Diagnosis of Dementia: Update

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10 C A 1 2 Normal SMI MCI Early Dementia B Moderate Dementia 3 Severe Dementia 4 5 D AD, VD, FTD, DLB, PDD Depression Dementia d/t GMC Modifiable risk factors and preventive factors for dementia 6-5 -

Step 1 : (A,B,C,D) - Activities of daily living ( ) - Behavior problem () - Cognitive Function () Step 2 : (D: disease) Step 3 : (,, ) Step 2:Etiology of Dementia Differential Diagnosis (Delirium) (Mild cognitive Impairment) - 6 -

Step 1: Identification of Dementia : Neuropsychological Test Step 1: Identification of Dementia A. C.? A.? B.? Cognition:? - 7 -

- 8 -

: (Registration) (storage) (Retrieval),,,, (consolidation) Retrieval & Encdoing defect memory impairment Bedside Testing Memory K-MMSE Memory Recall (3) - 9 -

- 10 -

- 11 -

- 12 -

Step 1: Identification of Dementia : Neuropsychological Test Step 1: Identification of Dementia A. B. C. - 13 -

Step 1: Identification of Dementia : History 1. 2. 3. 4. 5. 6. 7., chaddock 8. (,,, ) 9. Step 1: Identification of Dementia : Neuropsychological Test Step 1: Identification of Dementia A. B. C. Step 1: Etiology of Dementia Step 2: 1. Hgb, HCT, Na/K, Bun/Creatinine, OT/PT (Ammmonia) Thyroid function test, VDRL, Vitamine B 12, Folic acid, Homocysteine Vitamine B1 2. :CT<< Brain MRI (Brain MRA, if needed) 3. PET (FDG or amyloid-pet, FP CIT PET) 4. (CNS infection or CSF abeta or tau) 5. (R/O Epileptic amnesia, limbic encephalitis) - 14 -

Brain MRI D; Differential Diagnosis of Dementia Alzheimer s Disease - 15 -

Dyanamic Biomarker of the Alzheimer s pathological Cascade (Leslie & Trojanowski et al, Lancet Neurol 2010) FDG-PET: Posterior cingulatelateral Temporal Frontal Structural MRI: Medial Temporal Lateral TemporalFrontal : PS1, PS2, APP19 First Drugs 1 st Vaccines: AN1792- Bapneuzimab-Solanezumab- Gantanerumab CSF Aβeta- & tau 1906 1960 1980 1993 1997 97 1999 2003 2004 2007 20111 2015 Amyloid & Tau FDG-PET (J Neuroimaging) MRI atrophy (Neurology) CSF Biomarker (Neurology ) PIB-PET (Ann Neurol) 18F-Florbetaben (piramar) 18F-Flutemetamol (GE) MCBP = 0.03 MCBP = 0.36 MCBP = 0.82 MCBP = 0.78 CDR 0 Negative Scan CDR 0 Weakly Positive Scan CDR 0 at scan (now CDR 0.5) Positive Scan CDR 0.5 DAT Positive Scan [ 11 C] PIB PET : Florbetaben FDG-PET : (PIRAMAR); & - 16 -

NINDCDS-ADRDA AD(1984) Revised Criteria of Probable AD(2007) Probable 1. Dementia established by clinical examination 2. Dementia confirmed with cognitive testing 3. Deficits in two or more domains of cognition 4. Progressive decline in memory and other cognitive functions 5. Preserved consciousness 6. Onset between ages 40 and 90 years 7. Absence of systemic or other brain disease that accounts for symptoms NINDCDS-ADRDA Probable AD(1984) Revised Criteria of Probable AD(2007) - 17 -

CASES OF LATE ONSET & EARLY ONSET DEMENTIA 76/, - 18 -

Brain MRI & FDG-PET (2006) - 19 -

MRI (2015) 58/, - 20 -

MRI (2013) CSF & Gene study APOE3/3 CSF study: Abeta 356, Total tau 589.34, Phospho tau 70 ttau/aβ42, 1.655; ptau181/aβ42, 0.198 PSEN2 V214L mutation: Autosomal Dominant AD Revised Criteria of Probable AD(2007) Supportive Feature: 1 1. Medial temporal Atrophy Hippocampus, entorrhinal, amygdala Quantitative (Visual scoring) or qualitative (Volumetry of ROI) 2. CSF biomarker: Aβ42, T-tau or phospho-tau 3. FDG-PET (temporoparietal hypometabolism) or PIB-PET(+) 4. Proven AD mutation within immediate family - 21 -

Conclusion : ABCD (MMSE or SNSB) & CDR or GDS Scale : Q. (K-DSQ) ALD: K-IADL, Barthel ADL, GeDepS, NPI : Lab & B. imaging (CT or MRI) CSF study (Aβ42, T-tau or phosphotau) Amyloid PET imaging - 22 -