Vascular cognitive impairment – an overview

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 circulationwhich plays an important protective role • Communications between the cerebral arteries at thecircle of Willis • Anastomoses between branches of the external carotid artery andthe 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 thedeep 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. Acute left anterior cerebral artery territory strokepresenting as mutism with abulia for contralateral functionBirns 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 strokepresenting as mutism with abulia for contralateral functionBirns 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 2849369 83516093 257361843 9406271351 Backwards 35 742 8496 38519 829514 8374139 91526732 629816429 8749261451

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

31. Choice reaction time test

35. Stroop test

36. Trail making test Digit symbol substitution test

38. Therapeutic implications • Primary prevention • Secondary prevention

41. Journal of Hypertension 2006; 24: 1907-1914 Effect of BP reduction on cognitive function

42. Why? • Heterogeneity - 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