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CHOLINESTERASE INHIBITOR
[ChEI]
• improve global function
• enhance cognition
• improve behaviour
• delay nursing home placement](https://image.slidesharecdn.com/dementia-130225215744-phpapp01/85/Dementia-52-320.jpg)
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Dementia
- 1. 1 DEMENTIA AN APPROACH TO MANAGEMENT AND PREVENTION DR. HASANAH CHE ISMAIL PSYCHIATRIST SCHOOL OF MEDICAL SCIENCES UNIVERSITI SAINS MALAYSIA
- 2. 2 Definitionof the dementia syndrome DEMENTIA • Multiple cognitive deficits – memory loss – aphasia – apraxia – agnosia – disturbance in executive function • These lead to functional decline
- 3. 3 Causes of dementia Reversible dementias Irreversible dementias • Common causes: • Common causes: – Depression – Alzheimer's disease – Drug toxicity – Vascular dementia • Other causes – Lewy body disease – Pick's disease (dementia of the frontal lobe type) – Parkinson's disease with dementia
- 4. 4 Differentiating AD fromother dementias dementias Cognitive impairment Exclude other causes (e.g. delirium and depression, etc) Dementia Exclude other dementias Alzheimer's disease
- 5. 5 DEMENTIA • AD represents over 50% of all dementia cases • AD prevalence doubles every 5 years after 60 years of age • AD affects 15 million people worldwide
- 6. Short history 1907 Alzheimer reports the first case of August D 1960s Re-emergence of interest in dementia 1970s Cholinergic deficits in AD identified 1980s First trials of cholinergic enhancing therapies 1994 First cholinesterase inhibitor licensed Present First launches of Reminyl, a cholinesterase inhibitor and nicotinic modulator Alois Alzheimer
- 7. 7 Prevalence of Alzheimer’sdisease 60 50% 50 Prevalence (%) 40 30% 30 20 16% 10 8% 2% 4% 1% 0 60-64 65-69 70-74 75-79 80-84 85+ 95+ Age (years) Kurz A. Eur J Neurol 1998; 5(Suppl 4): S1-8 Wimo A et al. Int J Geriatr Psychiatry 1997; 12: 841-56
- 8. 8 Clinical features of AD • Loss of cognition – short-term memory – language – visuospatial functions • Loss of daily function – instrumental activities of daily living (ADL) – self-maintenance skills • Abnormal behaviour
- 9. 9 ‘Normal’ ageing vs. dementia • Multiple cognitive domains affected • Decline of language and orientation • Deterioration in common activities of daily living
- 10. 10 Clinical features of AD Insidious onset Cognitive decline Functional * Memory loss impairment * Aphasia * IADL * Apraxia * ADL * Agnosia AD * Executive function Behavioral signs difficulties * Mood swings * Agitation Age over 60 years * Wandering No gait difficulties IPA AD Conference, 1996
- 11. 11 Natural history of Alzheimer’s disease Early diagnosis Mild-to-moderate Severe Mini-Mental State Examination (MMSE) 30 Symptoms 25 Diagnosis 20 Loss of functional independence 15 Behavioural problems 10 Nursing home placement 5 0 Death 1 2 3 4 5 6 7 8 9 Time (years) Feldman and Gracon. The Natural History of Alzheimer’s Disease. London: Martin Dunitz, 1996
- 12. 12 Anatomical features of AD • Gross atrophy Normal brain – shrinkage of brain – thinning of gyri – widened sulci Alzheimer brain
- 13. The pathological cascadeof AD Clinical symptoms Cholinergic dysfunction Neurodegeneration Neurofibrillary tangles Genetic TAU hypophosphorylation β-amyloid Apo-E risk factors PS1,2 Environmental APP Pathogenetic risk factors mutations
- 14. 14 The cholinergic system AChE = acetylcholinesterase Presynaptic Acetyl CoA ChAT = choline nerve terminal + acetyltransferase Choline = acetylcholine ChAT Acetylcholine N = nicotinic M = muscarinic M receptor N receptor Important in: Memory and learning Postsynaptic Sensory and nerve terminal M receptor N receptor attentional functions
- 15. 15 Cholinergic dysfunction inAD ∀ ↓ Cholinergic neurons ∀ ↓ Choline uptake ∀ ↓ Acetylcholine release ∀ ↓ Choline acetyltransferase ∀ ↓ Nicotinic receptors = progressively impaired memory and cognition
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- 17. 17 Making a diagnosis of AD Need for early Consistent onset, clinical diagnosis presentation and disease progression Practical assessment methods New symptomatic Patient and treatments caregiver support IPA AD Conference, 1996
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- 20. 20 PERUBAHAN MOTOR => TERBARING DI ATASKATIL =>MENELAN TERGANGGU =>MAUT
- 21. 21 Dementia or delirium Dementia Delirium * Insidious onset with unknown date * Abrupt, precise onset, known date * Slow, gradual, progressive decline * Acute illness, lasting days or * Generally irreversible weeks * Disorientation late in illness * Usually reversible * Slight day-to-day variation * Disorientation early in illness * Less prominent physiological OR * Variable, hour by hour changes * Prominent physiological changes * Consciousness clouded * Fluctuating levels of consciousness only in late stage * Short attention span * Normal attention span * Disturbed sleep-wake cycle; * Disturbed sleep-wake cycle; hour-to-hour variation day-night * Marked early psychomotor * Psychomotor changes late in illness changes Ham, 1997
- 22. 22 Dementia or depression Dementia Depression * Insidious onset * Abrupt onset * No psychiatric history * History of depression * Conceals disability * Highlights disabilities * Near-miss answers * ’Don't know' answers * Mood fluctuation day to day * Diurnal variation in mood * Stable cognitive loss OR * Fluctuating cognitive loss * Tries hard to perform but is * Tries less hard to perform unconcerned by losses and gets distressed by losses * Short-term memory loss * Short- and long-term memory * Memory loss occurs first loss * Associated with a decline in * Depressed mood coincides with social function memory loss * Associated with anxiety Ham, 1997, modified from Wells CE, 1979
- 23. 23 Diagnosing AD in primary care clinical history, questioning Ask the following questions: * How did it start? Was it sudden or gradual? * How long has it been going on? * Is the situation progressing? If so, how rapidly? * Is it step-wise or continuous? * Is it worsening, fluctuating or improving? * What changes have you noticed? * Has there been a change in personality? * Has the patient suffered any delusions or hallucinations? * Does the patient become agitated or wander? Clinical History
- 24. 24 Diagnosing AD in primary care functional assessment Score Score Maximum Actual Functional Activities Questionnaire (FAQ) 1. Dealing with financial matters, paying bills, writing checks 3 2. Keeping records of taxes, business affairs 3 3. Shopping for everyday necessities: groceries, clothes, etc 3 4. Hobbies or playing games 3 5. Making tea, turning the kettle on and off 3 6. Cooking a balanced meal 3 7. Perception of current events 3 8. Level of attention and understanding: books, television 3 9. Memory: remembering appointments and medications 3 10. Getting about: driving or taking public transport 3 Total 30 Functional Assessment Pfeffer et al 1982
- 25. 25 Diagnosing AD in primary care physical examination * Life-threatening conditions, e.g. mass lesions, vascular lesions and infections * Blood pressure and pulse * Vision and hearing assessments * Cardiac and respiratory function * Mobility and balance * Sensory and motor system examination (tone, reflexes, gait and coordination) and depressive symptoms (sleep and weight) Physical examination
- 26. 26 Diagnosing AD in primary care laboratory tests All patients Most patients * Complete blood count * ECG * Thyroid function * Chest X-ray * Vitamin B12 and folate * Syphilis serology * BUN and creatinine * Calcium * Glucose * Electrolytes * Urinalysis * Liver function tests Laboratory tests
- 27. 27 Diagnosing AD in primary care neuroimaging, computed (axial) tomography (CT) Various CT scan reports in AD * Normal examination for the patient's age * Generalized cerebral atrophy * Small vessel changes, areas of leucoencephalopathy * No signs of subdural hematoma (if head trauma suspected) * Absence of specific areas of cerebral infarctions or evidence of stroke Neuroimaging
- 28. 28 Diagnosing AD in primary care cognitive assessments, MMSE Score Score Maximum Actual Cognitive area Mini Mental State Examination: test outline and scoring Orientation *What is the (date, day, month, year, season)? 5 * Where are you (clinic, town, country)? 5 Memory *Name three objects. Ask the patient to repeat them 3 Attention *Serial sevens. Alternatively ask the patient to spell world 5 backwards (dlrow) Cognitive Assessment Folstein et al 1975
- 29. 29 Diagnosing AD in primary care cognitive assessments, MMSE (continued) Score Score Maximum Actual Cognitive area Mini Mental State Examination: test outline and scoring Recall *Ask for the three objects mentioned above to be repeated 3 Language *Name a pencil and watch 2 *Repeat, 'No ifs, ands or buts’ 1 *A three stage command 3 *Read and obey - CLOSE YOUR EYES 1 *Write a sentence 1 *Copy a double pentagon 1 Total 30 Cognitive Assessment Folstein et al 1975
- 30. 30 Clinical features of AD Mild stage of AD (MMSE 21-30) IMPAIRMENT Cognition Function Behavior * Recall/learning * Work * Apathy * Word finding * Money/shopping * Withdrawal * Problem * Cooking * Depression solving * Housekeeping * Irritability * Judgement * Reading * Calculation * Writing * Hobbies Adapted from Galasko, 1997
- 31. 31 Clinical features of AD Moderate stage of AD (MMSE 10-20) IMPAIRMENT Cognition Function Behavior * Recent memory * IADL loss * Delusions (remote memory * Misplacing * Depression unaffected) objects * Wandering * Language (names, * Getting lost * Insomnia paraphasias) * Difficulty * Agitation * Insight dressing * Social skills * Orientation (sequence and unaffected * Visuospatial ability selection) Adapted from Galasko, 1997
- 32. 32 Clinical features of AD Severe stage of AD (MMSE <10) IMPAIRMENT Cognition Function Behavior * Attention * Basic ADLs * Agitation * Difficulty -Dressing - Verbal performing -Grooming - Physical familiar activities -Bathing * Insomnia (apraxis) -Eating * Language -Continence (phrases, mutism) -Walking -Motor slowing Adapted from Galasko, 1997
- 33. 33 Diagnosing AD in primary care cognitive assessment The Clock Draw Test Time: 5.00 Time: .10.30 Score: 7 (normal) Score: 3 (demented) Time: 'no real time' Time: 1/4 past 25 Score: 2 (demented) Score: 3 (demented) Cognitive Assessment Thalmann et al 1996.
- 34. 34 AD prognosis Optimal case Mini Mental State Examination score 25 ---------------------| Symptoms 20 |----------------------| Diagnosis 15 |-----------------------| Loss of functional independence 10 |--------------------------------| Behavioral problems Nursing home placement 5 |-------------------------------------------| 0 Death |------------------------------------------ 1 2 3 4 5 6 7 8 9 Years Feidman and Gracon, 1996
- 35. 35 NEUROPSYCHIATRIC SYMPTOMS @ BPSD APATHY 72% AGITATION 60% IRRITABILITY 42% PACING ETC 38% DEPRESSION 38% ANXIETY 40% DELUSION 22% HALLUCINATION 10% EUPHORIA 8% DISINHIBITION 38%
- 36. 36 BPSD DELUSION : CROSS SECTIONAL STUDIES 20-50% LONGITUDINAL STUDIES 50-70% • THEFT • INFIDELITY • CAPGRAS • PHANTOM BOARDERS • PICTURE SIGN
- 37. 37 Neuropsychiatric disturbances in AD 80 70 60 Patients (%) 50 40 30 20 10 0 ll in x B el it a it ep Ha An Irr Ag Ap AM is D D D Mega MS et al. Neurology 1996; 46: 130–5
- 38. 38 BEHAVIOURAL CORRELATES •AGGRESSIVE •ACTIVITY DISTURBANCES COGNITIVE CORRELATES •DEMENTIA SEVERITY •LANGUAGE, MEMORY & EXECUTIVE FUNCTION
- 39. 39 Successful cholinergic enhancing strategies in AD Reduced breakdown of acetylcholine + Increased release of ACh into synapse = Increased availability of ACh at synapse
- 40. 40 Patient flow • AD is prevalent among primary care patients • However, patients and general practitioners (GPs) are often not aware of this • The diagnosis of AD comes too late • 30 memory clinics in Germany • Patients are normally followed up by GPs
- 41. 41 Reasons for delayed diagnosis • Cognitive decline seen as age-related • GPs feel unsure about diagnosis of AD • Lack of practical diagnostic tools • Expected benefits of treatment are low
- 42. 42 Diagnostic problems andpitfalls • Inadequate diagnostic tools • ‘Normal’ ageing vs. dementia • Interpretation of cerebrovascular findings • Problems of mixed pathologies
- 43. 43 Diagnostic problems andpitfalls • Inadequate diagnostic tools • ‘Normal’ ageing vs. dementia • Interpretation of cerebrovascular findings • Problems of mixed pathologies
- 44. 44 Problems of mixedpathologies • Stroke superimposed on AD • Alzheimer’s plus Parkinson’s disease • Dementia with Lewy bodies
- 45. 45 ANTIPSYCHOTICS • RISPERIDONE:1-2 mg • OLANZEPINE: 5-10 mg • QUETIAPINE: 25-250 mg • HALOPERIDOL: 0.5-3 mg
- 46. 46 AGITATION • physical aggression •verbal aggression • active resistance to care givers Rx: ANTIPSYCHOTIC ANTICONVULSANT
- 47. 47 DEPRESSION • major depressionuncommon • depressive symptoms frequent (40%) • more common with F/H • MD may precede the onset of AD
- 48. 48 ANTIDEPRESSANTS •SSRI = FLUVOXAMINE (LUVOX) • SNRI = VENLAFAXIN (EFFEXOR) • OTHER NEW ANTIDEPRESSANTS
- 49. 49 PERSONALITY CHANGES • APATHY 70% • IRRITABILITY 42% • DISINHIBITION 36%
- 50. 50 APATHY IN AD • most common behavioural change • indifference, loss of affection, decrease motivation • independent of depression • frontal hypoperfusion (mediofrontal) => correlates with cognitive decline
- 51. 51 CHOLINERGIC DEFICIT INAD • ATROPHY OF NUCLEAS BASALIS • DECREASE CAT SYNTHESIS • ACETYLCHOLINE DEFICIT • INTACT CHOLINERGIC RECEPERS
- 52. 52 CHOLINESTERASE INHIBITOR [ChEI] • improve global function • enhance cognition • improve behaviour • delay nursing home placement
- 53. 53 CHOLINESTERASE INHIBITORS ChEIs • TACRINE • DONEPEZIL • RIVASTIGMINE • GALANTAMINE
- 54. 54 Potential caregiver benefits • No sleep disruption • Maintenance of ADL • Suppression of behavioural symptoms = diminished caregiver burden
- 55. 55 The role of the primary care physician in mild to moderate AD * Define all contributory factors and other illnesses * Discuss the diagnosis, and differentiate other types of dementia * Withdraw non-essential drugs that may interfere with cognition * Treat or manage concomitant illness (e.g. depression, hearing loss) Gauthier, Burns and Pettit, 1997
- 56. 56 Therole of the primary care physician in mild to moderate AD (continued) * Discuss the use of symptomatic therapies * Monitor functional ability e.g. driving, safety * Referral to specialist if appropriate * Advise on will-making and advance directives * Refer to local AD association for support * Managing caregivers Gauthier, Burns and Pettit, 1997
- 57. 57 The role of the primary care physician in severe AD * Help caregivers discover and optimize the patient's preserved function * Monitor and treat complications * Facilitate caregiver support (respite and day care programs) * Be aware of caregiver burden and stress * Plan institutionalization, if needed * Assist with end-of-life decisions Gauthier, Burns and Pettit, 1997
- 58. 58 Diagnosing AD in primary care A systematic approach - summary CASE-FINDING CLINICAL ASSESSMENT Symptoms YES *Clinical history suggesting *Physical examination cognitive *Laboratory tests impairment *Functional assessment *Cognitive assessment Functional decline and cognitive impairment DIFFERENTIAL DIAGNOSIS MANAGEMENT OF AD *Exclude *Follow-up - delirium AD diagnosis *Patient and caregiver - depression counseling - other causes of dementia *Management and symptomatic *Evaluate evidence for treatment AD (neuroimaging) *Specialist referral if indicated
- 59. 59 A BCs ofBehaviour al
- 60. 60 Iceberg 20% 80%
- 61. 61 The caregiving burden in AD Hours dedicated per patient over 1 month (1 month = 720 hours, including 160 working hours) • Principal (non-professional) caregiver: 280 hours • Professional caregiver: 36 hours Rice DP et al. Health Aff (Millwood) 1993; 12: 164–76 Boada M et al. Med Clin (Barc) 1999; 113: 690–5
- 62. 62 Caregiver burden Psychological Physical Social Financial or emotional problems problems problems problems Family members (including principal caregiver) caring for Alzheimer patient Multidimensional: objective/subjective burden George, Gwyther, Hoening, Montgomery, Platt
- 63. 63 Spanish National Plan for Patients with AD & other Dementias “Plan Nacional de Atencion a los Enfermos de Alzheimer y otras demencias” Six main areas 1. Health services 2. Social services 3. Legal and economic protection 4. Family support 5. Education and training for professionals 6. Research
- 64. 64 A growing problem Projected prevalence of dementia to 2025 35 30 25 1980 Millions 20 2000 15 2025 10 5 0 1980 2000 2025 Years Alzheimer’s Disease International
- 65. 65 Qualitative changes inthe Alzheimer population in the next decade Improvement of Early Impact of care provided Medical diagnosis drugs by non- progress professionals Changes in the structure of society Health and social services
- 66. 66 AD risk and protective factors Risk factors Protective factors * Age * Genetic (ApoE-2) * Family History of AD * High educational level (ApoE-4) * Long-term anti- * Head trauma inflammatory * Low educational level drug use, e.g. * Environmental factors NSAIDS * Down’s syndrome * Long-term use of estrogens (in women) IPA AD Conference, 1996
Editor's Notes
- #2 The assessment for AD must begin by first diagnosing the existence of a dementia syndrome. Dementia has diverse etiologies. The characteristic clinical feature is that of multiple cognitive deficits including memory loss, aphasia (loss of power to understand spoken or written words), apraxia (inability to perform familiar activities), agnosia (inability to recognize familiar objects) and disturbance in executive function. The deficits are sufficiently severe and persistent to cause functional impairment (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM IV]). The exact clinical symptoms vary from patient to patient and their onset may be slow or rapid, taking from a few months (e.g. Creutzfeld Jakob disease) to many years (average 9 years in AD) to develop. A challenge is to first determine whether dementia is present and then to make a correct differential diagnosis. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington DC: APA, 1994. Copyright © 1994, The American Psychiatric Association, Washington DC. Reprinted by permission.
- #3 The assessment for AD must begin by first diagnosing the existence of a dementia syndrome. Dementia has diverse etiologies. The characteristic clinical feature is that of multiple cognitive deficits including memory loss, aphasia (loss of power to understand spoken or written words), apraxia (inability to perform familiar activities), agnosia (inability to recognize familiar objects) and disturbance in executive function. The deficits are sufficiently severe and persistent to cause functional impairment (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM IV]). The exact clinical symptoms vary from patient to patient and their onset may be slow or rapid, taking from a few months (e.g. Creutzfeld Jakob disease) to many years (average 9 years in AD) to develop. A challenge is to first determine whether dementia is present and then to make a correct differential diagnosis. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington DC: APA, 1994. Copyright © 1994, The American Psychiatric Association, Washington DC. Reprinted by permission.
- #4 'Reversible' or 'potentially/partially reversible' are terms used to distinguish a cognitive disorder in which normal or near-normal function may be restored. The potential to reverse or delay deterioration justifies the early diagnosis of dementia. The common causes of reversible dementia are depression, delirium, and drug toxicity. Other causes include normal pressure hydrocephalus, neoplasms, metabolic disorders, trauma, concomitant medication, and infection. 'Irreversible' dementias, however, are by far the most frequent causes of dementia, with AD being the most prevalent. Other irreversible dementias that occur less frequently include vascular dementia, Lewy body disease, and Pick's disease. These dementias can be more difficult to diagnose and patients suspected of suffering from these forms of dementia should be referred for specialist evaluation. Costa PT Jr, Williams TF, Somerfield M, et al. Recognition and Initial Assessment of Alzheimer's Disease and Related Dementias. Clinical Practice Guideline No 19. Rockville, MD: US Department of Health and Human Services, Public Health Service, 1996.
- #5 A systematic diagnostic approach using standardized clinical assessment techniques makes it possible to establish a differential diagnosis of AD. Following the identification of cognitive impairment, via case-finding or during the clinical history, it is important to identify or discount delirium or depression. Delirium usually results from acute illness or physiological change, often in another organ system than the brain. The causative illness may be life-threatening and may constitute a medical emergency. It is, therefore, imperative to diagnose and treat delirium. It can be completely reversible if the cause is quickly remedied. Depression and AD often coexist and depression with cognitive impairment (the dementia syndrome of depression or depressive pseudodementia) may be an early sign of AD. Depression should be identified and antidepressant treatment initiated. Once other causes such as delirium and depression have been ruled out, and it is decided that dementia is the most likely cause of the cognitive impairment, a comprehensive clinical history, assessment and neuroimaging will exclude other forms of dementia and help support a diagnosis of AD.
- #6 AD is one of the most prevalent dementing disorders, representing over 50% of all dementia cases in the elderly. The incidence of the disease is dependent on age, with the prevalence doubling approximately every 5 years from the age of 60 (4% at 75, 16% at 85, and 32% at 90). The impact of this insidious disease on patients, caregivers and physicians is colossal. In addition, it presents a tremendous economic burden on healthcare resources: an estimated annual cost of $90 billion in the USA (direct costs $40 000 and indirect costs $174 000 per patient). It is anticipated that the social and economic impact of AD will reach epidemic proportions as the aged population continues to grow. 1. Livingstone G. In: Burns A, Levy R (eds). Dementia. London: Chapman and Hall Medical, 1994:2135. 2. Katzman R and Kawas C. The epidemiology of dementia and Alzheimer's disease. In: Terry RD, Katzman R, Bick KL (eds). Alzheimer's Disease. New York: Raven Press, 1994: 105122. 3. World Alzheimer's Day Proclamation, Alzheimer's Disease International, http://www.ncf carleton. ca:12345/freeport/social.services/alzheimer/adi.dir/menu
- #11 AD is one of the most distinctive of the dementing illnesses, with an insidious onset and progressive decline. Although the clinical features are characteristic in most sufferers, there is, however, great heterogeneity in age of onset and the rate of disease progression. Many areas of cognition are compromised by AD in the early stages of the disease. Problems include memory loss, aphasia, apraxia, agnosia and difficulties in executive function and visuospatial abilities. Functional disability is intrinsically linked to cognitive decline and a deterioration in social and occupational activities is characteristically observed. Problems may arise in the Instrumental Activities of Daily Living (IADL) such as driving the car, paying bills, or functioning at work. Later in the disease, the basic Activities of Daily Living (ADL), such as dressing and bathing, are affected. Changes in behavior are also common and may include mood swings, agitation and wandering. The stage and course of AD can be monitored by evaluating the cognitive, functional and behavioural changes exhibited by individual patients. International Psychogeriatric Association, Alzheimer's Disease Applied Diagnosis and Assessment Conference, Geneva 1996.
- #12 Component title: Natural history of Alzheimer’s disease Description: In early AD, patients experience forgetfulness and are unable to recall recent events. In the moderate stage of the disease, patients may show disorientation, impaired concentration and changes in personality, mood and behaviour. In the severe stages of the disease, all aspects of memory fail progressively and patients may exhibit aphasia (loss of language), apraxia (loss of purposeful movement) and agnosia (loss of recognition). Finally, gross deficits in all intellectual function occurs. Marked neurological defects (e.g. seizures) may occur and patients become progressively incapacitated with increasing weight loss and ultimately, death. Figure adapted with kind permission from Feldman and Gracon, from The Natural History of Alzheimer’s Disease, 1996. Martin Dunitz Publications.
- #18 AD is no longer considered a diagnosis of exclusion, based purely on neuropathological findings or eliminating the possibility of other dementia syndromes. Opinions have changed. The implementation of existing skills and the development of new diagnostic techniques, coupled with a greater appreciation of the disease, now makes the clinical diagnosis of AD a realistic possibility during the lifetime of the patient. AD often has a consistent onset and disease progression which makes it one of the most characteristic of mental disease processes. Early intervention allows the initiation of community support and presents an opportunity for the patient and caregivers to come to terms with the illness and plan for the future. Although the prospect of developing a cure is unlikely in the foreseeable future, new symptomatic therapies are becoming available, which improve residual cognitive function, re-emphasizing the need for early diagnosis of AD. International Psychogeriatric Association, Alzheimer's Disease Applied Diagnosis and Assessment Conference, Geneva 1996.
- #22 Delirium can be mistaken for, or can coexist with, dementia and should be addressed promptly. Delirium is often under-diagnosed in the clinical setting. It is essential that delirium is discounted as early as possible. The underlying physical disorder, together with the cognitive decline, may constitute a medical emergency. Ham RJ. Confusion, dementia and delirium. In: Ham RJ, Sloane PD (eds). Primary Care Geriatrics. A Case-Based Approach, 3rd edn. St Louis: Mosby-Year Book, Inc., 1997:217259. Reproduced by kind permission.
- #23 It can be difficult to differentiate between dementia and depression. Depression can manifest as dementia, or the dementia syndrome of depression (depressive pseudodementia). Conversely, dementia can present with depressive symptoms in the early stages of the illness. Depression and dementia often coexist. Up to 50% of individuals diagnosed with dementia will have coexisting depressive symptoms at some stage of the illness. Ham RJ. Confusion, dementia and delirium. In: Ham RJ, Sloane PD (eds). Primary Care Geriatrics. A Case-Based Approach, 3rd edn. St Louis: Mosby-Year Book, Inc., 1997:217259. Reproduced by kind permission. Wells CE. Pseudodementia. Am J Psychiatry 1979;36:895900. Copyright © 1979, The American Psychiatric Association. Reprinted by permission.
- #24 A structured approach to questioning will help determine the problems being experienced and the pattern of disease progression. Careful interviewing of both the patient and the caregiver, using a set of questions such as these, will help to trigger a preliminary assessment of AD. The clinical history is an essential part of the assessment process. A more accurate assessment can be made if the patient and family are interviewed separately, initially. Family members are often reluctant to discuss problems in front of the patient for fear of upsetting the patient. Patients are often not aware of the symptoms or may be in a state of denial.
- #25 In the primary care setting the Functional Activities Questionnaire (FAQ) is a rapid and easy measure of functional ability. It may be necessary to adapt the questions according to gender and cultural bias. The FAQ is an informant-based questionnaire that provides a quick appraisal of patient performance and functional ability. The informant is asked to rate the performance of the patient in 10 areas of functioning (see slide). Scores can range from 030. A score of 9 or below is normal. Scores of 10 or above indicate reduced functional ability. Pfeffer RI, Kurosaki TT, Harrah CH, et al. Measurement of functional activities in older adults in the community. J Gerontol 1982;37:323329. Copyright © The Gerontological Society of America.
- #26 A complete physical examination should be undertaken: blood pressure, pulse, vision, hearing assessments, evaluation for cardiac and respiratory function, mobility and balance. Life-threatening conditions should be considered first, such as mass lesions, vascular lesions and infections. The examination should include a sensory and motor system examination, including tone, reflexes, gait and coordination.
- #27 A number of laboratory tests should be requested to rule out concomitant illness and other causes of dementia. HIV testing may be indicated in high-risk groups.
- #28 A CT scan without contrast is often recommended as part of the AD assessment. It is considered adequate in most cases to discount space-occupying lesions and is probably as effective as MRI for this purpose. CT can identify moderate to large areas of infarction and can detect significant subdural hematoma. A standard axial CT angle may reveal: *Extent of cortical atrophy *Presence of focal atrophy *Extent of white-matter change *Brain infarction *Tumors *Subdural hemorrhage Although a CT scan is used primarily to exclude other conditions, linear measurements of ventricular width, particularly the temporal horns of the lateral and third ventricles, can help support a diagnosis of AD. Generally the CT scan is interpreted by a specialist. This slide details a variety of common interpretations that appear on a CT scan report.
- #29 Functional disability is usually linked to a decline in cognitive functioning. However, the prime marker for AD is cognitive decline and this should always be evaluated. Standard, structured tests should be used to assess cognition. Two tests that can easily be deployed in the primary care setting are: *Mini Mental State Examination (MMSE) *Clock Draw Test (CDT) Mini Mental State Examination The next two slides will present the MMSE. The MMSE is a short collection of cognitive tests examining: orientation, memory, attention, recall and language. It is simple and easy to use and involves the patient completing a number of tests (see Slides 19 and 20). Scoring: 24 to 30 is considered normal; below 24 indicates a degree of cognitive decline (mild = 21 to 23, moderate = 11 to 20 and severe = 0 to 10). The score is influenced by a number of factors, including: years of schooling (normal individuals with 9 years of schooling have an MMSE score of 29, with 58 years, 26, and with 04 years, 22) and cultural background (the statement 'Close your eyes', for example, signifies death in the Chinese culture). Folstein MF, Folstein SE, McHugh PR. Mini Mental State: a practical method for grading the cognitive state of patients for the clinician. Reproduced by kind permission of J Psychiatr Res 1975;12:189198, (Elsevier Science).
- #30 Folstein MF, Folstein SE, McHugh PR. Mini Mental State: a practical method for grading the cognitive state of patients for the clinician. Reproduced by kind permission of J Psychiatr Res 1975;12:189198, (Elsevier Science).
- #31 Cognition: In the early stages of AD, the first symptom experienced is memory loss. Individuals experience forgetfulness that occurs much more frequently and persistently than that associated with normal aging. Common complaints include difficulty remembering appointments, conversation details or aspects of television programs. In this initial phase of the illness there are learning difficulties and delayed recall followed by language problems, such as difficulty finding specific words. In addition, elements of executive function can be affected, such as problem solving, judgement and calculation. Function: Impaired Instrumental Activities of Daily Living (IADLs), associated with the cognitive deficits, develop early in the course of AD. Activities particularly dependent on memory are affected. These include functioning at work, shopping, managing finances, participating in hobbies, reading, writing, and household tasks (cooking, etc). Remembering appointments and plans is difficult. Basic Activities of Daily Living (ADLs) are usually unaffected. Behavior: There is a relationship between the manifestation of behavioral symptoms and the progression of AD. It is, however, not possible to predict accurately who will develop these symptoms and when. Initial behavioral changes are subtle and include apathy, withdrawal and depressive symptoms (e.g. flat mood, reduced initiative, decreased activity). Often the patient becomes irritable in response to the frustration of dealing with the symptoms of AD. Important decisions regarding driving and personal finances should be considered at this stage of AD. Galasko D. Correlating cognition, behavior and function. Presented at an official satellite symposium, 'Managing the Burden of Alzheimer's Disease: Beyond Cognition', at the European Federation of Neurological Societies Meeting, 47 June 1997, Prague, Czech Republic.
- #32 Cognition: As AD progresses, recent memory becomes severely restricted, although remote memory remains unaffected. Generating new memories becomes difficult and patients will tend to dwell on past events. Details of television programs cannot be retained and it becomes difficult to participate in conversation as patients increasingly find it difficult to remember people's names and to select the correct words. Sentence structure becomes less complex. In addition, insight, orientation and visuospatial ability become impaired. Function: In the moderate stages of AD IADLs become severely restricted, so much so that the patient requires assistance from the caregiver or loses the ability to perform IADLs altogether. Misplacing objects such as spectacles or keys becomes increasingly more frequent and the patient often gets lost, even in familiar surroundings. Supervision is needed in dressing because it becomes difficult for the patient to select items of clothing and put them on in the right order. At this stage basic ADLs generally remain intact. Behavior: Delusions and depression are common (experienced by 2050% of patients). Common delusions include paranoia (people are stealing things) and misidentification (for example, their spouse is an impostor, the house is not their own, or TV images are real). In addition, motor dysfunction (e.g. wandering) and insomnia occur. Social graces remain intact. Galasko D. Correlating cognition, behavior and function. Presented at an official satellite symposium, 'Managing the Burden of Alzheimer's Disease: Beyond Cognition', at the European Federation of Neurological Societies Meeting, 47 June 1997, Prague, Czech Republic.
- #33 Cognition: It becomes more difficult to differentiate meaningful changes in cognition in the late stage of AD. Attention becomes severely impaired and patients find it difficult to perform familiar activities (apraxis), and follow commands. It becomes impossible to recall the names of familiar objects and family members. Language becomes restricted to a few simple phrases or words, and eventually the patient becomes mute. Function: A hierarchical loss of basic ADLs is observed; first dressing, then grooming, bathing, eating, and finally, continence, walking and motor slowing. The loss of each ADL is gradual. The patient becomes bed-bound and becomes completely dependent on the caregiver. Behavior: Agitation, both verbal (screaming) and physical, and insomnia, are characteristic in the later stages of AD. Galasko D. Correlating cognition, behavior and function. Presented at an official satellite symposium, 'Managing the Burden of Alzheimer's Disease: Beyond Cognition', at the European Federation of Neurological Societies Meeting, 47 June 1997, Prague, Czech Republic.
- #34 The Clock Draw Test (CDT) complements the MMSE by examining other cognitive areas including planning and constructive abilities. The test is easy to perform. The patient is simply asked to draw a clock. They are then asked to interpret the time they have depicted by writing in figures the time shown on the clock. Scores are given for: *The number 12 at the top 2 points *Exactly 12 numbers 1 points *Two discernible hands 2 points *Recording the clock time in figures 2 points Scores between 6 and 7 are normal; scores between 0 and 5 suggest cognitive impairment. Combining the CDT and the MMSE provides a broad and informative assessment of cognitive functioning. Thalmann B, Monsch AU, Ermini-Fünfschilling D, Stähelin HB, Spiegel R. Presented at the IPA Alzheimer's Disease Applied Diagnosis and Assessment Conference, Geneva 1996.
- #35 In the optimal case, the course of AD progression can be divided conveniently in to three stages, early, mild to moderate, and severe. In the early stages of the disease, the patient will generally remain symptom-free. As the illness progresses, the extent of cognitive impairment becomes such that patient and caregivers recognize that there is a problem. A progressive and insidious decline in cognition and functional ability marks the mild to moderate stage. Cognitive loss leads to functional decline and behavioral symptoms. The rate of decline varies from patient to patient. During the later severe stages of the illness functional ability is lost completely and institutionalization is inevitable. Although AD is a progressive disease for which there is currently no cure, symptomatic treatments are becoming available that maintain or may improve the patient's functional ability. Despite new symptomatic treatments having not been shown to affect the underlying disease process, the ability to maintain function or cognitive capabilities for longer should be viewed as a viable treatment objective. Expectations, however, should be realistic. Feldman H, Gracon S. Alzheimer's disease: symptomatic drugs under development. In: Gauthier S (ed). Clinical Diagnosis and Management of Alzheimer's Disease. London: Martin Dunitz, 1996:239259. Reproduced by kind permission.
- #46 Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #49 Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #50 Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #51 Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #52 Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #53 Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #54 Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #56 The next two slides examine the role of the primary care physician in mild to moderate AD. AD is probably the most common mental disorder affecting the elderly. In the community, however, perhaps up to half of all sufferers may remain unidentified. The primary care physician (PCP) currently cares for the majority of patients with AD, either at home or in long-term nursing homes. The PCP is in an excellent position to diagnose and manage AD within the community, and can provide the following support (see slides) in the early stages of the disease. Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #57 Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #58 In the later stages of AD, when the decline in the patient's functional ability is most pronounced, the PCP can help caregivers recognize and optimize the patient's remaining or preserved function. At this stage it is also important to regularly monitor and treat, if appropriate, complications and concomitant illnesses. In severe AD the stress and burden on the caregiver is at its greatest. If available, some form of caregiver support should be arranged, such as respite or day care programs, which are now becoming widely available. Inevitably it will be necessary to plan for institutionalization and assist in end-of-life decisions. Gauthier S, Burns A, Pettit W. In: Alzheimer's Disease in Primary Care. London: Martin Dunitz, 1997. Reproduced by kind permission.
- #59 A structured and systematic approach is required to ensure the early diagnosis and management of AD. The diagnostic process includes: Case-finding Clinical assessment Differentiating AD from other causes of dementia Management of AD
- #60 Once the diagnosis is certain, scheduled follow-up, initially at short intervals to answer questions, will be required. Continuing, scheduled follow-up visits will be needed, in order to implement a proactive, anticipatory approach that will reduce the impact of the illness on the patient and family. The progressive nature of AD makes follow-up and continuity of care essential. Careful, structured questioning during the follow-up assessments will monitor the progression of the disease, and determine how the caregivers are coping. At each follow-up visit ask about: *Cognitive function: evidence of deterioration since last visit, if any *Functionality, particularly in daily living skills essential for independence, such as driving, shopping, traveling *Behavioral issues, ask about mood and motivation and any difficulties the family has with handling the patient *General health questions, always include nutrition, weight, sleep, mobility/gait, balance problems/falls and any bladder (incontinence) or bowel (constipation) problems *Routine health maintenance (e.g. immunization, cancer checks, etc)
- #62 The economic burden of Alzheimer's disease care . Rice DP; Fox PJ; Max W; Webber PA; Lindeman DA; Hauck WW; Segura E. Health Aff (Millwood) 1993; 12: 164–76 This study examines total formal and informal care costs attributable to Alzheimer's disease for persons living in the community and in institutions. The total cost of caring for an Alzheimer's patient in northern California is approximately $47,000 per year whether the patient lives at home or in a nursing home, but the cost breakdown differs in the two settings. For community-resident patients, three-fourths of the total cost represents an imputed value for unpaid informal care compared with 12 percent for institutionalized patients. Formal services are financed primarily by individuals and their families. Over 60 percent of the services provided to patients in either care setting were paid out of pocket. With projected increases in the number of persons at risk of developing Alzheimer's disease, the economic impact of the disease on future long-term care costs will be significant. [Costs of health care resources of ambulatory-care patients diagnosed with Alzheimer's disease in Spain] Coste de los recursos sanitarios de los pacientes en regimen ambulatorio diagnosticados de enfermedad de Alzheimer en Espana. Boada M; Pena-Casanova J; Bermejo F; Guillen F; Hart WM; Espinosa C; Rovira J.Med Clin (Barc) 1999; 113: 690–5 The annual consumption and costs of the health care resources used by ambulatory Alzheimer's disease patients were estimated. Patients were classified according to the degree of severity of the disease using Folstein's Mini Mental State Examination scale. The sociodemographic characteristics of both patients and their careers were described. PATIENTS AND METHODS: Patients with an established diagnosis of Alzheimer's disease according to NINCDS/ADRDA criteria were included in the study. Information on the use of health and non-health care resources consumed during the last 12 months was recorded. The following scales were administered: MMSE, Global Deterioration Scale, Rapid Disability Rating Scale and Hachinski's scale modified by Rosen. Finally, the time dedicated by careers to look after the Alzheimer's disease patients was recorded. RESULTS: A total of 337 patients were considered to be valid for the analysis with an average of 72 (8.4) years and with an average duration of the disease of 48.3 (35.7) months. The average annual cost per patient was 3,194,664 ptas. The average cost per patient in the group with MMSE > 18 was 2,119,889 ptas; 2,723,159 ptas. in those with MMSE 12-18 and 3,676,707 ptas. in the MMSE < 12 group. CONCLUSIONS: In patients with Alzheimer's disease an increase in cost directly related to functional cognition state was observed. The most important cost component was that imputed to value time dedicated by principal career.
- #63 Caregiver burden and well-being: an elusive distinction. George LK Gerontologist. 1994; 34: 6–7. No abstract available. Social issues of the Alzheimer's patient and family. Gwyther LP Am J Med. 1998;104(Suppl 4A): S17–21; discussion S39–42. Review. Elderly psychiatric patients and the burden on the household. Hoenig J; Hamilton MW. Psychiatr Neurol (Basel) 1966; 152: 281–93 The family role in the context of long-term care. Montgomery RJ J Aging Health 1999; 11: 383–416
- #67 Risk factors: A variety of factors, both genetic and environmental can contribute concurrently to AD. Age is an obvious risk factor for AD, as the incidence of AD doubles every five years after the age of 60. In addition, as many as 1015% of all occurrences of AD may be familial. In 1993, an association between the gene coding for apolipoprotein E (ApoE) and the risk of AD was established. This gene is the most important genetic determinant of risk of sporadic and late-onset AD. The gene exists in three main isoforms (E-4, E-3 and E-2). The ApoE-4 allele appears to increase the risk of AD; however, its link with the onset of the disease in unclear. Some ApoE-4-positive individuals do not go on to develop the disease, while others without the allele do. With this in mind, ApoE genotyping cannot be used to predict the risk of AD in symptom-free individuals. ApoE genotyping may be clinically useful as an adjunct to other diagnostic procedures. Other factors include, head trauma, environmental factors (pollutants, etc.), coexisting vascular disease and Down's syndrome. Protective factors: There is evidence that the presence and frequency of the apolipoprotein E2 allele is a protective factor against the occurrence of AD. People with a higher level of education are less likely to develop the disease. Recent studies suggest that there may be a link between the long-term use of anti-inflammatory drugs and a reduced risk of AD. There is also evidence to suggest that similar effects occur with vitamin E and in women following long-term estrogen use. International Psychogeriatric Association, Alzheimer's Disease Applied Diagnosis and Assessment Conference, Geneva 1996.