The Future of Alzheimer s Disease Treatment Adam L. Boxer, MD, PhD Director, Alzheimer s Disease Clinical Trials Program Memory and Aging Center Assistant Professor of Neurology University of California, San Francisco What is dementia? An acquired, persistent, intellectual impairment involving multiple cognitive domains (memory, language, navigation, behavior), sufficient to cause a significant decline from a previous level of functioning. Dementia is not normal aging! Alzheimer s is one cause of dementia Alzheimer s disease Vascular (multi-infarct dementia) Dementia with Lewy Bodies/Parkinson s Frontotemporal dementia Dementia due to other illnesses (>100): alcohol multiple sclerosis Creutzfeldt Jakob disease schizophrenia Current Management of AD 1
Cognitive complaints in AD 1. Asking the same question over and over again. 2. Repeating the same story, word for word, again and again. 3. Forgetting how to cook, or how to make repairs, or how to play cards activities that were previously done with ease and regularity. 4. Losing one s ability to pay bills or balance one s checkbook. 5. Getting lost in familiar surroundings, or misplacing household objects. 6. Neglecting to bathe, or wearing the same clothes over and over again, while insisting that they have taken a bath or that their clothes are still clean. 7. Relying on someone else, such as a spouse, to make decisions or answer questions they previously would have handled themselves. NIA National Institute on Aging Current Management of AD Example of neuropsychological test: clock drawing Alzheimer s disease MRI scan 1. Volume loss (atrophy) 2. Absence of stroke, tumor, etc. Draw a clock that shows ten past eleven 2
Current Management of AD Current AD Therapies Diagnosis (exclusion of other causes): Mild Cognitive Impairment (no functional decline) Alzheimer s Disease (functional decline) Interventions (manage symptoms): Exercise (physical/mental) Minimize CV risk factors Minimize other CNS drugs Treat behavioral/psychiatric symptoms Caregiver support Acetylcholinesterase inhibitor (Aricept, Exelon or Razadyne ) and/or Memantine (Namenda ) Donepezil (Aricept) Rivastigmine (Exelon) Galantamine (Razadyne) Memantine (Namenda) What do the current AD drugs do? Current therapies help! Pfizer treated n = 135 NOT treated STOP n = 135 Lopez, et al., J Neurol Neurosurg Psychiatry 2002;72:310 314 3
Current Management of AD Diagnosis (exclusion of other causes): Mild Cognitive Impairment (no functional decline) Alzheimer s Disease (functional decline) Interventions (manage symptoms): Acetylcholinesterase inhibitor (Aricept, Exelon or Razadyne ) and/or Memantine (Namenda ) Exercise (physical/mental) Minimize CV risk factors Minimize other CNS drugs Treat behavioral/psychiatric symptoms Caregiver support End of Life Care Millions of people with AD in the U.S. Impact of Alzheimer s Treatment 14 12 10 8 6 Delay onset by 2 years 2003 2010 2020 2030 2040 2050 Memory and Aging Center year Delay onset by 5 years 300 200 100 Cost to society: $ billions Prevention of AD: Early Detection + Disease Modification Amyloid is a sticky, toxic protein that causes Alzheimer s disease autopsy specimen (microscope, thioflavin) Amyloid plaques pre-clinical detection disease-modifying treatment http://library.med.utah.edu/webpath/cow/cow046.html living people (PET scan) National Institute on Aging Klunk, et al. Ann Neurol 2004;55:306 319 4
New disease modifying treatments designed to stop disease Cognitive function symptomatic (current meds) disease-modifying Future Management of AD (prevention): Blood test (proteomic assay, etc.) Elevated brain amyloid Age 50 (+) Amyloid imaging (PIB, etc.) AD Norm New disease modifying therapies (+ current medications?) Time Cognitive status maintained More information on the internet UCSF Memory and Aging Center www.memory.ucsf.edu Alzheimer s Association: www.alz.org or www.alznorcal.org Alzheimer s Disease Education And Referral center (ADEAR; NIA): www.alzheimers.org Family Caregiver Alliance www.caregiver.org 5