Posterior Cortical Atrophy Josée Rivest, Ph.D., C.Psych. Baycrest : Neuropsychology and Cognitive...

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: journals.permissions@oxfordjournals.org.

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