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MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)
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MCRPsych09 - Evidence Based Diagnosis of Dementias (Nov09)

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This is a presentation on the science behind diagnosis of dementias (inc alzheimer's, FTD, lewy body). The take home message is that our clinical accuracy is modest. Includes images from several …

This is a presentation on the science behind diagnosis of dementias (inc alzheimer's, FTD, lewy body). The take home message is that our clinical accuracy is modest. Includes images from several sources. Delivered to MRCPsych Leicester 2009

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  • 1. Evidence Based Diagnosis of the Dementias Evidence Based Diagnosis of the Dementias Validity of criteria for diagnosing subtypes of dementia Validity of criteria for diagnosing subtypes of dementia Alex Mitchell www.psycho-oncology.info Department of Cancer & Molecular Medicine, Leicester Royal Infirmary Department of Liaison Psychiatry, Leicester General Hospital MRCPsych Leicester Nov 2009
  • 2. Pragmatic definition of dementia • Dementia is an acquired global impairment of intellectual functioning • Involving memory, language, thinking, and perception • Associated with disability • Usually is progressive and irreversible • Current Treatments make a modest difference to the disease course • Dementia is a syndrome with many underlying diseases • Some diseases may yet not be adequately described • Dementia is preceded by mild cognitive impairment (which may not come to medical attention) 2
  • 3. Concepts of Screening • Screening (possible case) High convenience » Eg MMSE • Case-Finding (probable case) » Eg NINCDS-ADRDA criteria, • Severity Rating » Eg ADAS-Cog • Gold Standard (definite case) » Pathology => disease High accuracy
  • 4. Concepts of Dementia High convenience • Symptoms and signs • Detailed symptoms (neuropsychology) • Gross pathology • In vivo pathology (neuroimaging) • Microscopic pathology • Immunochemistry • Genetics High accuracy
  • 5. Clinical Classification of Dementia
  • 6. Neurodegenerative Disorders Neurodegenerative Disorders Intraneuronal Extracellular Prion Protein Beta-Amyloid Cytoplasmic/Neuri Intracellular Creutzfeldt-Jakob disease Alzheimer’s disease tic Polyglutamine disorders α- Ubiquitin disorders synucleinopathies Huntington’s disease Motor Neuron Disease Parkinson’s disease SBMA Motor Neuron Dementia Lewy Body Dementia Spinocerebellar ataxia 1, 3, 7 Frontotemporal dementia (MND-type) Multiple System Atrophy dentatorubral-pallidoluysian atrophy Neuroaxonal dystrophy Tauopathies Triplet Band Double Band Taupathies Taupathies Triplet-Band Predominanty 4- Predominanty 3- Tauopathies repeats repeats Normal Aging Progressive Supranuclear Palsy Pick’s disease Alzheimer’s disease Corticobasal Degeneration Down’s Syndrome MSTD, PPND NPC, PEP, GSS Duke Family 1, 1684 ALS/PDC Microcellular Classification of Dementia
  • 7. Primer on Forgotten Neuroanatomy!
  • 8. Higher Cortical Functions and Association Cortices Attending Selecting Recognizing Association cortices = cognition Imitating Remembering
  • 9. The “Association Cortices” have a distinctive neocortex Cortical Maps: Brodmann Lateral Neocortex ~50 regions Medial Cytoarchitecture = Cell packing density and type
  • 10. Introduction to Dementias
  • 11. Distribution of AD in Different Settings AD in the Community AD within Institutions Moderate Moderate 44% 34% Mild Severe 46% Mild 55% 11% Severe 10% CSHA Working Group, CMAJ, 1994. CSHA Working Group, Can J Aging, 1994.
  • 12. Probability of Institutionalization by Severity 1.0 0.867 0.8 Institutionalization Probability of 0.6 0.4 0.345 0.2 0.017 0.0 Mild Moderate Severe (MMSE: 21–30) (MMSE: 11–20) (MMSE: 0–10) Severity of AD Hauber AB, Gnanasakthy, Snyder EH, et al. Pharmacoeconomics. 2000(April);17(4):35
  • 13. Outcome measures used in Alzheimer’s Disease ADAS-Cog Cognition Function Alzheimer’s Disease (ADAS-Cog) (DAD/ADCS- Assessment Scale, Cognitive ADL) subscale Global CIBIC-plus (CIBIC-plus) Clinician Interview-Based Impression of Change with Caregiver Input DAD Disability Assessment in Dementia Behaviour ADCS-ADL (NPI) Alzheimer's Disease Co- Operative Study – Activities of Daily Living NPI * Caregiver burden Neuropsychiatric Inventory *Contains subscale NPI-D, which measures caregiver distress SCGB Screen for Caregiver Burden
  • 14. Dementia Clinical Serie
  • 15. Primer on Neuropsychology of Memory Registration Memory Retrieval Retention Implicit Declarative Learning of Learning of Skills & Automatic Behaviours Information Working Memory Short-term Memory Long-term Memory Retention over Seconds Retention over Minutes Retention over days Motor Conditioning Priming Visuospatial Verbal Semantic Memory Episodic Memory Database of information Narrative Account
  • 16. Overview of Main Symptoms in Dementias Memory Language Visuospatial Attention Behavioural Neurological A.D. ++++ ++ ++ ++ + ± DLB/PDD. ++ + ++++ +++ + ++ FTD - Semantic + ++++ ± + + ± FTD - Frontal + + ± ++ ++++ ± FTD - P.N.F.A. ± ++++ ± + + ± Corticobasal + + +++ ++ ++ +++ PSP. + + + +++ ++ +++ Huntington's + + + +++ ++ +++ 20
  • 17. Alzheimer’s disease Auguste D, November 3, 1906 37th Assembly of Southwest German Psychiatrists in Tübingen, Germany “atrophied brain; numerous ganglia cells have disappeared” “remarkable changes in neurofibrils” “millet-seed lesions, characterized by the deposits of a peculiar substance spread over entire cerebral cortex” “we clearly have a distinct disease process”
  • 18. History of AD • 1906 Alzheimer presented Auguste D • 1910 Kraepelin Coined “Alzheimer’s disease” (Psychiatrie: Ein Lehrbuch fur Studierende und Ärzte, Leipzig) • 1960 Electron microscopic studies in the 1960s by M Kidd and R Terry (with H Wisniewski, M Shelanski, B Ghetti, K Iqbal, D Dickson, etc.) revealed the ultrastructural features of AD • 1968 Tomlinson, Blessed and Roth (1968, 1970) showed that the brains of healthy and demented older adults differ and that most demented persons have AD • 1976 Cholinergic deficit (ChAT) in AD brains (Davies and Maloney, 1976; Bowen et al., 1976 • 1991 APP mutation causing dominantly inherited AD (Goate et al., 1991) • 1991 Concept of mild cognitive impairment, or MCI (Flicker et al) • 1992 Presenilin 1 (St George-Hyslop et al., 1992) • 1993 ApoE identified as the major susceptibility gene for AD (Strittmatter et al., 1993) • 1993 Tacrine approved • 1995 Presenilin 2 (Rogaev et al., 1995) mutations identified • 1996 Donepezil approved • 2001 Galantamine approved • 2003 memantine approved
  • 19. Gross Pathology - AD
  • 20. Gross Pathology in Alzheimer’s Loss of tissue Wide Sulci Large ventricles 25
  • 21. CT Scan Loss of tissue Wide Sulci Large ventricles 26
  • 22. CT Scan 2 Normal Aging Alzheimer’s Disease (coronal section) (coronal section)
  • 23. Microscopic Pathology
  • 24. Neurofibrillary Tangles Neurons have an internal support structure partly made up of microtubules. A protein called tau helps stabilize microtubules. In AD, tau changes, causing microtubules to collapse, and tau proteins clump together to form neurofibrillary tangles.
  • 25. SPECT Scan Healthy AD
  • 26. What Makes a Diagnosis Correct?
  • 27. Density of Plaques and Tangles Progression of Plaques and tangles by region and diagnostic accuracy of p-tau from Mitchell JNNP (2009)
  • 28. Rate of memory decline increases 5.1 years before dementia diagnosis (Hall et al, 2000)
  • 29. Healthy Elderly
  • 30. Mild Cognitive Impairment
  • 31. Alzheimer’s disease
  • 32. Clock Drawing - Examples http://www.dementiaguide.com/images/DGI-Ill_5.1-ClockDrawing.jpg ltcif_cog_screen_0809 39
  • 33. Primer on the Science of Classification
  • 34. Simple Measures of Accuracy Dementia Dementia PRESENT ABSENT Test +ve True +ve False +ve PPV Test -ve False -Ve True -Ve NPV Sensitivity Specificity Prevalence
  • 35. Theory of Diagnostic Tests Point of Partial Rarity? Number of Cognitive Impairment Individuals Dementia True ‐ve True ‐ve True +ve True +ve False ‐ve False ‐ve False +ve False +ve Score on Hypothetical Diagnostic Test Optimum Cut‐off value
  • 36. Ganguli M et al. Detection and Management of Cognitive Impairment in Primary Care: The Steel Valley Seniors Survey. JAGS 52:1668–1675, 2004. GP Testing by Actual MMSE Score (n=162)
  • 37. MMSE modest sensitivity and specificity in dementia vs no dementia. Data from Cambridge CFAS
  • 38. Anim als nam ed in 1 m in (m m s>19) - CERAD data set 12 10 percent of total 8 6 4 2 0 0 10 20 30 40 num ber of anim als nam ed Normal Controls, CS = 1, n = 386 Alzheimer patients, CS = 0, n = 380
  • 39. Classification Systems in Dementia
  • 40. Dementia in DSMIV • Short-term memory impairment AND dementia • At least one of the following: » Aphasia - language impairments » Apraxia - motor memory impairments » Agnosia - sensory memory impairments » Abstract thinking / Exec. fn impairments • Impairment in social and/or occupational function • Not explainable by another disorder (such as delirium)
  • 41. Dementia in ICD10 • Dementia (memory and thinking) • Incidious onset > 6months • Poor function • Normal consciousness • Executive dysfunction
  • 42. Diagnostic criteria & dementia prevalence Canadian Study of Health and Aging (CSHA) Criteria (n=1879) % of CSHA population ICD-10 3.1 CAMDEX 4.9 ICD-9 5.0 DSM-IV 13.7 DSM-IIIR 17.3 DSM-III 29.1 Erkinjuntti T, Ostbye T, Steenhuis R, Hachinski V. The effect of different diagnostic criteria on the prevalence of dementia. NEJM 1997 337(23):1667-74. 50
  • 43. Diagnostic criteria & dementia prevalence
  • 44. Vascular Dementia
  • 45. Additional Behavioral Influences Small and Large Vessel Vascular Supply Blood vessels in human brain. A plastic emulsion was injected into brain vessels and brain tissue was dissolved. Zlokovic & Apuzzo: Neurosurgery 43(4):877-878, 1998.
  • 46. Vascular Dementia - SPECT
  • 47. Diagnosis - Hachinski Scale Item Score Sudden onset 2 Stepwise deterioration 1 Fluctuating course 2 Nocturnal confusion 1 Relative preservation of personality 1 Depression 1 Somatic complaints 1 Emotional incontinence 1 History of hypertension 1 History of stroke 2 Evidence of associated atherosclerosis 1 Maximum = 18 Focal neurological symptoms 2 7 : Vascular Focal neurological signs 2 5- 6 : Mixed < 4 : Alzheimer’s 55
  • 48. MRI Markers of SIVD Lacunar Infarction White Matter Hyperintensitie s
  • 49. Clinical criteria for VaD 1. National Institutes of Neurological Disorders and Stroke- Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN) 2. State of California Alzheimer’s Disease Diagnostic and Treatment Centers (ADDTC) 3. Diagnostic and Statistical Manual of Mental Disorders. 4th edition (DSM-IV) 4. Hachinski Ischemic scale 5. International Classification of Disease-10 (ICD-10)
  • 50. Criteria Sensitivity % Specificity % NINDS-AIREN 20-58 80-97 ADDTC 25-70 64-91 DSM-IV 50 84 Hachinski 43 88 ICD-10 20 94
  • 51. Subtype of VaD Macrovasculare thromboembolic (multi-infarct dementia ) Single strategic strokes Multiple subcortical lacunar strokes ( lacunar state ) Extensive WMLs or Binswanger’s disease Mixture of type 1,2,3,and 4 esp. lacunar-Binswanger Postischemic dementia Hemorrhagic dementia Genetic cerebrovascular disease Vascular-Alzheimer dementia Vasculitides and other miscellaneous causes
  • 52. Multi-infarct dementia (MID) • 21.6% of VaD • Large and medium vessels – Carotid artery atherosclerosis – MCA infarction – watershed infarction – Cardiac emboli
  • 53. Lacunar Stroke • 33-70 % of VaD • Lenticulostriate branches (MCA) Thalamogeniculate, choroidal and thalamoperforator branches (PCA, Pcom) • Frontal white matter 34.8% • Basal ganglia 34.2% • Pons 8% • > 10-15 infarctions of deep structures • 10 cm3 or 0.5% of intracranial volume • >1/4 white matter
  • 54. Comparison of VaD AD Features History Abrupt, stepwise Insidous and progression Risk factors Cerebrovascular risks Family hx, APOE4 allele Mental status Psychomotor slowing Recent memory Finding Frontal executive function Visuospatial decline Memory Retrieval and procedural Worse memory, orientation memory and recognition Language Sentence complexity and Naming and comprehension prosody Behavioral Apathy, depression, Delusion, poor insight emotional lability Neuro exam Focal neuro deficit none MRI WMLs and stroke Diffuse/ mesial temporal atrophy PET/SPECT Patchy, global or frontal Bilateral temporoparietal (hypometabolism )
  • 55. Fronto-Temporal Dementia (Picks)
  • 56. Fronto-temporal Dementia
  • 57. Fronto-temporal Dementia Semantic Dementia Progressive Non-Fluent Aphasia (PNFA) Social/Executive
  • 58. FTD Disease Progression
  • 59. Lewy Body Dementia + PDD
  • 60. 2005 Consortium Criteria DLB – Important Criteria • 1. Central feature (essential for a diagnosis of possible or probable DLB) • Dementia (progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function) • Prominent or persistent memory impairment • Deficits on tests of attention, executive function, and visuospatial ability may be especially prominent. • 2. Core features (two core features are sufficient for a diagnosis of probable DLB, one for possible DLB) • Fluctuating cognition with pronounced variations in attention and alertness • Recurrent visual hallucinations • Spontaneous features of parkinsonism • 3. Suggestive features (If one or more of these is present in the presence of one or more core features, a diagnosis of probable DLB can be made. In the absence of any core features, one or more suggestive features is sufficient for possible DLB. Probable DLB should not be diagnosed on the basis of suggestive features alone.) • REM sleep behavior disorder • Severe neuroleptic sensitivity • Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging
  • 61. 2005 Consortium Criteria DLB – Less Important Criteria • 4. Supportive features (commonly present but not proven to have diagnostic specificity) • Repeated falls and syncope • Transient, unexplained loss of consciousness • Severe autonomic dysfunction, e.g., orthostatic hypotension, urinary incontinence • Hallucinations in other modalities • Systematized delusions • Depression • Relative preservation of medial temporal lobe structures on CT/MRI scan • Generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity • Abnormal (low uptake) MIBG myocardial scintigraphy • Prominent slow wave activity on EEG with temporal lobe transient sharp waves • 5. A diagnosis of DLB is less likely • In the presence of cerebrovascular disease evident as focal neurologic signs or on brain imaging • In the presence of any other physical illness or brain disorder sufficient to account in part or in total for the clinical picture
  • 62. Special Notes on PDD vs LBD • DLB should be diagnosed when dementia occurs before or concurrently with parkinsonism (if it is present). The term Parkinson • disease dementia (PDD) should be used to describe dementia that occurs in the context of well-established Parkinson disease. In a practice setting the term that is most appropriate to the clinical situation should be used and generic terms such as LB disease are often helpful. In research studies in which distinction needs to be made between DLB and PDD, the existing 1- year rule between the • onset of dementia and parkinsonism DLB continues to be recommended. Adoption of other time periods will simply confound data • pooling or comparison between studies. In other research settings that may include clinicopathologic studies and clinical
  • 63. Gross Pathology in PD
  • 64. Lewy Body Inclusions • Characteristic inclusions in substantia nigra neurons of patients with Parkinson’s disease • Immunoreactive for neurofilaments, ubiquitin and alpha- synuclein, but not tau (NFT are tau and ubiquitin positive) • In substantia nigra it is cytoplasmic, round, eosinophilic with clear halo • In cortex less distinct appearance, best visualized with alpha-synuclein immunohistochemistry
  • 65. Pathology in Parkinson’s Disease
  • 66. Pathology in Parkinson’s Disease
  • 67. Predictive Value of Consensus Criteria Author Cases DLB Sens. Spec. Type Holmes 80 2 0.22 1.00 Prosp. Luis 56 23 0.65 0.90 Retro. Litvan 105 14 0.57 0.87 Retro McKeith 50 29 0.83 0.91 Prosp. Papka 40 19 0.43 xxx Retro McShane 102 9 0.58 0.89 Props. Mega 18 6 0.40 1.00 Retro.
  • 68. Lewy Body vs Alzheimer Dementia
  • 69. Dementia Screening Tests (briefly)
  • 70. Types of Recognition • Unassisted Clinical Ability • Clinician Prompts » GDS, CDR • Patient Complaints / Relatives QQ » Subjective Memory Complaints (SMC) • Simple (Bedside) Single Item Cognitive Tests » Verbal fluency, Name & Address, Orientation • Short Batteries » MMSE • Long Batteries » CAMCOG • Criterion Standard
  • 71. What Makes for a Good Screening Test? • Often Examined » Rapid training & administration » Simple scoring & interpretation » Good rule-out accuracy, ideally good rule-in accuracy also • Rarely Examined » High patient acceptance » Multiple validation samples & settings » Superiority to unassisted recognition » Minimal bias => education, language UK National Screening Committee (UK-NSC) www.nsc.nhs.uk/whatscreening/whatscreen_ind.htm
  • 72. GP Screening Preferences • 74% of people consult a GP first after noticing symptoms of cognitive decline 3 • 82% of GPs say screening for dementia is worthwhile » but 24% routinely screen (GPs) » 39% psychiatrists use the MMSE1 • 93% would use a brief effective tool2 1 Gilbody, House Sheldon (2002) Br J Psychiatry 2 Bush et al Can Fam Physician. 1997 3 Wilkinson et al (2004);
  • 73. Memory Complaints
  • 74. Simple Memory Complaints Accuracy? Lam et al. Int J Geriatr Psychiatry 2005; 20: 876–882. (n=306) 100 90 88 87.3 Controls 80.3 80 MCI 73.3 73.2 MCI=>Dementia 70.2 70 68.2 67.6 AD (CDR1) 63.8 60 58 48.5 50 45.1 43.7 41.3 39.4 40 35.1 30.3 30 28 25.5 20 16 10 0 Forgetting w here things are Unable to recall the nam es of Unable to follow and recall Subjective m em ory problem s* Consider ow n m em ory to be placed good friends* conversation** w orse than others of a sim ilar age**
  • 75. Clinician Accuracy (using GDS) HEUN et al IJGP 1998 Dementia Dementia Present Absent Clinician 20 8 71% PPV Yes Clinician No 37 250 93% NPV 54% (se) 96% (Sp) Prevalence = 10%
  • 76. Recognition of “Dementia” by GPs Using documentation of dementia in the medical notes Dementia Dementia (DSMIV) ABSENT Dementia in 54 4 58 notes PPV 93% No dementia in 58 1144 1202 notes NPV 95% 112 1148 1260 Sensitivity Specificity Prevalence 8% 48% 99.6%
  • 77. Recognition Rate of Dementia by Severity 100 97% 90 80 73% 71% 70 66% 60 50 46% 40 33% 30 20 10 0 Severe Severe Moderate Moderate Mild Mild Dementia Dementia Dementia Dementia dementia dementia (CI) (Dementia) (CI) (Dementia) (CI) (dementia)
  • 78. Predictors of Non-Recognition • Good Activities of daily living • Low years since symptoms first started • Low presence of somatic comorbidity [Van Hout, 2002] • male lived at home • Coped better • more depression Dementia: Predictors of diagnostic accuracy and the contribution of diagnostic recommendations Author(s): van Hout HPJ, Vernooij-Dassen MJFJ, • milder dementia Hoefnagels WHL, Kuin Y, Stalman WAB, Moons KGM, Grol RPTM Source: JOURNAL OF FAMILY PRACTICE 51 (8): 693-699 AUG 2002
  • 79. Accuracy of MMSE (n=10,400 x 19) Dementia Dementia Present Absent MMSE 2192 1005 68% (PPV) Yes MMSE 669 6534 90% (NPV) No 76% (se) 86% (Sp) Prevalence = 10% ceiling =>
  • 80. MMSE Limitations • Takes 8-13 minutes. Too long • Scores are affected by age, ethnicity, language and education • Little executive or memory • Some GPs find it difficult to interpret • Patients acceptability not the best
  • 81. Short Instruments • 7 minute screen • Mini-Mental State Examination (MMSE) • Short Form, Informant QQ on Cognitive Decline in the Elderly • Short and Sweet Screening (short IQCODE) Instrument (SASSI) • Abbreviated Mental Test (AMT) • Short Test of Mental Status (STMS) • Cambridge Cognitive Examination (CAMCOG) • The 6 Item Cognitive Impairment Test (6CIT) • Clock Drawing Test (CDT) • The General Practitioner • Memory Impairment Screen Assessment of Cognition (MIS) (GPCOG) • Mental Alternation Test (MAT) • The Rowland Universal • Mini-Cog Dementia Assessment Scale (RUDAS) • Time and change Test (T&C)
  • 82. Pre-dementia and MCI (briefly)
  • 83. Dementia Prognosis Early Symptoms 90% (Mini-Mental State Examination Score) (Brain Volume / Intracranial Volume) Pathological Burden 30 PRE-SYMPTOMATIC Diagnosis Diagnosis 85% PRE-CLINICAL Mild Cognitive Impairment Death Death 80% 23 CLINICAL Mild Dementia 75% Disease Severity 20 Moderate Dementia Unmodified Dementia 70% 12 Dementia with Risk Factors Severe Dementia T-10 T-5 T0 T+5 T+10 Time in Years Explanation See text for details Further Reading: Fox NC, Crum WR, Scahill RI et al. (2001) Lancet 358, 201-205 Imaging of onset and progression of Alzheimer’s disease with voxel compression of serial magnetic resonance images
  • 84. Dementia Treatment Early Symptoms 90% Pathological Burden 30 ((Mini-Mental State Examination Score) (Brain Volume / Intracranial Volume) PRE-SYMPTOMATIC Diagnosis PRE-CLINICAL 85% Institutional Care CLINICAL Mild Cognitive Impairment Unmodified 23 80% Treatment A Treatment B Mild Dementia 75% Care Treatment C 20 Disease Severity Care Moderate Dementia Care 70% 12 Severe Dementia T-10 T-5 T T+5 T+10 T+15 0 Time in Years Explanation See text for details
  • 85. Biochemical Progression of AD-Tau Delacourte, Andre. The natural and molecular history of Alzheimer’s disease. J Alzheimer’s Disease 2006;9:1
  • 86. tive tic olic r ra cula Etiology uma ene tab Vas Deg Me Tra MCI Clinical classifi cation Amnestic MCI Multiple Domain MCI Single Non-memory Domain Heterogeneity of MCI from clinical and etiological perspectives. Open cells are most common.

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