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Alzheimer's disease: Clinical Assessment and Management


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This PPT is a seminar on the Alzheimer's disease which was prepared for sensitizing post graduate psychiatry students on the day of World Alzheimer's Day.

Published in: Health & Medicine
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Alzheimer's disease: Clinical Assessment and Management

  2. 2. WHAT IS ON PLATE TODAY?  What is Dementia?  What is Alzheimer’s Disease?  Symptomatology  Clinical Assessment  Management: Brief
  3. 3. WHAT IS DEMENTIA?  Dementia refers to a spectrum of brain disorders all of which involve cognitive impairment but vary widely in terms of cause, course and prognosis.  Progressive loss of cognitive/intellectual functions.  Without impairment of consciousness.  There is disturbance of multiple higher cortical functions, including memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgment.
  4. 4. DEMENTIA: BACKGROUND  Dementia : De = Out from + mens = the mind  Loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning  Usually irreversible disorder  Egyptians and Greeks of the period 2000-1000 BC were aware of age related memory decline  India : Dementia : Smiriti Bhransh : 800 BC : Sathiya Gaye (Turned 60) : Satar- Batar (Turned 70) : “Chinan” in South India
  5. 5. EPIDEMIOLOGY  AD is the most common cause of dementia amongst people aged 65 and older  Prevalence among people over 60 years–5% to 8 %  Starting with 0.5% prevalence at 55 yrs., it goes on doubling every five years (60yrs-1%; 65yrs-2%; 70yrs- 4%; 75yrs- 8% and so on)  Risk at the age of 80 years is around 15 to 20%  At present nearly 47.5 million people worldwide with dementia. It is expected to be 74.7 million by 2030 and 131.5 million by 2050.  About 7.7 million new cases of dementia each year.  A new case detected in every 3 seconds somewhere in world. (WHO) Average prevalence of dementia in India: 3.7%
  6. 6. DEMENTIA OF ALZHEIMER’S TYPE  Alzheimer’s disease (AD) is the most common form of dementia, representing approximately 55-60% of all cases.  In 1907, Alois Alzheimer first described the condition that later assumed his name.  It is a cortical dementia characterized by a slow, progressive loss of cognitive functions.  AD is the fourth leading cause of death in USA. No Indian data is available regarding it.
  7. 7. DEMENTIA OF ALZHEIMER’S TYPE Characterized by: Progressive loss of cortical neurons Formation of amyloid plaques (beta-amyloid is major component) Intra-neuronal neurofibrillary tangles (hyper phosphorylated tau proteins is major constituent)
  8. 8. PATHOGENESIS AND PATHOPHYSIOLGY AD is characterized by generalized cerebral cortical atrophy with widespread cortical neuritic (or senile) plaques (NPs) and neurofibrillary tangles (NFTs). Following mechanisms have been attributed for the development of Alzheimer’s dementia  Amyloid cascade theory  Neuronal loss  Cholinergic hypothesis  Excitotoxicity  Genetic factors
  9. 9. DIAGNOSIS OF AD (DSM IV TR) A. The development of multiple cognitive deficits manifested by both 1. Memory impairment (impaired ability to learn new information or to recall previously learned information) 2. One (or more) of the following cognitive disturbances: A. Aphasia (language disturbance) B. Apraxia (impaired ability to carry out motor activities despite intact motor function) C. Agnosia (failure to recognize or identify objects despite intact sensory function) D. Disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting) B. The cognitive deficits in Criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning. C. The course is characterized by gradual onset and continuing cognitive decline. D. The cognitive deficits in Criteria A1 and A2 are not due to any of the following: 1. Other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor) 2. Systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection) 3. Substance-induced conditions E. The deficits do not occur exclusively during the course of a delirium.
  10. 10. DIAGNOSTIC TYPES  Early onset: < 65 years; familial types; 1, 14 and 21 chromosomes.  Late onset: >65 years usually in 70s; sporadic form; Chromosome 19.  Mixed: not fitting into above two  Unspecified:
  11. 11. STAGES OF ILLNESS DEVELOPMENT Stage 1: Normal Stage 2: Normal aged forgetfulness Stage 3: Mild Neuro-cognitive disorder (MCI) Stage 4: Mild Alzheimer’s Disease Stage 5: Moderate Alzheimer’s Disease Stage 6: Moderately severe Alzheimer’s Disease Stage 7: Severe Alzheimer’s Disease
  12. 12. FAST SCALE (FUNCTIONAL ASSESSMENT STAGING) STAGE 1: No impairment STAGE 2: Complaints of forgetting location of objects. Subjective work difficulties STAGE 3: Decreased job functioning evident to co- workers. Difficulty in traveling to new places. Decreased organizational capacity. STAGE 4: Decreased ability to perform complex tasks, e.g., planning dinner for guests, handling personal finances, difficulty in marketing etc. STAGE 5: Requires assistance in choosing proper clothing to wear for the day, season or occasion, e.g., patient may wear the same clothing repeatedly, unless supervised.
  13. 13. FAST SCALE (FUNCTIONAL ASSESSMENT STAGING) Stage 6: a) Improperly putting on clothes without assistance or cuing occasionally or more frequently over the past few weeks b) Unable to bathe properly c) Inability to handle mechanics of toileting d) Urinary incontinence e) Fecal incontinence
  14. 14. FAST SCALE (FUNCTIONAL ASSESSMENT STAGING) Stage 7: a) Ability to speak limited to approximately a half a dozen intelligible different words or fewer, in the course of an average day or in the course of an intensive interview. b) Speech ability limited to the use of single intelligible word in an average day or in the course of an intensive interview (may repeat the word over and over) c) Ambulatory ability lost d) Cannot sit up without assistance e) Loss of ability to smile f) Loss of ability to hold up head independently
  15. 15. STAGING OF AD IN 3 CATEGORIES: Mild: Although work or social activities are significantly impaired, the capacity for independent living remains, with adequate personal hygiene & relatively intact judgment (~1-3 yrs) Moderate: Independent living is hazardous & some degree of supervision is necessary (~2-8 yrs) Severe: Activities of daily living are so impaired that continuous supervision is required, e.g., unable to maintain minimal personal hygiene; largely incoherent or mute.
  16. 16. EARLY SYMPTOMS:  Forgetfulness, especially for recent events  Difficulty doing tasks with many steps  Feeling lost or disoriented in familiar places  Difficulty making quick decisions  Problems finding the right words  Moodiness, loss of interest in new projects, social activities, anxiety, or depression
  17. 17. TEN WARNING SIGNS OF AD 1. Memory loss that affects job skills 2. Difficulty performing familiar tasks 3. Problems with language 4. Disorientation to time and place 5. Poor or decreased judgment 6. Problems with abstract thinking 7. Misplacing things 8. Changes in mood or behavior 9. Changes in personality 10.Loss of initiative (Alzheimer’s
  18. 18. NEURO-PSYCHIATRIC SYMPTOMS IN AD Neuro-psychiatric domains: 1. Delusions 2. Hallucinations 3. Agitation/Aggression 4. Depression/Dysphoria 5. Anxiety 6. Elation/Euphoria 7. Apathy/Indifference 8. Disinhibition 9. Irritability/Lability 10.Aberrant motor behavior Vegetative domains: 11.Sleep and Nighttime Behavior Disorders 12.Appetite and Eating Disorders Neuro-Psychiatry Inventory
  19. 19. OTHERS: Sundowning: Drowsiness, confusion, ataxia, falls Catastrophic reaction Wandering Incontinence Inappropriate Sexual Behaviors
  20. 20. PERSONALITY CHANGES  Loss of awareness and normal responsiveness to environment  Individuals may become more anxious or fearful  There is flattening of affect and a withdrawal from challenging situations  Aggressiveness may be exhibited
  21. 21. TYPICAL WORK-UP OF AD PATIENTS: History taking Physical and Neurological examination Mental status Functional assessment Laboratory work-up Neuro-imaging
  22. 22. HISTORY TAKING History taking: Collateral history is very important From patient Informant: one who lives with the patient throughout the day, taking care of patient, helping in daily activities Another informant: to confirm findings, suspected cases of abuse and neglect Attention should be paid to  Mode of onset,  Course of progression,  Pattern of cognitive impairment  Presence of non-cognitive symptoms such as behavioral disturbance, hallucinations and delusions
  23. 23. HISTORY TAKING: History taking as per ABC: A: Activities of daily living (ADL) B: Behavioral and Psychological symptoms of dementia C: Cognition
  25. 25. HISTORY TAKING: o Activities of daily living: (ADL)  Basic activities: •Bathing, dressing, toileting, transferring, continence, Feeding etc.  Instrumental activities: • Ability to use telephone • Shopping • Food preparation • Laundry • House keeping • Ability handle finances, responsibility of own medications, mode of transportation
  26. 26. HISTORY TAKING: o Behavioral and Psychological symptoms of dementia:  Types of delusions encountered in AD: patient believe that  he/she is in danger ‐ that others are planning to hurt him/her?  others are stealing from him/her?  his/her spouse is having an affair?  unwelcome guests are living in his/her house?  his/her spouse or others are not who they claim to be?  his/her house is not his/her home?  family members plan to abandon him/her?  television or magazine figures are actually present in the home? (Does he/she try to talk or interact with them?)
  27. 27. HISTORY TAKING: Past history: Family history: Medication history: Medical history: Family assessment: Examination: General Physical Examination Systemic examination: Neurological Mental status examination:
  28. 28. COGNITIVE ASSESSMENT: Can be done by: MMSE: Mini Mental Status Examination HMSE: Hindi Mental Status Examination HCST: Hindi Cognitive Screening Test  Detailed assessment can be done by separate tests for each cognitive domains  Based on the basic assessment the patient can be categorized into:  Mild: 20-24  Moderate: 10-19  Severe: <10 • CDT (clock drawing test): if the patient has MMSE more than 24 than try CDT • If CDT is abnormal than dementia is confirmed • CDT + Delayed recall: MINI Cog
  29. 29. RECOMMENDATIONS FOR DIAGNOSTIC CRITERIA o DSM-IV or NINCDS-ADRDA criteria should be used for the diagnosis of Alzheimer’s disease o The Hachinski Ischemic Scale or NINDS-AIRENS criteria may be used to assist in the diagnosis of vascular dementia. o Diagnostic criteria for dementia with Lewy bodies and fronto- temporal dementia should be considered in clinical assessment. o Clinical criteria for dementia with Lewy bodies (Consortium for DLB criteria) fronto-temporal dementia (Lund-Manchester criteria) are not closely associated with neuropathological diagnoses but can still provide useful differentiating clinical features NINCDS-ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association NINDS-AIREN: National Institute of Neurological Disorders and Stroke- Association Internationale pour la Recherche et l'Enseignement en Neurosciences
  30. 30. DIAGNOSIS: Initial Cognitive Testing:  MMSE is used widely for screening purpose  It provides superficial assessment of memory, language, visuoperceptual function.  Processing speed and executive function are not tested.  Evidence from a systematic review has shown that the MMSE is suitable for the detection of dementia in individuals with suspected cognitive impairment Recommendations: In individuals with suspected cognitive impairment, the MMSE should be used in the diagnosis of dementia.  Initial cognitive testing can be improved by the use of Addenbrooke’s Cognitive Examination, Montreal Cognitive Assessment (MoCA)  A questionnaire, such as the IQCODE, completed by a relative or friend may be used in the diagnosis of dementia (The Informant Questionnaire on Cognitive Decline in the Elderly) MoCA assesses executive functions, it is particularly useful for patients with vascular impairment, including vascular dementia.
  31. 31. DETAILED ASSESSMENT: o Alzheimer’s Disease Assessment Scale- Cognitive and Non-Cognitive Sections (ADAS-Cog, ADAS Non-Cog) o Cambridge Assessment of Memory and Cognition (CAM Cog) o PGI Battery of Brain Dysfunction (PGIBBD) o NIMHANS neuropsychological battery for elderly o AIIMS comprehensive neuropsychological battery in Hindi: assessment of Lobar functions
  32. 32. RECOMMENDATIONS FOR NEUROPSYCHOLOGICAL TESTING  Assessment of cognition is useful in both the initial and differential diagnosis of dementia  It is possible to detect even very early Alzheimer’s disease using neuropsychological testing.  Neuropsychology is superior to imaging in discriminating people with AD from controls.  Neuropsychological testing also aids in the differential diagnosis of dementia: • FTD is characterized by deficits of semantic memory and attention/executive function rather than the episodic memory deficit seen in AD • Dementia with Lewy bodies has more pronounced visuoperceptual and frontal impairment compared to AD • Vascular dementia exhibits executive dysfunction • Depression shows a subcortical pattern of cognitive impairment
  33. 33. RECOMMENDATIONS FOR NEUROPSYCHOLOGICAL TESTING o Recommendation: Neuropsychological testing should be used in the diagnosis of dementia, especially in patients where dementia is not clinically obvious. o It may be useful to repeat neuropsychological testing after six to 12 months in patients where:  The diagnosis is unclear  Measurement of the progression of deficits in a typical pattern supports a diagnosis of dementia and helps in differential diagnosis.
  34. 34. LABORATORY WORK UP: Routine Blood Examination: o CBC o RFT o LFT o RBS o Lipid profile o Vit. B12 and folate (based on affordability) o Vit. D3 (Based on affordability) o Serum Homocysteine level (if Vascular risk factors present) o Urine Routine and microscopic examination • ECG and CXR: When needed • HB1AC: Diabetes, when RBS is increased • Screening for syphilis: only in high risk individual • HIV screening: only in high risk individual Screening for Genetic markers: Not recommended
  35. 35. THE ROLE OF CEREBROSPINAL FLUID AND ELECTROENCEPHALOGRAPHY:  There is insufficient evidence to support routine use of CSF markers in the diagnosis of dementia.  Recommendations:  CSF and EEG examinations are not recommended as routine investigations for dementia.  CSF and EEG examinations may be useful where CJD is suspected.
  36. 36. IMAGING: The use of Imaging: The ability of clinical examination (for example, history-taking and physical examination) to predict a structural lesion has been reported as having sensitivity and specificity of 90%. Imaging can be used to detect reversible causes of dementia and to aid in the differential diagnosis of dementia. The choice of imaging technique varies widely, and includes CT scan, MRI, SPECT and PET. Assessment of delayed recall is at least as good as volumetric MRI in distinguishing people with probable AD from controls. Recommendation: Structural imaging should ideally form part of the diagnostic workup of patients with suspected dementia. Recommendation: CT may be used in combination with CT to aid the differential diagnosis of dementia when the diagnosis is in doubt.
  37. 37. PHARMACOLOGICAL INTERVENTIONS: Core symptoms:  Cognitive decline: all cholinesterase inhibitors  Functional decline: all cholinesterase inhibitors  Social decline: no evidence Associated symptoms:  Agitation: Trazodone and ? SSRI  Aggression: Antipsychotics  Depression: Antidepressants  Psychosis: Donepezil, Rivastigmine, Antipsychotics  Repetitive vocalization: no evidence ? SSRI  Sleep disturbance: no evidence  Non-specific behavior disturbance: all cholinesterase inhibitors and antidepressants
  38. 38. PHARMACOLOGICAL INTERVENTIONS: DONEPEZIL Recommendations for Donepezil: o Donepezil, at daily doses of 5 mg and above, can be used to treat cognitive decline in people with Alzheimer’s disease. o Age and severity of Alzheimer’s disease should not be contraindications to the use of donepezil. o A systematic review of the use of donepezil in people with vascular dementia demonstrated some benefit to patients with mild to moderate cognitive impairment examined over a six month period. o Donepezil, at daily doses of 5 mg and above, can be used for the management of associated symptoms in people with Alzheimer’s disease.
  39. 39. PHARMACOLOGICAL INTERVENTIONS: GALANTAMINE  Galantamine is effective for the maintenance of cognition in people with mild to moderate Alzheimer’s disease.  There is evidence of some cognitive benefit to patients with mixed Alzheimer’s disease and cerebrovascular disease.  Recommendations for Galantamine:  Galantamine, at daily doses of 16 mg and above, can be used to treat cognitive decline in people with Alzheimer’s disease and people with mixed dementias.  Galantamine should be used with slow escalation to doses of up to 24 mg.  Galantamine, at daily doses of 16 mg and above, can be used for the management of associated symptoms in people with Alzheimer’s disease.
  40. 40. PHARMACOLOGICAL INTERVENTIONS: RIVASTIGMINE Recommendations for Rivastigmine:  Rivastigmine, at daily doses of 6 mg and above, can be used to treat cognitive decline in people with Alzheimer’s disease.  Rivastigmine, at daily doses of 6 mg and above, can be used to treat cognitive decline in people with dementia with Lewy bodies and dementia associated with Parkinson’s Disease.  Rivastigmine, at daily doses of 6 mg and above, can be used for the management of associated symptoms in people with Alzheimer’s disease and dementia with Lewy bodies.
  41. 41. PHARMACOLOGICAL INTERVENTIONS: Memantine:  The efficacy of memantine has been examined in people with moderate to severe Alzheimer’s disease and mild to moderate vascular dementia. Recommendations:  Memantine can be used in the dose of 20 mg per day in a patient with moderate to severe Alzheimer’s disease. Antidepressants:  The use of antidepressants for patients with dementia accompanied by depressive symptoms is widespread, but their effect on depression and cognitive function is uncertain.  Antidepressants can be used for the treatment of comorbid depression in dementia providing their use is evaluated
  42. 42. PHARMACOLOGICAL INTERVENTIONS: ANTIPSYCHOTICS Recommendation: If necessary, conventional antipsychotics may be used with caution, given their side effect profile, to treat the associated symptoms of dementia.  The atypical antipsychotics, olanzapine and risperidone are useful in the management of psychotic symptoms, aggression and other behavioral problems associated with dementia.  Atypical antipsychotics with reduced sedation and extrapyramidal side effects may be useful in practice, although the risk of serious adverse events such as stroke must be carefully evaluated.  In patients on stable antipsychotic regimens, who are free from behavioral disturbances, withdrawal of antipsychotic treatment may not be associated with relapse. An individualized approach to managing agitation in people with dementia is required. Where antipsychotics are inappropriate cholinesterase inhibitors may be considered.
  43. 43. PHARMACOLOGICAL INTERVENTIONS: Trazodone:  One small RCT of trazodone showed reduction in agitation when accompanied by depressive symptoms in patients with dementia.  Trazodone may be considered for patients with depressive symptoms and dementia associated agitation. Clinically Ineffective Interventions:  Anti-inflammatories  Melatonin  Estrogen  Physostigmine  Selegiline
  44. 44. PHARMACOLOGICAL INTERVENTIONS: Intervention lacking evidence of clinical effectiveness Anticonvulsants:  Anticonvulsants may be considered for the symptomatic treatment of seizures or myoclonus associated with dementia but are not recommended for other symptoms of dementia. Aspirin:  Aspirin is only recommended in people with vascular dementia who have a history of vascular disease. Benzodiazepines:  No systematic reviews or RCTs examining the usefulness of benzodiazepines in the management of associated symptoms of dementia, including anxiety, were identified. Lithium  In the absence of concurrent evidence of bipolar affective disorder lithium
  45. 45. TREATMENT FOR SLEEP DISTURBANCES: o Interventions include maintaining daytime activities and giving careful attention to sleep hygiene. Pharmacological intervention could be considered when other approaches have failed. o If a patient also requires medication for another psychiatric condition, an agent with sedating properties, given at bedtime, could be selected. o Primarily for the treatment of sleep disturbance, medications with possible effectiveness include trazodone, zolpidem, or zaleplon Benzodiazepines are not recommended for other than brief use because of risks of daytime sedation, tolerance, rebound insomnia, worsening cognition, falls, disinhibition, and delirium. Diphenhydramine is not recommended because of its
  46. 46. NON-PHARMACOLOGICAL INTERVENTIONS: BRIEF Non-pharmacological interventions are used to ensure that underlying causes of behavioral disturbance are explored and to provide personalized approaches to presenting problems. CORE SYMPTOMS:  Cognitive decline  Functional decline  Social decline ASSOCIATED SYMPTOMS:  Agitation  Aggression  Depression  Psychosis  Repetitive Vocalization  Sleep disturbance  Non-specific behavior Disturbance
  47. 47. NON-PHARMACOLOGICAL INTERVENTIONS: BRIEF COGNITIVE DECLINE: Cognitive stimulation: may occur informally through recreational activities, or formally through specific activities Recommendation: Cognitive stimulation should be offered to individuals with dementia. Reality Orientation Therapy: [ROT] The purpose of ROT is to reorientate the person by means of continuous stimulation and repetitive orientation to the environment. Recommendation: Reality orientation therapy should be used by a skilled practitioner, on an individualized basis, with people who are disorientated in time, place and person.
  48. 48. NON-PHARMACOLOGICAL INTERVENTIONS: BRIEF Functional Decline:  Caregiver intervention programs: Caregiver intervention ranges from the simplest reassurance to the most complex multi-faceted interaction with the person with dementia, including in one case, a caregiver residential program. Improvement in associated symptoms of dementia Improvement in basic daily activities and other functional activities Delay in nursing home placement  Recommendation: Caregivers should receive comprehensive training on interventions that are effective for people with dementia.  Reality orientation therapy has been also found to be effective Social Decline: No robust evidence identified
  49. 49. NON-PHARMACOLOGICAL INTERVENTIONS: BRIEF Agitation: Aromatherapy and recreational activities are beneficial Aggression: no robust evidence identified Depression: Behavior management is beneficial Psychosis: no robust evidence identified Repetitive vocalization: no robust evidence identified Sleep disturbance: no robust evidence identified, sleep hygiene Non-specific behavior disturbance: Care giver intervention and training, multisensory stimulation and recreational activities have shown benefits
  50. 50. NON-PHARMACOLOGICAL INTERVENTIONS: BRIEF Interventions showing short term benefit but the benefits are not sustained once intervention stopped:  Aroma therapy  Light therapy  Music therapy  Multi sensory stimulation  Physical activities  Recreational activities  Simulated presence  Validation therapy
  51. 51. INFORMATION FOR DISCUSSION WITH PATIENTS AND CARERS Supportive information for patients and carers:  Patients and carers should be offered information tailored to the patient’s perceived needs.  Good communication between healthcare professionals, patients and carers is essential. Disclosure of the diagnosis:  Healthcare professionals should be aware that many people with dementia can understand their diagnosis, receive information and be involved in decision making.  Healthcare professionals should be aware that some people with dementia may not wish to know their diagnosis.  Healthcare professionals should be aware that in some situations disclosure of a diagnosis of dementia may be inappropriate.  The wishes of the person with dementia should be upheld at all times.  The diagnosis of dementia should be given by a healthcare professional skilled in communication or counselling.
  52. 52. INFORMATION FOR DISCUSSION WITH PATIENTS AND CARERS Information at other stages of the patient journey:  Information provision at other stages of the patient’s journey of care is generally more focused on carer needs than that of the patient.  In decision making, people with mild dementia are more involved, largely in a collaborative role. Beyond that carers generally make final decisions.  Patients and carers should be provided with information about the services and interventions available to them at all stages of the patient’s journey of care.  Information should be offered to patients and carers in advance of the next stage of the illness. Methods of disseminating information which may be appropriate for people with dementia and their carers include:  Written information  Individual education programs  Group education programs  Counselling  Telemedicine service  Communication workshops  Cognitive behavior therapy (CBT)  Stress management  Combinations of the above.
  53. 53. Thanks for your patience
  54. 54. Non-pharmacological management of Dementia Dementia management guidelines