1. Vascular cognitive impairment – an overview
Jonathan Birns
Consultant in Stroke Medicine, Geriatrics & General Medicine
Guy’s & St Thomas’ NHS Foundation Trust

2. Vascular cognitive impairment (VCI)
encompasses all forms of cognitive loss associated with cerebrovascular disease and ischaemic brain injury
related to:
Stroke
Cortical infarcts
Subcortical infarcts
Silent infarcts
Strategic infarcts
White matter lesions associated with small vessel disease
Specific arteriopathies e.g. CADASIL

3. Vascular cognitive impairment (VCI)
plays an important role in patients with other forms of dementia
most common form of cognitive impairment in older people
prevalence: 5% in people > 65
likely to increase

4. Objectives To review VCI: Pathology Pathophysiology
Characteristic cognitive deficits
Therapeutic implications

5. Background
The cerebral circulation has a well developed collateral circulation which plays an important protective role
Communications between the cerebral arteries at the circle of Willis
Anastomoses between branches of the external carotid artery and the intracerebral circulation
Anastomoses between cerebral vessels on the brain surface

6. Vascular Territories of the Cerebral Hemisphere

7. Vascular Territories of the Cerebral Hemisphere

9. An internal watershed region exists in the deep white matter
between centripetal and centrifugal arterial networks
Centripetal supply to white matter Centrifugal supply to white matter

10. Perfusion of the deep white matter
Supplied by perforating end-arteries
(< 400 mm in diameter)
Each end-artery gives off perpendicularly oriented short branches
Each branch provides the blood supply to a cylindrically shaped metabolic unit
One distributing vessel irrigates one metabolic unit

11. Cerebral small vessel disease
Perforating arteries undergo age-related, arteriosclerotic changes
- intimal atheroma formation
- medial smooth muscle hypertrophy
- hyaline deposition
Arteriosclerosis is accelerated by disease states such as chronic hypertension and diabetes mellitus

12. Cerebral small vessel disease

13. Cerebral small vessel disease

14. Pathophysiological mechanisms in VCI

15. Risk factors for VCI
E.g. age, ethnicity, hypertension, diabetes mellitus, cigarette smoking, ischaemic heart disease, hyperfibrinogenemia
Vascular risk profile scoring measures correlate inversely with subcortical cognitive performance
Evidence suggests that:
control of vascular risk factors could prevent VCI
treatment of vascular risk factors should reduce VCI once present

16. Cerebrovascular Diseases 2008; 25: 408-416
p<0.001

17. Clinical features of VCI
Strategic lacunar infarcts
- abrupt onset of cognitive impairment and/or striking behavioural effects
- often associated with lacunar strokes involving:
- inferior genu of internal capsule
- thalamus
- caudate nucleus

18. Clinical features of VCI
Cognitive impairment and gait apraxia that may be subtle and insidious in onset

19. These clinical manifestations result from:
cortical-subcortical and corticocortical disconnection,
due to white matter tract disruption,
compromising the integration of information from large-scale neural networks

20. Diffusion tensor imaging MRI
- measures the diffusion of water molecules in biological tissues
- used to study white matter properties and alterations of fibre integrity

21. Clinical features of VCI
A number of distinct fibre systems have been described:
- dorsolateral prefrontal-subcortical circuits mediating executive function
- orbitofrontal-subcortical circuits providing frontal inhibition of the limbic system preventing impulsivity and uninhibited behaviour
- anterior cingulate-subcortical circuits whose interruption results in apathy and abulia

22. Pre-existing treated hypertension Awoke with:
Acute left anterior cerebral artery territory stroke presenting as mutism with abulia for contralateral function Birns J, Siddiqui A, Holmes P, Rudd AG. BJHM (in press)
74 year-old lady
Pre-existing treated hypertension
Awoke with:
Mutism
Lack of initiation
Urinary incontinence
O/E
Mute but no receptive dysphasia
Spontaneity for left-sided actions but lacking volitional right-sided functions both spontaneously and to command
‘Lead-pipe’ increase in tone in the right upper limb
Extensor right plantar response

23. Acute left anterior cerebral artery territory stroke presenting as mutism with abulia for contralateral function Birns J, Siddiqui A, Holmes P, Rudd AG. BJHM (in press)

24. Clinical features of VCI
Cognitive deficits of subcortical VCI are variable
Impairment of attention and executive function with slowing of motor performance and information processing predominate

25. Clinical features of VCI
VCI may be clinically silent to the physician
Executive dysfunction impacts on ability to undertake complex, goal-directed, purposeful ADLs
Relatives and carers may report:
abnormal behaviour
reduced speed of cognitive processing
personality changes

26. Clinical features of VCI
Episodic memory is relatively spared
Cognitive impairments associated with subcortical VCI are not readily identified by commonly used measures
» Attention and processing speed tests and assessments of executive function are better at discriminating patients with subcortical VCI

28. Assessments for subcortical VCI
Tests sensitive to impairments in:
- Attention
- Information processing
- Executive function

29. Tasks include: Digit span tests Forwards 27 381 4587 38416 715046
Backwards 35
742
8496
38519
829514

30. Verbal fluency tests
Phonemic F A S
Semantic
E.g. animals

31. Choice reaction time test

35. Stroop test

36. Digit symbol substitution test
Trail making test
Digit symbol substitution test

38. Therapeutic implications
Primary prevention
Secondary prevention

41. Effect of BP reduction on cognitive function
Journal of Hypertension 2006; 24:
Effect of BP reduction on cognitive function

42. Why? Heterogeneity ? Minimal cognitive decline in study participants
- study populations, cognitive domains, treatment strategies
? Minimal cognitive decline in study participants
? Over-representation of cognitively impaired patients who withdraw, die, lost to follow-up etc
Battery of tests used to assess cognitive function might be insensitive to small changes
? increase in cerebral microbleeds in patients given aspirin

43. Symptomatic treatment
Nimodipine
Cholinesterase inhibitors
Memantine

44. Conclusions
Subcortical white matter harbours an internal watershed vulnerable to ischaemia
Chronic ischaemic damage to the deep white matter interrupts cortical-subcortical and corticocortical pathways
VCI is characterised by executive dysfunction
As the baby boomer generation reaches 65 to 70 years by 2015, we will experience the predicted upswing in dementia