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
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
Backwards
27
381
4587
38416
715046
2849369
83516093
257361843
9406271351
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
Trail making
test
Digit symbol
substitution test
Therapeutic implications

Primary prevention

Secondary prevention
Journal of Hypertension 2006; 24: 1907-1914
Effect of BP reduction on cognitive function
Review:
Comparison:
Outcome:
Blood pressure reduction and cognitive function - a meta analysis
01 Blood pressure reduction versus control
08 Decrease in delayed logical memory score
Study
or sub-category
N
Treatment
Mean (SD)
183
16
62
34
73
-1.20(3.10)
0.20(3.00)
-0.34(0.00)
-1.30(3.00)
-1.00(2.01)
168
16
59
35
71
368
Total (95% CI)
Test for heterogeneity: Chi² = 0.90, df = 3 (P = 0.83), I² = 0%
Test for overall effect: Z = 3.01 (P = 0.003)
349
Veterans Affairs
McCorvey et al.
Leonetti et al.
HOPE
Fogari et al.
Control
Mean (SD)
N
WMD (fixed)
95% CI
-0.60(3.30)
0.00(3.00)
-0.50(0.00)
-0.50(3.20)
-0.20(2.00)
42.27
4.41
-10
-5
0
Favours treatment
Review:
Comparison:
Outcome:
Weight
%
5
WMD (fixed)
95% CI
8.90
44.41
-0.60 [-1.27, 0.07]
0.20 [-1.88, 2.28]
Not estimable
-0.80 [-2.26, 0.66]
-0.80 [-1.46, -0.15]
100.00
-0.67 [-1.11, -0.23]
10
Favours control
Blood pressure reduction and cognitive function - a meta analysis
01 Blood pressure reduction versus control
04 Change in trail making test A time
Study
or sub-category
Veterans Affairs
McCorvey et al.
HOPE
MRC (diuretic)
N
Treatment
Mean (SD)
183
16
34
633
-10.20(34.30)
-1.00(10.00)
-8.00(22.00)
-10.92(1.10)
866
Total (95% CI)
Test for heterogeneity: Chi² = 1.06, df = 3 (P = 0.79), I² = 0%
Test for overall effect: Z = 22.26 (P < 0.00001)
N
168
16
35
1311
Control
Mean (SD)
WMD (fixed)
95% CI
Weight
%
-11.60(35.10)
0.00(10.00)
-5.00(19.00)
-12.04(0.90)
0.02
0.02
0.01
99.95
1530
100.00
-10
-5
Favours treatment
0
5
Favours control
10
WMD (fixed)
95% CI
1.40
-1.00
-3.00
1.12
[-5.87, 8.67]
[-7.93, 5.93]
[-12.71, 6.71]
[1.02, 1.22]
1.12 [1.02, 1.22]
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 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