Vascular cognitive impairment – an overview

Jonathan Birns

Consultant in Stroke Medicine, Geriatrics & General MedicineGuy’s & St Thomas’ NHS Foundation Trust

Vascular cognitive impairment Vascular cognitive impairment – an overview– an overview

Vascular cognitive impairment (VCI) 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)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

ObjectivesObjectives

To review VCI:

– Pathology– Pathophysiology– Characteristic cognitive deficits– Therapeutic implications

BackgroundBackground

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

The cerebral circulation has a well developed collateral circulation which plays an important protective role

Vascular Territories of the Cerebral Vascular Territories of the Cerebral HemisphereHemisphere

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 thePerfusion of thedeep white matterdeep white matter

Supplied by perforating end-arteries

(< 400 m 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 diseaseCerebral 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 diseaseCerebral small vessel disease

Cerebral small vessel diseaseCerebral small vessel disease

Pathophysiological mechanisms in VCIPathophysiological mechanisms in VCI

Risk factors for VCIRisk 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

p<0.001

Cerebrovascular Diseases 2008; 25: 408-416

Clinical features of VCIClinical 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

Cognitive impairment and gait apraxia that may be subtle and insidious in onset

Clinical features of VCIClinical features of VCI

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 MRIDiffusion 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 VCIClinical features of VCI

- 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

A number of distinct fibre systems have been described:

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 strokeAcute left anterior cerebral artery territory strokepresenting as mutism with abulia for contralateral functionpresenting as mutism with abulia for contralateral function

Birns J, Siddiqui A, Holmes P, Rudd AG. BJHM (in press)Birns J, Siddiqui A, Holmes P, Rudd AG. BJHM (in press)

Acute left anterior cerebral artery territory strokeAcute left anterior cerebral artery territory strokepresenting as mutism with abulia for contralateral functionpresenting as mutism with abulia for contralateral function

Birns J, Siddiqui A, Holmes P, Rudd AG. BJHM (in press)Birns J, Siddiqui A, Holmes P, Rudd AG. BJHM (in press)

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 VCIClinical 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 VCIClinical 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

Clinical features of VCIClinical features of VCI

Tests sensitive to impairments in:

- Attention

- Information processing

- Executive function

Assessments for subcortical VCIAssessments for subcortical VCI

Digit span testsDigit span tests

Tasks include:

Forwards

273814587384167150462849369835160932573618439406271351

Backwards

357428496385198295148374139915267326298164298749261451

Verbal fluency testsVerbal fluency tests

Phonemic– F– A– S

Semantic– E.g. animals

Choice reaction time Choice reaction time testtest

Stroop testStroop test

Digit symbol Digit symbol substitution testsubstitution test

Trail making Trail making testtest

Therapeutic implicationsTherapeutic implications

Primary prevention

Secondary prevention

Review: Blood pressure reduction and cognitive function - a meta analysisComparison: 01 Blood pressure reduction versus control Outcome: 04 Change in trail making test A time

Study Treatment Control WMD (fixed) Weight WMD (fixed)or sub-category N Mean (SD) N Mean (SD) 95% CI % 95% CI Year

Veterans Affairs 183 -10.20(34.30) 168 -11.60(35.10) 0.02 1.40 [-5.87, 8.67] 1990McCorvey et al. 16 -1.00(10.00) 16 0.00(10.00) 0.02 -1.00 [-7.93, 5.93] 1993HOPE 34 -8.00(22.00) 35 -5.00(19.00) 0.01 -3.00 [-12.71, 6.71] 1996MRC (diuretic) 633 -10.92(1.10) 1311 -12.04(0.90) 99.95 1.12 [1.02, 1.22] 1996

Total (95% CI) 866 1530 100.00 1.12 [1.02, 1.22]Test for heterogeneity: Chi² = 1.06, df = 3 (P = 0.79), I² = 0%Test for overall effect: Z = 22.26 (P < 0.00001)

-10 -5 0 5 10

Favours treatment Favours control

Effect of BP reduction on cognitive functionEffect of BP reduction on cognitive function

Review: Blood pressure reduction and cognitive function - a meta analysisComparison: 01 Blood pressure reduction versus control Outcome: 08 Decrease in delayed logical memory score

Study Treatment Control WMD (fixed) Weight WMD (fixed)or sub-category N Mean (SD) N Mean (SD) 95% CI % 95% CI Year

Veterans Affairs 183 -1.20(3.10) 168 -0.60(3.30) 42.27 -0.60 [-1.27, 0.07] 1990McCorvey et al. 16 0.20(3.00) 16 0.00(3.00) 4.41 0.20 [-1.88, 2.28] 1993Leonetti et al. 62 -0.34(0.00) 59 -0.50(0.00) Not estimable 1994HOPE 34 -1.30(3.00) 35 -0.50(3.20) 8.90 -0.80 [-2.26, 0.66] 1996Fogari et al. 73 -1.00(2.01) 71 -0.20(2.00) 44.41 -0.80 [-1.46, -0.15] 2004

Total (95% CI) 368 349 100.00 -0.67 [-1.11, -0.23]Test for heterogeneity: Chi² = 0.90, df = 3 (P = 0.83), I² = 0%Test for overall effect: Z = 3.01 (P = 0.003)

-10 -5 0 5 10

Favours treatment Favours control

Journal of Hypertension 2006; 24: 1907-1914

Why?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

Symptomatic treatmentSymptomatic treatment

Nimodipine

Cholinesterase inhibitors

Memantine

ConclusionsConclusions

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