Sandra Weintraub, Ph.D. Cognitive Neurology and Alzheimer s Disease Center Northwestern University, Feinberg School of Medicine Chicago, Illinois
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1 Sandra Weintraub, Ph.D. Cognitive Neurology and Alzheimer s Disease Center Northwestern University, Feinberg School of Medicine Chicago, Illinois
2 Presenter Disclosure Information Employee of: Author of: Consultant for: Stockholder in: Member: Research support: Honoraria from: Copyrights (NU): Northwestern University Boston Naming Test, 1973, 1984 (no royalties) None None Alzheimer s Association Scientific Program Committee NIA, NIDCD, NINDS None Northwestern Naming Battery, Northwestern Anagram Test
3 PART 1: What is Dementia? What is PPA? PART 2: How is PPA diagnosed? What characterizes its subtypes? PART 3: Testing for Language and Non Language deficits in PPA
4 PART 1: What is Dementia? What is PPA?
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6 CNADC WHAT CAUSES A DEMENTIA SYNDROME? ACUTE ONSET GRADUAL ONSET, PROGRESSION Metabolic Vascular Toxic Infectious Epileptic Paraneoplastic Tumor Hydrocephalus Vascular Neurodegenerative Non Alzheimer Diffuse Lewy Body FTLD Prion Other Alzheimer Disease Tauopathies TDP-43proteinopathy FUS
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8 CNADC TYPES OF NEUROPATHOLOGY ASSOCIATED WITH DEMENTIA Frontotemporal Lobar Degeneration With TDP-43 Proteinopathy Frontotemporal Lobar Degeneration With Tau Inclusions - e.g. Pick s disease Frontotemporal Lobar Degeneration With FUS Inclusions Plaques and Tangles- Alzheimer s Disease NORMAL BRAIN TISSUE Cortical Lewy Body Disease Courtesy Eileen Bigio MD NORTHWESTERN CNADC
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11 Clinical Dementia Diagnosis Dementia of the Alzheimer Type Posterior Cortical Atrophy Behavioral Variant Frontotemporal Dementia Dementia with Lewy Bodies Corticobasal degeneration Progressive supranuclear palsy Vascular Dementia Creutzfeldt-Jakob Disease Salient Clinical Features Memory loss aka amnesia Visuospatial deficits Social cognition, personality changes Hallucinations, delusions, parkinsonism Asymmetric motor findings Gaze paralysis Mixed deficits Rapid, focal deficits
12 CNADC 3 LEVELS OF CHARACTERIZING DEMENTIA DUE TO NEURODEGENERATIVE BRAIN DISEASE CLINICAL = SYMPTOMS NEUROANATOMICAL SIGNATURE = LOCATION NEUROPATHOLOGIC = TISSUE DISEASE
13 CNADC DEMENTIA= SYMPTOMS EARLY NEUROPSYCHOLOGICAL DEMENTIA PROFILE: APHASIA AKA Primary Progressive Aphasia NEUROANATOMY= REGIONS OF ATROPHY, DYSFUNCTION 30-40% AD Neuropathology 1-2% OTHER CJD, Cortical Lewy Body NEUROPATHOLOGY= UNDER THE MICROSCOPE 60-70% FTLD Neuropathology
14 DEMENTIA= SYMPTOMS EARLY NEUROPSYCHOLOGICAL DEMENTIA PROFILE: AMNESIA aka Dementia of the AD type NEUROANATOMY= REGIONS OF ATROPHY, DYSFUNCTION 85% AD Neuropathology 5-10% OTHER Cortical Lewy Body NEUROPATHOLOGY = UNDER THE MICROSCOPE 5-10-% FTLD Neuropathology
15 PART 2: How is PPA diagnosed? What characterizes its subtypes?
16 Neurological examination: Rate of onset, other localizing symptoms; other illness. Etiologystroke vs neurodegenerative vs tumor vs other? Are there sensorimotor deficits? Neuroimaging: Rule out other diseases. Evidence of asymmetric atrophy or metabolic activity? Neuropsychological examination: Profile: Language domain impairment, no other cognitive and behavioral deficits. No episodic memory loss; preserved ADL
17 CNADC Classification Of Primary Progressive Aphasia and Its Variants Gorno-Tempini, Hillis, Weintraub, et al, Neurology, 2011 Consensus guidelines for unifying classification of PPA and its three variants, Agrammatic (PPA-G), Semantic (PPA-S) and Logopenic (PPA-L) 1. Clearly delimits clinical diagnosis from sources of supporting evidence and etiology (i.e., neuroimaging, neuropathology) 2. Detailed clinical descriptors 3. Adds to clinical features increased certainty with presence of Supportive Neuroimaging 2. Adds to clinical features increased certainty with presence of Supportive Neuropathology 2. Systematic data collection
18 ROOT DIAGNOSIS OF PRIMARY PROGRESSIVE APHASIA Mesulam 2003; Gorno-Tempini et al, 2011 INSIDIOUS ONSET AND PROGRESSION OF SYMPTOMS: 1. Language deficits are most prominent feature of the examination: word-finding pauses, paraphasias, agrammatism, comprehension, reading, etc. 2. Aphasia is the identifiable and principal cause of impairment in ADL, which are otherwise normal. 3. Aphasia is the sole (or most prominent) deficit at onset and for the initial stages of disease.
19 CNADC ROOT DIAGNOSIS OF PRIMARY PROGRESSIVE APHASIA Mesulam 2003; Gorno-Tempini et al, 2011 EXCLUSIONARY CRITERIA 1. Other diseases can account for the symptoms: stroke, tumor 2. Psychiatric diagnosis accounts for the symptoms 3. Predominant initial episodic memory (visual and verbal), visuospatial/perceptual, and/or executive function deficits 4. Prominent initial behavioral disturbances (e.g., disinhibition, emotional detachment, hyperorality, compulsive behaviors; personality change)
20 CLINICAL DIAGNOSTIC CRITERIA FOR PPA-G: NONFLUENT/AGRAMMATIC SUBTYPE At least one of the following core features must be present: 1. Agrammatism in language production 2. Effortful, halting speech with inconsistent speech sound errors and distortions (apraxia of speech) At least 2 of 3 of the following other features must be present: 1. Impaired comprehension of syntactically complex sentences 2. Spared single-word comprehension 3. Spared object knowledge Gorno-Tempini, Hillis, Weintraub, et al, Neurology, 2011
21 CLINICAL DIAGNOSTIC CRITERIA FOR PPA-S: SEMANTIC SUBTYPE Both of the following core features must be present: 1. Impaired confrontation naming 2. Impaired single-word comprehension At least 3 of the following other diagnostic features must be present: 1. Impaired object knowledge, particularly for low frequency or lowfamiliarity items 2. Surface dyslexia or dysgraphia 3. Spared repetition 4. Spared speech production (grammar and motor speech) Gorno-Tempini, Hillis, Weintraub, et al, Neurology, 2011, Do not copy or distribute without permission
22 CLINICAL DIAGNOSTIC CRITERIA FOR PPA-L: LOGOPENIC SUBTYPE Both of the following core features must be present: 1. Impaired single-word retrieval in spontaneous speech and naming 2. Impaired repetition of sentences and phrases At least 3 of the following other features must be present: 1. Speech (phonologic) errors in spontaneous speech and naming 2. Spared single-word comprehension and object knowledge 3. Spared motor speech 4. Absence of frank agrammatism Gorno-Tempini, Hillis, Weintraub, et al, Neurology, 2011
23 PPA-Agrammatic PPA-Semantic PPA-Logopenic Mesulam, Wienecke, Rogalski, Cobia, Thompson, Weintraub, Arch Neurol 2009
24 Mesulam, Wienecke, Rogalski, Cobia, Thompson, Weintraub, Arch Neurol 2009
25 Rogalski E, Cobia D, Harrison TM, Wieneke C, Weintraub S, Mesulam M-M. Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia. Neurology, (21):
26 PART 3: Testing for Language and Non Language deficits in PPA
27 CNADC APHASIA ASSESSMENT IN PPA LANGUAGE COMPONENTS PHONOLOGY Sound Discrimination, Production SEMANTICS Single Word Comprehension, Naming GRAMMAR (SYNTAX, MORPHOLOGY) Production, Comprehension
28 CNADC APHASIA ASSESSMENT IN PPA: BATTERIES Western Aphasia Battery (WAB-R) Boston Diagnostic Aphasia Examination (BDAE) Psycholinguistic Assessment of Aphasia (PALPA) Speech Auditory Comprehension (words, sentences) Complex Commands Repetition (words, sentences) Naming Reading (oral, comprehension) Writing (spelling)
29 CNADC APHASIA ASSESSMENT IN PPA SPECIAL FOCUS BATTERIES Northwestern Naming Battery (NNB-R) (Thompson and Weintraub, 2012) Northwestern Assessment of Verbs and Sentences (NAVS) (Thompson, 2012) Northwestern Assessment of Verb Inflections (NAVI) (Thompson, experimental) Northwestern Anagram Test (NAT) (Thompson, Weintraub, Mesulam, 2012)
30 Profiles of language impairment in PPA can differ from those associated with classical aphasia syndromes.
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33 SPONTANEOUS SPEECH SAMPLE Picture Description Components: Articulation Flow (Words per minute) Word finding pauses Mean length of utterance Noun:Verb ratio Grammatical complexity (syntax and morphology)
34 Dissociations Between Fluency And Agrammatism In Primary Progressive Aphasia Thompson CK, Cho S, Hsu CJ, Wieneke C, Rademaker A, Weitner BB, Mesulam M-M, Weintraub S Aphasiology, 2012
35 NORTHWESTERN ANAGRAM TEST (NAT) Weintraub, Mesulam, Thompson, AJAD girl boy tickle the tickling boy girl the is
36 Weintraub et al, 2009
37 Northwestern Anagram Test, Do not copy or distribute without permission
38 CNADC Dissociations Between Fluency And Agrammatism In Primary Progressive Aphasia Thompson CK, Cho S, Hsu CJ, Wieneke C, Rademaker A, Weitner BB, Mesulam M-M, Weintraub S Aphasiology, 2012 Fluent Non Fluent =PPA-G; =PPA-L; =PPA-S
39 CNADC DISSOCIATION OF FLUENCY FROM GRAMMAR IN THE FRONTAL LOBES: NAT VS MLU MFG IFS IFGp IFGa FLUENCY AND GRAMMAR DO NOT ALWAYS GO TOGETHER IN PPA Rogalski et al, J Cog Neurosci, 2011
40 THE ANATOMY OF PRIMARY PROGRESSIVE APHASIA IFG pars opercularis pre- SMA/anterior cingulate lateral OFC anterior temporal lobe IFG pars orbitalis pre-sma/sfg anterior temporal lobe anterior temporal lobe pre-sma/sfg IFG pars operculari s IFG pars opercularis IFG pars orbitalis anterior temporal lobe anterior temporal lobe IFG pars orbitalis IFG pars orbitalis anterior temporal lobe Catani, et al., Brain, 2013 Figure courtesy of M. Catani
41 FRONTAL CNADC ASLANT DEGENERATION CORRELATES WITH VERBAL FLUENCY IMPAIRMENT BUT NOT AGRAMMATISM IN PPA pre-sma/sfg Catani, et al., Brain, 2013 Figure courtesy of M. Catani IFG pars orbitalis anterior temporal lobe Frontal Aslant Tract (FA) Pearsons=0.569 p=0.004 Frontal Aslant Tract (FA) Pearsons=0.598 p= Mean Length of Utterance Words Per Minute
42 CNADC NEUROPSYCHOLOGY OF PPA
43 The Neuropsychological Signature of Primary Progressive Aphasia Zakzanis, Brain and Language, 1999 ORDER OF SEVERITY OF IMPAIRMENTS BY DOMAIN (Most to Least) Verbal Skills Delayed Recall (Verbal) Cognitive Flexibility and Abstraction Memory Acquisition Attention/Concentration Performance Skill (Generally non verbal)
44 CHALLENGES FOR TESTING THE INTEGRITY OF NON LANGUAGE DOMAINS Tests Contain Complex Verbal Instructions: Block Designs, WCST, Picture Completion Tests Contain Verbal Stimuli: Word list memory, story recall, MMSE, Trail Making B Tests Require Spoken Output: Similarities, Arithmetic, Verbal Memory
45 RECOMMENDATIONS FOR TESTING NON LANGUAGE DOMAINS CHOOSE TESTS WITH MINIMAL VERBAL REQUIREMENTS IF WRITING IS BETTER THAN SPEECH- allow patient to respond in writing to test relevant construct (e.g. RAVLT) Memory: Rey-Osterrieth, WMS: Faces, Visual Reproduction Recognition, Design Memory; Warrington Recognition Memory Test, Brief Visuospatial Memory Test, Rivermeade Behavioral Memory Test, Three Words Three Shapes Test Reasoning: Visual-Verbal Test, WAIS Matrix Reasoning Visual Perception: Line Orientation, Facial Recognition, Do not copy or distribute without permission
46 DOMAIN-FOCUSED NEUROPSYCHOLOGICAL TESTS Visual Attention Object Knowledge Semantic Associates NNB Retentive Memory 3W3S Executive Reasoning Executive Attention Spatial Perception
47 How can episodic memory be tested in the aphasic patient? FOCUS ON THE DOMAIN OF INTEREST AND ELIMINATE INTERFERENCE FROM OTHER, IRRELEVANT TASK COMPONENTS (Kaplan Process Approach) 1. THREE WORDS THREE SHAPES (MEMORY) 2. VISUAL-VERBAL TEST (COGNITIVE FLEXIBILITY)
48 CNADC THREE WORDS THREE SHAPES MEMORY TEST (3W3S) Verbal and Nonverbal Material Both in Visual Modality CONDITION COPY INCIDENTAL RECALL COMPONENT TESTED Assures attention to stimuli, verifies writing and drawing ability impact on performance How much is remembered without forewarning? ACQUISITION TRIALS Re-expose stimuli on two learning trials (30 secs each) followed by immediate reproduction to assure encoding, level of criterion DELAYED RECALL MULTIPLE CHOICE PRIDE Retrieval/retention over time Recognition memory HUNGE STATION R Weintraub et al, 2003
49 CNADC THREE WORDS THREE SHAPES TEST- COPY Early Amnestic Dementia Dementia of the AD type
50 THREE WORDS THREE SHAPES TEST Incidental Recall Early Amnestic Dementia Dementia of the AD type Then, only 1 Acquisition Trial To Reach Criterion
51 THREE WORDS THREE SHAPES TEST 5 Minute Delayed Recall Early Amnestic Dementia - Probable AD
52 CNADC THREE WORDS THREE SHAPES TEST 30 minute Recall Early Amnestic Dementia Dementia of the AD type
53 CNADC THREE WORDS THREE SHAPES TEST - PPA Copy
54 3W 3S PPA Incidental Recall 15 minute Delay 30 min Delay
55 THREE WORDS THREE SHAPES TEST COPY DAT (Amnestic Dementia) Cognitively Normal Control W S W S W S W S 0 W S W S W S W S COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL PPA (Aphasic Dementia) W S W S W S W S COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL Weintraub et al, 2012
56 THREE WORDS THREE SHAPES TEST COPY DAT (Amnestic Dementia) Cognitively Normal Control W S W S W S W S 0 W S W S W S W S COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL PPA (Aphasic Dementia) W S W S W S W S COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL Weintraub et al, 2012
57 THREE WORDS THREE SHAPES TEST COPY DAT (Amnestic Dementia) Cognitively Normal Control W S W S W S W S 0 W S W S W S W S COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL PPA (Aphasic Dementia) W S W S W S W S COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL Weintraub et al, 2012
58 THREE WORDS THREE SHAPES TEST COPY DAT (Amnestic Dementia) Cognitively Normal Control W S W S W S W S 0 W S W S W S W S COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL RECOGNITION PPA: All words and shapes CNC: All words and shapes DAT: Poor both PPA (Aphasic Dementia) W S W S W S W S COPY INCIDENTAL EFFORTFUL ENCODING DELAYED RECALL Weintraub et al, 2012
59 Visual-Verbal Test (Feldman & Drasgow, 1959) SORT SHIFT SORT
60 S H I I F T S CNADC Wicklund, Johnson, Weintraub, 2004 NC ONC PPA PPA PRAD FTD * S O R T S NC ONC PPA PPA PRAD FTD *
61 CNADC ACTIVITIES OF DAILY LIVING QUESTIONNAIRE (ADLQ) Johnson, et al, ADAD, 2009 SEV MOD MILD Wicklund et al, ADAD, 2007
62 CNADC CONCLUSIONS 1. PPA is a dementia syndrome characterized by progressive language deficits and associated with 2. Structural and physiological dysfunction in the left hemisphere language network 3. Different subtypes are characterized by distinctive language deficits and neuroanatomical signatures 3. Several different neuropathologic diseases can cause PPA with FTLD most common and AD less common 4. Integrity of other cognitive functions and ADL can be shown with tests that circumvent the aphasia 5. Cognitive strengths can be used to plan interventions
63 Clinicians may view video case samples of PPA subtypes on this website but must first register
64 We need more SLP s across the country! If you have expertise working with patients with PPA and their caregivers and wish to be included in the CNADC referral list, please enter your information at:
65 Collaborators Eileen Bigio Derin Cobia Changiz Geula Marsel Mesulam Darby Morhardt Todd Parrish Ken Paller Emily Rogalski Cynthia Thompson Lei Wang Extramural Collaborators Kia Nobre (Oxford) Rik Vandenburghe(Leuven) Marco Catani (London) Students/Postdocs Adam Christensen Tamar Gefen Stephanie Kielb Amanda Cook Robert Hurley Daniel Ohm Social Work Staff Mary O Hara Clinical Core Mallory Swift Laura Martindale PPA Project Coordinator Christina Wieneke Technicians Amanda Rezutek Kristen Whitney Adam Martersteck Melanie Peterson Anne Koronkiewicz
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Presenter Disclosure Information. I have no financial relationships to disclose:
Sandra Weintraub, Ph.D. Cognitive Neurology and Alzheimer s Disease Center Northwestern University, Feinberg School of Medicine Chicago, Illinois http://www.brain.northwestern.edu/dementia/ppa/index.html
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