Vascular dementia refers to any dementia related to cerebrovascular disease.1 It is a syndrome, not a disease, caused by a cerebrovascular or cardiovascular disease that results in vascular brain injury or dysfunction. Vascular dementia is the second most common dementia after Alzheimer's disease (AD), accounting for at least 20% of people with dementia.1,2
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 (AHA) for cognitive impairment caused by, or associated with, vascular factors.3 VCI is, therefore, a broader term that covers the full spectrum from mild cognitive impairment (MCI) to dementia caused by cerebrovascular disease.3
Etiology and Underlying Pathology
Many cerebrovascular and cardiovascular diseases can lead to VCI by disrupting brain function to cause cognitive impairment through brain ischemia or vascular integrity loss resulting in brain hemorrhage.4 Causes of ischemic stroke (eg, large artery atherosclerosis, cardioembolism, and cerebral small vessel disease), intracerebral hemorrhage, or subarachnoid hemorrhage can cause VCI if the resulting brain injury is severe enough.5 A large single infarct or multiple infarcts are often the cause. Damage to a single important brain location (eg, language cortices, thalamus, or medial temporal lobe) is often referred to as a strategic infarct, can be sufficient to cause clinically significant cognitive impairment.6 The association between the cerebrovascular injury and the onset of cognitive impairment is relatively clear in the context of a symptomatic acute stroke, classified as poststroke VCI.5
The most common cause of VCI is cerebral small vessel disease,7 including arteriolosclerosis, cerebral amyloid angiopathy (CAA), and other less common causes, (eg, genetic disorders, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL], small vessel vasculitides, and venous collagenosis.7 Cerebral small vessel disease manifests as a progressive or stepwise cognitive decline without a concurrent history of symptomatic stroke and with imaging or neuropathologic evidence.8,9 In many cases, cerebral small vessel disease may not even be suspected clinically until neuroimaging is performed.
In arteriolosclerosis, the small artery and arteriole walls exhibit thickening, hyalinization, lipohyalinosis, microaneurysm formation, and vascular integrity loss.7 Arteriolosclerosis prominently affects subcortical brain regions, including the corona radiata and basal ganglia, and patients typically have multiple lacunar infarcts or extensive, confluent white matter lesions (Figure 1).9,10 More subtle manifestations in the cortex, including microinfarcts and secondary neurodegeneration resulting in cortical thinning, have also been identified.11,12
Figure 1. Multiple lacunes and confluent white matter hyperintensities in a patient with arteriosclerosis and vascular cognitive impairment. Fluid-attenuated inversion recovery (FLAIR) MRI sequence in a man, age 67, with dementia demonstrates multiple lacunes (arrows) and confluent white matter hyperintensities of presumed vascular origin.
The second most common cerebral small vessel disease, CAA is caused by β-amyloid deposition in the small arteries and arterioles of the leptomeninges and cerebral cortex.13 Rare genetic causes of CAA are marked by deposition of other types of amyloid.13 Vascular integrity loss resulting in large symptomatic and small asymptomatic brain hemorrhages is characteristic of CAA. These hemorrhages are restricted to typical cortical or subcortical white matter locations (ie, lobar locations), sparing the basal ganglia and brainstem (Figure 2).14,15
Figure 2. MRI findings associated with cerebral amyloid angiopathy. Lobar microbleed and areas of cortical superficial siderosis in a patient with a history of lobar intracerebral hemorrhage, meeting Boston criteria for probable cerebral amyloid angiopathy (CAA) (A). Extensive and confluent white matter T2 hyperintensity is common in CAA, as demonstrated here on the fluid-attenuated inversion recovery (FLAIR) sequence (B). Multiple perivascular spaces, visible as faint small hyperintense dots, are commonly seen on T2-weighted sequences as seen here (C).
Based on autopsy studies, however, pure vascular dementia is less common than multiple-etiology (ie, mixed) dementia, in which vascular dementia is only one etiology.16,17 Alzheimer neuropathology, with characteristic β-amyloid plaques and tangles, is the most common co-occurring pathology with vascular dementia. Other co-occurring neuropathologic processes include a-synucleinopathy, tau pathology, TAR DNA-binding protein-43 pathology, and microglial reactions.18
The major risk factors for vascular dementia and new dementia after stroke are listed in the Table.19, 20
The prevalence and incidence of VCI increase with age.20 Based on clinicopathologic evidence, pure vascular dementia accounts for approximately 10% of dementia.17 Multiple-etiology dementia with a vascular component, most often in combination with AD, is more common, accounting for 30% to 40% of dementia.17 The increased risk of cerebrovascular disease-related dementia, as well as dementia due to AD, seems to decline at very old ages.21 A reason for this change might be that other dementia causes including mixed pathology, are more common with very advanced age.21
The main syndromes that characterize vascular dementia are poststroke dementia and vascular dementia without a recent history of stroke.3
Patients with poststroke dementia experience a stepwise cognitive decline following a clinically diagnosed stroke. The link between the cerebrovascular disease and the onset of cognitive impairment is usually relatively clear. Prominent impairment of executive functions, with relative sparing of episodic memory is often seen.22 There may be stroke-related symptoms and signs, including aphasia, motor weakness, and sensory impairment. Cognitive impairment may improve or remain static and nonprogressive if there are no recurrent strokes and vascular risk factors are treated. Approximately 10% of patients develop new dementia 1 to 4 years after a clinically diagnosed stroke, but this is usually more than 1 year later in relation to a recurrent stroke.19
Vascular dementia can also manifest as a progressive or stepwise cognitive decline without a concurrent history of symptomatic stroke. This presentation is often associated with imaging evidence of clinically unrecognized cerebral small vessel disease (eg, multiple lacunar infarcts or extensive white matter lesions).9,10 The cognitive profile of cerebral small vessel disease, including arteriolosclerosis and CAA is marked by prominent executive function and processing speed impairments.23 More global impairments, including memory and other functions, can also occur.23 Slowing of gait is common in patients with advanced cerebral small vessel disease.24 Neuro-psychiatric symptoms, including depression, apathy, abulia, and psychosis with delusions or hallucinations may occur.
Several organizations have introduced diagnostic criteria for VCI, including the American Heart Association (AHA),25 the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),26 and the International Society of Vascular Behavioural and Cognitive Disorders (VAS-COG).5
In all criteria, VCI is classified as either vascular MCI (referred to as “vascular minor neurocognitive disorder” in DSM-5) or vascular dementia (referred to as “vascular major neurocognitive disorder” in DSM-5). Cerebrovascular disease should be identified either by a history of stroke or by the identification of silent cerebrovascular disease using neuroimaging.25 Newer criteria specify that significant impairment in only 1 domain is sufficient to diagnose MCI or dementia.5 In MCI, there is a relative preservation of daily functioning compared to dementia. All criteria specify that a high burden of clinically unrecognized silent cerebrovascular disease can be sufficient to cause dementia.25
Evaluation of patients with suspected VCI begins with clinical history and a physical examination. The history should focus on the time course of cognitive decline in relation to any prior history of stroke. The physical examination should aim to identify gait impairment, bradykinesia, rigidity, and focal signs suggestive of cerebral small vessel disease or stroke. A cognitive screen should be performed to identify whether there is objective evidence of cognitive impairment, required for a diagnosis of MCI or dementia. The Montreal Cognitive Assessment (MoCA) is preferred and appears to be more sensitive than the Folstein Mini-Mental State Examination for detecting VCI.27
Routine investigations include laboratory evaluation consisting of complete blood count, electrolytes, creatinine, calcium, liver enzymes, vitamin B12, and thyroid-stimulating hormone to exclude causative or contributing metabolic or endocrine disorders. Magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for signs of cerebral small vessel disease, including microbleeds, and therefore is preferred over CT if it is not contraindicated.
The aim of management for patients with VCI is to improve cognitive and behavioral symptoms and daily functioning, prevent further cognitive decline, and manage any other disabilities associated with the underlying cerebrovascular disease. A team of health professionals is often required, including nurses, physiotherapists, occupational therapists, psychologists, and social workers. Appropriate and adequate education and support for relatives and caregivers are also essential.
Some experts recommend considering acetylcholinesterase inhibitors for cognitive enhancement in patients with vascular dementia.25 This is based on the observation of improvement in cognitive performance in patients with vascular dementia in randomized controlled trials.28 This response, however, did not consistently translate into apparent functional or behavioral benefits in daily life across the trials.28
Because of metabolic syndrome risk and mortality associated, with some antipsychotics (eg, haloperidol and risperidone), these drugs should be used cautiously for the management of agitation, aggression, or psychosis in patients with vascular dementia.29 For individuals with comorbid major depression, selective serotonin reuptake inhibitors (SSRIs) are preferred over tricyclic antidepressants, owing to better tolerability in elderly individuals and fewer cardiovascular adverse effects.
Since the majority of VCI risk factors are modifiable, targeting these risk factors might reduce the incidence of VCI. Possible preventive measures for VCI include targeting individuals at high risk to improve their control of vascular risk factors and cardiovascular diseases. Pharmacological therapies or lifestyle modifications, including exercise, can be applied. A multimodal intervention simultaneously targeting dietary modification, physical exercise, cognitive training, and control of vascular risk factors has been proposed as a potential approach to prevent vascular dementia in at-risk individuals.30
The current guidelines for the prevention of recurrent stroke should be followed for individuals with a history of stroke and might include the use of antithrombotics, antihypertensives and lipid-lowering agents, and nonpharmacological interventions, such as exercise and diet modification.31, 32
1. Smith EE. Clinical presentations and epidemiology of vascular dementia. Clin Sci (Lond). 2017;131:1059-1068.
2. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Pathological correlates of late-onset dementia in a multicenter, community-based population in England and Wales. Lancet. 2001;357:169-75.
3. Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke-Canadian Network vascular cognitive impairment harmonization standards. Stroke. 2006;37:2220-2242.
4. Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844-866.
5. Sachdev P, Kalaria R, O'Brien J, et al. Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis Assoc Disord. 2014;28:206-218.
6. Meguro K, Akanuma K, Ouchi Y, et al. Vascular dementia with left thalamic infarction: neuropsychological and behavioral implications suggested by involvement of the thalamic nucleus and the remote effect on cerebral cortex. The Osaki-Tajiri project. Psychiatry Res. 2013;213:56-62.
7. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689-701.
8. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348:1215-2122.
9. Pantoni L, Garcia JH. Pathogenesis of leukoaraiosis: a review. Stroke. 1997;28:652-659.
10. Roman GC, Erkinjuntti T, Wallin A, et al. Subcortical ischaemic vascular dementia. Lancet Neurol. 2002;1:426-436.
11. Smith EE, Schneider JA, Wardlaw JM, Greenberg SM. Cerebral microinfarcts: the invisible lesions. Lancet Neurol. 2012;11:272-282.
12. Duering M, Righart R, Csanadi E, et al. Incident subcortical infarcts induce focal thinning in connected cortical regions. Neurology. 2012;79:2025-2028.
13. Revesz T, Holton JL, Lashley T. Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol. 2009;118:115-130.
14. Gilbert JJ, Vinters HV. Cerebral amyloid angiopathy: incidence and complications in the aging brain. I. Cerebral hemorrhage. Stroke. 1983;14:915-923.
15. Vinters HV, Gilbert JJ. Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke. 1983;14:924-928.
16. White L, Petrovitch H, Hardman J, et al. Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. ANN N Y Acad Sci. 2002;977:9-23.
17. Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69:2197-2204.
18. Lin WL, Castanedes-Casey M, Dickson DW. Transactivation response DNA-binding protein 43 microvasculopathy in frontotemporal generation and familial Lewy body disease. J Neuropathol Exp Neurol. 2009;68:1167-1176.
19. Pendlebury ST, Rothwell PM. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol. 2009;8:1006-1018.
20. Hebert R, Lindsay J, Verreault R, et al. Vascular dementia: incidence and risk factors in the Canadian study of health and aging. Stroke. 2000;31:1487-1493.
21. Savva GM, Wharton SB, Ince PG, et al. Age, neuropathology, and dementia. N Engl J Med. 2009;360:2302-2309.
22. Sachdev PS, Brodaty H, Valenzuela MJ, et al. The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients. Neurology. 2004;62:912-919.
23. Case NF, Charlton A, Zwiers A, et al. Cerebral amyloid angiopathy is associated with executive dysfunction and mild cognitive impairment. Stroke. 2016;47:2010-2016.
24. Staekenborg SS, van der Flier WM, van Straaten EC, et al. Neurological signs in relation to type of cerebrovascular disease in vascular dementia. Stroke. 2008;39:317-322.
25. Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American heart association/American stroke association. Stroke. 2011;42:2672-2713.
26. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
27. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695-699.
28. Smith EE, Cieslak A, Barber P, et al. Therapeutic strategies and drug development for vascular cognitive impairment. J Am Heart Assoc. 2017;6:e005568.
29. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med. 2005;353:2335-2341.
30. Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at risk people (FINGER): a randomized controlled trial. Lancet. 2015;385:2255-2263.
31.Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for health professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160-2236.
32. Smith EE, Saposnik G, Biessels GJ, et al. Prevention of stroke in patients with silent cerebrovascular disease: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017;48:e44-e71.
SA has no financial or other relationships relevant to this content to disclose. EES has received research grants from the Canadian Institutes of Health Research and Brain Canada; royalties from UptoDate; and research service contracts with McMaster University, the University of Ottawa Heart Institute, and St. Michael's Hospital in Toronto, Canada.