Etiology, clinical manifestations, and diagnosis of vascular dementia

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 of vascular cognitive impairment and 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

●Brain imaging identifies vascular brain injury in a patient with dementia but without a clinical history of stroke

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 of vascular cognitive impairment and 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 of the etiologies 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 persons with MCI 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 had cognitive impairment but not dementia (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, 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]. (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 [30,44,45]. 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 [45,46]. 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) [47-49]. (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 [50]. 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) [51].

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]. Using voxel-based lesion symptom mapping, a large study showed that infarction in the left frontotemporal lobes, left thalamus, and right parietal lobe were predictive of poststroke cognitive impairment [52]. 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 'Pathogenesis'.)

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 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 [50]. 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 should consist 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 [45,86].

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.

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 cardiac rhythm monitoring such as a 24-hour Holter monitor. 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 [45], the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [44], and the International Society of Vascular Behavioural and Cognitive Disorders (VAS-COG) [30].

The diagnostic criteria are conceptually similar (table 3). Common elements include [30,44,45]:

●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) [30,44,45]. 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 [30,44]. 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 [30,44,45]. 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 [30,44,45]. 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 [30,44,45]. The American Heart Association criteria call this syndrome "diffuse, subcortical cerebrovascular disease pathology" [45]. 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 alone 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 AND RECOMMENDATIONS

●Definition – 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.)

●Epidemiology – 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.)

●Pathogenesis – 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.)

●Clinical syndromes – There are two main syndromes of vascular dementia:

•Poststroke dementia – These patients 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.)

•Vascular dementia without recent stroke – These patients experience progressive or stepwise cognitive decline with prominent impairment in executive function and processing speed. Brain imaging shows evidence of cerebrovascular disease. (See 'Vascular dementia without recent stroke' above.)

●Differential diagnosis – 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. (See 'Differential diagnosis' above.)

●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, 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, usually MRI, 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.)

●Diagnosis – In most cases, clinical history and neuroimaging are sufficient to make a clinical diagnosis of vascular dementia, AD, or multiple-etiology dementia with vascular dementia and AD. 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.

ACKNOWLEDGEMENT — The views expressed in this topic are those of the author(s) and do not reflect the views of the National Institutes of Health, the Department of Health and Human Services, or the United States government.