Treatment and Management of the Elderly Patients with Alzheimer's Disease
Division of Geriatric Medicine, Nippon Medical School
Alzheimer's disease (AD) is the most common cause of dementia in older people. Cerebral deposition of amyloid plaques containing amyloid beta-peptide (Aβ) has traditionally been considered the central feature of AD. γ-Secretase is the pivotal enzyme in generating the C terminus of Aβ, that determines its aggregability and propensity for deposition. Drugs that regulate the production of Aβ by inhibiting gamma-secretase activity could provide an effective therapeutics for AD, however we can't use these drugs clinically now. Anti-amyloid immunotherapy for AD has received considerable attention following reports that amyloid pathology was reduced in an amyloid precursor protein (APP) transgenic mouse model on vaccination with aggregated Aβ42. Clinical trials were terminated after four early reports of autoimmune meningoencephalitis, but a post-mortem study in one patient showed evidence of plaque reduction. Currently, no effective pharmacologic interventions have been researched enough to support their use in prevention of AD. Many epidemiological studies suggest that apolipoprotein E type 4 allele, diabetes, obesity, hypertension, and hyperlipidemia were associated the risk factor for late onset AD. Two key treatment approaches for AD have been driven by retrospective epidemiology: non-steroidal anti-inflammatory drugs and cholesterol-lowering statins. In both cases, the exact target in the disease cascade remains to be elucidated. In constant, only one acetylcholinesterase inhibitor, donepezil has been proven effective and used for patients with mild or moderate AD in Japan. Donepezil have demonstrated the effectiveness in stabilizing cognitive function and delaying behavioral symptoms. Given the likelihood that agents will become available that reliably delay onset and/or slow progression of AD, it will be important to detect preclinical AD as early as possible for maximal treatment effect. Cognitive function is generally examined by Mini-mental State Examination (MMSE), revised version of Hasegawa's Dementia Rating Scale (HDS-R) and Wechsler adult intelligence scale-revised (WAIS-R). The positron emission tomography or the single photon emission computed tomography were used for diagnosis of early stage AD. Caregivers should analyze behaviors and environmental factors which precede harmful abnormal conduct and try to avoid them.
日医大医会誌 2006; 2(3), 145-147
Alzheimer's disease, treatment, management, elderly
Hiroshi Nakano, Division of Geriatric Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan