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Vascular Dementia

Diagnosis and Treatment of


Subcortical Ischemic Vascular
Dementia
The small-vessel variant of ischemic vascular disease appears to have been neglected in the
vascular dementia (VAD) model and the overall cerebrovascular pathologic picture.
Subcortical ischemic vascular dementia (SIVD) is quite difficult to identify and diagnose
due to the difficulty of establishing a causal relationship between the changes and cognitive
deficits seen by a primary-care physician, as well as identified through various
brain-mapping techniques.

By Peter N. McCracken, MD, FRCPC

A poplectic dementia was the


term utilized in the past when
patients presented with sudden
was a term applied to a number of
different dementia syndromes, in-
cluding at times, and erroneously,
sel disease to the overall cere-
brovascular pathologic picture.
Hence, this article pertains to the
cerebral bleeding, softening or Alzheimers disease (AD). small-vessel variant of ischemic
tumors that resulted in an abrupt vascular disease: SIVD.
change in cognition, which could Vascular Dementia
be progressive and incurable. In Modern concepts of VAD began to Subcortical Ischemic Vascular
the early 1900s, it was widely evolve in the 1970s when studies Dementia
accepted that atherosclerosis from Newcastle revealed that sub- The greatest challenge in diagnos-
caused gradual stenosis of the jects with dementia and little, if any, ing SIVD lies in establishing a
brain vessels, causing parenchy- AD pathology demonstrated a rela- causal relationship between the
mal lesions that lead to dementia. tionship between lost tissue volume magnetic resonance imaging (MRI)
However, the differentiation bet- from infarctions and the degree of changes and the cognitive deficit(s)
ween other dementias and VAD global cognitive decline. Hachin- from the viewpoint of a primary-care
were not clear, and the association ski1 subsequently introduced the physician. One can argue that
between clinical strokes and cogni- term multi-infarct dementia (MID) causality is irrelevant, but if a
tive changes were not firmly estab- in 1974, which includes a history of patient has SIVD, management of
lished. Hardening of the arteries clinical strokes with focal neurolog- the vascular risk factors should be
ic signs and symptoms, and step- optimized, regardless of their exact
wise cognitive decline. role in causing the dementia syn-
Peter N. McCracken, MD, FRCPC The medical community has drome. What is clear is that the eti-
Professor Emeritus of Medicine,
perhaps over-focused on this ology of SIVD involves hyperten-
Division of Geriatric Medicine,
University of Alberta model of VAD, neglecting the size- sion and diabetes mellitus (DM),
Edmonton, Alberta able contribution from small-ves- particularly if poorly controlled.

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Subcortical Ischemic Vascular Dementia

Although there are minor differ- neural circuits. Widespread lesions connected with the prefrontal lobes.
ences in wording, most dementia def- of the white matter have major Dementias associated with such
initions share the following elements: effects on initiation and frontal strategic syndromes are featured by
1) acquired intellectual decline executive function because of pref- marked apathy, impaired attention
despite a clear sensorium; erential disruption of long associa- and mental control, with anterograde
2) effects on multiple cognitive tion fibres. However, it should be and retrograde amnesia, as well as
domains which usually include remembered that such changes at striking executive dysfunction.3
memory; and times remain clinically silent, grad- Binswangers syndrome was first
3) sufficient severity to interfere with
customary everyday activities.2 The greatest challenge in diagnosing SIVD lies in
During the past five years, establishing a causal relationship between the magnetic
emphasis has been placed on iden- resonance imaging (MRI) changes and the cognitive
tifying early stages of vascular cog-
deficit(s) from the viewpoint of a primary-care physician.
nitive impairment in order to
administer treatments earlier in the
disease. Three historic syndromes ually exhausting the clinical reserve described by Otto Binswanger.7 He
fall under the current rubric of of affected individuals. outlined eight cases of slowly pro-
SIVD:3 Clinical SIVD features include gressive mental deterioration and
1) lacunar state, first described by sudden hemiparesis, dementia, dy- pronounced white-matter changes
Marie4 and Perraud;5 sarthria, pseudobulbar palsy, and with secondary dilatation of the
2) thalamic or strategic infarction changes in affect including inap- ventricles. Alzheimer subsequently
dementia; and propriate laughing or crying, reported the microscopic features,
3) subcortical arteriosclerotic ence- small-stepped gait, and urinary including severe gliosis of the white
phalopathy, or Binswangers incontinence. Aphasia and hemi- matter and hyalination, intimal
syndrome. anopsia are usually absent. The dis- fibrosis, and onion-skinning of the
These syndromes are associated tribution of lacunes in the subcorti- long medullary arteries. Chronic
with frontal-type behavioral symp- cal gray matter and diffuse softening hypoperfusion of the periventricular
toms. A unifying hypothesis based of the white matter, particularly of and deep white-matter zones is pos-
on disruption of cortical and subcor- the frontal lobes, have been noted. tulated as the mechanism of injury.
tical circuits has been proposed.6 Behavioral symptoms include lack The clinical features of Bins-
Three such circuits are relevant to of volition and akinetic mutism, wangers include an insidiously
non-motor behavior:
1) a dorsomedial prefrontal circuit Clinical SIVD features include sudden hemiparesis,
related to executive function;
dementia, dysarthria, pseudobulbar palsy, and changes in
2) a medial prefrontal circuit relat-
ed to initiation and drive; and
affect including inappropriate laughing or crying,
3) an orbital prefrontal circuit relat- small-stepped gait, and urinary incontinence.
ed to social behavior.
An alternate hypothesis is that which were thought to be character- progressive dementia, persistent
deep white-matter lesions disrupt istic of prefrontal lobe lesions.3 hypertension or systemic vascular
the white-matter tracts necessary Strategic infarct dementia (e.g., disease, lengthy clinical course
for cognition and emotion. These thalamic dementia) typically invo- with long plateaus, and the accu-
include association and commissur- lves distribution of the paramedian mulation of focal neurologic signs
al, striatal and subcortical fibres thalamic artery. This usually inclu- including asymmetric weakness,
that interconnect with distributed des the dorsomedial nuclei, closely pyramidal signs, pseudobulbar

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Vascular Dementia

Table 1 Pathophysiology
Diagnosis of Subcortical Ischemic Vascular Disease (SIVD)3 Small arteries refer to arterioles
within the brain parenchyma.
Findings that increase the likelihood of SIVD These vessels range in size from
1. History of sudden onset or stepwise decline in neurologic or cognitive 100 to 600 microns in diameter,
function. and do not have an internal elastic
2. History of chronic hypertension or DM, especially if inadequately treated. lamina. Arteriolosclerosis refers to
3. History of small stroke (pure motor or sensory). the progressive deposition of hya-
4. Focal neurologic findings such as reflex asymmetry, pronator drift, line in the smooth-muscle wall of
Babinski sign, small-stepped or shuffling gait. the small arteriole. Hypertension
5. Evidence of hypertensive or diabetic end-organ disease (e.g., retinopathy, and DM accelerate this degenera-
LV hypertrophy, nephropathy).
tive process. As the media of the
6. Evidence of SIVD on structural neuroimaging study.
small artery undergoes progres-
sive lipohyalinosis, the lumen nar-
rows and the vessel becomes more
palsy, and gait disturbances. The clinical and research opportunities. tortuous and coiled. Ultimately,
neurobehavioral symptoms inclu- High-yield MRI at three or more the process leads to fibrinoid
de apathy, lack of drive, depres- tesla offer unprecedented anatomic necrosis and increased risk of
sion, and alterations of mood. Of resolution; functional MRI and thrombosis or hemorrhage.
course, the periods of slowly pro- perfusion MRI give excellent tem- Two pathophysiologic pathways
gressive deterioration can mimic poral resolution; and diffusion ten- cause ischemic brain injury associ-
AD. Sensitivity for detecting vas- sor imaging provides information ated with small-artery disease. The
cular brain injury widened signifi- about architectural integrity. first pathway involves an occlusion
cantly with the advent of modern of an arterial lumen and leads to
imaging: computed tomography Epidemiology lacunar infarction. The second is
(CT) in the 1970s, and MRI in the After AD, cerebrovascular disease characteristic of a generalized nar-
1980s and 1990s. The previous is the second most common type of rowing of small arterioles and
threshold occurred at the level of dementia. The incidence and preva- hypoperfusion, which leads to
symptomatic stroke. More recent- lence of SIVD, however, is un- incomplete infarction of the deep
ly, neuroimaging has revealed evi- known.8 white matter. While both pathways
dence of silent brain injury with- Epidemiologic studies tend to share roots in common risk factors
out a history of a corresponding focus on a broad category of VAD, and small-artery disease, they differ
clinical event. often adapting different classifica- in the anatomic location and patho-
However, we should be clear tions, and being frequently unable to logic extent of their injury, as well
that evidence-based standards that reliably identify mixed AD/VAD.9 as the accompanying clinical symp-
address sensitivity and specificity Furthermore, few epidemiologic tomatology. The end stages of these
of clinical criteria against a refer- studies employ neuroimaging, lead- two pathways are known as lacunar
ence standard are limited. In con- ing to underestimates or precluding state and Binswangers syndrome.
trast to AD, there is no gold stan- SIVD. Among patients hospitalized At later stages, the two pathways
dard agreed upon for the diagnosis for first stroke, the proportion of often converge.
of VAD. Several findings in the events attributed to SIVD is 10% to When the lumen of an artery is
clinical history and examination 30%.8 In another study, the propor- occluded, acute ischemic injury is
increase the likelihood of SIVD tion of cases attributed to SIVD centered in its primary irrigation
(Table 1).3 The versatility and varies from 36% to 67%10 among territory. For small penetrating
power of MRI do offer exciting patients diagnosed with VAD. arteries, the resulting so-called

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Subcortical Ischemic Vascular Dementia

lacunar infarct is usually < 1.5 cm in lized depending on the exact details Even though this study included
diameter. Sites of predilection of the clinical situation. Several lon- more than simply SIVD, energetic
include the white matter, especially gitudinal community-based studies, treatment of those vascular risk
in the frontal lobe, followed by the including the Framingham Heart factors can been seen to alter long-
putamen, thalamus, pons, and cau- Study,11 Rotterdam Scan Study,12 term outcomes favorably. On the
date. Arterial occlusion is associated and the Honolulu Asian Study,13 other hand, previous cross-section-
with complete infarction of all tis- provide evidence that identification al studies have suggested that
sue elements, eventually leading to and control of risk factors in midlife MRI-defined SIVD is associated
cystic necrosis. Small, or non-strate-
gically located infarcts may be com- The primary treatment and prevention of SIVD is to
pletely asymptomatic or silent. manage the vascular risk factors to prevent further
Symptomatic lesions are recognized strokes. Close attention should be paid to the lowering of
by the sudden appearance of neuro-
blood pressure and the control of DM.
logic dysfunction such as pure
motor weakness, pure sensory loss,
or behavior or cognitive change. may reduce the risk for cognitive with marked cognitive impairment
impairment late in life. Of note, there and, specifically, deficits of mental
Clinical Treatment are very few long-term trials measur- speed, attention, and executive
The primary treatment and preven- ing treatment outcomes in SIVD. skills. The LADIS Study15 revealed
tion of SIVD is to manage the vas- In the follow-up of the Systolic that SIVD subjects seemed to be
cular risk factors to prevent further Hypertension in Europe Study, vulnerable to a rapid period of cog-
strokes. Close attention should be long-term antihypertensive treat- nitive decline in these domains.15
paid to the lowering of blood pres- ment over 3.9 years reduced the Further work will be required to
sure and the control of DM. risk of dementia by 55%, from 7.4 hone in much further on this partic-
Antiplatelet agents should be uti- to 3.3 cases per 1,000 patients.14 ular subset.

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2(7874):207-10. Klin Wochenachr 1894; 31:102-5; Association of diabetes mellitus and
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Heinemann, pp. 1901-52. Cornerstone 2001; 3(4):40-51. The association between midlife blood
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dementia. Neurol Clinic 2007; Efficacy of galantamine in probable function. The Honolulu Asian Aging
25(3):717-40. vascular dementia and Alzheimers Study. JAMA 1995; 274:1846-51.
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desintegration et differents autres etats disease: a randomized trial. Lancet Prevention of dementia in randomized
cavitaire de cerveau. Rev Med 1901; 2002; 359:1283-90. double blind placebo-controlled systolic
21:281-98. [Article in French] 10. Chiu HC. Vascular dementia, a new hypertension in Europe study. Lancet
5. Ferrand J. Essai sur lhemeplegie des veil- beginning: shifting focus from clinical 1998; 352:1347-51.
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brale. First Edition. Thesis. Rousset, Paris, Neurol Clin 2000; 18:951-78. Longitudinal cognitive decline in subcorti-
1902. [Book in French] 11. Elias MF, DAgostino RB, Elias PK, et al. cal ischemic vascular diseasethe LADIS
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