Memory: What is normal, and what is Alzheimer s?

Transcription

1 Memory: What is normal, and what is Alzheimer s? Andrew Frank M.D. B.Sc.H. F.R.C.P.(C) Cognitive Neurologist, and Medical Director, Bruyère Memory Program Élisabeth Bruyère Hospital Ottawa, Ontario

2 Memory: What is normal? Some degree of memory loss may be normal as someone gets older Having more difficulty with people s names Forgetting why one has entered a room Normal for answer to these questions to come later, after a few minutes, or sometimes hours Memory is intact, but somewhat slower to respond

3 Memory: What is not normal? Forgetting important details from recent conversations or events Repeating questions or statements within the same day or conversation, without recollection of saying the same thing before Memory loss which other people notice, when someone does not notice it in themselves

4 Memory: What is not normal? Forgetting names of simple objects, or close family members, not always remembering them later Becoming lost in very familiar locations, such as in and around one s home Forgetting how to perform activities, which previously were done very well (e.g. knitting, card games) Difficulty solving problems, or displaying poor very poor judgment Significant personality change, such as becoming very childish, or extremely quiet/unmotivated

5 Memory: What is not normal? Memory loss which begins to impair independent daily functioning Taking medications properly Managing bills correctly Shopping Cooking / Cleaning Driving a car safely Dressing Hygiene

6 What is Dementia? Dementia is a medical term which applies to memory loss which is significant enough to impair someone s daily independent functioning Mild Dementia Some help required with bills and medications Moderate Dementia Some help required with dressing and hygiene Severe Dementia Help required with all daily functioning

7 What is Alzheimer s disease (AD)? Alzheimer s disease is a build-up of specific proteins in the brain (amyloid and tau), which causes the brain to lose recent memories, and eventually other thinking functions Alzheimer s disease is the most common cause of Dementia Other causes: Stroke, Parkinson s disease, Head Injury

8 Dementia and Alzheimer s Alzheimer s disease is the cause Dementia is the effect

9 Dr. Alzheimer s disease 1906 Amyloid Plaques Tau Tangles

10 The Creation of Amyloid Amyloid Fragment

11 The Toxic Effect of Amyloid Amyloid Fragments Amyloid Oligomers Brain Toxicity Amyloid Plaques

12 Development of Alzheimer s Genetic Factors Environmental Factors Age Abnormal Amyloid Deposition Tau Tangle Formation Neuron Loss Dementia

13 How common is Alzheimer s? Aged 65: 2.5% Aged 70: 5% Aged 75: 10% Aged 80: 20% Aged 85: 40% Doubling of prevalence with every 5 years of age after age 65 Dementia due to Alzheimer s disease (AD) is a clear threat to the population

14 The Threat of Alzheimer s US prevalence 4.5 million (2000) 13.2 million (2050) Hebert et al. Arch Neurol Aug;60(8):

15 The Threat of Alzheimer s In Canada 2012: Estimated 747,000 Canadians have Alzheimer's or a related dementia Twice as many women as men 2038: Estimated 1,125,000 Canadians will have Alzheimer's or a related dementia Economic cost rising from $15 billion in 2008 to $150 billion in 2038 Alzheimer Society of Canada Rising Tide Study (January 2010)

16 How is Alzheimer s diagnosed? Memory Testing (paper and pencil tests) CT or MRI scan of the brain Blood tests Neurologist or other Physician Assessment

17 Visualizing Alzheimer s disease PET scan with Pittsburgh compound- B (injected intravenously before scan) allows amyloid protein to be visualized

18 Is there any treatment for Alzheimer s? Mild Symptom treatment Cholinesterase Inhibitors Aricept/donepezil Reminyl/galantamine Exelon/rivastigmine Available as a transdermal (skin) patch Moderate Symptom treatment Ebixa/memantine

19 Mean change (± SE) from baseline in ADAS-cog scores Cholinesterase Inhibitors p < p < 0.01 Improvement Placebo Donepezil 5 mg/day Donepezil 10 mg/day Endpoint Deterioration Weeks Burns A et al. Dement Geriatr Cogn Discord. 1999;10:

20 Mean change (± SE) from baseline in ADAS-cog scores Cholinesterase Inhibitors Improvement Donepezil-treated group 95% confidence interval Historical control Weeks 5 years Deterioration Rogers SL et al. Eur Neuropsychopharmacol. 2000;10:

21 Time to Nursing Home 5 years n=596 Feldman et al. Poster presentation at the European Federation of Neurological Societies, Paris, France, 2004

22 Side Effects of Cholinesterase Inhibitors Side effects Nausea Vomiting Diarrhea Weight Loss Dizziness Muscle cramping Insomnia Vivid dreaming 10-20%

23 How does Alzheimer s progress? Early Mild-to-moderate Severe M M S E Symptoms Diagnosis Loss of functional independence Behavioral problems Nursing home placement Death Time (years) Feldman, H. and Gracon, S. Clinical Diagnosis and Management of Alzheimer s Disease.1996:

24 Can Alzheimer s disease be prevented? Control vascular (blood vessel) risk factors High blood pressure (hypertension) High cholesterol High blood sugar / Diabetes Stopping smoking Loss of excess weight Mental and Physical exercises Social Involvement Balanced Diet

25 Does Alzheimer s disease run in families? Having close family members who have developed Alzheimer s disease does raise the risk that other members of the same family will develop Alzheimer s disease Risk increase is present, but only relatively small

26 Does anything in the environment cause Alzheimer s disease? Aluminum is no longer associated with increased risk of Alzheimer s disease No clear environmental risk factors for Alzheimer s disease have been identified at this time

27 Hormone Replacement Therapy (HRT) Women s Health Initiative Memory Study (WHIMS) Combined Estrogen/Progesterone HRT in women over 65 increased occurrence of dementia Earlier use of HRT (ages 50-55) was safe Use of HRT for significant perimenopausal symptoms is acceptable

28 Testosterone Replacement Studies of testosterone replacement have not shown convincing evidence of cognitive benefit, nor of any value in preventing or treating Alzheimer s disease

29 What is Mild Cognitive Impairment Definition of MCI (MCI)? Memory symptoms have been noticed Memory testing is mildly abnormal Daily functioning remains normal MCI is a risk state in which there is added risk of progression towards dementia due to Alzheimer s disease Closer follow-up with physicians recommended

30 Is there hope for new treatments for Alzheimer s disease? Huge effort worldwide to discover new treatment Now attempting to remove amyloid and tau build-up which causes Alzheimer s disease

31 Anti-Amyloid Antibody Intravenous Anti-Amyloid Antibody Phase 3 studies now underway worldwide Solanezumab Crenezumab Aducanumab

32 Tau-Rx Anti-Tau Treatment Prevents clumping of tau protein tangles Initial studies promising Phase 3 studies currently underway

33 Also Under Investigation Secretase Inhibitors Slows production of amyloid fragment Phase 3 studies now underway PBT-2 Captures copper and zinc in the brain, preventing clumping of amyloid Nerve Growth Factors Promotes regrowth of neurons Stem Cell Research

34 Research Information

35 Bruyère Memory Program Located at Élisabeth Bruyère Hospital in Ottawa OHIP covered Referral from physician required Memory testing performed by nurse or neuropsychologist Appointment with memoryspecialized physician arranged to review results

36 Bruyère Memory Program Diagnosis and treatment plan organized Access to clinical trials available Access to community services arranged Follow-up provided Wait time: 3-5 months

37 Conclusions Dementia due to Alzheimer s disease is an imminent threat to individuals, their families, and to society as a whole, now and over the next generation

38 Conclusions Current treatments, such as cholinesterase inhibitors and memantine, have a modest cognitive benefit, and may delay time to serious disability or time to placement in a nursing home Management of vascular risk factors, and a healthy lifestyle, are recommended

39 Conclusions Treatment of the underlying amyloid and tau protein deposition in Alzheimer s disease is being tested New treatment options may be available within the next 3-5 years