Vascular Dementia

Primer

Vascular dementia is a neurodegenerative disorder (dementia) that occurs due to cerebrovascular disease and hypoperfusion. This can range from large vessel stroke to microvascular disease. The symptoms and presentation can be heterogenous, depending on the extent of vascular lesions and the anatomical location. Lesions can be limited to a single site, multifocal, or diffusely distributed. As such, there are also varied definitions and criteria for the diagnosis of vascular dementia.

Epidemiology
  • The prevalence is higher in males than in females.
  • The prevalence for vascular dementia ranges from 0.2% in the 65-70 years age group to 16% in 80 years and older.
  • Within 3 months post-stroke, 20%-30% of individuals are diagnosed with dementia.
  • It is suggested that the vascular dementia is overdiagnosed, as non-significant cerebrovascular lesions may be overcalled as the main etiology for the presenting dementia.[1][2]
Prognosis
  • Patients with vascular dementia often have multiple infarctions, and there is often an acute onset and stepwise decline (i.e. - symptoms stay the same for a while and then suddenly get worse, due to a sudden cerebrovascular event).
    • There can be intervening periods of stability and even improvement in some cases.[3]
Comorbidity
  • Most individuals with vascular dementia have one or more cardiovascular risk factors such as diabetes, dyslipidemia, and/or hypertension.
Risk Factors
  • Cardiovascular risk factors such as diabetes, dyslipidemia, and/or hypertension are also risk factors for vascular dementia.
Terminology
  • There is often confusing and poorly defined terminology in the medical literature that is used interchangeably for vascular dementia, including: vascular cognitive impairment, post-stroke dementia, post-stroke cognitive impairment, and multi-infarct dementia.
  • Recent consensus groups have attempted to define new terminology to improve diagnostic terms.

DSM-5 Diagnostic Criteria

Criterion A

The criteria are met for major or mild neurocognitive disorder.

Criterion B

The clinical features are consistent with a vascular etiology, as suggested by either of the following:

  1. Onset of the cognitive deficits is temporally related to one or more cerebrovascular events.
  2. Evidence for decline is prominent in complex attention (including processing speed) and frontal-executive function.
Criterion C

There is evidence of the presence of cerebrovascular disease from history, physical examination, and/or neuroimaging considered sufficient to account for the neurocognitive deficits.

Criterion D

The symptoms are not better explained by another brain disease or systemic disorder.

Probable vs. Possible

Probable vascular neurocognitive disorder is diagnosed if one of the following is present; otherwise possible vascular neurocognitive disorder should be diagnosed:

  1. Clinical criteria are supported by neuroimaging evidence of significant parenchymal injury attributed to cerebrovascular disease (neuroimaging-supported)
  2. The neurocognitive syndrome is temporally related to one or more documented cerebrovascular events
  3. Both clinical and genetic (e.g. - cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) evidence of cerebrovascular disease is present.

Possible vascular neurocognitive disorder is diagnosed if the clinical criteria are met but neuroimaging is not available and the temporal relationship of the neurocognitive syndrome with one or more cerebrovascular events is not established.

Specifiers

Specifiers

Specify if:

  • Probable major vascular neurocognitive disorder, with behavioral disturbance
  • Probable major vascular neurocognitive disorder, without behavioral disturbance
  • Possible major vascular neurocognitive disorder, with behavioral disturbance
  • Possible major vascular neurocognitive disorder, without behavioral disturbance

NINDS–AIREN Criteria

The Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) proposed a set of criteria in 1993 that remain in use for clinical research for vascular dementia.[4]

I

The criteria for the clinical diagnosis of probable vascular dementia include all of the following:

  1. Dementia defined by cognitive decline from a previously higher level of functioning and manifested by impairment of memory and of two or more cognitive domains (orientation, attention, language, visuospatial functions, executive functions, motor control, and praxis), preferable established by clinical examination and documented by neuropsychological testing; deficits should be severe enough to interfere with activities of daily living not due to physical effects of stroke alone.
  2. Cerebrovascular disease, defined by the presence of focal signs on neurologic examination, such as hemiparesis, lower facial weakness, Babinski sign, sensory deficit, hemianopia, and dysarthria consistent with stroke (with or without history of stroke), and evidence of nof relevant CVD by brain imaging (CT or MRI) including multiple large vessel infarcts or a single strategically placed infarct (angular gyrus, thalamus, basal forebrain, or PCA or ACA territories), as well as multiple basal ganglia and white matter lacunes, or extensive periventricular white matter lesions, or combinations thereof.
  3. A relationship between the above two disorders, manifested or inferred by the presence of one or more of the following: (a) onset of dementia within 3 months following a recognized stroke; (b) abrupt deterioration in cognitive functions; or fluctuating, stepwise progression of cognitive deficits.

Exclusion Criteria

Exclusion criteria: cases with disturbance of consciousness, delirium, psychosis, severe aphasia, or major sensorimotor impairment precluding neuropsychological testing. Also excluded are systemic disorders or other brain diseases (such asAlzheimer's) that in and of themselves could account for deficits in memory and cognition.
II

Clinical features consistent with the diagnosis of probable vascular dementia include the following:

  • (a) Early presence of gait disturbance (small-step gait or marche a petits pas, or magnetic, apraxic-ataxic or parkinsonian gait)
  • (b) history of unsteadiness and frequent, unprovoked falls
  • (c) early urinary frequency, urgency, and other urinary symptoms not explained by urologic disease
  • (d) pseudobulbar palsy; and
  • (e) personality and mood changes, abulia, depression, emotional incontinence, or other subcortical deficits including psychomotor retardation and abnormal executive function
III

Features that make the diagnosis of vascular dementia uncertain or unlikely include:

  • (a) early onset of of memory deficit and progressive worsening of memory deficit and progressive worsening of memory and other cognitive functions such as language (transcortical sensory aphasia), motor skills (apraxia), and perception (agnosia), in the absence of corresponding focal lesions on brain imaging
  • (b) absence of focal neurological signs, other than cognitive disturbance; and
  • (c) absence of cerebrovascular lesions on brain CT or MRI
IV

Clinical diagnosis of possible vascular dementia may be made in the presence of dementia (section I-1) with focal neurologic signs in patients in whom brain imaging studies to confirm definite CVD are missing; or in the absence of clear temporal relationship between dementia and stroke; or in patients with subtle onset and variable course (plateau or improvement) of cognitive deficits and evidence of relevant CVD.

V

Criteria for diagnosis of definite vascular dementia are:

  • (a) clinical criteria for probable vascular dementia
  • (b) histopathologic evidence of CVD obtained from biopsy or autopsy
  • (c) absence of neurofibrillary tangles and neuritic plaques exceeding those expected for age; and
  • (d) absence of other clinical or pathological disorder capable of producing dementia
VI

Classification of vascular dementia for research purposes may be made on the basis of clinical, radiologic, and neuropathologic features, for subcategories or defined conditions such as cortical vascular dementia, subcortical vascular dementia, BD, and thalamic dementia.

The term “AD with CVD” should be reserved to classify patients fulfilling the clinical criteria for possible AD and who also present clinical or brain imaging evidence of relevant CVD. Traditionally, these patients have been included with VaD in epidemiologic studies. The term “mixed dementia,” used hitherto, should be avoided.

VICCCS (Vascular Cognitive Impairment) Criteria

The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) Criteria were established in 2017, and proposed a detailed set of criteria to define vascular cognitive impairment.[5]

Post‐stroke Dementia

Post-stroke dementia (VICCCS Criteria)

Skrobot, O. A. et al. (2017). The vascular impairment of cognition classification consensus study. Alzheimer's and Dementia, 13(6), 624-633.

Post‐stroke dementia (PSD) patients may or may not have presented evidence of mild cognitive impairment before stroke. The patient may exhibit immediate and/or delayed cognitive decline that begins after, but within 6 months, of stroke, that does not recover. PSD results from different vascular causes and changes in brain. It includes cases with multiple corticosubcortical infarcts, strategic infarcts, subcortical ischemic vascular dementia, and various forms of neurodegenerative pathology, including AD, which develop within 6 months of stroke*. This temporal basis for cognitive decline after stroke differentiates PSD from other forms of major VCI (VaD).

* = Because a key facet of the definition of PSD is a time component of the appearance of decline within 6 months of having a stroke that does not recover, then irrespective of the presence or absence or comorbid neurodegenerative pathology, the aspect of time should be the primary variable for delineating between PSD (with or without neurodegenerative pathology which if present should be described) and mixed pathology (where the contributing components are described). In other words, PSD and mixed dementias could both have mixed pathology but PSD is recognized by its more acute presentation.

Mixed Dementias

Mixed dementias (VICCCS Criteria)

Skrobot, O. A. et al. (2017). The vascular impairment of cognition classification consensus study. Alzheimer's and Dementia, 13(6), 624-633.

Mixed dementias is a standalone umbrella subgroup termed mixed dementias includes all the phenotypes specified for each combination, that is VCI‐AD, VCI‐DLB, so forth. It is recommended that a patient is referred to as having “VCI‐AD”, according to the phenotypes present, rather than less specific mixed dementia, for example. Where discrimination is possible, the order of terms should reflect the relative contribution of the underlying pathology, that is AD‐VCI or VCI‐AD.

Subcortical ischemic vascular dementia (SIVaD)

Post-stroke dementia (VICCCS Criteria)

Skrobot, O. A. et al. (2017). The vascular impairment of cognition classification consensus study. Alzheimer's and Dementia, 13(6), 624-633.

Subcortical ischemic vascular dementia (SIVaD):† Small‐vessel disease is the main vascular cause of SIVaD. Lacunar infarct and ischemic white matter lesions are the main type of brain lesions, which are primarily located subcortically. It incorporates the overlapping clinical entities of Binswanger's disease and the lacunar state.‡

† = As part of the efforts in VICCCS to standardize the nomenclature and abbreviations to be used in the future, VICCCS diagnosis participants were asked which abbreviation, from those most commonly used for SIVaD, should be taken forward. Initially, no consensus was reached (SIVaD, 36%; SIVD, 23%; SiVaD, 19%; SiVD, 4%, with 18% stating no preference) but in the subsequent round, where participants were asked to choose their preference from the two most favored abbreviations from round 4, most support was for SIVaD (65%) and therefore adopted. ‡ = Ninety-nine percent of respondents asked about this definition in the VICCCS diagnosis study supported this original definition of SIVaD, whereas 92% supported it as a diagnostic category. Seventy-six percent of respondents stated that they would use this term clinically.

Multi‐infarct dementia (MID)

Multi‐infarct dementia (VICCCS Criteria)

Skrobot, O. A. et al. (2017). The vascular impairment of cognition classification consensus study. Alzheimer's and Dementia, 13(6), 624-633.

Multi‐infarct dementia (MID) relates to the involvement, and likely contribution, of multiple large cortical infarcts in the development of dementia.“§ The previously mentioned VICCCS definition of PSD is built on the definition of O'Brien et al.[6]

§ = 69% of VICCCS diagnosis respondents agreed that MID should be a diagnostic category; however, opinion was split on the use of this term in the clinical setting, with only 52% in favor of it. There was a consensus (72%) support for the original definition of MID by Hachinski et al. MID reflects the traditional view that multiple large cortical infarcts are required for dementia to develop; however, the most frequent objection was use of the word “required.” Therefore, to give opportunity for this objection to be considered, a modified definition was also presented along with the original definition for participants to state their support in the subsequent round. The modified definition, as given above, proposed received a consensus support (72%)

Differential Diagnosis

Screening

Screening Tools for Vascular Cognitive Impairment

Name Rater Description Download
NINDS-CSN Harmonization VCI Neuropsychological Protocols Clinician The NINDS-CSN battery consists of 3 protocols (5, 30 and 60 min) and bridges the gap between comprehensive neurocognitive assessment and brief screening tests.[7] N/A
Montreal Cognitive Assessment (MoCA) Clinician The MoCA is a brief cognitive screening test with high sensitivity and specificity for detecting mild cognitive impairment and can assess for executive dysfunction associated with vascular disease Download
Mini-Mental Status Exam (MMSE) Clinician The MMSE is less sensitive to subtle changes in mild cognitive impairment Download

Pathophysiology

Distinct vascular and parenchymal pathologies and lesions all share a common final pathway, where cellular death or injury results in decreased cholinergic transmission, leading to vascular cognitive impairment or vascular dementia. Hypertension, diabetes, genetics, hypercholesterolemia, cardiovascular disease are all risk factors that can lead to cerebral vascular damage, and subsequent cognitive impairment or dementia.

Parenchymal Lesions

There are multiple distinct parenchymal lesions that can occur including:

  • Large vessel infarcts (strategic single infarcts or large territorial infarcts)
    • Multiple infarcts
    • Single strategically placed infarct
  • Small vessel infarcts
    • Multiple lacunar infarcts in white matter and deep gray matter nuclei
    • Ischemic white matter change
    • Dilatation of perivascular spaces
    • Cortical microinfarcts and microhemorrhages
  • Hemorrhage
    • Intracerebral hemorrhage
    • Multiple cortical and subcortical microbleeds
    • Subarachnoid hemorrhage
  • Hypoperfusion
    • Hippocampal sclerosis
    • Laminar cortical sclerosis

Vascular Lesions

Vascular lesions can occur include any one of the following:[8]

  • Atherosclerosis
  • Cardiac, atherosclerotic and systemic emboli
  • Arteriolosclerosis
  • Lipohyalinosis
  • Amyloid angiopathy
  • Vasculitis – infectious and non-infectious
  • Venous collagenosis
  • Arteriovenous fistulae – dural or parenchymal
  • Hereditary angiopathies – cerebral autosomal dominant arteriopathy with subcorticalinfarcts and leukoencephalopathy, CADASIL; cerebral autosomal recessive arteriopathy with subcortical autosomal recessive leukoencephalopathy, CARASIL, etc.
  • Giant cell arteritis
  • Berry aneurysms
  • Miscellaneous vasculopathies - fibromuscular dysplasia, Moya-Moya
  • Systemic microangiopathies without vascular inflammatory cell infiltrates
  • Cerebral venous thrombosis

Large vs. Small Vessel Disease

Adapted from: Cummings, J. L. at al. (1994). The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44(12), 2308-2308.
Pathology Large vessel disease Small vessel disease
Lesion location Cortical (and subcortical) Subcortical
Neurological signs Focal (stroke findings) None (40%) or mild
Cognition “Stroke syndromes”, including aphasia, apraxia, agnosia, neglect, inattention, visual field loss, and/or memory loss • Executive Dysfunction
• Poor memory retrieval
Insight Retained Impaired
Mood disturbances Post-stroke depression Apathy, anxiety, lability, irritability, low mood

Investigations

Neuroimaging

In order to diagnose probable vascular dementia, there must be abnormalities on found on neuroimaging. However, if the neurocognitive impairment is temporally associated with one or more well-documented strokes, a probable diagnosis can be made in the absence of neuroimaging. For mild vascular dementia, history of a single stroke or extensive white matter disease is generally sufficient. For major vascular dementia, two or more strokes, a strategically placed stroke, or a combination of white matter disease and one or more lacunar is necessary.[9]

Neuroimaging evidence (either Magnetic Resonance Imaging (MRI) or Computed Tomography (CT)) of cerebrovascular disease should show:

  • One or more large vessel infarcts or hemorrhages, or
  • A single infarct or hemorrhage (e.g., in angular gyrus, thalamus, basal forebrain), or
  • Two or more lacunar infarcts outside the brain stem, or
  • Extensive and confluent white matter lesions (also known as small vessel disease or subcortical ischemic changes)

MRI Measures

Adapted from: Hachinski, V. et al. (2006). National Institute of Neurological Disorders and Stroke–Canadian stroke network vascular cognitive impairment harmonization standards. Stroke, 37(9), 2220-2241.
Feature Recommended MRI Measure Acceptable MRI Measure
Brain atrophy Quantitative measurement of brain volume normalized for head size • Estimates of Atrophy and Ventricular Size using the CHS Scale
• Estimates of Medial Temporal Lobe Atrophy using Scheltens Scale
White Matter Hyperintensities (WMH) • Quantitative measurement of WMH volume normalized for head size
• Anatomical mapping also encouraged 		• Preferred: ARWMC scale
• Also Acceptable: CHS WMH scale
Infarction • All infarcts should be localized using a standard approach to generate quantitative measures of volume and location. Ideally, identified infarcts would also be mapped to a common stereotatic space • Also Acceptable: CHS WMH scale
• No. and size at specified locations
Size (largest diameter): Large = 1.0 cm, Small = 3 mm-10 mm
• Location (Encourage use of Talairach atlas for precise anatomical localization):*
• Anatomical locations
• Supratentorial
• Hemisphere
• Cortical (may include subcortical)
• Exclusively Subcortical white matter
• Exclusively Subcortical gray matter
• Infratentorial
Hemorrhage • All lesions should be localized using a standard approach to generate quantitative measures of volume and location. Ideally, identified lesions would also be mapped to a common stereotatic space • No. and size in each locations
• Size (largest diameter)
Large hemorrhage: >1cm in diameter
Microhemorrhage: <1 cm, susceptibility on gradient echo
• Must report lower size limit cut-off, field strength
• Criterion in development and further work is necessary
Other Mass lesions, AVMs, extra-axial fluid collections, malformations, dysplasia or any other lesion that might complicate assessment of cerebrovascular disease -

CT Measures

Adapted from: Hachinski, V. et al. (2006). National Institute of Neurological Disorders and Stroke–Canadian stroke network vascular cognitive impairment harmonization standards. Stroke, 37(9), 2220-2241.
• Ventricular size
• Hippocampus: medial temporal atrophy
• Diffuse white matter: ARWMC
• Discrete hypodensities
a. (CSF density; consistent with infarction or old hemorrhage)
b. 3mm-1.0 = small
c. 1.0 = large
d. No., volume, location same as MRI
• Acute hemorrhage

Treatment

Risk Factor Management

In patients with a stroke history, lowering blood pressure is effective for reducing the risk of post-stroke depression.

Pharmacotherapy

  • Acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) as a class are modestly efficacious for patients with mixed AD and vascular dementia pathology, and a trial of these medications is recommended for most patients diagnosed with AD.[10]
  • However, in isolated vascular dementia, there is insufficient and inconsistent evidence support on whether acetylcholinesterase inhibitors are effective.[11]

Pharmacotherapy for Vascular Dementia

Ritter, A., and Pillai, J. A. (2015). Treatment of vascular cognitive impairment. Current treatment options in neurology, 17(8), 35.
Medication Level of Evidence Comments Recommendations
Donepezil Class IIa, level A, for “pure” VaD Modest benefit for cognitive scores, less strong evidence for functional improvement. Doses studied: 5 and 10 mg/day. No dose response effects noted Donepezil can be used to improve cognition in VaD
Galantamine Class IIa, level A, for mixed dementia; class IIb for “pure” VaD Modest benefit in cognitive measures in pure VaD. Benefit in both cognition and function in mixed dementia. Doses studied; titration up to 24 mg/day. Galantamine can be used to improve cognition and functional abilities in mixed dementia (AD + VaD)
Rivastigmine Class IIa, level A for “pure” VaD Modest benefit on cognitive measures in pure VaD. Doses studied: 1–4 and 6–12 mg/day Rivastigmine can be used to improve cognition in VaD
Memantine Class IIb, level A Modest cognitive benefits only. Doses studied; titration up to 20 mg/day Role of Memantine in VaD yet to be clarified

Guidelines

Vascular Cognitive Impairment Guidelines

Guideline Location Year PDF Website
Canadian Consensus Conference on Diagnosis and Treatment of Dementia (CCCDTD) Canada 2020 - Link
Heart and Stroke Foundation of Canada Canada 2019 - Link

Resources

For Providers

References

1) Niemantsverdriet, E., Feyen, B. F., Le Bastard, N., Martin, J. J., Goeman, J., De Deyn, P. P., & Engelborghs, S. (2015). Overdiagnosing vascular dementia using structural brain imaging for dementia work-up. Journal of Alzheimer's Disease, 45(4), 1039-1043.
2) Brust, J. C. (1988). Vascular dementia is overdiagnosed. Archives of Neurology, 45(7), 799-801.
3) Strub, R. L. (2003). Vascular dementia. Ochsner Journal, 5(1), 40-43.
4) Román, G. C., Tatemichi, T. K., Erkinjuntti, T., Cummings, J. L., Masdeu, J. C., Garcia, J. H., ... & Moody, D. M. (1993). Vascular dementia: diagnostic criteria for research studies: report of the NINDS‐AIREN International Workshop. Neurology, 43(2), 250-250.
5) Skrobot, O. A., O'Brien, J., Black, S., Chen, C., DeCarli, C., Erkinjuntti, T., ... & Roman, G. C. (2017). The vascular impairment of cognition classification consensus study. Alzheimer's & Dementia, 13(6), 624-633.
6) T O'Brien, J., Erkinjuntti, T., Reisberg, B., Roman, G., Sawada, T., Pantoni, L., ... & Rockwood, K. (2003). Vascular cognitive impairment. The Lancet Neurology, 2(2), 89-98.
7) Xu, X., Chan, Q. L., Hilal, S., Ikram, M. K., Venketasubramanian, N., Tan, B. Y., Dong, Y., Chen, C. L., & Collinson, S. L. (2016). The Diagnostic Utility of the NINDS-CSN Neuropsychological Battery in Memory Clinics. Dementia and geriatric cognitive disorders extra, 6(2), 276–282.
8) Sachdev, P., Kalaria, R., O'Brien, J., Skoog, I., Alladi, S., Black, S. E., Blacker, D., Blazer, D. G., Chen, C., Chui, H., Ganguli, M., Jellinger, K., Jeste, D. V., Pasquier, F., Paulsen, J., Prins, N., Rockwood, K., Roman, G., Scheltens, P., & Internationlal Society for Vascular Behavioral and Cognitive Disorders (2014). Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer disease and associated disorders, 28(3), 206–218.
9) Hachinski, V., Iadecola, C., Petersen, R. C., Breteler, M. M., Nyenhuis, D. L., Black, S. E., ... & Vinters, H. V. (2006). National Institute of Neurological Disorders and Stroke–Canadian stroke network vascular cognitive impairment harmonization standards. Stroke, 37(9), 2220-2241.
10) Herrmann, N., Lanctôt, K. L., & Hogan, D. B. (2013). Pharmacological recommendations for the symptomatic treatment of dementia: the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012. Alzheimer's research & therapy, 5(1), S5.
11) Herrmann, N., Lanctôt, K. L., & Hogan, D. B. (2013). Pharmacological recommendations for the symptomatic treatment of dementia: the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012. Alzheimer's research & therapy, 5(1), S5.