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

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

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

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

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

Vascular Territories of the Cerebral Hemisphere

Vascular Territories of the Cerebral Hemisphere

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

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

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

Cerebral small vessel disease

Cerebral small vessel disease

Pathophysiological mechanisms in VCI

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

Choice reaction time test

Stroop test

Digit symbol substitution test Trail making test Digit symbol substitution test

Therapeutic implications Primary prevention Secondary prevention

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

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

Symptomatic treatment Nimodipine Cholinesterase inhibitors Memantine

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