Dementia Neurocognitive Disorders

1. DementiaNeurocognitive Disorders Prof. Kammant Phanthumchinda Chulalongkorn University

2. Japan Singapore 30.0 Indonesia Thailand 20.0 (%)‏ Myanmar Vietnam Malaysia Philippines 10.0 Lao People's Democratic Republic Cambodia Brunei Darussalam 0.0 2000 2010 2020 2030 2040 2050 Aging population in Asia 65 years or older United Nations, Population Division,2003

3. Global prevalence of dementia Western Europe 7.3% (7 million) Central Europe 5.8% North America 6.8% (4.4 million) Central Asia 5.8% East Asia 5.0% (5.5 million) South Asia 5.7% (4.5 million) Central Africa 3.2% Southeast Asia 6.4% Latin America 8.5% Latin America 8.5% Australasia 6.9% Southern Africa 3.5% World Health Organization (WHO). Dementia: a public health priority. Geneva: WHO; 2012.

4. Burden of dementia • 44 million people worldwide were living with dementia in 2013 • Number is predicted to double every 20 years, reaching 76 million by 2030, and 136 million by 2050 • Annually, there are 7.7 million new cases of dementia globally • Estimated worldwide annual socioeconomic cost of dementia was US$604 billion in 2010, which was higher than the costs of cancer and cardiovascular disease combined

6. Dementia&Neurocognitive Disorders

7. Dementia • Syndrome • Disturbance of multiple higher cortical functions • Disturbances of behavior – emotional & personality • Chronic & Progressive • Disturbances significantly interfere with work or usual social activities or relations with others • No delirium or impaired level of consciousness

8. Neurocognitive disorder (NCD)DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS FIFTH EDITION DSM-5American Psychiatric Association • NCD encompasses the group of acquired disorders in which the primary clinical deficit is in cognitive function • Impaired cognition represents a decline from a previously attained level of functioning • Major neurocognitive disorder • Cognitive deficits interfere with capacity for independence in everyday activities • Mild neurocognitive disorder • Cognitive deficits do not interfere with capacity for independence in everyday activities

9. DSM-5 DSM-I (1952) DSM-II (1968) Seventh printing of the DSM-II, 1974 DSM-III (1980) DSM-III-R (1987) DSM-IV (1994) DSM-IV-TR (2000) DSM-5 (2013) dementia = major neurocognitive disorder mild cognitive impairment = mild neurocognitive disorder Sachdev P.S. 2014

10. Neurocognitive disordersNCDDSM-5 • Major neurocognitive disorder • Dementia • Mild neurocognitive disorder • Mild cognitive impairment • DSM-5 has a new list of neurocognitive domains • "New separate criteria are presented" for major or mild NCD due to various conditions • Substance/medication-induced NCD and unspecified NCD are new diagnoses

11. Domains • Complex attention • Sustained attention, divided attention, selective attention, information precessing speed • Executive ability • Planning, working memory , responding to feed back/error correction, novel situation, overriding habbits, mental flexibility, judgement • Learning and memory • Immediate memory, recent memory including free recall, cued recall and recognition memory • Language • Naming expressive, grammar and syntax, receptive • Visuoconstruction- perceptual ability • Construction, visual perception,and reasoning • Praxis-gnosis-body schema • Praxis, gnosis,right/left disorientation, calculation disability ,body schema, facial recognition • Social cognition • Recognition of emotions and social cues, appropriate social inhibitions, empathy

12. Neurocognitive Disorders • Major Neurocognitive Disorder • Mild Neurocognitive Disorder • Major or Mild Neurocognitive Disorder Due to Alzheimer’s Disease • Major or Mild FrontotemporalNeurocognitive Disorder • Major or Mild Neurocognitive Disorder With Lewy Bodies • Major or Mild Vascular Neurocognitive Disorder • Major or Mild Neurocognitive Disorder Due to Traumatic Brain Injury • Major or Mild Neurocognitive Disorder Due to HIV Infection • Major or Mild Neurocognitive Disorder Due to Prion Disease • Major or Mild Neurocognitive Disorder Due to Parkinson’s Disease • Major or Mild Neurocognitive Disorder Due to Huntington’s Disease • Substance/Medication-Induced Major or Mild Neurocognitive Disorder • Major or Mild Neurocognitive Disorder Due to Another Medical Condition • Major or Mild Neurocognitive Disorder Due to Multiple Etiologies • Unspecified Neurocognitive Disorder

15. Causes of dementia • Primary dementia • Progressive • Neurodegenerative diseases • Secondary dementia • Arrestable or reversible if treatable • Progressive if untreatable • May be • Primary CNS diseases • Systemic diseases

16. Causes of dementia Primary dementia • Alzheimer’s disease (AD) • Frontotemporal dementia (FTD) • Dementia with Lewy bodies (DLB) • Parkinson disease (PD) • Progressive supranuclear palsy (PSP) • Corticobasal degeneration (CBD) • Others neurodegenerative diseases

17. Temporal Patterns of Signs and Symptomsprimary dementia • Early primary dementia affect selected region of the brain • Selected region of the brain reflects clinical features of different primary dementia syndrome • Late primary dementia will globally affect the whole brain and dementia syndrome cannot be clinically differentiated

18. Lars Bertram and Rudolph E. Tanzi, 2005

19. Staging of tau deposition in Alzheimer's disease

20. Staging of Lewy body in Parkinson's disease

21. Clinical syndrome in primary dementia • Cortical dementia : common in primary dementia especially AD and FTD • Anterior – behavioral & personality disorders :FTD • Posterior - memory & visuospatial disorders : AD • Subcortical common in other primary dementia from neurodegenerative diseases • Parkinsonism and other extrapyramidal tract syndrome • Pyramidal tract syndrome • Cerebellar syndrome • Autonomic syndrome • Varied in cognitive and neuropsychiatric syndrome

22. Typical Temporal Patterns of Signs and Symptoms in common Neurodegenerative Subtypes of Dementia AD • Amnesia • Visuospatial disorders • Apraxia • Paranoid , agitation DLB • Poor attention and cognition • Extrapyramidal syndrome • Florid visual hallucination FTD 1. Personality change , disinhibition 2. Semantic aphasia 3. Motor neuron disease

23. Causes of dementia Secondary dementia Vascular causes Infectious causes Toxic- Metabolic- nutritional disorders Autoimmune diseases Metastases/Neoplasm/other mass lesions Endocrine diseases Other systemic diseases

24. Clinical syndrome in secondary dementia • Diverse clinical features depend on location and nature of pathology • Clinical syndromes • Associated focal neurological deficits • Clinical course • Associated with systemic manifestation

25. Clinical clues for secondary dementia • Clinical and natural history not compatible with known neurodegenerative dementia syndrome • Alzheimer’s disease • Frontotemporal dementia • Dementia of Lewy body • Parkinson disease • Evidence of causation demonstrated by both of the following: • 1. Dementia has developed in close temporal relation to secondary causes • 2. either or both of the following: • a) Dementia has significantly worsened in parallel with the secondary causes • b) Dementia has significantly improved or resolved after improvement of the secondary causes

26. Clinical clues for secondary dementia • Focal neurological deficits • Headache • Early • Convulsive disorders • Myoclonus • Gait disturbance • Urinary incontinence • Acute onset • Rapid progressive course • Early age of onset • Associated systemic diseases

27. Rapidly progressive dementia diagnostic criteria • No formal diagnostic criteria • Course of RPDs • Two years or less in duration • Rate of progression is much faster than observed for more common neurodegenerative diseases • Hyperacute RPDs : develops over days or weeks • Subacute RPDs : develops over months or 1-2 years • Exclusion of delirium

28. Typically natural history of neurodegenerative Dementias • AD typically survive a median of 11.7 (SD ±0.6) years • FTD patients 11 years (SD ±0.9) • PSP/CBD patients 11.8 years (SD ±0.6) • PSP alone 5.6 years • DLB is often shorter than for many other neurodegenerative dementias; one study suggests 3 year survival

29. Rapidly progressive Dementia • Jakob-Creutzfeldt disease (CJD; sporadic, iatrogenic, familial) • Autoimmune encephalitis • CNS malignancy • HIV dementia • Progressive Multifocal Leukoencephalopathy (PML) • Subacute sclerosing panencephalitis (SSPE; young adults) • Parasites • Syphilis • Acquired hepatocerebral degeneration • Intoxication • Bismuth toxicity • Lithium toxicity • Mercury toxicity

30. Rapidly progressive Dementia Autoimmune • Hashimoto's Encephalopathy • Paraneoplastic (autoimmune) limbic encephalopathy (PLE) • Non-paraneoplastic autoimmune (e.g., anti-VGKC mediated) • Lupus cerebritis • Other CNS Vasculitides

31. Rapidly progressive Dementiamalignancy • Primary CNS lymphoma • Intravascular lymphoma • Gliomatosis cerebri • Lymphomatosis cerebri

32. CDC's Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD), 2010 • Sporadic CJD • Definite: • Diagnosed by standard neuropathological techniques; and/or immunocytochemically; and/or Western blot confirmed protease-resistant PrP; and /or presence of scrapie-associated fibrils. • Probable: • Rapidly progressive dementia; and at least two out of the following four clinical features: • Myoclonus • Visual or cerebellar signs • Pyramidal/extrapyramidal signs • Akineticmutism • AND a positive result on at least one of the following laboratory tests: • a typical EEG (periodic sharp wave complexes) during an illness of any duration; and/or • a positive 14-3-3 cerebrospinal fluid (CSF) assay in patients with a disease duration of less than 2 years • Magnetic resonance imaging (MRI) high signal abnormalities in caudate nucleus and/or putamen on diffusion-weighted imaging (DWI) or fluid attenuated inversion recovery (FLAIR) • AND without routine investigations indicating an alternative diagnosis.

33. CDC's Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD), 2010 • Sporadic CJD • Possible: • Progressive dementia; and at least two out of the following four clinical features: • Myoclonus • Visual or cerebellar signs • Pyramidal/extrapyramidal signs • Akineticmutism • AND the absence of a positive result for any of the three laboratory tests that would classify a case as “probable” (see tests a-c above)AND duration of illness less than two yearsAND without routine investigations indicating an alternative diagnosis.

34. CDC's Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD), 2010 • Iatrogenic CJD • Progressive cerebellar syndrome in a recipient of human cadaveric-derived pituitary hormone; orsporadic CJD with a recognized exposure risk, e.g., antecedent neurosurgery with dura mater implantation. • Familial CJD • Definite or probable CJD plus definite or probable CJD in a first degree relative; and/or Neuropsychiatric disorder plus disease-specific PrP gene mutation.

35. Creutzfeldt-Jakob Diseaseribboning

36. Autoimmune encephalitis

37. HIV-Associated Cognitive Motor Complex

38. Progressive multifocal leukoencephalopathy

39. Gliomatosiscerebri

40. Lymphomatosis cerebri

41. Intravascular lymphoma

42. Major exclusion syndromein Dementia

43. Delirium

45. Diagnostic Criteria • A. Disturbance of consciousness (eg, reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention. • B. Change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance. • C. Disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day.

46. Three Types of Delirium, Based on Etiology • Three criteria (A-C) are common to delirium caused by • (1) general medical condition, • (2) substance intoxicationor withdrawal • (3) multiple etiologies

47. Signs & Symptoms • Cognitive disturbances • Memory • Language • Disorientation • Perception • Attention • Concentration • Motor • Sleep-wake cycle

48. Clinical Course • Acute – subacute onset • Clinical fluctuation • Treatment • Specific causes • Cure if correct and early intervention • Reduce cost and hospital stay • Symptomatic and supportive intervention

49. Psychiatric disordersand dementia

50. Depression & Dementia