OVERVIEW ON ALZHEIMER DISEASE

1. OVERVIEW ON ALZHEIMER DISEASE NABIL NAJA M.D GERIATRIC MEDECINE DAIH- CMC- AAL

2. What is dementia? Dementia is a general term used to describe a group of diseases that affect the brain. Alzheimer’s disease is the most common form of dementia. The damage caused by all types of dementia leads to a progressive loss of brain tissue. As brain tissue cannot be replaced, symptoms become worse over time. These generally reflect a loss of skills and increased Dependance.

3. How common is dementia? • Prevalence of dementia of 6.4% in people 65 years of age or over • Under age 60, dementia is rare • At the age of 85–99, 45% of people could be expected to have dementia Jorm et al 1987; Kokmen et al 1989; Lobo et al 2000; Ritchie & Kildea 1995

4. What causes dementia? The different causes of dementia are: • Alzheimer’s disease (AD) • vascular dementia (VaD) • mixed dementia • Lewy body dementia • Parkinson’s disease • severe alcohol abuse • Creutzfeldt-Jacob disease • Huntington’s disease • frontal lobe or fronto-temporal lobe dementia (including Pick’s disease) • AIDS • Other conditions :Reversible causes

5. Prevalence of four major types of dementia Other FLD 5% Pure DLB 3% 5% AD VaD DLB FLD Other 15% DLB with AD, 12% 60% Mixed VaD and AD, 10% 15% Pure VaD 5%

6. Potentially reversible causes of DEMENTIA • D Drugs • E Eyes, ears • M Metabolic • E Emotion (i.e. depression) • N Normal pressure hydrocephalus • T Tumor • I Infection (e.g. neurosyphilis) • A Anemia (i.e. B12 deficiency)

7. ALZHEIMER’S DISEASE Alois Alzheimer • German neuro-psychiatrist and neuropathologist • Described several brain diseases causing dementia • Importance of his discovery not appreciated in his lifetime

8. Auguste D. • 1906 / 1907: Dr Alzheimer reported patient Auguste D. • 53 years old at onset • Cognitive decline • Psychosis • Died within 5 years

9. Charles Bronson Perry Como Thomas Dorsey Rita Hayworth Famous People with Alzheimer's Norman Rockwell Barry Goldwater Charlton Heston Sugar Ray Robinson Alfred Van Vogt Ronald Reagan Iris Murdoch

10. CLINICAL PROGRESSION OF ALZHEIMER’S DISEASE • Insidious Onset • progressive disease • Duration between 2 and 10 years Median duration:5-7 years. Henderson & Jorm 2000

11. AD Stages

12. Causes of AD and Risk Factors The precise cause is unknown Established risk factors are: Old Age A family history of AD Gender Apolipoprotein E (ApoE) Education Head trauma

13. AD pathology -Neuronal degradation in AD is associated with accumulation of: Neurofibrillary tangles (NFTs) Amyloid plaques (APs) -These changes are accompanied by: Reduction in brain volume Disruption of neurotransmitter systems APsNFTs

14. Neurochemical changes in AD • Several changes in neurotransmitter balance accompany the microscopic changes in the AD brain • The two neurotransmitters that have gained most prominence in recent years are: • Acetylcholine • Glutamate • Other neurotransmitters affected by AD are: • Noradrenaline • Dopamine • Serotonin Gsell et al. Curr Pharm Des 2004; 10: 265–293

15. Care Givers Burden

16. What is the societal burden and impact of AD? • Impact on society • AD is the third most costly disease after cancer and heart disease, due to the direct medical costs, nursing home and homecare costs • Impact on carers • Approximately 80% of AD sufferers are living at home • Carers of people with AD often demoralised, isolated and psychologically distressed • Nearly 60% of carers reported suffering ill health or nervous problems • The impact on carers’ health and work, and the consequential cost to society should be recognised Cacabelos et al. Int J Geriatric Psychiatry 1999; 14: 3-47Fillit & Hill. Am J Geriatr Pharmacother 2005; 3 (1): 39-49

17. Hours per day caring for person with dementia: current severity Percentage of early stage patients Percentage of middle stage patients Percentage of late stage patients Georges et al, Int J Geriatr Psychiatry 2008

18. ABC–The Key Symptom Domains of Alzheimer’s Disease Activities of Daily Living Behavior cognition

19. Diagnosis of AD DSM IV criteria Multiple cognitive deficits - In memory - One or more of language, praxis, gnosis, executive functioning Causing -Significant impairment & decline in social or occupational functioning - Gradual onset and continuing cognitive decline NOT due to - Other nervous system or substance-induced conditions - Deficits not exclusively during course of delirium & not better accounted for by depression or schizophrenia

20. Typical clinical presentation of early Alzheimer’s disease – I Patient usually brought to doctor by relatives Head Turning Sign General anxiousness (During assessment) Tendency to minimize/rationalize symptoms – may become upset when family describes problems and gives examples

21. Typical clinical presentation of early Alzheimer’s disease – II Patient denying any cognitive impairment, and blaming the physician for his “idiot” questions Patient is repetitive in interview and carer reports repetitive questioning Patient does not look ill and health is good Medical/neurological examinations are unremarkable, except for higher cortical functions with no history of seizures or stroke

22. Diagnosis : • History • Physical Exam • Lab.Tests • Brain MRI / CT ( # Reversible causes: Thyroid dys.,NPH,Brain tumor,V.B12 def…..)

23. MRI scans:showing atrophy also in temporal lobe Normal brain cortex AD patient

24. The Changing Brain AD and the Brain: No one knows what causes AD to begin, but we do know a lot about what happens in the brain once AD takes hold. PET Scan of Normal Brain PET Scan of Alzheimer’s Disease Brain

25. Neuropsychological Assessment • General Principles • Standardized Exploration • Validated Instruments • Normal reference (age / sociocultural level) • Material • Scales ,Composite instruments (MMS, ADAS, Mattis, WAIS…) • Assessment of specific function (memory, language etc…)

27. NeuropsychologyClock Drawing Test (CDT) NOT part of the MMSE; tests abstraction and visual-spatial cognition Draw a circle, and ask the patient to write in all the numbers, then tell them to place the hands Use the same time used in the original studies: “Please set hands of the clock to 10 after 11” Numbers and hands should be both normal Normal AbN “concrete” clock.

28. Clinical disease progression Mild Moderate Severe 30 Cognitive Symptoms 25 Diagnosis 20 Loss of Functional Independence 15 MMSE Score Behavioral Problems 10 Nursing Home Placement 5 Death 0 0 1 2 3 4 5 6 7 8 9 Years Reprinted from Clinical Diagnosis and Management of Alzheimer’s Disease, 2nd Edition by Professor S. Gauthier, 1999, Martin Dunitz Publishers (Taylor & Francis Group)

29. Most problematic symptoms: overview Activities of daily living (68%) Showering/bath 25% Being left alone 20% Incontinence 19% Finding belongings 16% Moving in general 14% Sleeping 12% Behaviour (50%) Agitation/aggression 16% Personality changes 16% Irritability 11% Wandering/restlessness 10% Depression 8% Cognition (45%) Memory/confusion 32% Concentration/attention 12% Orientation 12% Recognising people 7% Communication (36%) Following conversation 17% Comprehension of language 14% Speaking 12% Writing/reading 3% Georges et al, Int J Geriatr Psychiatry 2008 Base: all respondents (1,181)

30. Functional Impairments ADLs Bathing Dressing Toileting Transfers Continence Feeding • IADLs • Using telephone • Shopping • Food preparation • Housekeeping • Laundry • Transportation • Medications • Managing money

31. Behavioral problems in Alzheimer’s Disease

32. Prevalence of BPSD in AD Very common 50% of AD patients will experience at least one behavioural symptom >80% of people with AD will experience behavioural symptoms at any stage in the disease BPSD fluctuate over time, recurrence rate is high BPSD become more frequent as disease progresses Most common BPSD are: Apathy, agitation, anxiety, irritability Wynn & Cummings. Dement Geriatr Cogn Disord 2004; 17: 100–108; Howard et al. Int J Geriatr Psychiatry 2001; 16 (7): 714–717; Mega et al. Neurology 1996; 46: 130–135; Levy et al. Am J Psychiatry 1996; 153: 1438–1443

33. The spectrum of Behavioural and psychological symptoms (BPSD) in AD Psychotic symptoms Hallucinations1 Delusions1 Misidentifications2 Behavioural symptoms Aberrant motor behaviour1 Irritability1 Agitation/aggression1 Night-time behaviour1 Stereotypes3 Hyperorality4 Appetite/eating changes1 Hypersexuality4 Affective symptoms Depression/dysphoria1 Anxiety1 Apathy1 Elation/euphoria1 Disinhibition1

34. Assessment of behavioural symptomsNPI Apathy Disinhibition Irritability/lability Aberrant motor behaviour Night time behaviour Appetite/eating change • Delusions • Hallucinations • Agitation/aggression • Dysphoria • Anxiety • Euphoria Cummings. Neurology 1997: 48 (5 Suppl 6): S10–S16

35. Treatment & Management of Alzheimer’s Disease

36. Alzheimer’s Disease: treatment goals Cure Maintenance of function Cognitive and functional decline Diagnosis Slowing of disease progression Treatment Symptomaticbenefit • Symptomatic improvements • Cognitive, behavioural and functional improvement • Modifying the disease process Natural progression Time

37. Pharmacological Treatment * Ache Inhibitors: Donepezil Rivastigmine Galantamine * NMDA receptor antagonist: Memantine

38. Non pharmacological • Cognitive enhancement • Orientation in time & place ( clock, calender, signs…) • Treating non AZH’s diseases • Preserving autonomy • Attention to safety • Environmental modification • Communication with family, caregivers

39. Managing Anxiety • Reassure, don’t ignore • Distract - engage person in other activities (Music, simple tasks, hobby-type (activities • Simplify the environment • Cover windows and mirrors; use night lights

40. Managing Aggression • Identify the cause (noise, fear, etc.) • Focus on the person’s feelings • Avoid getting angry or upset • Simplify the environment to limit distractions • Music, exercise, etc. as a soothing activity • Shift the focus to another activity

41. Thank you