Etiology, Clinical Manifestations, and Diagnosis of Vascular Dementia PDF

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Etiology, clinical manifestations, and diagnosis of vascular dementia

Authors: Eric Smith, MD, Clinton B Wright, MD, MS
Section Editors: Kristine Yaffe, MD, Scott E Kasner, MD
Deputy Editor: Janet L Wilterdink, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2019. | This topic last updated: Nov 30, 2018.
INTRODUCTION
Vascular dementia refers to any dementia that is primarily caused by cerebrovascular disease or impaired cerebral
blood flow and falls within the spectrum of vascular cognitive impairment (VCI), a syndrome that includes all
cognitive disorders in which cerebrovascular disease or impaired cerebral blood flow is a contributing causative
factor. Vascular dementia is the second most common form of dementia, only exceeded by Alzheimer disease (AD)
in terms of prevalence and incidence [1].
Neuroimaging has vastly improved the ability to detect and diagnose stroke and silent manifestations of
cerebrovascular disease that impair cognition [2]. However, neuroimaging can also detect cerebrovascular brain
injury in asymptomatic older adults [3]; therefore, the mere presence of any cerebrovascular brain injury is not
sufficient to diagnose vascular dementia. Clinical features and the location and severity of cerebrovascular brain
injury detected on brain imaging must be used to make a clinical judgment whether cerebrovascular disease is
sufficient to cause vascular dementia. As with the later-life neurodegenerative diseases such as AD, vascular
neuropathology becomes very common with advanced aging and is often accompanied by other neuropathologies.
This topic will review the epidemiology, clinical features, evaluation, and diagnosis of vascular dementia in adults.
Treatment and prevention of vascular dementia are reviewed separately. (See "Treatment and prevention of
vascular dementia".)
DEFINITIONS
Vascular dementia — Vascular dementia refers to any dementia that is primarily caused by cerebrovascular
disease or impaired cerebral blood flow, or in which cerebrovascular disease or impaired cerebral blood flow is a
contributing causative factor. Vascular dementia is typically recognized in either of two clinical scenarios [4]:
● A clinically diagnosed stroke is followed by dementia; or
● Vascular brain injury is identified on brain imaging in a patient with cognitive decline but without a clinical history
of stroke
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Clinical features and the location and severity of cerebrovascular brain injury detected on brain imaging must be
used to make a clinical judgment whether cerebrovascular disease is sufficient to cause vascular dementia. (See
'Evaluation' below and 'Diagnosis' below.)
It is important to recognize that vascular dementia is a syndrome, not a disease. Vascular dementia may be caused
by any cerebrovascular or cardiovascular disease that leads to vascular brain injury or dysfunction, including any of
the causes of ischemic stroke (eg, cardioembolism, large artery atherosclerotic disease, cerebral small vessel
diseases) or hemorrhagic stroke. The diagnosis of vascular dementia is not complete until the underlying
cerebrovascular or cardiovascular diseases have been identified, as this information is needed to design a plan for
secondary prevention of future vascular brain injury. (See "Treatment and prevention of vascular dementia".)
Vascular cognitive impairment — The term "vascular cognitive impairment" (VCI) has been proposed by the
writing group for National Institute of Neurological Disorders and Stroke (NINDS)-Canadian Stroke Network VCI
harmonization standards and the American Heart Association to refer to "cognitive impairment that is caused by or
associated with vascular factors" [5]. The VCI concept encompasses dementia as well as milder forms of
impairment, including mild cognitive impairment (MCI) caused by cerebrovascular disease.
Similar to vascular dementia, VCI is a syndrome that may be caused by any cerebrovascular or cardiovascular
disease that leads to vascular brain injury or dysfunction.
Multiple-etiology or mixed dementia — Autopsy studies suggest that pure vascular dementia is less common
than the situation in which vascular dementia is only one etiology of multiple-etiology (also termed "mixed")
dementia [6]. Alzheimer neuropathology, with characteristic beta-amyloid plaques and tangles, is the most common
co-occurring pathology with vascular dementia.
Multiple-etiology dementia may be diagnosed clinically when a patient with vascular dementia also meets
consensus diagnostic criteria for another neurodegenerative disorder such as Alzheimer disease (AD). (See
"Clinical features and diagnosis of Alzheimer disease" and "Epidemiology, pathology, and pathogenesis of
Alzheimer disease", section on 'Cerebrovascular disease'.)
EPIDEMIOLOGY
Quantifying the contribution of vascular disease to dementia is challenging because it is frequently seen in
asymptomatic older adults as well as in persons with dementia, and it frequently coexists with other
neurodegenerative pathologies of aging such as Alzheimer disease (AD) [1].
Thus, there are opportunities for misclassification (eg, misclassifying multiple-etiology dementia with a vascular
component as pure AD). Misclassification can be reduced with the use of neuroimaging to detect clinically
unrecognized vascular brain injury [2], with the use of biomarkers of the AD pathophysiologic process to detect AD
pathology during life [7], or with neuropathologic confirmation.
Incidence and prevalence — Vascular disease is a cause or contributor in 25 to 50 percent of cases of dementia,
and vascular dementia is the second most common type of dementia in clinic- and population-based studies [1,6].
Clinicopathologic studies from dementia specialty clinics indicate that pure vascular dementia is relatively
uncommon, accounting for approximately 10 percent of all dementia cases [6,8]. Multiple-etiology dementia with a
vascular component, most often in combination with AD, is more common and accounts for approximately 30 to 40
percent of all dementia cases [6,8].
In the population-based Medical Research Council Cognitive Function and Aging Study (MRC CFAS)
neuropathology study, cerebral small vessel disease accounted for 12 percent of dementia risk, cerebral amyloid
angiopathy (CAA) accounted for 7 percent of risk, and multiple vascular pathologies accounted for 9 percent of risk
[9]. In the Baltimore Longitudinal Study on Aging, cerebral small vessel disease accounted for 33 percent of
dementia risk [10].
The estimated prevalence of vascular dementia among individuals 65 years of age and older is 1.6 percent and
rises with increasing age [11]. Among the participants 60 years or older recruited to the Framingham Heart Study
from 2004 to 2008, 0.4 persons out of 100 (95% CI 0.2-0.7) developed vascular dementia over a five-year period
[12].
There are far fewer studies of the prevalence of vascular mild cognitive impairment (MCI) and the risk of
progressing from vascular MCI to dementia. A community-based study of patients with MCI patients found that 16
percent had infarcts as their sole pathology, while 17 percent had both infarcts and AD pathology [13]. A population-
based study found that 15 percent of patients who were cognitively impaired but not demented (CIND) were
clinically diagnosed with vascular disease as the cause, but autopsy confirmation was not available [14]. The same
population-based study found that 46 percent of patients with vascular CIND had progressed to dementia by five
years, with approximately half of the new dementia cases attributed to progressive or recurrent cerebrovascular
disease [15].
Risk factors in the general population — Because stroke can cause vascular dementia, risk factors for stroke are
also risk factors for vascular dementia in the general population. In population-based studies, the major risk factors
for vascular dementia include [11,16-24]:
● Advanced age
● Hypertension
● Diabetes
● Elevated total cholesterol levels
● Lower physical activity
● Low or high body mass index
● Smoking
● Coronary artery disease
● Atrial fibrillation
There have been marked improvements in population vascular risk factor control over the last 40 years, with
substantial decreases in stroke incidence and mortality [25]. A similar trend in vascular dementia incidence was
identified in the population-based Framingham Heart Study, in which the five-year incidence of vascular dementia
dropped from 0.8 to 0.4 per 100 persons from the five-year period between 1977 and 1983 to the period between
2004 and 2008 [12]. Better vascular risk factor control and better prevention and treatment of stroke were implicated
by the study authors as potential reasons for the decline.

Factors related to cognitive reserve probably play a role in determining risk of vascular dementia, but the role of
cognitive reserve has been understudied in vascular dementia compared with AD. Cognitive reserve refers to the
brain's ability to compensate for a given level of pathology. Factors such as higher education and occupational
attainment have been associated with lower risk for cognitive decline in the setting of cerebrovascular pathology
[26].
Risk factors for poststroke dementia — Dementia is common both before and after stroke. In a systematic review
that identified 22 hospital-based stroke cohort studies, 14 percent of patients hospitalized with stroke had a
preceding history of dementia, and 12 percent of patients without prestroke dementia had dementia following a first
stroke [27].
Risk factors for new dementia after stroke include [27,28]:
● Prestroke factors (advanced age, nonwhite race, low education, diabetes, and atrial fibrillation)
● Stroke factors (intracerebral hemorrhage, aphasia, left hemisphere location, and multiple or recurrent strokes)
● Stroke complications (incontinence, confusion, or seizures)
● Lower brain reserve (brain imaging evidence of leukoaraiosis, general atrophy, medial temporal lobe atrophy,
and beta-amyloid deposition)
ETIOLOGY AND PATHOPHYSIOLOGY
Vascular dementia is caused by diseases of the cerebral vasculature and of the cardiovascular system, including
hypoperfusion and embolism from the heart [29]. The dominant paradigm is that these diseases disrupt normal
brain function and cause cognitive impairment through brain ischemia or loss of vascular integrity with hemorrhage.
Any cause of ischemic stroke (cardioembolism, large artery atherosclerosis, cerebral small vessel disease),
intracerebral hemorrhage, or subarachnoid hemorrhage can cause vascular dementia if the resulting brain injury is
severe enough (table 1) [30].
Aside from clinical stroke, cerebral small vessel diseases play an outsized role in the burden of vascular dementia.
Although only accounting for 20 to 25 percent of stroke, cerebral small vessel disease is the most common
neuropathologic correlate of both vascular dementia and multiple-etiology ("mixed") dementia with a vascular
component [31]. Frequently, cerebral small vessel disease is clinically unrecognized until it is detected on brain
imaging or neuropathology.
The main types of cerebral small vessel disease are [32]:
● Arteriolosclerosis – Arteriolosclerosis due to aging, hypertension, and conventional stroke-related vascular risk
factors is the most common type of cerebral small vessel disease. The walls of small arteries and arterioles
exhibit changes such as thickening, hyalinization, lipohyalinosis, microaneurysm formation, and loss of vascular
integrity with cracking and perivascular hemosiderin deposits [33].
Arteriolosclerotic cerebral small vessel disease prominently affects subcortical brain regions including the basal
ganglia and corona radiata [32]. This is presumed to be because there are fewer subcortical collateral vessels

compared with the rich collateralization of the cerebral cortex [34]. As a result, patients with arteriolosclerotic
cerebral small vessel disease typically have multiple lacunes or extensive, confluent white matter lesions as the
pathogenic basis for their symptoms [34]. Synonyms for this vascular dementia syndrome include Binswanger
disease [35] and subcortical ischemic vascular dementia [36,37]. Although the subcortical changes are obvious,
there may be subtler manifestations in the cortex including microinfarcts [38] and secondary neurodegeneration
with apoptosis, leading to cortical thinning [39].
● Cerebral amyloid angiopathy (CAA) – CAA is the second most common type of cerebral small vessel disease.
CAA is usually caused by deposition of beta-amyloid in small arteries and arterioles in the leptomeninges and
cerebral cortex. Rare genetic causes of CAA are marked by deposition of other types of amyloid [40].
One of the most prominent changes in CAA is a loss of vascular integrity resulting in both large, symptomatic
and small, asymptomatic brain hemorrhages (image 1). Hemorrhages are restricted to typical locations in the
cortex or subcortical white matter (also called "lobar" locations) with sparing of the basal ganglia and brainstem
[41,42]. Although the reason for this distinct distribution of vascular changes is not known, it has been exploited
to derive CAA diagnostic criteria based on hemorrhage location (table 2) [43,44]. (See "Cerebral amyloid
angiopathy".)
● Others – There are many other less common or rare causes of cerebral small vessel disease, including genetic
disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL), small vessel vasculitides and other inflammatory disorders, and venous collagenosis [32]. (See
"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)".)
Although consensus diagnostic criteria emphasize the role of vascular brain injury from ischemia or hemorrhage in
producing vascular dementia, the cerebral vasculature does more than just deliver blood [30,45,46]. As a
neurovascular unit, the blood vessels function in a harmonious, tightly integrated fashion along with pericytes,
astrocytes, microglia, and neurons to support brain activity [46,47]. Supportive functions include maintaining blood-
brain barrier permeability, trafficking of immune cells into and out of the brain, secretion of trophic factors, and
clearing the brain of wastes. It is possible, but unproven, that loss of these vascular functions may play a role in
causing vascular dementia or even other neurodegenerative diseases such as Alzheimer disease (AD) [48-50].
(See "Epidemiology, pathology, and pathogenesis of Alzheimer disease", section on 'Cerebrovascular disease'.)
CLINICAL FEATURES
The essential feature of vascular dementia is disabling cognitive decline that is clinically attributed to a vascular
cause. There are two main syndromes of vascular dementia: poststroke dementia and vascular dementia without
recent stroke.
Poststroke dementia — Patients with poststroke dementia experience a stepwise cognitive decline following a
clinically diagnosed stroke. The link between cerebrovascular disease and the onset of cognitive impairment is thus
relatively clear in most cases.
The cognitive profile of poststroke dementia is often marked by prominent impairment of executive functions,
sometimes with relative sparing of episodic memory [51]. It may be accompanied by other cortical signs of stroke

including aphasia and apraxia. However, there is wide interindividual variation in the cognitive profile, related in part
to the heterogeneity in stroke location and size.
Not all patients exhibit the classic syndrome of disproportionate executive function impairment. For example,
anterior thalamic infarction can cause isolated memory impairment with preservation of other domains, which could
mimic the cognitive profile of Alzheimer disease (AD) [52].
Several patterns of stroke-related brain injury have been associated with vascular dementia and have been
categorized as [30]:
● Multi-infarct (or multi-hemorrhage) dementia – Damage to multiple brain regions has the cumulative effect of
disrupting brain function, resulting in clinically significant cognitive impairment. Attempts to identify a threshold
of infarct volume that predicts poststroke dementia have failed, with inconsistent results across studies. The
inability to identify a threshold probably relates to variation in cognitive and brain reserve among individuals and
inadequate consideration of the role of lesion location. Therefore, clinical judgment is needed to determine
whether an individual pattern of vascular brain injury is sufficient to account for cognitive impairment. (See
'Diagnosis' below.)
● Strategic infarction (or hemorrhage) – Damage to a single brain location can be sufficient to cause clinically
significant cognitive impairment. Examples include the medial frontal lobes (anterior cerebral artery territory),
language cortices, thalamus, and medial temporal lobes [30]. In addition to stroke location and severity, factors
related to cognitive and brain reserve influence the likelihood of poststroke dementia [27,28]. (See 'Risk factors
for poststroke dementia' above.)
Cognitive impairment may improve as part of the stroke recovery process. After recovery, poststroke cognitive
impairment may be static and nonprogressive if vascular risk factors are treated and there are no recurrent strokes.
However, a systematic review identified that approximately 10 percent of patients develop new dementia one to four
years after stroke [27], and population-based studies confirm that the average rate of cognitive decline accelerates
after stroke [53].
Up to half of the new dementia cases that occur more than one year after stroke are related to new, recurrent
strokes [27]. The rest of the new dementia cases, related to progressive cognitive symptoms, are likely due to
progressive cerebral small vessel disease and not AD, according to a cohort study that included beta-amyloid
imaging [54].
Vascular dementia without recent stroke — Vascular dementia can also manifest as a progressive or stepwise
cognitive decline without a concurrent history of symptomatic stroke, but with imaging evidence of clinically
unrecognized cerebrovascular disease. Although frequently called "silent," this clinically unrecognized
cerebrovascular disease is better termed "covert" because it is associated with lower cognitive performance and
elevated risk for dementia [55-57]. (See 'Etiology and pathophysiology' above.)
The cognitive profile of arteriolosclerotic cerebral small vessel disease is marked by prominent impairment in
executive function and processing speed [58]. Impairment is not exclusive to these domains, however, and more
global impairments in memory and other functions can occur [59]. Compared with patients with AD, patients with
vascular cognitive impairment (VCI) tend to have better verbal learning and recall, on average, and worse executive
function. (See 'Neuropsychological testing' below.)

Cognitive impairment can progress in a series of stepwise declines, suggesting unrecognized strokes, or can be
smooth and progressive [60], mimicking the course of a neurodegenerative disease [32,34]. Synonyms for this
vascular dementia syndrome include Binswanger disease and subcortical ischemic vascular dementia. (See
'Etiology and pathophysiology' above.)
Cerebral small vessel disease due to cerebral amyloid angiopathy (CAA) can cause cognitive impairment in the
absence of hemorrhagic stroke [61,62]. The typical cognitive profile of CAA is similar to that of arteriosclerotic
cerebral small vessel disease, with impaired executive function and processing speed [63,64]. On average, episodic
memory is not impaired to the same degree as in AD, even though it may not be normal [63]. (See "Cerebral
amyloid angiopathy", section on 'Cognitive impairment'.)
Neuropsychiatric and motor signs — Vascular dementia may be accompanied by neuropsychiatric signs such as
depression, abulia, apathy, and psychosis with delusions or hallucinations [65-68]. Patients may exhibit pathologic
laughing or crying, a phenomenon known as pseudobulbar affect [69]. Slowing of gait is common in patients with
cerebral small vessel disease [70] and may lead to a syndrome described as lower body parkinsonism [71].
Increased urinary frequency may be seen [72].
Symptoms and signs related to past history of stroke may also be present, including aphasia, motor weakness, and
sensory impairments [70]. (See 'Poststroke dementia' above.)
DIFFERENTIAL DIAGNOSIS
Vascular dementia must be distinguished from other causes of acquired cognitive decline in older adults. However,
it is important to remember that many dementias are due to multiple etiologies, of which vascular disease is one of
the most common contributors. Brain imaging is useful to identify signs of silent (also called covert) cerebrovascular
brain injury, which indicates a vascular contribution to the dementia. (See 'Neuroimaging' below.)
● Alzheimer disease – Alzheimer disease (AD) produces a gradual, progressive decline that can be mimicked
by progressive cerebral small vessel disease. However, the typical cognitive profile of AD differs from vascular
dementia in that there is usually more prominent impairment in episodic memory [73]. Atypical presentations of
AD, such as the frontal variant, can make it difficult to distinguish from vascular dementia. (See "Clinical
features and diagnosis of Alzheimer disease", section on 'Cardinal symptoms'.)
In most cases, clinical history and routine neuroimaging are probably sufficient to make a clinical diagnosis of
vascular dementia, AD, or multiple-etiology dementia due to vascular dementia and AD. The Hachinski
ischemic score is a simple clinical tool that uses elements of the history and routine physical examination to
help predict the likelihood of vascular dementia or a vascular contribution to multiple-etiology dementia. (See
'History' below.)
Amyloid positron emission tomography (PET) or measurements of beta-amyloid and phosphorylated tau in the
cerebrospinal fluid determine the presence or absence of AD pathology with high sensitivity and specificity but
are expensive and may not be available or practical in many clinical settings. On 18-F fluorodeoxyglucose
(FDG) PET, a typical pattern of parietal and temporal hypometabolism suggests the presence of AD pathology,
whereas the pattern of hypometabolism is more patchy and heterogeneous in patients with vascular dementia.
(See "Clinical features and diagnosis of Alzheimer disease", section on 'Neuroimaging'.)
● Parkinson disease and other related dementias – Lewy body diseases (eg, Parkinson disease, dementia
with Lewy bodies) produce a gradual, progressive decline with symptoms of gait-slowing that can mimic the
progressive cognitive and gait impairment seen in cerebral small vessel disease. Vascular parkinsonism differs
from Parkinson disease and other Lewy body diseases in that bradykinesia affects the legs more than the arms
("lower-body parkinsonism") and, in contrast to Parkinson disease, there is no resting tremor [71]. The
presence of rapid eye movement (REM) sleep behavior disorder, fluctuations in level of alertness, and
prominent visuospatial dysfunction favor dementia with Lewy bodies as the cause of or contributor to the
dementia [74]. (See "Cognitive impairment and dementia in Parkinson disease", section on 'Clinical features'
and "Clinical features and diagnosis of dementia with Lewy bodies", section on 'Core clinical features'.)
● Normal pressure hydrocephalus – Normal pressure hydrocephalus (NPH) produces decline in cognition,
slowed gait, and urinary incontinence that can mimic symptoms of progressive cerebral small vessel disease.
The cognitive profile is similar to vascular dementia, with prominently impaired executive function presumed
due to pressure on periventricular white matter tracts from the frontal lobes [75]. Both NPH and vascular
dementia are associated with slowed gait, but the classic gait sign in NPH is an apraxic, wide-based "magnetic"
gait [76]. In cerebral small vessel disease, the gait base is narrower and more closely resembles the gait
disorder seen in parkinsonism. (See "Normal pressure hydrocephalus".)
● Depression – Patients with depression may exhibit apathy, psychomotor slowing, and executive dysfunction
that mimic the neuropsychological profile of vascular dementia. However, when the onset of depression is in
later life (after age 50), clinicians must also consider whether depression is the initial manifestation of
neurodegeneration or vascular cognitive impairment (VCI), rather than an alternative diagnosis. The syndrome
of mild behavioral impairment defines patients with later-life newly acquired neurobehavioral symptoms that
raise suspicion for neurodegeneration [77]. Late-life depression is associated with higher burden of magnetic
resonance imaging (MRI)-defined silent cerebrovascular disease and confers increased risk for future diagnosis
of vascular dementia, as well as all-cause dementia [78,79]. The evaluation and diagnosis of late-life
depression are reviewed separately. (See "Diagnosis and management of late-life unipolar depression".)
EVALUATION
The evaluation of patients with suspected vascular dementia should focus on the severity and profile of cognitive
decline, any clinical history of stroke, risk factors and causes of stroke or silent cerebrovascular disease, brain
imaging evidence of silent cerebrovascular disease, and the presence of clinical features or biomarkers of other
neurodegenerative diseases that might be an alternative or accompanying cause of dementia.
History — The history should focus on identifying the time course of cognitive decline and its relationship to basic
and instrumental activities of daily living. Prior history of stroke should be ascertained, as well as its timing relative
to the onset of cognitive symptoms.
The Hachinski ischemic score uses information from the past medical history, cognitive course, psychiatric
symptoms, and neurologic examination to predict the likelihood of a vascular contribution to dementia [80]. If
present, each of the following features is assigned two points:
● Abrupt onset

● Fluctuating course
● History of stroke
● Focal neurologic symptoms
● Focal neurologic signs
The remaining features are each assigned one point:
● Stepwise deterioration
● Nocturnal confusion
● Preservation of personality
● Depression
● Somatic complaints
● Emotional incontinence (pseudobulbar affect)
● Hypertension
● Associated atherosclerosis
A score of 7 or greater indicates that a vascular contribution is likely. The score has been validated against autopsy
data and accurately discriminates pure or mixed vascular dementia from pure Alzheimer disease (AD) dementia
[81].
Cognitive screening tests — A cognitive screen should be performed to identify whether there is objective
evidence of cognitive impairment, required for a diagnosis of mild cognitive impairment (MCI) or dementia. The
Montreal Cognitive Assessment (MoCA) [82] is a 10-minute, 30-point cognitive screening instrument that seems to
be more sensitive than the Folstein Mini-Mental State Examination for detecting vascular cognitive impairment (VCI)
[83]. The MoCA is available free online and in multiple languages.
Although cutoffs are variably defined and scores are not meant to substitute for an integrated clinical diagnosis,
MoCA scores of 25 and below are generally considered abnormal. Use of the MoCA and other screening tools in
the evaluation of cognitive impairment is reviewed in detail separately. (See "Evaluation of cognitive impairment and
dementia", section on 'Cognitive testing'.)
Neuropsychological testing — Neuropsychological testing is suggested when the severity or pattern of cognitive
dysfunction remains unclear despite a cognitive screening test and neurologic examination.
Compared with normative scores, patients with VCI on average have the greatest impairments in speed, praxis,
executive function, and visual memory, with less prominent impairment in verbal episodic memory [51]. When
patients with similar degrees of global cognitive dysfunction due to either vascular dementia or AD are compared,
those with vascular dementia display better average performance on tests of verbal learning and recall and worse
average performance on tests of frontal executive function (eg, Wisconsin card sorting task) [84]. Performance on
tests of language, constructional abilities, memory registration, conceptual function, and attention and tracking tends
to be similar.
Limitations of most studies include lack of biomarker confirmation of AD pathology and lack of derived thresholds for
calculation of sensitivity and specificity. One study with autopsy confirmation found that a combination of better
categorical than phonemic fluency and better word list recall differentiated vascular dementia from AD with a
sensitivity of 85 percent and specificity of 67 percent; however, the sample sizes were small [85]. When interpreting

neuropsychological test profiles, clinicians must keep in mind that vascular dementia is a highly heterogenous
syndrome, and individual patients may have a cognitive profile that overlaps with AD.
Physical examination — Physical examination should seek to identify evidence of gait impairment, bradykinesia,
rigidity, hyperreflexia, and focal signs to suggest the presence of cerebral small vessel disease or stroke. (See "The
detailed neurologic examination in adults".)
Laboratory evaluation — Laboratory evaluation consists of electrolytes, creatinine, calcium, liver enzymes,
complete blood count, vitamin B12, and thyroid-stimulating hormone to exclude causative or contributing metabolic
or endocrine disorders.
Neuroimaging — Structural brain imaging should be performed to identify clinically unrecognized silent
cerebrovascular disease as a contributor to cognitive decline and is useful to confirm the presence of infarction or
hemorrhage in patients with a clinical history of stroke [46,86].
Magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for signs of cerebral small
vessel disease, including microbleeds that can point to a diagnosis of cerebral amyloid angiopathy (CAA). MRI is
therefore preferred over CT unless there are cost constraints or contraindications to MRI, although MRI is unlikely to
identify a treatable cause of dementia not visualized on CT.
Standards for Reporting Vascular Changes on Neuroimaging (STRIVE) criteria provide radiologic definitions and
terms for brain changes due to cerebral small vessel disease (figure 1) [2]. These criteria are endorsed in an
American Heart Association statement on stroke prevention in patients with silent cerebrovascular disease [87]. The
best described signs are [2]:
● Nonlacunar infarcts – Infarcts >15 mm or infarcts of any size in the cerebral cortex (image 2). These infarcts
may result from cardioembolic sources. Cortical infarcts <5 mm in size are also termed microinfarcts.
● Lacunes of presumed vascular origin – Small, ≤15 mm infarcts in the subcortical brain regions (image 3).
● White matter hyperintensities (on MRI) or hypodensities (on CT) of presumed vascular origin – Areas of
increased water signal in the white matter, corresponding to areas of demyelination, axon loss, and
oligodendrocyte loss (image 4).
● Microbleeds – Small (<10 mm) rounded areas of signal loss (hypointensity) on MRI susceptibility-weighted
sequences, corresponding to areas of hemosiderin deposition (image 1).
● Superficial siderosis – Linear hypointensity along the cortical surface visible on MRI susceptibility-weighted
sequences. When it is seen along single or multiple supratentorial gyri, it is usually a sign of CAA, although
other causes of superficial bleeding (eg, vascular malformations or cortical venous thrombosis) need to be
excluded.
● Perivascular spaces – Although not typically reported in routine radiologic practice, perivascular spaces
become more visible in patients with cerebral small vessel diseases (image 5).
● Atrophy – Cerebral small vessel disease is associated with accelerated brain atrophy.
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Evaluation for causes of cerebrovascular disease — An assessment of vascular risk factors and causes of
stroke is necessary to implement targeted secondary prevention for recurrent stroke.
A scientific statement from the American Heart Association provides suggestions for investigations for patients with
silent cerebrovascular disease [87]. At minimum, these investigations should include:
● A history of behavioral and lifestyle risks (smoking, diet, and obesity)
● Blood pressure measurement
● An assessment of pulse for evidence of atrial fibrillation
In patients with embolic-appearing silent infarcts, it is reasonable to perform prolonged cardiac rhythm monitoring. In
addition, if the embolic-appearing infarcts are in the perfusion territory of the carotid artery and the patient would be
a candidate for carotid revascularization, it is reasonable to also obtain noninvasive vascular imaging of the carotid
arteries to rule out carotid stenosis [87]. (See "Overview of the evaluation of stroke".)
DIAGNOSIS
Consensus diagnostic criteria for vascular dementia have been offered by several organizations: the American
Heart Association [46], the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [45], and
the International Society of Vascular Behavioural and Cognitive Disorders (VAS-COG) [30].
The diagnostic criteria are conceptually similar (table 3). Common elements include [30,45,46]:
● Classification of vascular cognitive impairment (VCI) as either vascular mild cognitive impairment (MCI; referred
to as "vascular minor neurocognitive disorder" in DSM-5) or vascular dementia (vascular major neurocognitive
disorder)
● A requirement that cerebrovascular disease be identified either by history of stroke or by neuroimaging

identification of silent cerebrovascular disease
● A judgment that the cerebrovascular disease be considered sufficient to cause cognitive impairment
Cognitive impairment should be categorized as either MCI (mild neurocognitive disorder) or dementia (major
neurocognitive disorder) [30,45,46]. In contrast to older criteria, some of the newer criteria specify that significant
impairment in only one domain can be considered sufficient to diagnose MCI or dementia, and do not require that
memory be one of the affected domains [30,45]. MCI is distinguished from dementia primarily by a relative
preservation of functioning. (See "Evaluation of cognitive impairment and dementia", section on 'Criteria for
dementia' and "Mild cognitive impairment: Epidemiology, pathology, and clinical assessment", section on
'Definitions'.)
Assessing cognition and cognitive-related functional decline can be challenging when there are additional effects of
stroke present. Severe aphasia may prevent assessment of any cognitive abilities other than language itself.
However, all of the modern diagnostic criteria specify that poststroke dementia can be diagnosed when aphasia
prevents independent function in activities of daily living [30,45,46]. When assessing the impact of cognition on

function, clinical judgment may be required to separate the impact of cognitive impairment from the impact of motor
and sensory impairments after stroke.
In all criteria, a history of stroke followed by new onset of dementia is sufficient proof of a vascular cause [30,45,46].
The clinician should obtain a retrospective history to verify the presence or absence of cognitive decline prior to
stroke, which, if present, suggests that there is an additional superimposed neurodegenerative disease present or
progressive cerebral small vessel disease. In most cases, clinical history and routine neuroimaging are probably
sufficient to make a clinical diagnosis of vascular dementia, Alzheimer disease (AD), or multiple-etiology dementia
with vascular dementia and AD. (See 'Differential diagnosis' above.)
All criteria specify that a high burden of clinically unrecognized silent cerebrovascular disease can be sufficient to
cause dementia [30,45,46]. The American Heart Association criteria call this syndrome "diffuse, subcortical
cerebrovascular disease pathology" [46]. The VAS-COG criteria provide the most specific criteria for burden of silent
cerebrovascular disease that may be sufficient to cause VCI [30]. According to these criteria, one to two large
vessel infarcts, a single large or strategically placed infarct, multiple lacunar infarcts (>2) outside the brainstem, one
to two strategically placed lacunes or in combination with extensive white matter lesions, or extensive and confluent
white matter lesions of presumed vascular origin may be considered sufficient to cause vascular MCI or dementia
[30].
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: Cognitive impairment and dementia".)
SUMMARY
● Vascular dementia refers to any dementia that is primarily caused by cerebrovascular disease or impaired
cerebral blood flow, or in which cerebrovascular disease or impaired cerebral blood flow is a contributing
causative factor. (See 'Definitions' above.)
● Vascular disease is a cause or contributor in 25 to 50 percent of cases of dementia, and vascular dementia is
the second most common type of dementia. (See 'Epidemiology' above.)
● Vascular dementia is caused by diseases of the cerebral vasculature and of the cardiovascular system,
including hypoperfusion and embolism from the heart. Any cause of ischemic stroke, intracerebral hemorrhage,
or subarachnoid hemorrhage can cause vascular dementia if the resulting brain injury is severe enough (table
1). In addition, cerebral small vessel diseases play an outsized role in the burden of vascular dementia. (See
'Etiology and pathophysiology' above.)
● There are two main syndromes of vascular dementia: poststroke dementia and vascular dementia without
recent stroke.
• Patients with poststroke dementia experience a stepwise cognitive decline following a clinically diagnosed
stroke. The cognitive profile is often marked by prominent impairment of executive functions, sometimes

with relative sparing of episodic memory. It may be accompanied by other cortical signs of stroke including
aphasia and apraxia. (See 'Poststroke dementia' above.)
• Patients with vascular dementia without recent stroke experience progressive or stepwise cognitive decline
with prominent impairment in executive function and processing speed. Brain imaging shows evidence of
clinically unrecognized cerebrovascular disease. (See 'Vascular dementia without recent stroke' above.)
● The differential diagnosis of vascular dementia includes other causes of acquired cognitive decline in older
adults, such as Alzheimer disease (AD), Lewy body diseases, and normal pressure hydrocephalus (NPH).
However, it is important to remember that many dementias are due to multiple etiologies, of which vascular
disease is one of the most common contributors. In most cases, clinical history and routine neuroimaging are
probably sufficient to make a clinical diagnosis of vascular dementia, AD, or multiple-etiology dementia with
vascular dementia and AD. (See 'Differential diagnosis' above.)
● The evaluation of patients with suspected vascular dementia should focus on the severity and profile of
cognitive decline, any clinical history of stroke, risk factors and causes of stroke or silent cerebrovascular
disease, brain imaging evidence of silent cerebrovascular disease, and the presence of clinical features or
biomarkers of other neurodegenerative diseases that might be an alternative or accompanying cause of
dementia. (See 'Evaluation' above.)
● Brain imaging should be performed to identify clinically unrecognized silent cerebrovascular disease as a
contributor to cognitive decline and is useful to confirm the presence of infarction or hemorrhage in patients with
a clinical history of stroke (figure 1). (See 'Neuroimaging' above.)
● Several organizations have published consensus diagnostic criteria for vascular dementia (table 3). Three
common elements include the following (see 'Diagnosis' above):
• Classification of vascular cognitive impairment (VCI) as either vascular mild cognitive impairment (MCI;
also referred to as "vascular minor neurocognitive disorder") or vascular dementia (vascular major
neurocognitive disorder).
• A requirement that cerebrovascular disease be identified either by history of stroke or by neuroimaging

identification of silent cerebrovascular disease.
• A judgment that the cerebrovascular disease be considered sufficient to cause cognitive impairment.
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Topic 5085 Version 27.0

GRAPHICS
Pathologic basis of vascular cognitive impairment
Parenchymal lesions of vascular etiology*
1. Large vessel or atherothromboembolic disease

a. Multiple infarcts
b. Single strategically placed infarct
2. Small vessel disease

a. Multiple lacunar infarcts in white matter and deep gray matter nuclei
b. Ischemic white matter change
c. Dilatation of perivascular spaces
d. Cortical microinfarcts and microhemorrhages
3. Hemorrhage
a. Intracerebral hemorrhage
b. Multiple cortical and subcortical microbleeds
c. Subarachnoid hemorrhage
4. Hypoperfusion
a. Hippocampal sclerosis
b. Laminar cortical sclerosis
Types of vascular lesions
1. Atherosclerosis
2. Cardiac, atherosclerotic, and systemic emboli
3. Arteriolosclerosis
4. Lipohyalinosis
5. Amyloid angiopathy
6. Vasculitis – infectious and noninfectious
7. Venous collagenosis
8. Arteriovenous fistulae – dural or parenchymal
9. Hereditary angiopathies – CADASIL, CARASIL, etc
10. Giant cell arteritis
11. Berry aneurysms
12. Miscellaneous vasculopathies – fibromuscular dysplasia, Moya-Moya
13. Systemic microangiopathies without vascular inflammatory cell infiltrates
14. Cerebral venous thrombosis
CADASIL: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASIL: cerebral autosomal recessive
arteriopathy with subcortical infarcts and leukoencephalopathy.
* Microinfarcts may be localized in cortical and subcortical structures because of different etiologies.
From: Sachdev P, Kalaria R, O'Brien J, et al. Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis Assoc
Disord 2014; 28:206. DOI: 10.1097/WAD.0000000000000034. Copyright © 2014. Reproduced with permission from Wolters Kluwer Health.
Unauthorized reproduction of this material is prohibited.
Graphic 118574 Version 1.0

Lobar versus nonlobar hemorrhage and microbleeds
Axial SWI magnetic resonance imaging from two different patients. In panel A, there are multiple lobar hemorrhages including
a left parietal lobar hematoma (arrowhead) and many lobar microbleeds (arrows), without microbleeds in the basal ganglia or
brainstem (not shown), meeting criteria for probable cerebral amyloid angiopathy. In panel B, there is a left thalamic
hematoma (arrowhead) with microbleeds in the basal ganglia (arrows). This pattern of nonlobar hemorrhages is not consistent
with cerebral amyloid angiopathy, and instead is probably caused by hypertension.
SWI: susceptibility-weighted imaging.
Courtesy of Eric Smith, MD.

Modified Boston criteria for cerebral amyloid angiopathy (CAA)
Modified Boston criteria
Definite CAA Full postmortem examination demonstrating:
Lobar, cortical, or cortical-subcortical hemorrhage
Severe CAA with vasculopathy
Absence of other diagnostic lesion
Probable CAA with supporting Clinical data and pathologic tissue (evacuated hematoma or cortical biopsy)
pathology demonstrating:
Lobar, cortical, or cortical-subcortical hemorrhage
Some degree of CAA in specimen
Absence of other diagnostic lesion
Probable CAA Clinical data and MRI or CT demonstrating:
Multiple hemorrhages restricted to lobar, cortical, or cortical-subcortical regions (cerebellar

hemorrhage allowed), or
Single lobar, cortical, or cortical-subcortical hemorrhage and focal* or disseminated ¶ superficial
siderosis
Age ≥55 years
Absence of other cause of hemorrhage or superficial siderosis
Possible CAA Clinical data and MRI or CT demonstrating:
Single lobar, cortical, or cortical-subcortical hemorrhage, or

Focal* or disseminated ¶ superficial siderosis
Age ≥55 years
Absence of other cause of hemorrhage or superficial siderosis
MRI: magnetic resonance imaging; CT: computed tomography.

* Siderosis restricted to three or fewer sulci.
¶ Siderosis affecting at least four sulci.
Reproduced with permission from: Linn J, Halpin A, Demaerel P, et al. Prevalence of superficial siderosis in patients with cerebral amyloid
angiopathy. Neurology 2010; 74:1346. Copyright © 2010 Lippincott Williams & Wilkins.

STRIVE criteria for classifying brain lesions caused by cerebral small vessel disease
The table shows examples (first row) and schematic representation (second row) of MRI features for changes related to small vessel
disease, with a summary of imaging characteristics for individual lesions.
DWI: diffusion-weighted imaging; FLAIR: fluid-attenuated inversion recovery; T2*: T2-star; SWI: susceptibility-weighted imaging; GRE: gradient-
recalled echo; MRI: magnetic resonance imaging.
Reproduced from: Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to
ageing and neurodegeneration. Lancet Neurol 2013; 12:822. Illustration used with the permission of Elsevier Inc. All rights reserved.

Cortical (nonlacunar) brain infarct
Axial FLAIR magnetic resonance imaging demonstrating a T2-hyperintense chronic cortical (nonlacunar) infarct in the
right parietal lobe (arrow).
FLAIR: fluid-attenuated inversion recovery.

Lacunar brain infarcts
Axial FLAIR magnetic resonance imaging demonstrating lacunar infarcts (arrows). Lacunes are defined
radiologically as round or ovoid, subcortical, fluid-filled cavities (signal similar to cerebrospinal fluid) of
between 3 and approximately 15 mm in diameter.

White matter hyperintensities of presumed vascular origin
Axial FLAIR magnetic resonance imaging demonstrating white matter hyperintensities of presumed vascular origin
(arrows).

Prominent perivascular spaces
Axial T1-weighted magnetic resonance images demonstrating prominent perivascular spaces (arrows).

Key aspects of AHA/ASA, VAS-COG, and DSM-5 criteria for vascular cognitive impairment
AHA/ASA VAS-COG Society DSM-5
Cognitive criteria
Discriminates between vascular mild Discriminates between mild and major Discriminates between mild and major
cognitive impairment and vascular vascular cognitive disorder (dementia). vascular neurocognitive disorder.
dementia.
Criteria for probable vascular cognitive impairment
There is imaging evidence of Either: The criteria are met for mild or major
cerebrovascular disease and either: The onset of cognitive deficits follows neurocognitive disorder.
There is a clear temporal one or more strokes or there are The clinical features are consistent with a
relationship between a vascular physical signs consistent with stroke. vascular etiology, as suggested by either
event (eg, clinical stroke) and OR of the following:
onset of cognitive deficits. If history of stroke or transient Onset of the cognitive deficits is
OR ischemic attack is absent, then there temporally related to one or more
There is a clear relationship in the is evidence of cognitive decline in cerebrovascular events.
severity and pattern of cognitive speed of information processing, OR
impairment and the presence of complex attention, or frontal Evidence for decline is prominent in
diffuse, subcortical cerebrovascular executive functions, accompanied by complex attention (including
disease pathology. one or more of: gait disturbances, processing speed) and frontal
There should be no history of urinary symptoms, or personality and executive function.
gradually progressive cognitive deficits mood changes. There is evidence of the presence of
before or after stroke that suggest the There should be neuroimaging evidence cerebrovascular disease from history,
presence of a nonvascular cognitive of either large vessel infarct, strategically physical examination, and/or
disorder (eg, Alzheimer disease). placed single infarct(s) or intracerebral neuroimaging considered sufficient to
hemorrhage(s), multiple (more than two) account for the neurocognitive deficits.
lacunar infarcts outside the brainstem, or The symptoms are not better explained
extensive and confluent white matter by another brain disease or systemic
lesions. disorder.
There should not be evidence of other Probable vascular neurocognitive disorder
nonvascular cognitive, medical, is diagnosed if one of the following is
psychiatric, or neurologic disorders present; otherwise possible vascular
sufficient to explain the cognitive neurocognitive disorder should be
impairment (including Alzheimer diagnosed:
disease).
Clinical criteria are supported by
neuroimaging evidence of significant
parenchymal injury attributed to
cerebrovascular disease
(neuroimaging supported).
OR
The neurocognitive syndrome is
temporally related to one or more
documented cerebrovascular events.
OR
Both clinical and genetic (eg, cerebral
autosomal dominant arteriopathy with
subcortical infarcts and
leukoencephalopathy) evidence of
cerebrovascular disease is present.
Criteria for possible vascular cognitive impairment
Meets criteria except that there is no Meets criteria except that neuroimaging Clinical criteria are met but neuroimaging
clear relationship between the is not available. is not available and the temporal
vascular disease and the cognitive relationship of the neurocognitive
impairment, there is insufficient syndrome with one or more
information (eg, neuroimaging studies cerebrovascular events is not established.
are not available), severe aphasia
precludes accurate cognitive
assessment, or there is evidence of
other neurodegenerative conditions
(eg, Alzheimer disease) in addition to
cerebrovascular disease.
Classification when other potential causes are present (ie, mixed disease)

Possible vascular mild cognitive Vascular mild/major cognitive disorder Not specifically addressed.
impairment or dementia should be with concomitant Alzheimer disease may
diagnosed when there is evidence of be diagnosed when the patient
other neurodegenerative conditions. additionally meets criteria for probable or
possible Alzheimer disease.
AHA/ASA: American Heart Association/American Stroke Association; VAS-COG: International Society of Vascular Behavioural and Cognitive
Disorders; DSM-5: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
From: Smith EE. Vascular cognitive impairment. Continuum (Minneap Minn) 2016; 22:490. DOI: 10.1212/CON.0000000000000304. Copyright
© 2016 American Academy of Neurology. Reproduced with permission from Wolters Kluwer Health. Unauthorized reproduction of this material is
prohibited.

Contributor Disclosures
Eric Smith, MD Nothing to disclose Clinton B Wright, MD, MS Nothing to disclose Kristine Yaffe, MD Consultant/Advisory
Boards: Eli Lilly [Dementia (Data and Safety Monitoring Board)]. Scott E Kasner, MD Grant/Research/Clinical Trial Support: WL
Gore and Associates [Stroke (PFO closure)]; Bayer [Stroke (rivaroxaban)]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke].
Consultant/Advisory Boards: Bayer; BMS; Merck; Boehringer Ingelheim; Abbvie; J&J; Medtronic; Urovant; Janssen
[Stroke]. Janet L Wilterdink, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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Etiology, clinical manifestations, and diagnosis of vascular dementia

● A clinically diagnosed stroke is followed by dementia; or

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Risk factors for new dementia after stroke include [27,28]:

● Stroke complications (incontinence, confusion, or seizures)

ETIOLOGY AND PATHOPHYSIOLOGY

The main types of cerebral small vessel disease are [32]:

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The remaining features are each assigned one point:

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● A history of behavioral and lifestyle risks (smoking, diet, and obesity)

● Blood pressure measurement

● An assessment of pulse for evidence of atrial fibrillation

● A requirement that cerebrovascular disease be identified either by history of stroke or by neuroimaging

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SOCIETY GUIDELINE LINKS

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• A requirement that cerebrovascular disease be identified either by history of stroke or by neuroimaging

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29. Iadecola C. The pathobiology of vascular dementia. Neuron 2013; 80:844.

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Topic 5085 Version 27.0

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Pathologic basis of vascular cognitive impairment

Parenchymal lesions of vascular etiology*

1. Large vessel or atherothromboembolic disease

2. Small vessel disease

Types of vascular lesions

Graphic 118574 Version 1.0

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Lobar versus nonlobar hemorrhage and microbleeds

SWI: susceptibility-weighted imaging.

Courtesy of Eric Smith, MD.

Graphic 119376 Version 1.0

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Modified Boston criteria for cerebral amyloid angiopathy (CAA)

Modified Boston criteria

Definite CAA Full postmortem examination demonstrating:

Lobar, cortical, or cortical-subcortical hemorrhage

Severe CAA with vasculopathy

Absence of other diagnostic lesion

Lobar, cortical, or cortical-subcortical hemorrhage

Some degree of CAA in specimen

Absence of other diagnostic lesion

Probable CAA Clinical data and MRI or CT demonstrating:

Multiple hemorrhages restricted to lobar, cortical, or cortical-subcortical regions (cerebellar

Age ≥55 years

Absence of other cause of hemorrhage or superficial siderosis

Possible CAA Clinical data and MRI or CT demonstrating:

Single lobar, cortical, or cortical-subcortical hemorrhage, or

Age ≥55 years