Clinical Assessment of Cognition: New & Emerging Tools for Diagnosing Dementia DISCLOSURES NONE TO REPORT Freddi Segal Gidan, PA, PhD USC Keck School of Medicine Rancho/USC California Alzheimers Disease Center Objectives THE EPIDEMIC of 21 st Century At the conclusion of this session participants will be able to Apply new DSM V nomenclature to practice Discuss the new NIH AA Alzheimers Disease Diagnosis Guidelines and their applicability to current clinical practice Explain the role of biomarkers in the diagnosis of Alzheimers disease 1
An Epidemic of AD Alzheimers Challenges 13.5 million by 2050 Lifetime risk of AD in 65 yo is 10.5% Decline in workforce Primary care Geriatricians & neurologists $/minute care of AD patient is low related to other conditions/diseases Dementing Diseases in the Elderly Cardiovascular Health Study (n=707) DSM V Definition of Dementia Neurocognitive Disorders acquired evidence of a decline from previous level of neurocognitive function (based on report by a patient and/or a significant other, evidence from longitudinal data, or cross sectional assessment of prior function) a) Minor Neurocognitive Disorder (Mild Cognitive Impairment or MCI) neurocognitive impairment in only one domain b) Major Neurocognitive Disorder or Dementia, typically involve at least two domains. However, memory impairment would not be necessary for diagnosing either of these conditions (i.e. aphasia in ) 2
Neurocognitive Disorder Sub classification: ETIOLOGY Minor and Major Neurocognitive Disorders subclassified according to etiology Alzheimers disease Non Alzheimers Vascular Lewy Body Frontotemporal Mixed Clinical Evaluation History Medication review Physical examination Mental status/cognitive screening Laboratory tests Routine (CBC, Chem, TSH, B12) CSF + Imaging Structural; CT/MRI + Functional; PET + + = biomaker New Clinical Guidelines Preclinical phase(s) Mild Cognitive Impairment (MCI) DSM 5 mild neurocognitive disorder Alzheimers disease Shift in emphasis to Biomarkers: Atrophy, Glucose metabolism, beta amyloid and p tau [CSF and PET]). 3
Pre Clinical Phase (No correlate prior to 2011) Stage I Asymptomatic amyloidosis High PET amyloid tracer retention Low CSF a beta 1 42 Stage 2 Amyloidosis + Neurodegeneration Neuronal dysfunction on FDG PET/MRI High CSF tau p tau Cortical thinning /hippocampal thinning on MRI Stage 3 Amyloidosis + Neurodegeneration + Subtle Cognitive Decline Poor performance more challenging cognitive tests Does not yet meet MCI criteria Preclinical Phase Issues Primary care not trained to assess Lack of validated screening tools PET scan for a beta Trigger for ordering? Insurance coverage & cost CSF Risk:Benefit Mild Cognitive Impairment (MCI) More clearly defined than pre 2011 Clinical criteria Concern regarding cognitive change Impairment in one or more domains Memory Executive function Attention Language Visuo spatial skills Preservation of functional independence Mild IADL impairment MCI Clinical Criteria Concern about change in cognition Impairment in one (or more) domains Memory Executive function Attention Language Visuospatial skills Preservation of functional independence Mild IADL impairment possible 4
NEW CRITERIA All Cause Dementia Functional impairment &/or decline No Delirium or Psychiatric Disorder Cognitive or behavioral impairment (2+) Ability to acquire and remember new information * Reasoning and judgment Visuo spatial abilities Language function Personality, behavior, or comportment NEW! NIA AA Criteria for AD Fulfills criteria for dementia Definite AD (characteristic presentation + wide spread neurofibrillary tangles and neuritic plaques) Probable AD (characteristic presentation, insidious onset, exclusion criteria) + biomarkers! Possible AD (sudden onset or etiologically mixed) + biomarkers! * Hallmark of pre 2011 criteria G.M. McKhann et al. / Alzheimer s & Dementia 7 (2011) 263 269 Biomarkers in AD Diagnosis Misfolded Proteins and Amyloid Fibrils in Neurodegenerative Disorders Atrophy CT, MRI, PET Glucose Metabolism PET Beta Amyloid CSF, PET Tau CSF Fronto Temporal Dementia (FTLD) (tau or TDP 43) Alzheimer Disease (AD) (Amyloid ß; tau) Parkinson Disease (PD, DLB) (α synuclein Lewy bodies) Prion Disease (CJD) (Prion deposits) Huntington Disease (HD) (Huntingtin deposits)) 5
Comparison of Clinical, Cognitive, Structural, Metabolic, and Biochemical Changes as a Function of Estimated Years from Expected Symptom Onset. (DIAN Study) Different Misfolded Proteins: Cerebrospinal fluid biomarkers Beta amyloid Phospho Tau Alpha Synuclein TDP 43 AD XXX XXX X DLB Behavior Aphasia Vascular XXX XX XXX Blood vessel problem; Not due to a misfolded protein Bateman RJ et al. N Engl J Med 2012;367:795-804. Different Cognitive Profiles Different Patterns of Atrophy & Glucose Hypometabolism Attention Memory Language Visual Spatial Executive Behavior Frontal Temporal Parietal AD XXX XX XX XX XX DLB XXX XXX AD XX Medial XX temporal DLB X X X Behavior XXX Aphasia Vascular X X X XX XXX Behavior Aphasia XX Right Anterior Temporal Left Anterior Temporal spared spared Vascular X X X 6
MRI Progressive atrophy of Hippocampii in AD (Scheltens et al. 1992) Frontotemporal Lobar Degeneration (FTLD) Behavioral Variant Language Variant Primary Progressive Aphasia 0 1 2 Semantic Type 3 4 Agrammatic (non fluent) type Boxer, Alzheimer Dis Assoc Disord. 2005 Oct Dec;19 Suppl 1:S3 6 Different Patterns of Glucose Hypometabolism Imaging AD Amyloid during life with Pittsburgh Compound B (PIB) Control AD FTLD Jagust, W. et al. Neurology 2007;69:871 877 Klunk W. Ann Neurol 2004; 55: 306 319. 7
In vivo PET Amyloid imaging in aging and dementia using 11 C Pittsburgh Imaging B (PIB) compound NIA-AA Criteria: Two Categories of Biomarkers. 1. Amyloid beta protein deposition: Low CSF amyloid β Positive PET amyloid imaging 2. Neuronal degeneration or injury: High CSF tau (total and phos ) Hippocampal atrophy on MRI FDG hypometabolism Masdeu J, Continuum 2008; 14: 144-163. NIA Alzheimer s Association Criteria CONCLUSION Significant advances in: underlying biology preclinical diagnosis clinical diagnosis Awaiting disease modifying treatment G.M. McKhann et al. / Alzheimer s & Dementia 7 (2011) 263 269 8
Alzheimers disease burdens an increasing number of our nation s elder and their families, and it is essential that we confront the challenge it poses to our public health. President Barak Obama Presidential Proclamation, National AD Awareness Month, 2011 9