Presentation from the International Congress of the Royal College of Psychiatrists 24-27 June 2014, London

2. Cognitive assessment, brain
networks and the dementias
Professor Adam Zeman
University of Exeter Medical School

3. Cognition, networks, dementias
• What is dementia?
• Dementia vs delirium
• Cortical vs subcortical dementia
• Cognitive
– Domains
– Networks
– Assessment
– Dementias
• The ACE-R/ACE-III

4. What is dementia?
• A disorder of two or more domains of cognition:
– memory
– language
– visuoperceptual ability
– Praxis
– abstract thinking and judgement
– personality
– social conduct
• Not primarily due to disordered attention
• Substantially impacting everyday life

5. Delirium vs dementia
FEATURE DELIRIUM DEMENTIA
Onset abrupt/sub-acute insidious
Course fluctuating slow progression
Duration hours-weeks months-years
Alertness abnorm high or low typically normal
Sleep-wake disrupted typically normal
Attention impaired relatively normal
Orientation impaired intact in early dement.
Working mem impaired intact in early dement.
Episodic mem impaired impaired
Thought disorganised, delus. impoverished
Speech slow/rapid, incoh. word-finding difficulty
Perception illusn/halln common us. intact in early dem.
Behaviour withdrawn/agitated varies: oft. intact early

6. Cortical vs subcortical dementia
FUNCTION CORTICAL SUBCORTICAL
eg AD eg MS
Alertness normal ‘slowed up’
Attention normal early impaired
Executive ftn normal early impaired
Episodic mem amnesia forgetfulness
language aphasic reduced output
Praxis apraxia relatively normal
Perception + vis/sp impaired impaired
Personality preserved (unless apathetic, inert
frontal type)

7. Causes of ‘dementia’
• Inherited HD, Wilson’s, leucodystrophies
• Primary degen Alzheimer’s, Cortical Lewy Body disease ,
Fronto-temporal dementia
• Vascular multi-infarct, subcortical, strategic infarction
• Infective HIV, TSE, HSE, Whipple’s, SSPE
• Inflammatory MS, vasculitis, Hashimoto’s
• Neoplastic 1o
/2o
CNS tumours, limbic encephalitis
• Traumatic Post head injury
• Structural hydrocephalus, chronic subdurals
• Metabol/endoc hypothyroidism
• Deficiency B12/folate
• Sleep-related OSA
• Substances/drugs alcohol, anticholinergics, hypnotics etc
• Psychiatric depression (pseudo-dementia)

8. Domains and disorders
• Domain
• Network
• Assessment
• Disorder

9. Domains
• Consciousness
• Attention
• Memory
• Executive function
• Language
• Perception
• Praxis

10. Domains
• Consciousness
• Attention
• Memory
• Executive function
• Language
• Perception
• Praxis

15. Daytime sleepiness:
Epworth Sleepiness Scale
– Sitting and reading
– Watching TV
– Sitting inactive in a public
place eg theatre, meeting
– Passenger in a car for an
hour
– Lying down to rest in the
afternoon
– Sitting and talking to
someone
– Sitting quietly after lunch
– In a car while stopped in
traffic
• 0 = would never dose
• 1 = slight chance of dosing
• 2 = moderate chance
• 3 = high chance

17. Domains
• Consciousness
• Attention
• Memory
• Executive function
• Language
• Perception
• Praxis

19. Assessing attention
• Sustained attention:
– Serial 7s
– WORLD backwards
– Months backwards

20. Disorders of attention
• Sustained attention
– Delirium/confusional states

22. Domains
• Consciousness
• Attention
• Memory
• Executive function
• Language
• Perception
• Praxis

24. Domains
• Consciousness
• Attention
• Memory
– episodic
• Executive function
• Language
• Perception
• Praxis

28. Memory Assessment
• Working (short term) memory
– Registration of 3 items or name
and address
• Long term (episodic) memory
– Recall of 3 items or name and
address after filled delay
• Long term (semantic memory)
– Naming, general knowledge

29. Alzheimer’s disease
• Episodic memory impairment -> widespread cognitive decline
• apathy, disinhibition, agitation; psychosis; mood disturbance
• slowly progressive: circa 3 point MMSE decline/year
• pyramidal, extrapyramidal signs; primitive reflexes; epilepsy
• neuritic plaques: Abeta amyloid derived from APP
• neurofibrillary tangles: hyperphosphorylated tau
• Cholinergic deficit
• <5% autosomal dominant: presenilin 1(14), 2(1), APP (21)
• Apolipoprotein E alleles 2, 3 and 4; Down’s syndrome; vascular risk
factors
• CT, MRI, SPECT, PET, amyloid imaging
• central Achase inhibitors; memantine

34. Domains
• Consciousness
• Attention
• Memory
– semantic
• Executive function
• Language
• Perception
• Praxis

36. Memory Assessment
• Working (short term) memory
– Registration of 3 items or name
and address
• Long term (episodic) memory
– Recall of 3 items or name and
address after filled delay
• Long term (semantic memory)
– Naming, general knowledge

40. Domains
• Consciousness
• Attention
• Memory
• Executive function
• Language
• Perception
• Praxis

41. Executive function
• Planning
• problem-solving
• initiation of action
• sequencing of action
• self-monitoring
• set-shifting
• social judgement
• empathy

45. Executive function: tests
• Verbal fluency: letter, category
• Luria three hand position test
• go - no go
• cognitive estimates

46. Frontotemporal dementia
• 10-15% dementia < 65 years, 25-50% familial
• Frontal lobe (behavioural) variant
– personality and behavioural change with loss of insight
• Temporal lobe variant
– L: semantic dementia
– R: recognition + knowledge of people
• Progressive non-fluent aphasia
• NB relative preservation of episodic memory
• Pathologies: tau +ve, tau -ve
• Imaging: focal atrophy

49. Domains
• Consciousness
• Attention
• Memory
• Executive function
• Language
• Perception
• Praxis

53. Classification of dysphasia
Type fluency Comprhn Reptn Naming
Global + + + +
Broca’s + - + +
Wernicke’ - + + +
Condn - - + +
Transc
mot
+ - - +
Transc
sens
- + - +

54. Frontotemporal dementia
• 10-15% dementia < 65 years, 25-50% familial
• Frontal lobe (behavioural) variant
– personality and behavioural change with loss of insight
• Temporal lobe variant
– L: semantic dementia
– R: recognition + knowledge of people
• Progressive non-fluent aphasia
• NB relative preservation of episodic memory
• Pathologies: tau +ve, tau -ve
• Imaging: focal atrophy

56. Domains
• Consciousness
• Attention
• Memory
• Executive function
• Language
• Perception
• Praxis

58. Testing visual perception
• Overlapping pentagons
• cube
• clock face
• Dot counting
• Fragmented letters
• Object recognition…

59. Posterior cortical atrophy - PCA
• Circa 5% AD cases have ‘visual presentation’
• Early onset, typically mid 50s-early 60s
• Mild female predominance
• Most common features are
– Alexia and agraphia
– Simultanagnosia
– Optic ataxia
• ‘dorsal stream’ symptoms and signs predominate but
both ventral and dorsal streams affected
• Relative preservation of memory, insight, language,
executive function

65. Atypical presentations of AD
• <10% AD
• Posterior cortical atrophy (PCA)
– Almost always due to AD
• Slowly progressive aphasia
– More varied pathology
– Usually non-fluent, occasionally fluent in AD
• Slowly progressive apraxia
• Dysexecutive or ‘behavioural’ presentation

66. MEMORY
Amnesia
EXECUTIVE FUNCTION
‘Frontal lobe
syndrome’
PRAXIS
Apraxia
PERCEPTUO-
SPATIAL FUNCTION
Agnosia
Spatial disorientation
LANGUAGE
Aphasia
Alexia
Agraphia
Acalculia
AROUSAL

67. Domains
• Consciousness
• Attention
• Memory
• Executive function
• Language
• Perception
• Praxis

69. Testing praxis
• Mimes
• Unfamiliar hand positions
• Look out for:
– utilisation behaviour
– imitation behaviour
– alien limb

70. PSP + CBD
• PSP
• supranuclear gaze palsy
• truncal rigidity, instability,
akinesia, falls
• bulbar features
• subcortical dementia
• mood, personality, behaviour
• neurofibrillary tangles (tau) in
basal ganglia and brain stem
• MRI: midbrain atrophy
• CBD
• asymmetric limb apraxia
• alien limb phenomena
• limb myoclonus
• Parkinsonism
• cognitive impairment
• neurofibrillary tangles (tau) in
frontal and parietal cortex and
basal ganglia
• MRI: frontoparietal atrophy

72. PSP

73. PSP

74. Cognition, networks, dementias
• What is dementia?
• Dementia vs delirium
• Cortical vs subcortical dementia
• Cognitive
– Domains
– Networks
– Assessment
– Dementias
• The ACE-R