Posterior Cortical Atrophy Josée Rivest, Ph.D., C.Psych. Baycrest: Neuropsychology and Cognitive Health Program York University: Psychology, Glendon College Centre for Vision Research October 6, 2014 The visual variant of Alzheimer’s Disease
Dec 18, 2015
Posterior Cortical Atrophy
Josée Rivest, Ph.D., C.Psych.
Baycrest: Neuropsychology and Cognitive Health Program
York University: Psychology, Glendon College Centre for Vision Research
October 6, 2014
The visual variant of Alzheimer’s Disease
Outline• Review —The Visual System: Anatomy & Cognitive Deficits
• Posterior Cortical Atrophy: Syndrome
• Parallel with the anatomy of the visual system• Case presentation: Data over 4 years
Objectives
• Learn what is Posterior Cortical Atrophy (PCA)• Establish parallels with the visual system • Compare PCA and AD
Dorsal and Ventral Streams
Motion
Form & Color
Ungerleider, L.G., Mishkin, M. (1982). Two cortical visual systems. Cambridge (MA): MIT Press p. 549-586.
Goodale, M.A., Milner, A.D. (1992). Separate visual pathways for perception and action. Trends in Neurosciences. 15:20-25.
Dorsal stream:Where/How system
Ventral stream:What system
ACTION
Modular organizationVisual System
RECOGNITION
Ventral Stream
• Shape• Pattern• Texture• Color
• Vision for perception (recognition)
• Allocentric coding• Sustained representations• Critically linked to awareness
Schenk, T., & Mcintosh, R. D. (2010). Discussion Paper: Do we have independent visual streams for perception and action? Cognitive Neuroscience, 1(1), 52-78.
• Spatial aspects (where)
Dorsal Stream
“The visual brain in action”
(Miller & Goodale, 1995, 2006)
• Vision for action• Egocentric coding• Transient representations• Independent of awareness
• Visual neglect• Visuo-motor impairment (optic ataxia)• Extinction• Simultagnosia• Apraxia• Akineotopsia (motion blindness)• Spatial dysperception (e.g. depth, length, size)• Hand-eye incoordination• Finger agnosia• Right-left confusion• Dysgraphia/agraphia: writing• Dyscalculia/acalculia: math
Damaged Dorsal Stream
Damaged Dorsal Stream
Bálint syndrome • Ocular apraxia: Inability to voluntarily look around in space • Optic ataxia: Inability to reach for an object under visual guidance• Simultagnosia
Gerstmann syndrome• Agraphia• Acalculia• Finger agnosia• Left-right disorientation
• Object agnosia • Prosopagnosia • Alexia• Achromatopsia
Damaged Ventral Stream
Declined:
Neurodegenerative syndromeTermed in 1988 by Benson et al.
Posterior Cortical Atrophy
Visuo-spatial Visuo-perceptualLiteracyPraxic
Skills
LanguageMemoryInsight
Benson, D.F., Davis, R.J. Snyder, B.D. (1988). Posterior Cortical Atrophy. Arch. Neurol., 45, 789-793.
Preserved:
“Visual variant of AD; Biparietal AD; Benson syndrome”
Non Verbal IQ < Verbal IQ
Clinical presentation
Posterior Cortical Atrophy
• Depressive symptoms: tearfulness sadness insomnia loss of weight
• Non-specific visual complaints: Poor vision:
optometry, ophthalmology: “nothing is wrong”
• Visuo-spatial & visuo-perceptual impairments
Neuropsychological features
Posterior Cortical Atrophy
• Alexia
• Bàlint’s syndrome: Simultagnosia
Oculomotor apraxiaOptic ataxia
• Gerstmann’s syndrome: AcalculiaAgraphiaFinger agnosiaLeft-right disorientation
• Prosopagnosia
Neuropsychological features
Posterior Cortical Atrophy
• Achromatopsia
• Visual field defects
• Hemineglect
• Constructional dyspraxia
• Apraxia - dressing
- ideomotor: imitate hand gestures and voluntarily pantomime tool use
• Working memory
Posterior Cortical Atrophy
• Age of onset: 50-65 years
Snowden, J.S., Stopford, C.L., Julien, C.L. et al. (2007). Cognitive phenotypes in Alzheimer's disease and genetic risk. Cortex, 43(7), 835-845.
Epidemiology
Unknown: underestimation
• AD n=523 5% PCA (Snowden et al., 2007)
• No gender difference
Alzheimer’s Disease
• Age of onset: > 65 years
• 60-80% of all dementia cases
• Prevalence• < 65 4% of population• 65-74 6%• 85 + 46%
**** > 65 13% ****
• Women > Men
Pathologic heterogeneity
Posterior Cortical Atrophy
Dr. David Tang-WaiUniversity Health Network Memory clinic
Tang-Wai, D.F. & Graff-Radford, N.R. (2011). Looking into posterior cortical atrophy. Providing insight into Alzheimer disease. Neurology, 76, 1778-1779.
Causes: • Alzheimer’s disease: senile plaques & neurofibrillary tangles
• Dementia with Lewy bodies • Corticobasal degeneration • Prion disease (Creutzfeldt-Jacob disease
& Fatal-familial insomnia –transmissible spongiform
encephalopathies)
Tang-Wai, D.F. & Graff-Radford, N.R. (2011). Looking into posterior cortical atrophy. Providing insight into Alzheimer disease. Neurology, 76, 1778-1779.
Posterior Cortical Atrophy
Parietal, Occipital, & Occipito-temporal cortices
Atrophy or metabolic changes in the posterior regions:
3D MRI reconstruction and selected coronal sections of the brain of a PCA patient
Prominent widening of the parietal and lateral occipital sulci
PCA: Extensive & symmetrical hypoperfusion in the occipital, parietal & posterior temporal cortices
AD: Hypoperfusion in posterior associative cortex, prefrontal cortex & bilateral hippocampus
Kas, A., de Souza, L. C., Samri, D., Bartolomeo, P., Lacomblez, L., et al. (2011). Neural correlates of cognitive impairment in posterior cortical atrophy. Brain, 134, 1465-1478. doi: 10.1093/brain/awr055.
SPECT: 39 PCA, 24 AD & 24 controls
PCA: more hypoperfusion in the parieto-occipital cortex (blue)More higher perfusion in the frontal, anterior cingulate, inferior & medial temporal regions (red) than AD
Kas et al. (2011)
Different forms? Posterior Cortical Atrophy
Participants: N=20 PCA; n=20 matched controls
TASKS (basic visual functions):Form detectionForm coherence Form discriminationColor discriminationMotion coherencePoint localization
• Basic visual processing (striate cortex; caudal) form • Ventral form• Dorsal form
Lehmann, M., Barnes, J. Ridgway, G.R., Wattam-Bell, J., Warrington, E.K., Fox, N.C. & Crutch, S. J. (2011). Basic visual function and cortical thickness patterns
in posterior cortical atrophy. Cerebral Cortex, 21, 2122-2132.
Related to:
• Recognition (ventral form)?• Action/Space (dorsal form)?
Cortical thickness PCA < Controls
Cortical thickness PCA > Controls
Lehmann, et al. (2011)
Findings
1. Each PCA participant impaired on at least one basic visual processing task
2. Heterogeneity within the basic visual processing capacities
3. Type of basic visual processing dysfunction:• Impact upon the nature of their higher-order visual dysfunctions:
—form detection, form coherence, & color performance object and space perception
—form detection object but not space perception—point localization space but not object perception
• No impact upon nonvisual parietal functions (e.g. calculation & spelling)• No correlation with recognition memory, MMSE, or disease duration
Lehmann, et al. (2011)
ANATOMY
Space subgroup greater posterior parietal cortical thinning? Object subgroup greater inferior temporal cortical thinning?
Space (dorsal) PCA vs. Controls Object (ventral) PCA vs. Controls
Cortical thickness PCA < Controls
Cortical thickness PCA > Controls
Lehmann, et al. (2011)
Object (ventral) vs. Space (dorsal)
Cortical thickness Space < Object
Cortical thickness Space > Object
Space subgroup thinning in the occipital & inferior parietal lobesObject subgroup thinning in the fusiform gyrus & inferior temporal lobe
BUT NO significant difference multiple common areas of tissue loss across the subgroups
Findings
Lehmann, et al. (2011)
Different forms?
Posterior Cortical Atrophy
Lehmann, M., Barnes, J. Ridgway, G.R., Wattam-Bell, J., Warrington, E.K., Fox, N.C. & Crutch, S. J. (2011). Basic visual function and cortical thickness patterns in posterior cortical atrophy. Cerebral Cortex, 21, 2122-2132.
• Basic visual processing (striate cortex; caudal) form? — one dysfunction
• Ventral form• Dorsal form
Continuous range of object-space difference
• Myelodysplasia (bone marrow malfunction insufficient
number of normal blood cells)
• Arrhythmia• Prostate cancer• Pneumonia• Hypercholesterolemia
Case presentation: GB• 79 year old man• Born in New Zealand• Immigrated in Canada in 1962; Specialized MD (retired)• Lives with his wife & has 2 healthy children• Red/green color deficiency• Hobbies: reading, music, theatre, golf
Medical history:
GB
Neuropsychology• cognitive profile followed yearly since 2010
Complaints (2010) • Reading** (even after cataract surgery)
• Word finding difficulties
Neurology • Dr. Tang Way:
MRI (2010-2011): enlargement of cortical sulci and lateral
ventricles (cerebral atrophy)
2011
GB
2012GB
2012GB
Kaplan–Baycrest Neurocognitive Assessment (KBNA)
Mean KBNA index scores of Group Dementia and Control expressed as (M = 50, SD = 10).
Leach L Arch Clin Neuropsychol 2010;25:359-370
© The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].
Results
Seq
SpLocW
L1CF1
WL2
CF2
WLRec
CFRec
VisSp
PhF
SemF
PReas
Vocab
Simi
Blk D
es
Mat
Rea
sBNT
TMTA
TMTB
LMI
LMII
DigSpn
0
2
4
6
8
10
12
14
16
18
20
KBNA & WASI Subtest Scores
Ag
e C
orr
ec
ted
Sc
ale
d S
co
res
GB: Cognitive Profile
Verbal IQ
Non-Verbal IQ
June 2011
KBNA
Visual memory
Verbal fluency
Verbalmemory
Results
Seq
SpLocW
L1CF1
WL2
CF2
WLRec
CFRec
VisSp
PhF
SemF
PReas
Vocab
Simi
Blk D
es
Mat
Rea
sBNT
TMTA
TMTB
LMI
LMII
DigSpn
0
2
4
6
8
10
12
14
16
18
20
KBNA & WASI Subtest Scores
Ag
e C
orr
ec
ted
Sc
ale
d S
co
res
KBNAJune 2011
December 2011
GB: Cognitive Profile
GB: very superior IQ (VIQ: 143; PIQ: 120)Consistent with IQ Low average; BorderlineAverage
• Verbal memory
• Naming to visual confrontation
• Concept formation/Mental flexibility
• Visuo-motor working memory
• Speed of visual attention
• Reading (letter-by-letter reader)
• Visual controlled (accuracy)
• Auditory divided• Motor speed
• Alternating concepts
Executive functions
Attention
Learning & Memory
• Visual automatic (accuracy)
• Visual memory
Language functions
• Auditory selective
• Speech• Auditory comprehension • Written expression
December 2011
December 2011
Immediate recall
GB: Visuo-Perceptual Assessment
Normal
• Finger localization
• Visuo-constructional abilities (slow)
• Praxis & Reaching
• Stereopsis
• Judgment of line orientation
• No sensory extinction
• Visual search & scanning slow & found more objects on the left side
• Writing
• Reading (letter-by-letter)
• Space perception
• Face matching (slow)
• Picture naming (black & white drawings)
• Object decision
• Visual puzzles
• Recognition of silhouettes
• Item match (leaf vs. leaf/flower)
• Copy
• Foreshortened match (canonical vs. non canonical/ another object)
• Association match (car vs. road/train track)
• Object recognition
Lower than expected Impaired
Birmingham Object Recognition Battery (BORB)
Foreshortened match
Object decisionX√
Hooper Visual Organization Test
Visual Puzzles
X
Visual Object and Space Perception Battery (VOSP)
X
XX
√
Visual Object and Space Perception Battery (VOSP)
√ √
√ √
Benton Face Recognition Test
√X
GB: 2010 2011 2012No difference Decline
• Focused attention: slower
• Perceptual reasoning • Visual scanning & attention
• Visuo-constructional abilities
• Processing speed
• Verbal memory
• Spoken language
• Reading
• Face matching: slower & more hesitant
• Verbal fluency
• Praxis
• Cognitive flexibility
• Object recognition
• Working memory
• Visual memory
2013
KBNA
2011 2012 20130
5
10
15
20
25
30
35
40
45
Verbal Memory
Visual Memory
Verbal Flexibility
Overall Cognitive Skills
Spatio-Temporal Flexibility
Su
m o
f S
cale
d S
core
s
Boston Naming Test
Now…
X
June 2014 --Assessment
Verbal reasoning – WASI:Similarities Working memory – WAIS: Digit Span
-- Arithmetic (oral)
Attention/ Concentration VERBAL MEMORY
Verbal LearningDelayed Verbal Recall
Delayed Verbal Recognition
Language –Auditory Comprehension & Repetition
Praxis (Transitive, Intransitive & Buccofacial) Practical Reasoning Expression of emotions
June 2014 —RESULTS
Verbal reasoning – WASI:Similarities Working memory – WAIS: Digit Span
-- Arithmetic
Attention/ Concentration: Disorientated to the year,
month, day & time VERBAL MEMORY
Verbal LearningDelayed Verbal Recall
Delayed Verbal Recognition Average-High Average Language –Auditory Comprehension & Repetition
Praxis (Transitive, Intransitive & Buccofacial) Practical Reasoning Expression of emotions
DECLINE: borderline/impaired
Unchanged
KBNA
2011 2012 20130
5
10
15
20
25
30
35
40
45
Verbal Memory
Visual Memory
Verbal Flexibility
Overall Cognitive Skills
Spatio-Temporal Flexibility
Su
m o
f S
cale
d S
core
s
2014
Review Article
Posterior Cortical Atrophy
Crutch, S.J., Lehmann, M.S., Rabinovici, G. D., Rossor, M.N., & Fox, N.C. (2012). Posterior Cortical Atrophy. Lancet Neurology, 11, 170-178.
Borruat, F.-X. (2013). Posterior Cortical Atrophy: Review of the Recent Literature. Curr. Neurol. Neurosci. Rep., 13-406, 2-8.
Thank youDr. Dmytro Rewilak Dr. Kathy Stokes
• Tang-Wai & Petersen (amongst others) in 2006 recommended the following as diagnostic criteria:
• Core:– Insidious onset and gradual progression– Presentation of visual complaints in absence of
significant primary ocular disease– Disabling visual impairment throughout disorder– Absence of stroke or tumour– Absence of early parkinsonism and hallucinations
– Any of the following:• Simultanagnosia (with or without optic ataxia or
ocular apraxia)• Constructional dyspraxia• Visual field defect• Environmental disorientation• Any of the elements of Gerstmann syndrome
• Supportive features:– Alexia– Presenile onset– Ideomotor or dressing apraxia– Prosopagnosia
• Investigations:– Neuropsychological deficits due to parietal and/or
occipital involvement– Focal or asymmetric atrophy in parietal and/or occipital
regions on structural imaging– Focal or asymmetric hypoperfusion/ hypo-metabolism
in parietal and/or occipital regions on functional imaging
December 2011
• Occipitotemporal (Ventral) subgroup– Manifest either impairments in basic visual
abilities (primary visual cortex involved), or– Disruption of ventral stream of higher order
visual processing, vital for object, face and written word identification
– Symptoms/findings of object agnosia, alexia, Gerstmann’s syndrome (agraphia, acalculia, R-L confusion, finger agnosia), simultanagnosia, possibly impaired colour vision and stereopsis, visual extinction, restricted visual fields
• Bi-parietal (Dorsal) subgroup– Typically have intact visual fields, basic
perceptual abilities, object recognition and reading
– Disruption of dorsal stream of visuomotor processing critical for object location and visually guided movements
– Reflects also damage to parietal areas involved with general motor programming and writing
– Symptoms/findings of Balint’s syndrome, visuospatial difficulty, agraphia and dyspraxia
• Primary Visual subgroup– Less frequent– Affects primary visual cortex– Reflected in impairment of basic perceptual
abilities, restricted visual fields
GB: Visuo-Perceptual assessmentNormal Impaired
Object processing (recognition & matching)
• Hooper Visual Organization Test
• Picture naming (animate drawings)
• Object decision
• Item match (leaf vs. leaf/flower)
• Copy
• Picture naming (inanimate drawings)
• Foreshortened match (canonical vs. non canonical/ another object)
Birmingham Object Recognition Battery (BORB)
• Association match (car vs. road/train track)
• Shape detection• Incomplete letters
• Silhouettes• Object decision
Visual Object and Space Perception Battery (VOSP)
Lehmann M, Crutch SJ, Ridgway GR et al. (2009). Cortical thickness and voxel-based morphometry in posterior cortical atrophy and typical Alzheimer's disease. Neurobiology of Aging. doi:10.1016/j.neurobiolaging.2009.08.017.
Cortical thickness PCA (n=48)tAD (n=30)
Cortical thickness PCA < tAD
Cortical thickness PCA > tAD
PCA: • Greater density of senile plaques & neurofibrillary tangles in occipital, posterior parietal, & temporo-occipital cortex
• Fewer pathological changes in more anterior areas such asprefrontal cortex
Lehmann, et al. (2011)
ExpectationsSpace subgroup greater posterior parietal cortical thinning Object subgroup greater inferior temporal cortical thinning
Cortical thickness PCA < Controls
Cortical thickness PCA > Controls
Space (dorsal) PCA vs. Controls Object (ventral) PCA vs. Controls
June 2011
Immediate recall
June 2011