research is the new cholinomimetic agent E2020(Donepezil),which is a highly selective acetylcholinesterase inhibitor.As a result of clinical trials,statistically significant improvements were seen in cognitive function of AD patients.However,E2020is one of the neurotransmitter substitution therapies and is not specifically linked to the etiological treatment.We have to make efforts to establish a definitive therapy for AD and this depends on basic research,such as the molecular biology of AD.Many AD patients and their families expect fruitful result from this symposium,which will be a big milestone for the research of AD toward the 21st Century.Strategies against Alzheimer’s disease (AD)

Dementia sufferers

Prevalence of AD

Donepezil (E2020)

ALZHEIMER’S disease (AD)is the most common causative brain disease of primary dementia in the elderly.It is characterized by progressive cognitive deterioration.Memory deficits are the most frequently observed symptom,often accompanied by disorienta-tion,language difficulties,impairment of judgement,and emo-tional and behavioral disturbances.Neuropathological findings include extensive loss of neurones,the presence of neuritic plaques and neurofibrillary tangles within neurones,and deposits of ␤-amyloid protein.The incidence of AD rises exponentially with age.Many countries,where the aging population is a national problem,have to face how to cope with AD.The main strategies against AD include:1)the estimation of the exact size of the problem;2)the elucidation of etiology of AD;3)the development of effective treatment;and 4)the establishment of the caring system for AD sufferers in the community.

As to the size of the problem,the Japanese Ministry of Health and Welfare estimates that the number of dementia sufferers including AD patients is currently about 1.3million (about 6.9%of the total aged population of 65years old and over)and will increase to 1.9million by the year 2005(7.4%).

In the USA,AD afflicts as many as 4million people and 1.3million of them are categorized as having severe-stage AD.In addition to severe disabilities in patients and the emotional burden upon family members,AD’s costs to society are substantial.Although estimates vary,AD exacts a societal toll of more than $100billion each year according to public health reports in the U.S.

Since 1974,when the first large scale prevalence study on age-associated dementia was carried out by the author in Tokyo,about 30local governments throughout Japan have administered similar population surveys on the people aged 65years and over.There have been consistent findings.The prevalences of vascular dementia (VD)were consistently higher than those of Alzheimer’s disease (AD)in most Japanese surveys,which appeared to be in the opposite direction from Western surveys.However,several recent studies have shown a changing pattern:AD occurring more frequently than VD.This change might be due to the immense effort by local health care centers where the management and control of high blood pressure as well as the preventive life counseling have been administered by health professionals.The findings would give us some evidence in which the preventive measures to cerebrovascular disease would be a great value for the prevention of VD.In the near future,we will succeed in the prevention of AD by elucidating some definite risk factors of AD.Another recent fruit of the clinical research is the new cholin-omimetic agent E2020(Donepezil)developed by Eizai,a Japanese pharmaceutical company.E2020is a highly selective acetylcho-linesterase inhibitor with a long duration of action and exerts little peripheral activity.S.Rogers et al.(1)succeeded in the clinical trial on E2020and it obtained approval from FDA last November.Their results of randomized,double-blind,placebo-controlled trials in mild-to-moderately severe AD demonstrate that E2020administered once daily is well tolerated,and that adverse events are mild and transient.No hepatotoxicity was observed.Statisti-cally significant improvements were seen in cognitive function,as measured by the well-validated ADAS-cog scale,and in patient global function,as measured by the CIBI-C Plus.E2020is one of the neurotransmitter substitution therapies and is not specifically linked to the etiological treatment.Therefore,it is a symptomatic treatment.Under present circumstances,where no pharmacologi-cal therapy is available,we have to be satisfied with this limitation.We have to make efforts to establish a definitive therapy for AD,and this depends on basic research such as the molecular biology of AD.Another issue is the absence of a good animal model for AD,which is also essential to perform preliminary studies in human subjects.

In this sense,many AD patients and their families expect a fruitful result from this symposium,which will be a big milestone for the research of AD toward the 21st

Century.

Neurobiology of Aging,Vol.19,No.1,pp.S107–S108,1998

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