46. Posterior Cortical Atrophy
The visual variant of Alzheimer’s Disease
Josée Rivest, Ph.D., C.Psych.
Baycrest: Neuropsychology and Cognitive Health Program
York University: Psychology, Glendon College
Centre for Vision Research
October 6, 2014

47. Objectives Outline Learn what is Posterior Cortical Atrophy (PCA)
Establish parallels with the visual system
Compare PCA and AD
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

48. Visual System Dorsal and Ventral Streams Dorsal stream:
Modular organization
Dorsal and Ventral Streams
ACTION
Dorsal stream:
Where/How system
Motion
Form & Color
Ventral stream:
What system
RECOGNITION
Ungerleider, L.G., Mishkin, M. (1982). Two cortical visual systems.
Cambridge (MA): MIT Press p
Goodale, M.A., Milner, A.D. (1992). Separate visual pathways for perception and action.
Trends in Neurosciences. 15:20-25.

49. Dorsal Stream Ventral Stream
Spatial aspects (where)
Shape
Pattern
Texture
Color
“The visual brain in action”
(Miller & Goodale, 1995, 2006)
Vision for action
Egocentric coding
Transient representations
Independent of awareness
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),

50. Damaged Dorsal Stream
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

51. 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

52. Damaged Ventral Stream
Object agnosia
Prosopagnosia
Alexia
Achromatopsia

53. Neurodegenerative syndrome
Posterior Cortical Atrophy
Neurodegenerative syndrome
Termed in 1988 by Benson et al.
“Visual variant of AD; Biparietal AD; Benson syndrome”
Skills
Declined:
Preserved:
Visuo-spatial
Visuo-perceptual
Literacy
Praxic
Language
Memory
Insight
Non Verbal IQ < Verbal IQ
Benson, D.F., Davis, R.J. Snyder, B.D. (1988). Posterior Cortical Atrophy. Arch. Neurol., 45,

54. Posterior Cortical Atrophy
Clinical presentation
• Depressive symptoms:
tearfulness
sadness
insomnia
loss of weight
• Non-specific visual complaints:
Poor vision:
optometry, ophthalmology:
“nothing is wrong”

55. Posterior Cortical Atrophy
Neuropsychological features
• Visuo-spatial & visuo-perceptual impairments
• Alexia
• Bàlint’s syndrome: Simultagnosia
Oculomotor apraxia
Optic ataxia
• Gerstmann’s syndrome:
Acalculia
Agraphia
Finger agnosia
Left-right disorientation

56. Posterior Cortical Atrophy
Neuropsychological features
• Prosopagnosia
• Achromatopsia
• Visual field defects
• Hemineglect
• Constructional dyspraxia
• Apraxia
- dressing
- ideomotor: imitate hand gestures and voluntarily pantomime tool use
• Working memory

57. Posterior Cortical Atrophy
Epidemiology
Unknown: underestimation
• AD n=523  5% PCA (Snowden et al., 2007)
• No gender difference
• Age of onset: 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),

58. Alzheimer’s Disease • 60-80% of all dementia cases
• Age of onset: > 65 years
• Prevalence
• < 65  4% of population
•  6%
•  46%
**** > 65  13% ****
• Women > Men
The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040.

59. University Health Network Memory clinic
Posterior Cortical Atrophy
Pathologic heterogeneity
Dr. David Tang-Wai
University Health Network Memory clinic
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,

60. Posterior Cortical Atrophy
Atrophy or metabolic changes in the posterior regions:
Parietal, Occipital, & Occipito-temporal cortices
Prominent widening of the parietal and lateral occipital sulci
3D MRI reconstruction and selected coronal sections of the brain of a PCA patient
Tang-Wai, D.F. & Graff-Radford, N.R. (2011). Looking into posterior cortical atrophy. Providing insight into Alzheimer disease. Neurology, 76,

61. SPECT: 39 PCA, 24 AD & 24 controls
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, doi: /brain/awr055.

62. 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)

63. Posterior Cortical Atrophy
Different forms?
• 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,
Participants: N=20 PCA; n=20 matched controls
TASKS (basic visual functions):
Form detection
Form coherence
Form discrimination
Color discrimination
Motion coherence
Point localization
Related to:
• Recognition (ventral form)?
• Action/Space (dorsal form)?

64. Cortical thickness PCA > Controls Cortical thickness
Lehmann, et al. (2011)

65. 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)

66. 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)

67. Findings
Space subgroup  thinning in the occipital & inferior parietal lobes
Object subgroup  thinning in the fusiform gyrus & inferior temporal lobe
Object (ventral) vs. Space (dorsal)
Cortical thickness
Space > Object
Cortical thickness
Space < Object
BUT
NO significant difference  multiple common areas of tissue loss across the subgroups
Lehmann, et al. (2011)

68. Posterior Cortical Atrophy
Different forms?
• Basic visual processing (striate cortex; caudal) form?
— one dysfunction
• Ventral form
• Dorsal form
Continuous range of
object-space difference
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,

69. Case presentation: GB Medical history: • 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:
• Myelodysplasia (bone marrow malfunction
 insufficient number of normal blood cells)
• Arrhythmia
• Prostate cancer
• Pneumonia
• Hypercholesterolemia

70. GB Complaints (2010) • Reading** (even after cataract surgery)
• Word finding difficulties
Neurology
• Dr. Tang Way:
MRI ( ):
enlargement of cortical sulci and lateral ventricles
(cerebral atrophy)
Neuropsychology
• cognitive profile followed yearly since 2010
Reading described as: slow, effortful, inefficient, not automatic, still reads books but much slower and tiresome
Decrease of self confidence
Could write and speak

71. GB
2011

72. GB
2012

73. GB
2012

74. Kaplan–Baycrest Neurocognitive Assessment (KBNA)

75. Mean KBNA index scores of Group Dementia and Control expressed as (M = 50, SD = 10).
Mean KBNA index scores of Group Dementia and Control expressed as (M = 50, SD = 10). Error bars represent 95% confidence intervals. Abbreviations: AC = Attention/Concentration; MIR = Memory-Immediate Recall; MD = Memory-Delayed Recall; MDRec = Memory-Delayed Recognition; SP = Spatial Processing; VF = Verbal Fluency; RCS = Reasoning/Conceptual shifting; TI = Total Index.
Leach L Arch Clin Neuropsychol 2010;25:
© The Author Published by Oxford University Press. All rights reserved. For permissions, please

76. Results GB: Cognitive Profile KBNA Verbal IQ Verbal memory
Verbal fluency
Non-Verbal IQ
Visual memory
June 2011

77. GB: Cognitive Profile
Results
June 2011
KBNA
December 2011

78. GB: very superior IQ (VIQ: 143; PIQ: 120)
Consistent with IQ
Average
Low average; Borderline
Executive functions
• Concept formation/
Mental flexibility
• Alternating concepts
Attention
• Motor speed
• Auditory divided
• Visual automatic (accuracy)
• Auditory selective
• Visual controlled (accuracy)
• Speed of visual attention
Learning & Memory
• Verbal memory
• Visual memory
• Visuo-motor working memory
Not deep alexia: better reading of content words (e.g. nouns & verbs) than functors (e.g. prepositions): Grammatical class reading from PALPA – missed 3 nouns and 2 verbs – thus not deep alexia
Language functions
• Speech
• Auditory comprehension
• Written expression
• Naming to visual confrontation
• Reading
(letter-by-letter reader)

79. December 2011

80. Immediate recall
December 2011

81. GB: Visuo-Perceptual Assessment
Normal
Lower than expected  Impaired
• Visuo-constructional abilities (slow)
• Reading (letter-by-letter)
• Finger localization
• Face matching (slow)
• Praxis & Reaching
• Picture naming (black & white drawings)
• Stereopsis
• Recognition of silhouettes
• Judgment of line orientation
• Object decision
• No sensory extinction
• Visual puzzles
• Space perception
• Visual search & scanning
slow & found more objects on the left side
• Writing
Not deep alexia: better reading of content words (e.g. nouns & verbs) than functors (e.g. prepositions): Grammatical class reading from PALPA – missed 3 nouns and 2 verbs – thus not deep alexia
• Object recognition
• Foreshortened match
(canonical vs. non canonical/ another object)
• Item match (leaf vs. leaf/flower)
• Association match
(car vs. road/train track)
• Copy

82. X √ Birmingham Object Recognition Battery (BORB) Foreshortened match
Object decision

83. Hooper Visual Organization TestX
Visual Puzzles

84. Visual Object and Space Perception Battery (VOSP)√ X X X

85. Visual Object and Space Perception Battery (VOSP)√ √ √ √

86. Benton Face Recognition Test√ X

87.  2013 GB: 2010  2011  2012 No difference Decline
• Cognitive flexibility
• Processing speed
• Perceptual reasoning
• Visual scanning & attention
• Verbal memory
• Focused attention: slower
• Visuo-constructional abilities
• Reading
• Spoken language
• Face matching: slower & more hesitant
• Praxis
• Object recognition
Not deep alexia: better reading of content words (e.g. nouns & verbs) than functors (e.g. prepositions): Grammatical class reading from PALPA – missed 3 nouns and 2 verbs – thus not deep alexia
• Verbal fluency
• Working memory
• Visual memory

88. KBNA

89. Now…
Boston Naming Test X

90. June Assessment
Verbal reasoning – WASI:Similarities
Working memory – WAIS: Digit Span
-- Arithmetic (oral)
Attention/ Concentration
VERBAL MEMORY
Verbal Learning
Delayed Verbal Recall
Delayed Verbal Recognition
Language –Auditory Comprehension & Repetition
Praxis (Transitive, Intransitive & Buccofacial)  
Practical Reasoning
Expression of emotions

91. June 2014 —RESULTS Verbal reasoning – WASI:Similarities DECLINE:
Working memory – WAIS: Digit Span
-- Arithmetic
Attention/ Concentration:
Disorientated to the year, month, day & time
VERBAL MEMORY
Verbal Learning
Delayed 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

92. KBNA
2014

93. Posterior Cortical Atrophy
Review Article
Crutch, S.J., Lehmann, M.S., Rabinovici, G. D., Rossor, M.N., & Fox, N.C. (2012). Posterior Cortical Atrophy. Lancet Neurology, 11,
Borruat, F.-X. (2013). Posterior Cortical Atrophy: Review of the Recent Literature. Curr. Neurol. Neurosci. Rep., , 2-8.

94. Thank you
Dr. Dmytro Rewilak
Dr. Kathy Stokes

96. 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

97. 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

98. Supportive features: Investigations: 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

100. December 2011

101. 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

102. 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

103. Primary Visual subgroup
Less frequent
Affects primary visual cortex
Reflected in impairment of basic perceptual abilities, restricted visual fields

104. GB: Visuo-Perceptual assessment
Normal
Impaired
Object processing (recognition & matching)
Birmingham Object Recognition Battery (BORB)
• Picture naming (animate drawings)
• Picture naming (inanimate drawings)
• Foreshortened match (canonical vs. non canonical/ another object)
• Object decision
• Item match (leaf vs. leaf/flower)
• Association match
(car vs. road/train track)
• Copy
Not deep alexia: better reading of content words (e.g. nouns & verbs) than functors (e.g. prepositions): Grammatical class reading from PALPA – missed 3 nouns and 2 verbs – thus not deep alexia
Visual Object and Space Perception Battery (VOSP)
• Shape detection
• Incomplete letters
• Silhouettes
• Object decision
• Hooper Visual Organization Test

105. Cortical thickness
PCA (n=48)
tAD (n=30)
PCA:
• Greater density of senile plaques & neurofibrillary tangles in occipital, posterior parietal, & temporo-occipital cortex
• Fewer pathological changes in more anterior areas such as
prefrontal cortex
Cortical thickness
PCA > tAD
Cortical thickness
PCA < tAD
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: /j.neurobiolaging

106. Expectations
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)

107. Immediate recall
June 2011

108. June 2011