Evolution of the dementia concept DEMENTIA Binswanger Alzheimer
Evolution of the dementia concept DEMENTIA Binswanger, Alzheimer Arteriosclerotic Brain Atrophy Willis Post Alzheimer’s stroke Disease dementia Erkinjuntti Cortical vs Subcortical DSM-III MID Hachinski Scale NINCDSADRDA Criteria for AD Roman Lacunar Dementia NINDSAIREN Criteria DSM-IV Executive Dysfunction 1672 1894 1910 1952 1974 1976 1980 1984 1985 1987 1992 1993 1994 Va. D AD
The four domains of Alzheimer’s Disease Global function Cognitive function Caregiver burden Activities of daily living Neuropsychiatric symptoms (Behavior)
Alzheimer’s Disease - 100 years 1907 paper by Alois Alzheimer became index case for “Alzheimer’s disease”, -- describing the neurofibrillary degeneration and senile plaques are the two histopathological hallmarks of AD; however the term did not receive broad endorsement until eighth edition of Emil Kraepelin’s “Textbook of Psychiatry” published in 1910. The 1985 articles in the Archives of Neurology “Diagnosis of Alzheimer’s disease” represent a small chapter in the prolonged efforts to characterize the distinct clinical-pathological features of Alzheimer’s disease (AD) The recent introduction of the construct of “Mild cognitive impairment” (MCI) as a potential precursor or prodrome of the disease was another significant mile-post.
During the Past 40 years … 40 years ago: AD was regarded as a hopelessly untreatable condition. Except for a handful of investigators, the area attracted little interest and virtually no support for research. 35 years ago: the essential clinical infrastructures for longitudinal studies of well-characterized patients did not exist. 30 years ago: idea about “cure” and “prevention” were unconceivable; such things as diagnostic criteria, standardized assessment instruments, cadres of specialized professionals, memory disorder clinics, family support groups or outreach programs, all taken for granted now, were not fully developed. 25 years ago: the knowledge on biological underpinnings and gene associated with the disease had not been identified. 20 years ago: animal models of the disease were not available. 15 years ago: person risk for the disease could not be identified and the concept of clinical trials to delay the symptoms was unconceivable Till 2004: the A beta protein hallmark lesions of the disease , could not be directly visualized in patients.
The First Drug 1986 - Tacrine first result in the New England Journal of Medicine 1996 – Donepezil (Aricept-愛憶欣) 1998 – Rivastigmine (Exelon-憶思能) 2000 – Galantamine (Reminyl-利憶靈) 2002 - Memantine for NMDA receptor antagonist All of the drugs provide temporary relief of symptom but do not halt the progress of the disease
THE CHOLINERGIC HYPOTHESIS ACh. E and Bu. Ch. E degrade ACh Receptors Presynaptic Terminal Action Potential Postsynaptic Terminal Summated Potential ACh receptors ACh. E or Bu. Ch. E inhibitors block ACh. E and Bu. Ch. E ACh Ch. E inhibitor Mc. Neil. Alzheimer’s Disease: Unraveling the Mystery. 1995: 1– 48.
Cholinergic Synaptic Transmission Presynaptic Acetyl Co. A Ch. AT Choline ACh release ACh Choline + acetate ACh. E inhibitor ACh Postsynaptic ACh receptors ACh Ch. E inhibitors reduce acetylcholine hydrolysis in remaining neurons and help to normalize cholinergic function
Memantine treatment in mild-to-moderate Alzheimer’s disease : ADAS-cog Placebo (n=198) Peskind et al, Poster presented at AAGP 2004 p=0. 003 Deterioration � Memantine (n=195) p=0. 002 Improvement � p=0. 003 p=0. 009
Thank you for your attention
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