DEMENTIA Epidemiology, Economic-Impact and Clinical’s Aspect

1. RusdiLamsudin Department of Neurology Faculty of Medicine Indonesian Islamic University Yogyakarta, INDONESIA DEMENTIAEpidemiology, Economic-Impact and Clinical’s Aspect

2. Overview • Epidemiology • Economic Impacts • Definition • Clinical presentation • Diagnosis • Differential Diagnosis • Etiology • Workup • Non-pharmacologic Treatments • Drug Treatments • Terminal Care

3. EPIDEMIOLOGY

4. Epidemiology • Dementia affects 17–25 million people worldwide • Estimated 4 million in the US and an estimated 800,000 people in the UK [Ritchie, 1995; Keefover, 1996]. • It affects predominantly elderly people, The prevalence of dementia in people over the age of 65 is 5% and in people over 80, it is 20%. • It has been estimated that 26% of women and 21% of men over the age of 85 have some form of dementia, of whom approximately 50% have Alzheimer’s disease (AD) [Melzer, 1997].

5. Epidemiology • In case of AD: • Age specific prevalence rates almost double with every additional 5 years of age from 1% of 65, rising to about 8-10% at age 80 and 30-40%at age 90 • African-Americans and Hispanics may have a higher risk than Caucasians-Americans. It also occurs less frequently in Asians than Americans

6. Growth of numbers of people with dementia • The World Alzheimer Report (2009) estimated: • 35.6 million people living with dementia worldwide in 2010 • Increasing to 65.7 million by 2030 • 115.4 million by 2050

7. Economic Impact

8. Worldwide cost of dementia • The societal cost of dementia is already enormous. • Dementia is already significantly affecting every health and social care system in the world. • The economic impact on families is insufficiently appreciated. • The total estimated worldwide costs of dementia are US$604 billion in 2010. • These costs are around 1% of the world’s GDP 0.24% in low income 1.24% in high income

9. Worldwide costs of dementia • The World Alzheimer Report (2010) estimated that: If dementia care were a country, it would be the world’s 18th largest economy

10. Definition

11. Definition • a syndrome characterized by progressive decline of intellectual ability from a previously attained level • the decline in mental inability usually involves variable deterioration in  speech  memory judgment  mood without alteration of consciousness medslides.com

12. Definition • Multiple Cognitive Deficits: • Memory dysfunction • especially new learning, a prominent early symptom • At least one additional cognitive deficit • aphasia, apraxia, agnosia, or executive dysfunction • Cognitive Disturbances: • Sufficiently severe to cause impairment of occupational or social functioning and • Must represent a decline from a previous level of functioning

13. Clinical Presentation

14. Clinical Presentation • onset of dementia it is usually insidious • dementia is often progressive (degenerative disease) but may be static (post-traumatic brain injury) • initial presentation may include slight forgetfulness, attention and concentration deficits, and increasing repetitiousness or inconsistencies in usual behavior • later presentation may display impaired judgment, inability to abstract or generalized, and personality change with rigidity, perseveration, irritability, and confusion; affective disturbances may be prominent with loss of personality and self-care medslides.com

15. Impairment of 2 or more cognitive domain 1 Memory loss 2 Language 3 Abstract thinking & Judgment 4 Praxis (learned motor behavior) 5 Spatial processing 6 Personality 7 Social conduct

16. Risk Factors for Dementia • Gender: male • Age: 60-70 years • Prior stroke • Hardening of the arteries • Heart disease • High blood pressure • Diabetes • Cholesterol problems • Atrial fibrillation • Smoking • Education • Race • Family history (CADASIL-cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)

17. Most common causes of dementia • Alzheimer’s disease • Vascular dementia • Lewy body dementia • Frontotemporal dementia

18. Established risk factors for dementia • Age • Female sex • Head trauma • Low level of education

19. Coronary artery disease High dietary saturated fat and cholesterol Serum cholesterol Hyperhomocysteinemia Smoking Diabetes mellitus Hypertension Apolipoprotein E status Risk factors for dementia All these are vascular risk factors!

20. Diagnosis and Diffeerential Diagnosis

21. Differential Diagnosis:TopTen(commonly used mnemonic device: AVDEMENTIA) 1. Alzheimer Disease (pure ~40%, + mixed~70%) 2. Vascular Disease, MID (5-20%) 3. Drugs, Depression, Delirium 4. Ethanol (5-15%) 5. Medical / Metabolic Systems 6. Endocrine (thyroid, diabetes), Ears, Eyes, Environ. 7. Neurologic (other primary degenerations, etc.) 8. Tumor, Toxin, Trauma 9. Infection, Idiopathic, Immunologic 10. Amnesia, Autoimmune, Apnea, AAMI

22. Comparison of the Clinical Features COURSE, PROGRESSION, ATTENTION, MEMORY, THINKING

23. Neurologic Diseases Associated with Intellectual Dysfunction DISEASE PHYSICAL SIGNS CLINICAL FEATURES Creutzfeldt-Jakob Myoclonus, cerebellar signs, Subacute course; EEG has specific abnormalities, eye movement abnormalities brain biopsy diagnostic Huntington's disease Choreiform movements, Often positive family history; caudate atrophy corticospinal signs by CT or MRI Multiple sclerosis Brainstem signs, optic atrophy, Usually long-standing disease; episodic illness corticospinal signs with remissions; often extensive white matter abnormalities by MRI Wilson's disease Extrapyramidal signs, hepatic Onset in adolescence or young adult life, dysfunction, Kayser-Fleischer psychiatric disorders rings Progressive Failure of vertical downgaze, Eye movement abnormalities; differentiate fromsupranuclear extrapyramidal signs Parkinson's disease; unresponsive or onlypalsy transiently responsive to levodopa * = invariably present; all other physical signs are neither invariably present nor pathognomonic. medslides.com

24. Etiologic Diagnosis of Progressive Dementias in Adults • Neurodegenerative Diseases • Alzheimer’s disease • Parkinson’s disease • Diffuse Lewy body disease • Progressive supranuclear palsy • Multisystem atrophy • Huntington’s disease • Frontotemporal dementias – e.g. Pick’s disease

25. Etiology contd. • Structural Disease or Trauma • Normal pressure hydrocephalus • Neoplasms • Dementia pugilistica • Vascular Disease • Vascular dementia • Vasculitis • Heredometabolic Disease • Wilson’s disease • Other late-onset lysosomal storage diseases

26. Etiology contd. • Demyelinating or Dysmyelinating Disease • Multiple sclerosis • Infectious Disease • Human immunodeficiency virus, type 1 • Tertiary syphilis • Creutzfeldt-Jakob disease • Progressive multifocal leukoencephalopathy • Whipple’s disease • Chronic meningitis – e.g. Cryptococcal

27. DELIRIUM • Acute brain dysfunction characterized by: • Global symptoms (affecting both cerebral hemispheres) including impairment of consciousness and attention • Primary physiological changes with potential for reversibility • ‘waxing and waning’ symptoms – usually worse in evening • Life-threatening conditions underlying the syndrome

28. Symptoms of Delirium • Common symptoms of a delirium include: • Waxing and waning levels of consciousness • Poor attention and disorientation • Disturbed memory (long and short term) • Psychosis • Sleep dysregulation • Fearfulness with agitation and aggression • Seriously impaired insight and judgment

29. Epidemiology of Delirium • Very Common - 10-15% med/surg inpatients (30%+ if elderly) • 30% of Adult Burn Patients • 80%of delirious patients have pre-existing dementia • Predisposing Factors: old age, postcardiotomy, s/p burns prexisting brain damage drug withdrawal states AIDS

30. Causes of Delirium • Often multifactorial • Infections, trauma, brain diseases • Cardiac diseases, lung disease, hypoxia, hypoglycemia • Toxins, or intoxications • Medication effects • Substance withdrawals (e.g. DTs) • Endocrinopathies • In elderly dementia patients: UTI, dehydration and pneumonia are the most common causes

31. DELIRIUM - TREATMENT • Must look for medical cause(s) and treat • Symptoms can be helped by antipsychotic drugs such as haldoperidol or risperidone (especially psychosis, agitation) • Consider anticholinesterases for anticholinergic delirium • Comfort measures include reorientation strategies, reducing stimulation, frequent reassurance

32. Delirium vs Dementia(summary) • General rules of thumb: DeliriumDementia acute chronic reversible irreversible physiological structural primary attention primary memory deficits deficits • Delirium and dementia can coexist; in fact delirium is very common in demented patients

33. Work-up

34. Workup • History • Physical Examination • Laboratory studies medslides.com

35. History - etiology • the most important component of the initial evaluation • adequate history with help of a family member is critical • description of • cognitive, memory, and behavior problems • effect on daily life - difficulty with driving, work, or family relationships • details on temporal course of illness • chronic • progressive (Alzheimer or other neurodegenerative disease) • stepwise (multi-infarct) • static (traumatic injury, episode of severe hypotension) medslides.com

36. History - treatable causes • Vascular dementia - presence of cardiovascular risk factors (smoking, HTN, chol, diabetes) • Normal pressures hydrocephalus - triad of dementia, gait, incontinence with a prior history of meningitis or subarachnoid hemorrhage • Mass lesion - history of head trauma, unexplained focal neurologic deficit, unilateral headache worsening over time • Parkinson’s disease - resting tremor and rigidity • Wilson’s disease - hepatocellular disease and dementia • HIV and neurosyphilis - high-risk sexual behavior • hereditary - family history dementia, Down’s syndrome, psychiatric disorders medslides.com

37. History - treatable causes • B12 deficiency - previous gastric surgery • B12, thiamin, niacin deficiency - inadequate nutrition, alcohol abuse • medications - opiates, sedative-hypnotics, analgesics, anticholinergics, anticonvulsants, corticosteroids, centrally acting anti-hypertensives, psychotropics • symptoms of hypothyroidism, pituitary insufficiency • occupational history - exposure to toxic substances (aniline dyes, heavy metals) medslides.com

38. Diagnostic Criteria For Dementia Of The Alzheimer Type(DSM-IV, APA, 1994) • Multiple Cognitive Deficits 1. Memory Impairment 2. Other Cognitive Impairment • Deficits Impair Social/Occupational • Course Shows Gradual Onset And Decline • Deficits Are Not Due to: 1. Other CNS Conditions 2. Substance Induced Conditions • Do Not Occur Exclusively during Delirium F. Not Due to Another Psychiatric Disorder

39. Mental Status Examination • Examination should be geared to both the detection of focal lesions and to signs of general brain dysfunction • immediate memory testing (three object recall, recite digits forward and backward, recall a short story) • remote memory testing (recall of historical events, family milestones, or recent local or international news) • reproducible drawings • discern similarities among objects • decision-requiring tasks (finding a stamped letter or seeing a fire in a theater) medslides.com

40. Mini-Mental Status Tests Score Recall: 3 Ask for 3 objects repeated above. Give one point for each. Language: 2 Name a pencil and watch (2 points). 1 Repeat the following: "No ifs ands or buts." 3 Follow a 3-stage command: "Take a paper in your right hand: fold it in half, and put it on the floor." (3 points). 1 Read and obey the following: "Close your eyes." 1 Write a sentence. 1 Copy design. Total Score: [ ] Maximum Score: 30 medslides.com

41. Physical and Neurologic Examinations • Check for focal evidence of neovascular risk factors - carotid bruits, signs of alcoholism, hepatocellular injury, renal insufficiency, other systemic illnesses • specific neurologic abnormalities • frontal lobe release signs (grasp, suck, snout, root) • visual field cut and extraocular movement limitations • abnormal pupillary reactions • extrapyramidal features (carditis dyskinesis, tumors, asterixis, Korea, monoclonal disc, it) • sensory deficit and gait disorder medslides.com

42. Screening Laboratory Studies 1. Complete blood count and sedimentation rate 2. Chemistry panel (electrolytes, calcium, albumin, BUN, creatinine, transaminase) 3. Thyroid-stimulating hormone (TSH) 4. VDRL test for syphilis 5. Urinalysis 6. Serum B12 and folate levels 7. Chest x-ray 8. Electrocardiogram 9. Head computed tomography (CT) medslides.com

43. Neuroimaging • Head CT or MRI is appropriate in the presence of 1) history suggestive of a mass lesion 2) focal neurologic signs or symptoms 3) dementia of abrupt onset 4) history of seizures 5) history of stroke • MRI with gadolinium contrast enhancement is superior to CT for the diagnosis of multi-infarct dementia and problems referrable to the posterior fossa medslides.com

44. Other Ancillary Studies • Lumbar puncture • routine LP for initial evaluation of dementia is not justified • may be indicated when other clinical findings suggest an active infection or vasculitis and as part of the evaluation of normal pressure hydrocephalus • sugar, protein, cell count, cultures, gamma globulins, the serology for stiffness should be obtained medslides.com

45. Other Ancillary Studies • Electroencephalogram (EEG) • usually normal or with nonspecific rhythm slowing • indicated in patients with episodic altered consciousness and in whom seizures may be suspected • may occasionally raise suspicion of a particular etiology: • focal, delta slowing is seen with tumor • unilateral attenuation of voltage may suggest an extracranial mass such as subdural hematoma • excessive beta activity may be consistent with drug ingestion • Creutzfeldt-Jakob disease has a highly specific EEG pattern medslides.com

46. Other Ancillary Studies • Formal neuropsychologic evaluation • appropriate for more specific information when the diagnosis is in doubt • also helpful in providing additional information about the nature of impairment following focal brain injury • Speech analysis • may improve patient and family communication with therapy • Formal psychiatric assessment • may be desirable if depression in addition to dementia is suspected medslides.com

47. Studies of Limited or Uncertain Utility • Cerebral blood flow and metabolism measurements • PET and SPECT scans have no routine use at present • Brain biopsy • rarely justified for non-neoplastic or noninfectious diseases • Progressive multifocal leukoencephalopathy or Creutzfeldt-Jakobdisease is diagnosed by biopsy • Noninvasive neurovascular studies (carotid ultrasound, Doppler flow studies) • if MRI or CT demonstrates infarction, or • clinical course or physical examinations is suggestive of cerebralvascular disease medslides.com

48. Treatment

49. General Treatment Principles For Dementia • Treatment Of Underlying Disease Process (Primary Treatment) • Management Of Behaviors and Symptoms (Secondary Treatment) • Caregiver Support and Education

50. Primary Treatment Strategies(for progressive dementias) • 1. Prevention • Identify risks and mitigate • Develop neuroprotective strategies for those at risk • 2. Slow or halt progression of illness • Understanding pathophysiology leads to treatment ideas • 5 year delay in onset ---> 1/3 decrease in prevalence • Delaying institutionalization by 1 month saves $1.2 billion/yr • 3. Reverse symptoms • Compensate through augmentation of remaining neurons or other systems • Reversal of destructive processes & regeneration of tissue