Clinical Science (2017) 131 1059–1068
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Review Article
Clinical presentations and epidemiology of vascular
dementia
Eric E. Smith
Room 2941, Health Sciences Centre, University of Calgary, 3330 University Dr NW, Calgary, AB Canada T2N 2T9
Correspondence: Eric E. Smith (eesmith@ucalgary.a)
Received: 29 November 2016
Revised: 27 December 2016
Accepted: 15 February 2017
Version of Record published:
17 May 2017

c 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.
Cerebrovascular and cardiovascular diseases cause vascular brain injury that can lead to
vascular cognitive impairment (VCI). VCI is the second most common neuropathology of de-
mentia and mild cognitive impairment (MCI), accounting for up to one-third of the population
risk. It is frequently present along with other age-related pathologies such as Alzheimer’s
disease (AD). Multiple etiology dementia with both VCI and AD is the single most common
cause of later life dementia. There are two main clinical syndromes of VCI: post-stroke VCI
in which cognitive impairment is the immediate consequence of a recent stroke and VCI
without recent stroke in which cognitive impairment is the result of covert vascular brain
injury detected only on neuroimaging or neuropathology. VCI is a syndrome that can result
from any cause of infarction, hemorrhage, large artery disease, cardioembolism, small ves-
sel disease, or other cerebrovascular or cardiovascular diseases. Secondary prevention of
further vascular brain injury may improve outcomes in VCI.
Introduction
Vascular disease is the second most common cause of dementia [1]. Vascular cognitive impairment (VCI)
has been defined as clinical–radiological–pathological syndrome in which cognitive impairment, encom-
passing dementia as well as milder forms of impairment, can be attributed to vascular disease [2]. There
are two main clinical forms of VCI: one in which VCI is caused by symptomatic stroke and the other
in which VCI is instead caused by covert vascular brain injury recognized only on brain imaging or at
autopsy [3]. It is important to recognize that VCI frequently coexists along with other brain pathologies,
most frequently Alzheimer’s disease (AD) pathology, in persons with dementia. In fact, multiple etiology
dementia caused by vascular disease as well as AD (also called mixed dementia) is the most common
cause of later life dementia [1]. In clinical practice, neuroimaging plays a key role in VCI diagnosis by
confirming the clinical diagnosis of stroke and by identifying covert forms of injury (such as silent brain
infarction, hemorrhage, and white matter lesions) that cause cognitive impairment [4].
The clinical and cognitive profile of VCI differs from other causes of cognitive impairment and demen-
tia [5]. However, there is wide inter-individual variation in the manifestations of vascular brain injury
along with overlap with other non-VCI causes of dementia, such that clinical signs and symptoms may
suggest the diagnosis of VCI but radiological or pathological confirmation of vascular brain injury is usu-
ally needed.
In this review VCI diagnostic criteria, epidemiology, and clinical manifestations are reviewed. This
review is based on the author’s experience, published diagnostic criteria, and recent consensus statements
complemented by targeted literature searches and handsearching of relevant references.
Diagnostic criteria for vascular cognitive impairment
VCI is an umbrella term intended to describe any form of cognitive impairment that results from vascular
disorders [2].
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Table 1. Recently proposed diagnostic criteria for VCI.

AHA/ASA Vas-Cog society DSM-5

Cognitive classification Vascular MCI or vascular Vascular mild cognitive Mild vascular neurocognitive
dementia disorder or vascular major disorder or major vascular
cognitive disorder neurocognitive disorder
(dementia)
Clinical evidence of Either clear temporal Either onset of cognitive Either onset of cognitive
vascular cause relationship between a deficits follows strokes or deficits is temporally related
vascular event and onset of there are physical signs to one or more
cognitive deficits or clear consistent with stroke or cerebrovascular events or
relationship in the severity cognitive decline in speed evidence for prominent
and pattern of cognitive of information processing, decline in complex attention
impairment and the complex attention, or frontal (including processing
presence of diffuse, executive functions, speed) and
subcortical cerebrovascular accompanied by one or frontal-executive function;
disease pathology more of: gait disturbances, there should be evidence of
urinary symptoms or cerebrovascular disease
personality and mood from history, physical
changes examination, and/or
neuroimaging
Neuroimaging Yes Yes No
evidence of
cerebrovascular
disease required
Exclusionary criteria History of gradually Evidence of other Deficits are not better
progressive cognitive non-vascular cognitive, explained by another brain
deficits before or after medical, psychiatric or disease or systemic
stroke that suggests the neurological disorders disorder
presence of a non-vascular sufficient to explain the
cognitive disorder (e.g. AD) cognitive impairment
(including AD)
Criteria for ‘possible’ Meets criteria except no clear Meets criteria except that Clinical criteria are met but
VCI relationship between neuroimaging is not neuroimaging is not
vascular disease and the available available and the temporal
cognitive impairment, relationship of the
insufficient information (e.g. neurocognitive syndrome
no neuroimaging), aphasia with one or more
precludes accurate cerebrovascular events is
cognitive assessment, or not established
evidence of concomitant
neurodegenerative
conditions (e.g. AD)
Classification when Possible vascular MCI or Concomitant AD may be Not specifically addressed
other potential possible vascular dementia diagnosed when the patient
causes are present should be diagnosed when additionally meets criteria
(i.e. mixed disease) there is evidence of other for probable or possible AD
neurodegenerative
conditions

Clinical classification criteria for VCI have recently been offered by the American Heart Association (AHA) [6],
International Society of Vascular Behavioural and Cognitive Disorders (Vas-Cog) [5], and as part of the 5th revision
of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [7].
Common to these classification schemes is that some degree of cognitive impairment should be present along
with evidence – from some combination of history, physical examination, cognitive profile, and diagnostic testing
including neuroimaging – of a vascular contribution to the cognitive impairment (Table 1) [5–7]. VCI may be fur-
ther classified as probable or possible based on the completeness of the diagnostic work up and the presence or
absence of evidence for competing causes of dementia such as AD. In practice, pure VCI may be the minority
of cases because comorbid pathologies such as AD are commonly identified, or at least cannot be ruled out with
certainty.
Cognitive syndromes in VCI may be subdivided by severity as either mild cognitive impairment (MCI) or de-
mentia [5,6]. MCI is defined based on the presence of acquired cognitive concerns, representing a decline from

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a previous level of functioning, accompanied by objective evidence of impairment on cognitive testing but with
essentially preserved activities of living. In dementia, impairments are severe enough to interfere with activities of
living. In contrast with older definitions of dementia, newer definitions of vascular dementia do not require evidence
of memory impairment or impairments in more than one cognitive domain [5–7]. This allows a diagnosis of vascular
dementia to be made in the not uncommon setting where a patient with VCI has severely impaired executive function
but with preserved memory and other cognitive domains.
A special challenge in diagnosing MCI and dementia in the setting of previous stroke is that functional impair-
ments may also result from the motor and sensory consequences of the stroke, independent of the degree of impaired
cognition. Clinical judgment must be exercised to determine the degree to which functional impairments can be
attributed to cognitive impairment, as opposed to other consequences.
Another commonality of these criteria is that they distinguish post-stroke VCI from VCI that occurs in the absence
of recent stroke [5–7]. It is now clear that the absence of a clinical history of stroke does not exclude VCI. Neuroima-
ging and neuropathology studies have established that accrual of clinically silent, or ‘covert’, cerebrovascular disease
in the absence of stroke is sufficient to cause clinically relevant cognitive impairment [8,9].
Only the Vas-Cog criteria provide explicit criteria for classification of VCI according to the causative cerebrovas-
cular pathology [5]. However, identifying the causative pathology is critical to devise a rationale treatment plan to
prevent more vascular brain injury.

Epidemiology of vascular cognitive impairment

Despite variation in diagnostic criteria and screening methods, population-based cohort studies agree that vascular
dementia is the second most common type of dementia [10]. Using data from the Health and Retirement study, the
prevalence of vascular dementia was estimated to be 0.98% in 71–79 years old, 4.09% in 80–89 years old, and 6.10%
in >90 years old, representing a total of 594,000 cases in the United States in 2002 [10].
Epidemiological studies probably underestimate vascular contributions to dementia because of misclassification
of vascular or mixed dementia as AD. In particular, studies without systematic neuroimaging or neuropathology may
overlook vascular brain injury not associated with stroke. Autopsy-based studies are considered the gold standard
for identifying the pathological correlates of dementia. Clinic and community-based autopsy studies show that small
clinically unrecognized infarctions are very common and are associated with dementia [11–14]. Some degree of vas-
cular disease, predominantly small vessel disease, is seen neuropathologically in up to 80% of cases of dementia [15].
Microinfarcts, which are sub-millimeter infarcts only visible in light microscopy, are mostly undetectable on MRI
[16]; therefore, even when brain MRI is performed the degree of brain vascular injury can be underestimated [17].
Ultra-high field 7.0 Tesla MRI shows promise for detecting many microinfarcts, but only a minority of the microin-
farcts detectable at 7.0 Tesla are visible on routine clinical scans (about a quarter of the microinfarcts seen at 7.0 Tesla
are visible at 3.0 Tesla but few or none are visible at 1.5 Tesla) [18].
Given that vascular brain injury frequently coexists with other late-life neurodegenerative pathologies and that
criteria for multiple etiology dementia are not well defined, another approach to quantifying the public health impact
of VCI avoids attributing causes in each individual and instead uses statistical modeling to estimate the population
attributable risk of vascular brain injury. The population attributable risk estimates the proportion of dementia cases
that would be removed from the whole population if vascular brain injury no longer existed. This estimate accounts
for the fact that vascular brain injury often coexists with other pathologies, estimating the impact of vascular dementia
at the population level. Vascular brain injury accounts for up to 33% of dementia risk according to autopsy studies
[14,19]. This makes VCI an enormous public health problem. With more than 50 million prevalent cases of dementia
worldwide [20], vascular dementia may account for up to 17 million cases of dementia with annual costs of up to 200
billion U.S. dollars [21].
In contrast with vascular dementia, there is much less information on the epidemiology of vascular MCI. A
community-based study of the neuropathological basis of MCI found that 16% of MCI patients had infarcts as
their sole pathology, while 17% had both infarcts and AD pathology [22]. Infarcts were the sole cause of 13% of
amnestic MCI and 19% of non-amnestic MCI [22]. A clinic-based study found that 18% of cognitively impaired,
not demented (CIND) patients were clinically diagnosed with a vascular cause [23]. In the population-based Cana-
dian Study on Health and Aging, 15% of CIND participants were classified as due to vascular disease [24]. In the
population-based Cardiovascular Health Study, the presence of silent brain infarcts was associated with MCI [25],
and a community-based autopsy study found that cerebral infarcts were common in MCI (35%) with a frequency
that was intermediate between those who died with normal cognition and those who died with dementia [22].


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Figure 1. VCI occurs in two main settings

VCI may be classified into two main clinical syndromes: VCI, which is the immediate consequence of a clinically symptomatic stroke and
VCI, which results from the accumulation of clinically hard to detect vascular brain injury.

Overall, the frequency of cerebrovascular disease as a cause of MCI parallels the literature on vascular disease
as a cause of late-life dementia, with vascular disease as the second most common cause but as frequently or more
frequently coexisting along with AD pathology.
One of the most important clinical questions for the MCI patient is whether she or he will progress to dementia.
Because there are evidence-based therapies for control of vascular risk factors, it is possible that progression from
vascular to dementia MCI is preventable.
There are fewer data on the risk of progression from vascular MCI to dementia. In the Canadian Study on Health
and Aging, vascular CIND participants had a 46% risk of dementia at 5-year follow-up [26], while in a clinic-based
study 40% had converted into dementia by 2 years [27]. Of the incident cases of dementia, 40–50% were clinically
attributed to non-vascular causes (most commonly AD); however, because detailed neuroimaging or neuropathology
work-up was not done it is possible that in some cases progression of silent cerebrovascular disease progression was
misattributed as AD, such that the actual frequency of incident vascular or mixed dementia may have been underes-
timated. There are no adequately powered clinical trials of vascular risk reduction to prevent progression of MCI to
dementia.
Overall, the relatively scanty existing literature suggests that the syndrome of vascular MCI is not benign and is
associated with rates of progression to dementia that are similar to the rate of progression from MCI to AD dementia.
Progression to dementia may be caused by new strokes or progression of silent cerebrovascular disease, or may be
due to accrual of other age-related pathology (including AD) in a brain rendered vulnerable to other insults because
of the baseline presence of vascular brain injury.
The clinical course of VCI is variable, and there is hope that progression can be arrested by vascular risk factor con-
trol. However, many patients experience further cognitive decline. The trajectory of age-related cognitive decline is,
on average, accelerated after stroke [28], and the risk for dementia is increased [29], particularly (but not exclusively),
in patients with recurrent strokes [29].

Causes and risk factors

Risk factors for vascular dementia include age, hypertension, diabetes, and smoking [30]. Risk factors for stroke
are risk factors for vascular dementia, as stroke is a major pathway (but not the only pathway) linking cardiac and
cerebrovascular disease to vascular brain injury and VCI (Figure 1).
It is important not to overlook that VCI is a syndrome, not a disease. Any clinical diagnostic assessment of
VCI must seek to identify the individual or multiple cerebrovascular diseases that contribute to VCI in that indi-
vidual. The complexity of VCI is further compounded by the fact that the same cerebrovascular disease may lead to
VCI through multiple types of vascular brain injury, and the same form of vascular brain injury (e.g. white matter

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Figure 2. Pathophysiology of VCI

Risk factors lead to cardiac and cerebrovascular diseases that cause vascular brain injury, leading to impairment.

hyperintensity [WMH] of presumed vascular origin) may be caused by several different cerebrovascular diseases
(Figure 2) [31]. Ultimately, it is by unraveling these diseases and their pathways to brain injury and clinical con-
sequences that advances can be made in the diagnosis, prevention, and treatment of VCI [31]. A consensus scientific
statement has reviewed the treatment of VCI, finding that blood pressure lowering was the vascular risk reduction
strategy that is best supported by the current evidence [6].
Causes of VCI can be classified according to site of vascular disease: cardiac, large vessel, or small vessel disease
(Table 2) [5]. Of the three, small vessel disease – evidenced by manifestations of vascular brain injury such as small
infarcts, microbleeds, and WMH – appears to be the most common cause of VCI according to community-based
autopsy studies [14].
Small vessel disease can be subdivided into two main classes: arteriosclerosis due to hypertension, aging, and other
vascular risk factors; and cerebral amyloid angiopathy (CAA) caused by accumulation of amyloid in small arteries in
the leptomeninges and cortex [32].
CAA can be recognized clinically with high specificity (but without high sensitivity) in patients with lobar in-
tracerebral hemorrhage or transient focal neurological episodes based on a lobar pattern of hemorrhages, microb-
leeds, and superficial siderosis [33]. When there is more than one bleed (including superficial siderosis) affecting only
the lobar brain regions, without bleeds in non-lobar locations such as the basal ganglia, the likelihood of pathological
confirmation of CAA is very high [34]. Recent research shows that most CAA patients are cognitively impaired, with
a cognitive profile of executive dysfunction that is more similar to VCI than to the profile of prominent episodic
memory impairment seen in AD [35,36].

Clinical symptoms and signs

The syndrome of VCI must involve, by definition, some degree of cognitive impairment. The neuropsychological pro-
file of VCI depends on the location and severity of vascular brain injury, which differs by individual and by type of
cerebrovascular disease. Because cerebrovascular disease often involves frontal lobes and/or their white matter con-
nections with subcortical structures, patients with VCI tend to exhibit prominent impairments in executive function
[37]. However, VCI can affect any cognitive domain and can sometimes mimic the cognitive profiles of neurodegen-
erative diseases such as AD.
Cognitive symptoms reported by patients and families may include forgetfulness, confusion, or decreased ability
to perform cognitive demanding activities including household finances or occupational activities. In the author’s
experience, cognitive difficulties in many domains are expressed as ‘forgetting’, even when non-memory domains
are primarily involved. For example, patients with documented executive dysfunction in attention and set-shifting
may complain of ‘forgetting’ how to follow instructions or ‘forgetting’ items on a grocery list, despite intact episodic
memory on testing. A careful history of the setting and circumstances of forgetfulness usually allows the clinician to
anticipate which cognitive domains are involved.
Alterations in mood and behavior are common. Vascular brain injury has been associated with later life onset
depression [38], apathy [39], and psychosis [40]. There is increasing interest in early behavioral manifestations of


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Table 2. Pathophysiological causes of VCI.

Any process leading to vascular brain injury can cause VCI.

Injury type Mechanism Causes

Infarction Cardioembolism Atrial fibrillation

Cardiomyopathy with low ejection fraction
Other
Large artery disease Atherosclerosis
Small vessel disease (lacunar infarction) Lipohyalinosis
CADASIL
CARASIL
Other determined causes Venous thrombosis
Arterial dissection
Others
Undetermined causes (cryptogenic)
Hemorrhage Primary intracerebral hemorrhage Arteriosclerosis
CAA
Secondary intracerebral hemorrhage Vascular malformation
Venous thrombosis
Other
Subarachnoid hemorrhage Ruptured aneurysm
Vascular malformation
Other
White matter rarefaction Ischemic demyelination Other Arteriosclerosis/conventional vascular risk factors
(leukoaraiosis)
CAA
Genetic causes including CADASIL
Venous collagenosis
Undetermined

many cognitive disorders including VCI, but more work is needed to determine the behavioral profile of vascular
MCI and its prognostic implications [41].
Clinical examination of the VCI patient should aim to discover neurological dysfunction in a vascular territory
related to prior stroke, or subtle signs of motor and sensory dysfunction related to small vessel disease. Signs de-
scribed in patients with subcortical ischemic brain injury include increased tone, hyperreflexia, Babinski responses,
and frontal lobe release signs. Gait impairment is relatively common. A syndrome of lower body Parkinsonism may
be evident with increased leg tone, short stride length, and decreased gait speed despite normal arm and hand tone
and dexterity [42]. Gait impairment or subtle decrease in gait velocity may occur [43].

Cognitive assessment
The history must be complemented by an objective assessment of cognitive performance, either by a bedside assess-
ment tool or formal neuropsychological testing. Objective assessment is essential to place cognitive symptoms in the
appropriate context. It is not uncommon for dramatic cognitive symptoms to be revealed to be entirely subjective after
testing demonstrates normal range performance. Conversely, many patients with significant impairment express few
symptoms because of lack of insight, denial, or apathy.
A global cognitive screening tool can be used to objectively document cognitive impairments. The most commonly
used instruments are the Folstein Mini-Mental State exam [44] and the Montreal Cognitive Assessment (MoCA)
tool [45]. A systematic review showed that the MoCA is more sensitive than the Folstein Mini-Mental State exam at
detecting VCI, but at the cost of somewhat lower specificity [46].
When the presence, degree, or pattern of cognitive impairment remains uncertain after bedside testing, it may be
appropriate to obtain more detailed testing. Neuropsychological testing allows a more precise assessment of mul-
tiple cognitive domains often grouped as episodic memory, visual memory, executive functions (including attention,
working memory, and set-shifting), processing speed, language, and visuospatial function. Harmonization criteria

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Figure 3. VCI caused by strategic infarction

Example of VCI with impaired verbal memory, caused by strategic infarction. A 61-year-old smoker presented with acute onset of memory
loss. Neuropsychological testing showed impaired performance (below 2nd percentile) on delayed free recall (Wechsler Logical Memory II
test), delayed recognition of stories (Wechsler Logical Memory II test), and recall discriminability on the California Verbal Learning Test II.
Performances on tests of recall of visual material, executive function, and processing speed were within normal limits. MRI DWI showed a
single acute infarction in the anterior thalamus and genu of the internal capsule.

for VCI research have been developed that also serve as a useful guide for clinical and neuropsychological assessment
[47].
Although executive dysfunction is often cited as the hallmark of VCI, it need not be present in every case (Figure 3).
Conversely, executive dysfunction is not specific to VCI as it is a well-recognized consequence of other neurodegen-
erative pathologies too. Population-based studies clearly show that cerebral small vessel causes impairment on tests
of word list learning (a classic episodic memory task) as well as processing speed [48]. A consideration of the degree
of executive dysfunction and whether it is out of proportion to the degree of impairment in other domains such as
episodic memory is more helpful than looking at executive dysfunction alone [37]. A pattern of prominent executive
dysfunction and slow processing speed, out of proportion to other cognitive domains, should raise the possibility of
VCI. However, additional information (from history, physical exam, neuroimaging, or neuropathology) should be
sought to confirm the presence of vascular brain injury.
Comorbid β-amyloid pathology, which is commonly present, modifies the cognitive profile of VCI. In a study of
patients with subcortical ischemic VCI, 31% had a positive β-amyloid positron emission tomography (PET) scan and
these patients had worse episodic memory than the patients with a negative β-amyloid PET scan [49]. Patients with
positive β-amyloid PET scans exhibit faster decline [50].

Confirming the relationship to stroke or vascular brain injury

In post-stroke VCI, there is a clear temporal relationship between the onset of stroke and the onset of new cognitive
impairment. It is important to recognize that not all cognitive impairment after a recent stroke is necessarily attribut-
able to the stroke. The clinician should obtain a history of whether progressive cognitive decline was present prior to


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Figure 4. VCI without recent stroke

Example of VCI without recent stroke, due to subcortical ischemic vascular brain injury. A 69-year-old man presented with dementia and
failure to thrive. MoCA score was 11 out of 30. T2-weighed MRI fluid-attenuated inversion recovery (FLAIR) shows multiple chronic lacunar
infarcts in the basal ganglia (arrowheads) and severe confluent WMHs (arrow).

stroke as well, to identify additional potential contributors such as concomitant VCI from small vessel disease or co-
morbid neurodegenerative diseases such as AD [6]. The use of a standardized assessment tool such as the Informant
Questionnaire on Cognitive Decline in the Eldery (IQCODE) can be helpful to diagnose pre-stroke decline [51].
Many patients with post-stroke VCI have a history of multiple strokes. However, infarcts or hemorrhages in single
strategic brain locations can be sufficient to cause VCI [6]. An example is provided in Figure 3. Brain regions asso-
ciated with risk for post-stroke VCI include the left hemisphere language areas, medial frontal cortex, peri-caudate
region, medial or anterior thalamus, and the medial temporal lobe. The exact cognitive profile depends on the spe-
cialization of the brain region(s) affected by stroke.
VCI without recent stroke occurs when cognitive impairment accrues in the absence of a recent stroke, but vascular
brain injury sufficient to cause the impairment is detected on neuroimaging or neuropathology (Figure 4). In some
cases there may be a remote history of stroke, but the key difference from post-stroke VCI is that the onset of cognitive
impairment is not temporally linked to a symptomatic stroke. Most of the clinically recognized cases of VCI without
recent stroke are due to subcortical ischemic vascular brain injury, manifest as infarcts, WMH, and other signs of
small vessel disease. The entity of Binswanger’s disease, defined as multiple subcortical lacunar infarcts with ischemic
leukoencephalopathy, has been recognized as a pathological substrate for dementia for more than 100 years [52]. The
rare disease cerebral autosomal dominant arteriopathy with subcortical ischemic leukoencephalopathy (CADASIL) is
a genetic prototype of subcortical ischemic vascular brain injury [53]. More recently, there is an appreciation that cor-
tical microinfarction is an important mechanism for VCI without recent stroke [16]. Microinfarcts are sub-millimeter
infarcts that are histologically visible at autopsy but not detectable on routine clinical MRI, although newer research
suggests that the largest of them can be seen on high-resolution MRI at 3 Tesla [54].

Conclusions
VCI is a very common contributor to cognitive impairment, often in conjunction with neurodegenerative diseases
such as AD, accounting for up to one-third of the risk for dementia in the population. Although often viewed as a
disorder that prominently affects executive function, VCI is frequently accompanied by diverse clinical manifestations
that include alterations of other cognitive domains, behavioral disturbances, and impaired motor function and gait.
Additional research is needed on non-cognitive consequence of vascular cognitive disorders and on outcomes in
vascular MCI.

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Competing interests
The author declares that there are no competing interests associated with this manuscript.

Abbreviations
AD, Alzheimer’s disease; AHA, American Heart Association; ASA, American Stroke Association; CAA, cerebral amyloid an-
giopathy; CADASIL, cerebral autosomal dominant arteriopathy with subcortical ischemic leukoencephalopathy; CIND, cognitively
impaired, not demented; DSM-5, Diagnostic and Statistical Manual of Mental Disorders; MCI, mild cognitive impairment; MoCA,
Montreal Cognitive Assessment; PET, positron emission tomography; Vas-Cog, International Society of Vascular Behavioural and
Cognitive Disorders; VCI, vascular cognitive impairment; WMH, white matter hyperintensity.

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