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  • The major domains affected in AD include cognition, function in daily activities and behaviour. The benefits of Exelon can be considered in these three major areas.
  • 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.
  • Age : The risk of developing Alzheimer’s increases with age. One out of every 10 persons 65 years and older is a victim of Alzheimer's disease, although early-onset victims may be in their 40s and 50s. Approximately 20 percent of Americans between the ages of 75 and 84, and almost half of those 85 years and older suffer from Alzheimer's disease. * Genetics : Early-onset Alzheimer's has been clearly shown to be genetic in origin. While a mutation on chromosome 19 has been linked with late-onset Alzheimer's (the most common form), not everyone with the mutation develops the disease. The relationship between genetics and late-onset Alzheimer's is not fully known. * Other: Some studies have implicated prior traumatic head injury, lower education level, and female gender as possible risk factors. However, at the present time, no definitive causes have been identified. African Americans and Hispanics may have a higher risk than Caucasian Americans. Alzheimer's disease occurs less frequently in the Native American Cherokees and in Asians.  
  • AD: a progressive CNS disorder with a characteristic pathology AD is a progressive, neurodegenerative disorder of unknown aetiology with characteristic pathological and clinical features (Katzman, 1986; Cummings and Khachaturian, 1996; Bouchard and Rossor, 1996). It leads to destruction of neurones, particularly cholinergic neurones involved in the higher cortical functions (e.g. memory and learning). Characteristic histopathological features of AD include extracellular ‘senile plaques’ (composed largely of abnormal deposits of  -amyloid protein) and intracellular neurofibrillary tangles (containing paired helical filaments composed of hyperphosphorylated tau protein) (Katzman, 1986; Cummings and Khachaturian, 1996). The precise role of these features in the pathophysiology of the illness is not yet defined but their presence in AD is associated with neuronal degeneration (Geula and Mesulam, 1996).
  • The cholinergic deficit in AD underlies the clinical symptomatology Acetylcholine (ACh) is needed in sufficient amounts for maintaining proper neurotransmission. Reduction in ACh is the most predominant neurotransmitter deficit found in AD. The progressive loss of ACh available for neurotransmission has been correlated with the cognitive deficits found in AD patients (Perry et al.,1978). These findings have led to the formulation of the cholinergic hypothesis of AD (Bartus et al., 1982), which proposes that the cognitive deficits of AD are related to the observed decrease in central cholinergic activity and that increasing intrasynaptic ACh could enhance cognitive function and clinical well being. Furthermore, cholinergic deficits in the limbic and paralimbic structures may contribute to the development of certain behavioural abnormalities seen in AD (Cummings and Back, 1998).
  • The hippocampus, which is part of the limbic system and in part functions as the focal point where processes leading to memory storage and retrieval begin. The hippocampus is located in the floor of the lateral ventricle of the brain. It is involved in spatial orientation. It is also involved in the functioning of the limbic system, which is a complex system of nerve networks and nerve pathways in the brain. The limbic system is involved in expressions of instinct, such as self-preservation (searching for food, fighting) and preservation of the species (reproduction, care of offspring), and in expressions of mood, such as fear, rage and pleasure. It is also involved in the establishment of memory patterns. The cortex, which is used in forming associations between ideas and memories. One of the major components of the brain. The cortex is divided into four lobes (frontal, parietal, temporal, occipital). It also contains the sensory and motor areas.
  • 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.
  • 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.
  • 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).
  • 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).
  • 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.
  • “ She’s been acting superior ever since she got that pharmacology degree!’
  • This slide demonstrates the cholinergic synapse. Ach is released from vesicles in the pre-synaptic receptor, binding to both muscarinic and nicotinic receptors on the post-synaptic neuron. ACh is normally hydrolysed in the synapse by acetylcholinesterase. Cholinesterase inhibitors prevent the degredation of ACh, increasing ACh in the synapse and facilitating cholinergic neurotransmission.

Transcript

  • 1. DEMENTIADEMENTIA
  • 2. OVERVIEWOVERVIEW Introduction.Introduction. Dementia.Dementia. Alzheimer’ Disease.Alzheimer’ Disease. Delirium.Delirium. Caregiver Burden.Caregiver Burden. Conclusions.Conclusions.
  • 3. I- INTRODUCTIONI- INTRODUCTION
  • 4. Problems of Old AgeProblems of Old Age I- Lifespan vs. Healthspan.I- Lifespan vs. Healthspan. II- Physical Burden.II- Physical Burden. III- Poly-Pharmacy.III- Poly-Pharmacy. IV- Psychosocial Burden.IV- Psychosocial Burden. V- Common Psychiatric Disorders.V- Common Psychiatric Disorders.
  • 5. I- Lifespan vs. HealthspanI- Lifespan vs. Healthspan Lifespan:Lifespan: Length of life increased.Length of life increased. Healthspan:Healthspan: Length of healthy life beforeLength of healthy life before disability.disability. Factors affecting lifespan and healthspan:Factors affecting lifespan and healthspan: – Exercise:Exercise: Improves mood and cognitionImproves mood and cognition.. – Sleep pattern.Sleep pattern. – Eating pattern.Eating pattern. – Social networks:Social networks: Protective againstProtective against Psychosocial stressors and PsychiatricPsychosocial stressors and Psychiatric disordersdisorders..
  • 6. II- Physical BurdenII- Physical Burden Diminished Effectiveness of ManyDiminished Effectiveness of Many Systems:Systems: - Nervous system.- Nervous system. - Sensations.- Sensations. - Immune system.- Immune system. - Cardiovascular system.- Cardiovascular system. - Respiratory system.- Respiratory system. - Urinary system.- Urinary system. - GIT.- GIT. - Motor System.- Motor System.
  • 7. III- Poly-PharmacyIII- Poly-Pharmacy Multiple pathology.Multiple pathology. - Cardiac disease: HPT, IHD.- Cardiac disease: HPT, IHD. - Diabetes.- Diabetes. - Asthma/ COPD.- Asthma/ COPD. - Osteoporosis.- Osteoporosis. - Neurological diseases.- Neurological diseases. - Psychiatric disorders.- Psychiatric disorders. Multiple medications.Multiple medications. Multiple adverse effects.Multiple adverse effects. Drug-Drug interactions.Drug-Drug interactions.
  • 8. Bereavement.Bereavement. Retirement.Retirement. Relocated from their home.Relocated from their home. Stresses of elderly peopleStresses of elderly people leads to psychiatricleads to psychiatric disorders.disorders. So, We have toSo, We have to deal with stress.deal with stress. IV- Psycho-Social Stressors
  • 9. V- Psychiatric DisordersV- Psychiatric Disorders & Old Age& Old Age Psychiatric disorders of elderly persons may bePsychiatric disorders of elderly persons may be divided into two groups:divided into two groups: –Disorders of all ages:Disorders of all ages: Depressive disorders, Anxiety disorders, Psychosis,Depressive disorders, Anxiety disorders, Psychosis, Substance-related disorders & Sleep disorders.Substance-related disorders & Sleep disorders. –Disorders related to old age:Disorders related to old age: Cognitive disorders:Cognitive disorders: Delirium, Dementia &Delirium, Dementia & Amnesia (MCI).Amnesia (MCI). – Only about 20% receive mental health services.Only about 20% receive mental health services.
  • 10. Common Psychiatric DisordersCommon Psychiatric Disorders Disorder Community General Hospitals Dementia* 5-20% 20-60% Depression 5-15% 20-50% Sleep Disorders 5-15% 20-40% Anxiety Disorders 5-15% 3-10% Delirium* >1% 5-50% Psychotic Disorders ~1% ~2% Any Disorder ~50% ~70%
  • 11. Brain Environment Endocrine Glands Immune System Physiology and Behavior Nerves Hormones Action The Biological Basis of Psychiatric Disorders
  • 12. The Biological Basis ofThe Biological Basis of Psychiatric DisordersPsychiatric Disorders MindBrain Body Psychoneuro- Immunology Medically Unexplained Physical Symptoms Biopsychosocial model
  • 13. Diathesis-Stress ModelDiathesis-Stress Model Diathesis “Predisposing Causes” (Hereditary Predisposition) Stress “Precipitating Causes” (Situational Factors) Disorder Recovery “Maintaining Causes” Physical Conditions Bio-Psycho-Social Approach • Emphasizes Interaction of Biological and Social Factors
  • 14. II- DEMENTIAII- DEMENTIA
  • 15. DefinitionDefinition Persistent intellectual impairment.Persistent intellectual impairment. Impairment in:Impairment in: – Memory.Memory. – Abstract thinking.Abstract thinking. – Judgment.Judgment. – Impulse control.Impulse control. Disregard for social rules.Disregard for social rules. Neglect of personal appearance and hygiene.Neglect of personal appearance and hygiene.
  • 16. Language may not be affected.Language may not be affected. Personality change is common.Personality change is common. No change in L.O.C.No change in L.O.C. Slow, insidious onsetSlow, insidious onset Long duration; progressive.Long duration; progressive. Irreversible: reversible only in approximate 5%Irreversible: reversible only in approximate 5% of cases (e.g., Nutritional deficiencies).of cases (e.g., Nutritional deficiencies). In Summary:In Summary: Recent Memory Loss on Clear ConsciousnessRecent Memory Loss on Clear Consciousness
  • 17. Clinical PresentationClinical Presentation Initial presentation:Initial presentation: -- Slight forgetfulness.Slight forgetfulness. - Attention and concentration deficits.- Attention and concentration deficits. - Increase repetition.- Increase repetition. - Inconsistencies in usual behavior.- Inconsistencies in usual behavior. Later presentationLater presentation -- Impaired judgment.Impaired judgment. - Inability to abstract.- Inability to abstract. - Personality change.- Personality change. - Rigidity, perseveration, irritability & confusion.- Rigidity, perseveration, irritability & confusion. - Affective disturbances with loss self-care.- Affective disturbances with loss self-care.
  • 18. Non-Reversible Types ofNon-Reversible Types of Dementia (95%)Dementia (95%) Alzheimer’s disease.Alzheimer’s disease. Vascular Dementia.Vascular Dementia. Dementia with LewyDementia with Lewy bodies.bodies. Fronto-TemporalFronto-Temporal Dementia.Dementia. Others:Others: Parkinson’s Disease.Parkinson’s Disease. Huntington’s Disease.Huntington’s Disease. Creutzfeldt JakobCreutzfeldt Jakob Disease.Disease. Progressive SupranuclearProgressive Supranuclear Palsy.Palsy. Korsakoff’s Syndrome.Korsakoff’s Syndrome. Infection-RelatedInfection-Related Dementia (HIV, Syphilis).Dementia (HIV, Syphilis).
  • 19. Reversible Types of DementiaReversible Types of Dementia Malnutrition.Malnutrition. Dehydration.Dehydration. Metabolic Dysfunction.Metabolic Dysfunction. Vitamin B12 Deficiency.Vitamin B12 Deficiency. Depression.Depression. Delirium.Delirium. (5%)
  • 20. Risk Factors for DementiaRisk Factors for Dementia AgingAging MenopauseMenopause Family HistoryFamily History APOE GenotypeAPOE Genotype Serious Head TraumaSerious Head Trauma Low Educational LevelLow Educational Level Low Occupational LevelLow Occupational Level
  • 21. Medical Workup for DementiaMedical Workup for Dementia TESTS RATIONALE – rule out… Urinalysis & S. Creatinine Kidney dysfunction & toxic encephalopathy CBC, ESR & Electrolytes Anemia & electrolyte imbalance Liver function tests Liver dysfunction Thyroid function Thyroid dysfunction Serum B 12 Vitamin deficiency Syphilis serology Syphilis HIV test AIDS dementia Neuroimaging studies: (CT or MRI) Tumor, subdural hematomas, abscess, stroke or hydrocephalus
  • 22. Dementia Or Depression?Dementia Or Depression? Cognitive impairment:Cognitive impairment: There may be aThere may be a degree in both depression and dementia.degree in both depression and dementia. Early stages of dementia:Early stages of dementia: may mimicmay mimic depression (loss of interest, apathy anddepression (loss of interest, apathy and weight loss).weight loss). Pseudo-Dementia:Pseudo-Dementia: Depression may lead toDepression may lead to a degree of cognitive impairment severea degree of cognitive impairment severe enough to be confused with dementia.enough to be confused with dementia. Antidepressants:Antidepressants: may lead to anmay lead to an improvement in cognitive performance.improvement in cognitive performance.
  • 23. Differential DiagnosisDifferential Diagnosis Alzheimer's diseaseAlzheimer's disease 60 - 70%60 - 70% Multi-infarct dementiaMulti-infarct dementia 10 - 20%10 - 20% Brain tumorsBrain tumors ~ 5%~ 5% OthersOthers 10-15%10-15% (Including(Including [4 Ds][4 Ds]:: DDepression,epression, DDelirium,elirium, DDrugs,rugs, DDecline in memory[ecline in memory[MCIMCI]).]). So, AD is the most common subtype,So, AD is the most common subtype, (80% in mild to moderate stage & 20% severe).(80% in mild to moderate stage & 20% severe).
  • 24. III- ALZHEIMER’SIII- ALZHEIMER’S DISEASEDISEASE
  • 25. ALZHEIMER’S DISEASEALZHEIMER’S DISEASE In 1906In 1906 Dr. Alois AlzheimerDr. Alois Alzheimer was firstwas first toto describe Alzheimer's illness anddescribe Alzheimer's illness and since then millions of people havesince then millions of people have been diagnosed with the disease.been diagnosed with the disease.
  • 26. What Is Alzheimer’sWhat Is Alzheimer’s A progressive, degenerative illness thatA progressive, degenerative illness that attacks the brain and results in impairedattacks the brain and results in impaired memory, thinking and behavior.memory, thinking and behavior. The disease attacks nerve cells in allThe disease attacks nerve cells in all parts of the cortex of the brain, as wellparts of the cortex of the brain, as well as some surrounding structures.as some surrounding structures. In the end, an afflicted person loses allIn the end, an afflicted person loses all memory and mental functioning.memory and mental functioning.
  • 27. Prevalence of ADPrevalence of AD Kurz A. Eur J Neurol 1998; 5(Suppl 4): S1-8 Wimo A et al. Int J Geriatr Psychiatry 1997; 12: 841-56 0 10 20 30 40 50 60 60-64 65-69 70-74 75-79 80-84 85+ 95+ Age (years) Prevalence(%) 1% 2% 4% 8% 16% 30% 50%
  • 28. What Are the Warning Signs?What Are the Warning Signs? Memory loss that affects job skills.Memory loss that affects job skills. Difficulty performing familiar tasks.Difficulty performing familiar tasks. Problems with language.Problems with language. Disorientation to time and place.Disorientation to time and place. Poor or decreased judgment.Poor or decreased judgment. Problems with abstract thinking.Problems with abstract thinking. Misplacing things.Misplacing things. Changes in mood or behavior.Changes in mood or behavior. Changes in personality.Changes in personality. Loss of initiative.Loss of initiative.
  • 29. HISTORICAL POINTERSHISTORICAL POINTERS Forgetting recent events despite prompting.Forgetting recent events despite prompting. Failure to attend appointments.Failure to attend appointments. Frequent repetition of statements, stories orFrequent repetition of statements, stories or questions.questions. Frequent lost or misplaced items.Frequent lost or misplaced items. Losing track in conversation or word-findingLosing track in conversation or word-finding difficulty.difficulty. Difficulty understanding conversation orDifficulty understanding conversation or following the story in a book or on TV.following the story in a book or on TV. Confusion with time e.g., day, date, time of day.Confusion with time e.g., day, date, time of day. Becoming lost or unable to find the way.Becoming lost or unable to find the way.
  • 30. HISTORICAL POINTERSHISTORICAL POINTERS Difficulty handling money or paying bills.Difficulty handling money or paying bills. Difficulty working gadgets, planning orDifficulty working gadgets, planning or preparing meals or performing handyman tasks.preparing meals or performing handyman tasks. Neglect of personal care, home maintenance orNeglect of personal care, home maintenance or nutrition.nutrition. Withdrawal from previous community and socialWithdrawal from previous community and social activities (poor work performance if employed).activities (poor work performance if employed). Difficulty coping with new events or change toDifficulty coping with new events or change to routine.routine. Personality and behavior change.Personality and behavior change.
  • 31. Cognition Activitiesofdailyliving Behaviour ABC: The Key SymptomABC: The Key Symptom Domains Affected In ADDomains Affected In AD
  • 32. Natural History of ADNatural History of AD 1 2 3 4 5 6 7 8 9 0 5 10 15 20 25 30 Time (years) Symptoms Diagnosis Loss of functional independence Behavioural problems Nursing home placement Death Mini-MentalStateExamination(MMSE) Early Diagnosis Mild-to-Moderate Severe Feldman and Gracon. The Natural History of Alzheimer’s Disease. London: Martin Dunitz, 1996
  • 33. Risk Factors For ADRisk Factors For AD 1- General risk factors of Dementia.1- General risk factors of Dementia. 2- Age.2- Age. Number of cases of Alzheimer's diseaseNumber of cases of Alzheimer's disease doubles every five years in people over 65.doubles every five years in people over 65. 3- Family History.3- Family History. Evidence is not clear:Evidence is not clear: Cases where severalCases where several members of a single family are rare.members of a single family are rare. People with a FH of AD are at higher thanPeople with a FH of AD are at higher than average risk for AD due toaverage risk for AD due to GeneticsGenetics (ApoE-4 &(ApoE-4 & Down’s syndrome).Down’s syndrome). 4- Gender.4- Gender. A number of studies suggest that F M while˃A number of studies suggest that F M while˃ one reported that M F.˃one reported that M F.˃
  • 34. Protective Factors?Protective Factors? Genetic (ApoE-2).Genetic (ApoE-2). NSAID’s (Anti-inflammatories).NSAID’s (Anti-inflammatories). Statins (Cholesterol lowering).Statins (Cholesterol lowering). Prevent alcohol consumption.Prevent alcohol consumption. Higher education.Higher education. Ongoing intellectual stimulation.Ongoing intellectual stimulation. Physical and leisure / social activities.Physical and leisure / social activities. Diet (fruit and vegetables, low in saturated fat).Diet (fruit and vegetables, low in saturated fat). Long-term use of estrogens (in women).Long-term use of estrogens (in women).
  • 35. What Causes Alzheimer's?What Causes Alzheimer's? Scientists are still not certain.Scientists are still not certain. A slow actingA slow acting virusvirus.. Toxic substancesToxic substances (e.g., aluminum in non-(e.g., aluminum in non- natural sources).natural sources). HomocysteineHomocysteine (an amino acid that is harmful to(an amino acid that is harmful to nerve cells). It is a known risk factor in heartnerve cells). It is a known risk factor in heart disease and hypertension.disease and hypertension. Tau-proteinTau-protein abnormalities.abnormalities. Genetics: (CHGenetics: (CH 14, 19, 2114, 19, 21).). AcetylcholineAcetylcholine alterations (ACh).alterations (ACh). Alterations inAlterations in immune systemimmune system..
  • 36. Pathophysiology of Alzheimer’sPathophysiology of Alzheimer’s Amyloid Precursor Protein (APP):Amyloid Precursor Protein (APP): Production and accumulation ofProduction and accumulation of ß amyloid (AB)ß amyloid (AB) peptide is central to the pathogenesis of AD.peptide is central to the pathogenesis of AD. Mutations inMutations in APPAPP gene lead to early-onset AD bygene lead to early-onset AD by increasing production of AB which is neurotoxic inincreasing production of AB which is neurotoxic in vitro & leads to cell death.vitro & leads to cell death. In patients with trisomy 21 (In patients with trisomy 21 (Down’s syndrome: 3Down’s syndrome: 3 copies of the APP genecopies of the APP gene): neuro-pathological): neuro-pathological characteristics of AD develop by midlife.characteristics of AD develop by midlife.
  • 37. Pathophysiology of Alzheimer’sPathophysiology of Alzheimer’s Presenilins:Presenilins: PS 1 & PS 2 are homologous 43-50PS 1 & PS 2 are homologous 43-50 kD proteins & they are neurodegenerative in AD.kD proteins & they are neurodegenerative in AD. Plasmin:Plasmin: Lower levels of plasmin inLower levels of plasmin in hippocampus of AD brain.hippocampus of AD brain. Calcium:Calcium: Increased intracellular calcium elicitsIncreased intracellular calcium elicits the characteristic lesions of AD, including thethe characteristic lesions of AD, including the accumulation of ß amyloid, the hyper-accumulation of ß amyloid, the hyper- phosphorylation of TAU proteins and neuronalphosphorylation of TAU proteins and neuronal death.death.
  • 38. Brain Atrophy Senile Plaques Neurofibrillary Tangles Katzman, 1986; Cummings and Khachaturian, 1996 AD: A Progressive CNS DisorderAD: A Progressive CNS Disorder with A Characteristic Pathologywith A Characteristic Pathology
  • 39. Cholinergic deficit – Progressive loss of cholinergic neurons. – Progressive decrease in available Ach. – impairment in ADL, behavior and cognition. Hippocampus Cortex N. basalis Meynert Bartus et al., 1982; Cummings and Back, 1998, Perry et al., 1978 Cholinergic Deficit Underlies ClinicalCholinergic Deficit Underlies Clinical SymptomsSymptoms
  • 40. What Parts of The Brain areWhat Parts of The Brain are Affected?Affected? TheThe hippocampushippocampus,, which is part of thewhich is part of the limbic system and inlimbic system and in part functions as thepart functions as the focal point wherefocal point where processes leading toprocesses leading to memory storage andmemory storage and retrieval begin.retrieval begin. TheThe cortexcortex,, which iswhich is used in formingused in forming associations betweenassociations between ideas and memories.ideas and memories.
  • 41. The Pathological Cascade of AD Clinical symptoms Neuro-degeneration Neurofibrillary tangles β-amyloid Environmental Risk Factors Genetic Risk Factors Apo-E Pathogenetic Mutations APP PS1,2 Cholinergic dysfunction TAU hypophosphorylation
  • 42. 4444 Cognitive impairment Dementia Alzheimer's disease Exclude other causes (e.g. Delirium and Depression, etc) Exclude other dementias Differentiating AD from otherDifferentiating AD from other DementiasDementias
  • 43. 4545 Functional Activities Questionnaire (FAQ) 1. Dealing with financial matters, paying bills, writing checks 2. Keeping records of taxes, business affairs 3. Shopping for everyday necessities: groceries, clothes, etc 4. Hobbies or playing games 5. Making tea, turning the kettle on and off 6. Cooking a balanced meal 7. Perception of current events 8. Level of attention and understanding: books, television 9. Memory: remembering appointments and medications 10. Getting about: driving or taking public transport Pfeffer et al 1982 Score Maximum 3 3 3 3 3 3 3 3 3 3 Total 30 Score Actual Diagnosing AD In Primary CareDiagnosing AD In Primary Care Functional AssessmentFunctional Assessment
  • 44. 4646 Cognitive area MMSE: Test outline and Scoring: Orientation *What is the (date, day, month, year, season)? * Where are you (clinic, town, country)? Memory *Name three objects. Ask the patient to repeat them Attention *Serial sevens. Alternatively ask the patient to spell world backwards (dlrow) Folstein et al 1975 Score Maximum 5 5 3 5 Score Actual Diagnosing AD In Primary CareDiagnosing AD In Primary Care Cognitive Assessments, MMSECognitive Assessments, MMSE
  • 45. 4747 Recall *Ask for the three objects mentioned above to be repeated Language *Name a pencil and watch *Repeat, 'No ifs, ands or buts’ *A three stage command *Read and obey - CLOSE YOUR EYES *Write a sentence *Copy a double pentagon Score Maximum 3 2 1 3 1 1 1 Total 30 Score Actual Folstein et al 1975 Diagnosing AD In Primary CareDiagnosing AD In Primary Care Cognitive Assessments, MMSECognitive Assessments, MMSE
  • 46. 4848 The Clock Draw Test Time: 5.00 Score: 7 (normal) Time: 'no real time' Score: 2 (demented) Thalmann et al 1996. Time: .10.30 Score: 3 (demented) Time: 1/4 past 25 Score: 3 (demented) Diagnosing AD In Primary CareDiagnosing AD In Primary Care Cognitive AssessmentCognitive Assessment
  • 47. Treating Alzheimer’s Disease
  • 48. CHOLINESTERASE INHIBITORSCHOLINESTERASE INHIBITORS -Second Generation-Second Generation 1- Donepezil (Aricept): 8 CT, 2664 pts.1- Donepezil (Aricept): 8 CT, 2664 pts. 2- Rivastigmine (Exelon):2- Rivastigmine (Exelon): 7 CT, 3370 pts.7 CT, 3370 pts. 3- Galantamine (Reminyl):3- Galantamine (Reminyl): 6 CT, 3170 pts.6 CT, 3170 pts. 9204 patients in 21 clinical trials9204 patients in 21 clinical trials →→ modestmodest benefit in mild-moderate AD.benefit in mild-moderate AD.
  • 49. Post synaptic Acetyl CoA + Choline Choline + Acetate AChE ACh ACh ChAT Central Cholinergic Synapse X Cholinesterase Inhibitors (-) M2 Muscarinic 1 receptor (+)
  • 50. Memantine (Ebixa)Memantine (Ebixa) NMDA receptor antagonist.NMDA receptor antagonist. It normalize the transmission of nerveIt normalize the transmission of nerve signals involved in memory and othersignals involved in memory and other mental functions.mental functions. FDA approvrd in moderate to severeFDA approvrd in moderate to severe dementia.dementia. Modest benefit in cognition, function andModest benefit in cognition, function and behavior.behavior. Available in MOH.Available in MOH.
  • 51. Treatment of BehaviorTreatment of Behavior ProblemsProblems Antipsychotics should not be firstAntipsychotics should not be first choice, unless the patient ischoice, unless the patient is psychotic.psychotic. Consider the likelihood ofConsider the likelihood of depression and anxiety.depression and anxiety. Consider using behavioral methods.Consider using behavioral methods. Valproic acid may be of benefit.Valproic acid may be of benefit. BZD’s may aggravate confusion.BZD’s may aggravate confusion.
  • 52. AntipsychoticsAntipsychotics For agitation, aggression, hallucinationsFor agitation, aggression, hallucinations and thought disturbances:and thought disturbances: – Risperidone (Risperidal).Risperidone (Risperidal). – Olanzapine (Zyprexa).Olanzapine (Zyprexa). – Quetiapine (Seroquel).Quetiapine (Seroquel). Combination of Antipsychotics withCombination of Antipsychotics with Ebxia is contraindicatedEbxia is contraindicated
  • 53. IV- DELIRIUMIV- DELIRIUM
  • 54. DefinitionDefinition ImpairedImpaired consciousnessconsciousness.. Alterations in cognition:Alterations in cognition: – Orientation: (Orientation: (T.P.PT.P.P)).. – Attention.Attention. – Concentration.Concentration. – Memory: (Memory: (I.R.RI.R.R)).. – Thinking:Thinking: DisorganizedDisorganized.. – Language:Language: Incoherent speechIncoherent speech.. – Perception:Perception: Illusions and HallucinationsIllusions and Hallucinations.. Disturbances of sleep-awake cycle.Disturbances of sleep-awake cycle. Psychomotor changes.Psychomotor changes. Sudden onset & Short duration with fluctuation.Sudden onset & Short duration with fluctuation.
  • 55. SYNONYMS FOR DELIRIUMSYNONYMS FOR DELIRIUM Acute confusion state.Acute confusion state. Toxic-metabolic encephalopathy.Toxic-metabolic encephalopathy. Organic brain syndrome.Organic brain syndrome. ICU psychosis.ICU psychosis.
  • 56. DELIRIUMDELIRIUM Prevalence:Prevalence: 15-30% of hospitalized patients.15-30% of hospitalized patients. Highly prevalent in last weeks of life (40-85%).Highly prevalent in last weeks of life (40-85%). Due to:Due to: General Medical Condition.General Medical Condition. oror Substance – Induced:Substance – Induced: – Intoxication.Intoxication. – Withdrawal.Withdrawal. oror Multiple Etiologies.Multiple Etiologies.
  • 57. Causes of DeliriumCauses of Delirium Direct:Direct: – Primary CNS tumor.Primary CNS tumor. – Metastatic spread.Metastatic spread. Indirect:Indirect: – Hypoxia.Hypoxia. – MetabolicMetabolic encephalopathy.encephalopathy. – ElectrolyteElectrolyte imbalance.imbalance. – Withdrawal status.Withdrawal status. • Indirect (cont): – Infection. – Hematologic abnormalities. – Nutritional deficiencies. – Paraneoplastic syndrome. – Treatments side-effects. • Chemotherapy. • Steroids. • Radiation. • Opioids. • Anticholinergics. • Antiemetics.
  • 58. Assessment of EtiologyAssessment of Etiology Unclear, not found 50-60%.Unclear, not found 50-60%. Etiology found 40-50%.Etiology found 40-50%. Three or more etiologies usuallyThree or more etiologies usually present.present. Irreversible 30-40% of cases.Irreversible 30-40% of cases. 60-70% improve with treatment of60-70% improve with treatment of etiology.etiology.
  • 59. Management of DeliriumManagement of Delirium Find the cause(s): Usually multi-factorial.Find the cause(s): Usually multi-factorial. Look for medication toxicity.Look for medication toxicity. Re-orient the patient.Re-orient the patient. Quiet, non stimulating environment.Quiet, non stimulating environment. Antipsychotic medications for agitation.Antipsychotic medications for agitation. Benzodiazepines often makes deliriumBenzodiazepines often makes delirium worse except in delirium tremens.worse except in delirium tremens. One to one observation.One to one observation. Restraints only when needed.Restraints only when needed.
  • 60. PharmacologicalPharmacological InterventionsInterventions Thiamine:Thiamine: for alcoholics andfor alcoholics and malnourished.malnourished. Benzodiazepines:Benzodiazepines: for alcohol withdrawal.for alcohol withdrawal. Haloperidol:Haloperidol: was the drug of choice forwas the drug of choice for critically ill delirious patients.critically ill delirious patients. Atypical antipsychotics:Atypical antipsychotics: - Risperidone.- Risperidone. - Olanzapine.- Olanzapine.
  • 61. Distinguishing 3DsDistinguishing 3Ds Delirium Dementia DepressionDelirium Dementia Depression  OnsetOnset Acute Insidious GradualAcute Insidious Gradual  Course 24HrsCourse 24Hrs Fluctuate Stable StableFluctuate Stable Stable  CourseCourse Fluctuate Persist Slow remitFluctuate Persist Slow remit  ConsciousnessConsciousness Redused Clear ClearRedused Clear Clear  AttentionAttention ImpairedImpaired Intact IntactIntact Intact  CognitionCognition ImpairedImpaired ImpairedImpaired IntactIntact  PsychosisPsychosis VH, paranoia Occass S. casesVH, paranoia Occass S. cases  EEGEEG Abnormal Late Abnl. NormalAbnormal Late Abnl. Normal
  • 62. V- CAREGIVERSV- CAREGIVERS BURDENBURDEN
  • 63. CAREGIVERS BURDENCAREGIVERS BURDEN Physical Burden.Physical Burden. Financial Burden.Financial Burden. Time Burden.Time Burden. Role Burden.Role Burden. Emotional Burden.Emotional Burden. Others.Others.
  • 64. Caregiving BurdenCaregiving Burden Signs of Caregiver BurnoutSigns of Caregiver Burnout 1- Physical Burden:1- Physical Burden: Weight Change:Weight Change: Gain or LossGain or Loss.. Unexplained Somatic Complaints:Unexplained Somatic Complaints: ((Chronic headaches, backaches orChronic headaches, backaches or othersothers).). Caregiver’s Syndrome:Caregiver’s Syndrome: ((Fatique from physical strain & sleep lackFatique from physical strain & sleep lack).). Osteoporosis and Arthritis.Osteoporosis and Arthritis.
  • 65. Caregiving BurdenCaregiving Burden Signs of Caregiver BurnoutSigns of Caregiver Burnout 3- Time Burden:3- Time Burden: Caregiving is time-consuming.Caregiving is time-consuming. Less time for other tasks.Less time for other tasks. Activities can be stressful.Activities can be stressful. 4- Role Burden:4- Role Burden: Feelings of being pulled in differentFeelings of being pulled in different directions.directions. Family responsibilities.Family responsibilities. Pressure and tension.Pressure and tension.
  • 66. Caregiving BurdenCaregiving Burden Signs of Caregiver BurnoutSigns of Caregiver Burnout 5- Emotional Burden:5- Emotional Burden: Common feelings: Being overwhelmed, Anger, Frustration, Guilt, Exhaustion, Loneliness and Social withdrawal. Cognitive disturbances: Lack of concentration and finding it difficult to complete complex tasks. Sleep disorders: Sleeplessness / stressful dream. Anxiety: about facing another day and what the future holds. Depression: feeling sad and hopeless. Adjustment disorders.
  • 67. Psychiatric Disorders AmongPsychiatric Disorders Among Caregivers of Dementia PatientsCaregivers of Dementia Patients Depression.Depression. Anxiety disorders.Anxiety disorders. Unexplained Somatic Complaints.Unexplained Somatic Complaints. Adjustment disorders.Adjustment disorders. Sleep disorders.Sleep disorders.
  • 68. VI- CONCLUSIONSVI- CONCLUSIONS
  • 69. Overall Approach DementiaOverall Approach Dementia AdoptAdopt A Bio-Psycho-SocialA Bio-Psycho-Social approachapproach.. Treat inter-currentTreat inter-current Physical ProblemsPhysical Problems.. Identify majorIdentify major Psychological IssuesPsychological Issues.. ProvideProvide SupportSupport.. Give an opportunity for the patientGive an opportunity for the patient To TalkTo Talk.. AssessAssess Social SituationSocial Situation.. Organize appropriateOrganize appropriate InterventionsInterventions..
  • 70. NursingNursing Is of Paramount ImportanceIs of Paramount Importance In Dementia.In Dementia. We have to take care of theWe have to take care of the dementeddemented patientpatient and his/ herand his/ her caregivercaregiver.. TheThe goodgood physician will treat thephysician will treat the disease, but thedisease, but the greatgreat physician willphysician will treat the patient.treat the patient. Mental health care of old age meansMental health care of old age means enhancing physical treatment andenhancing physical treatment and decreasingdecreasing morbidity and mortalitymorbidity and mortality..
  • 71. ADVICE FOR OLD AGE PERSONADVICE FOR OLD AGE PERSON Caring For YourselfCaring For Yourself Maintain a positive outlook on life.Maintain a positive outlook on life. Take good care of your health.Take good care of your health. Remain active.Remain active. Stay in close contact with family and friends.Stay in close contact with family and friends. Eat right.Eat right. Remain mentally active & never stop learning.Remain mentally active & never stop learning.