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