Cognitive assessment, brain

networks and the dementias

Professor Adam Zeman

University of Exeter Medical School

Cognition, networks, dementias

• What is dementia?

• Dementia vs delirium

• Cortical vs subcortical dementia

• Cognitive

– Domains

– Networks

– Assessment

– Dementias

• The ACE-R/ACE-III

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

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Behaviour withdrawn/agitated varies: oft.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

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)

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/2

o 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)

Domains and disorders

• Domain

• Network

• Assessment

• Disorder

Domains

• Consciousness

• Attention

• Memory

• Executive function

• Language

• Perception

• Praxis

Domains

• Consciousness

• Attention

• Memory

• Executive function

• Language

• Perception

• Praxis

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

Domains

• Consciousness

• Attention

• Memory

• Executive function

• Language

• Perception

• Praxis

Assessing attention

• Sustained attention:

– Serial 7s

– WORLD backwards

– Months backwards

Disorders of attention

• Sustained attention

– Delirium/confusional states

Domains

• Consciousness

• Attention

• Memory

• Executive function

• Language

• Perception

• Praxis

Domains

• Consciousness

• Attention

• Memory

– episodic

• Executive function

• Language

• Perception

• Praxis

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

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

Domains

• Consciousness

• Attention

• Memory

– semantic

• Executive function

• Language

• Perception

• Praxis

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

Domains

• Consciousness

• Attention

• Memory

• Executive function

• Language

• Perception

• Praxis

Executive function

• Planning

• problem-solving

• initiation of action

• sequencing of action

• self-monitoring

• set-shifting

• social judgement

• empathy

Executive function: tests

• Verbal fluency: letter, category

• Luria three hand position test

• go - no go

• cognitive estimates

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

Domains

• Consciousness

• Attention

• Memory

• Executive function

• Language

• Perception

• Praxis

Classification of dysphasia

Type fluency Comprhn Reptn Naming

Global + + + +

Broca’s + - + +

Wernicke’ - + + +

Condn - - + +

Transcmot

+ - - +

Transcsens

- + - +

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

Domains

• Consciousness

• Attention

• Memory

• Executive function

• Language

• Perception

• Praxis

Testing visual perception

• Overlapping pentagons

• cube

• clock face

• Dot counting

• Fragmented letters

• Object recognition…

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

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

MEMORY

Amnesia

EXECUTIVE FUNCTION

‘Frontal lobe

syndrome’

PRAXIS

Apraxia

PERCEPTUO-

SPATIAL FUNCTION

Agnosia

Spatial disorientation

LANGUAGE

Aphasia

Alexia

Agraphia

Acalculia

AROUSAL

Domains

• Consciousness

• Attention

• Memory

• Executive function

• Language

• Perception

• Praxis

Testing praxis

• Mimes

• Unfamiliar hand positions

• Look out for:

– utilisation behaviour

– imitation behaviour

– alien limb

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

PSP

PSP

Cognition, networks, dementias

• What is dementia?

• Dementia vs delirium

• Cortical vs subcortical dementia

• Cognitive

– Domains

– Networks

– Assessment

– Dementias

• The ACE-R