Vascular Dementia

Author: Kannayiram Alagiakrishnan, MD, MBBS, MHA, MPH; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych (UK) more...Background

Vascular dementia is the second most common form of dementia after Alzheimer disease (AD). The condition is not a single disease; it is a group of syndromes relating to different vascular mechanisms. Vascular dementia is preventable; therefore, early detection and an accurate diagnosis are important.

Patients who have had a stroke are at increased risk for vascular dementia. Recently, vascular lesions have been thought to play a role in AD.

As early as 1899, arteriosclerosis and senile dementia were described as different syndromes. In 1969, Mayer-Gross et al described this syndrome and reported that hypertension is the cause in approximately 50% of patients. In 1974, Hachinski et al coined the term multi-infarct dementia. In 1985, Loeb used the broader term vascular dementia. Recently, Bowler and Hachinski introduced a new term, vascular cognitive impairment.

Case study

A 70-year-old woman came to the clinic with her son for assessment of her cognitive decline. The son is concerned about her short-term memory problems for the past 10 months. Patient had a fall 10 months ago; after that fall, she started to ask the same questions over and over. Patient had another fall 4 months ago and also an episode of dizziness 2 months ago. With these incidents, her son noticed further decline in cognition. Recently, her son noticed that she has become a bit more suspicious of her daughter-in-law and has been hoarding things. She has lost interest in her day-to-day activities and forgets to include the right ingredients when cooking. Family has to remind her to take her medications, and her son is helping with the management of her finances.

The patient has hypertension, diabetes, coronary artery disease, osteoarthritis, and osteoporosis. On the Mini-Mental Status Examination (MMSE), the patient scored 21/30 with abnormal clock drawing. On the Geriatric Depression Scale (GDS), the patient scored 2/15. CT scan of the head showed multiple lacunar infarcts in the right basal ganglia and left cerebellar region.

Next Section: Pathophysiology Pathophysiology

Many subtypes of vascular dementia have been described to date. The spectrum includes (1) mild vascular cognitive impairment, (2) multi-infarct dementia, (3) vascular dementia due to a strategic single infarct, (4) vascular dementia due to lacunar lesions, (5) vascular dementia due to hemorrhagic lesions, (6) Binswanger disease, (7) subcortical vascular dementia, and (8) mixed dementia (combination of AD and vascular dementia).

Vascular dementia is sometimes further classified as cortical or subcortical dementia.

Vascular disease produces either focal or diffuse effects on the brain and causes cognitive decline. Focal cerebrovascular disease occurs secondary to thrombotic or embolic vascular occlusions. Common areas of the brain associated with cognitive decline are the white matter of the cerebral hemispheres and the deep gray nuclei, especially the striatum and the thalamus. Hypertension is the major cause of diffuse disease, and in many patients, both focal and diffuse disease are observed together. The 3 most common mechanisms of vascular dementia are multiple cortical infarcts, a strategic single infarct, and small vessel disease.

Mild vascular cognitive impairment can occur in elderly persons. It is associated with cognitive decline that is worse than expected for age and educational level, but the effects do not meet the criteria for dementia. These people have subjective and objective evidence of memory problems, but their daily functional living skills are within normal limits.

In multi-infarct dementia, the combined effects of different infarcts produce cognitive decline by affecting the neural nets.

In single-infarct dementia, different areas in the brain can be affected, which may result in significant impairment in cognition. This may be observed in cases of anterior cerebral artery infarct, parietal lobe infarcts, thalamic infarction, and singular gyrus infarction.

Small vessel disease affects all the small vessels of the brain and produces 2 major syndromes, Binswanger disease and lacunar state. Small vessel disease results in arterial wall changes, expansion of the Virchow-Robin spaces, and perivascular parenchymal rarefaction and gliosis.

Lacunar disease is due to small vessel occlusions and produces small cavitary lesions within the brain parenchyma secondary to occlusion of small penetrating arterial branches. These lacunae are found more typically in the internal capsule, deep gray nuclei, and white matter. Lacunar state is a condition in which numerous lacunae, which indicate widespread severe small vessel disease, are present.

Binswanger disease (also known as subcortical leukoencephalopathy) is due to diffuse white matter disease. In Binswanger disease, vascular changes observed are fibrohyalinosis of the small arteries and fibrinoid necrosis of the larger vessels inside the brain.

In cerebral amyloid angiopathyassociated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. In hereditary cystatin-C amyloid angiopathy, patients have recurrent cerebral hemorrhages before age 40 years that can lead to dementia. Prevalence of cerebral amyloid angiopathy is consistently higher in patients with dementia than in patients without dementia, which indicates its significant role in the pathogenesis of dementia.[1] Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a rare autosomal dominant condition localized to chromosome arm 19q12 that affects small vessels supplying the deep white matter. Pathologically, multiple small infarcts are observed in the white matter, thalamus, basal ganglia, and pons.

Other less common syndromes may lead to vascular dementia. Rare arteriopathies such as inflammatory arteriopathy (eg, polyarteritis nodosa, temporal arteritis) and noninflammatory arteriopathy (eg, moyamoya disease, fibromuscular dysplasia) can cause multiple infarcts and can lead to vascular dementia. Hypoperfusion due to large vessel or cardiac disease can affect the watershed areas of the brain and lead to vascular dementia.

Leukoaraiosis greater than 25% is considered to be pathological. Subcortical vascular dementia is a diffuse small vessel disease with minimal or absent infarction with homogenous pathological and clinical features.[2, 3] White matter ischemic changes affect executive dysfunction and cause slower processing speed, rather than memory and language impairment.[4] Arterial stiffness, which reflects an alteration in arterial mechanics, can be a risk factor for vascular dementia.[5] Mixed dementia is diagnosed when patients have evidence of Alzheimer dementia and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions. Growing evidence indicates that vascular dementia and Alzheimer dementia often coexist, especially in older patients with dementia. Autopsy studies have shown an association between Alzheimer disease and vascular lesions.[6] Several recent studies also suggest that the risk of developing Alzheimer disease is increased when a patient is exposed to vascular risk factors such as hypertension, diabetes mellitus, peripheral arterial disease, and smoking, which usually are associated with cerebrovascular disease and vascular dementia. Recent evidence suggests that the vascular processes in both disorders may mutually induce each other. Apolipoprotein E may play a role in Alzheimer disease and vascular dementia. Apolipoprotein E4 also increases the risk of dementia in stroke survivors and is a strong risk factor for the development of cerebral amyloid angiopathy in patients with Alzheimer disease. In elderly individuals, many cases of dementia may be caused by the cumulative effect of cerebrovascular and Alzheimer pathology.

One-third of patients with vascular dementia are found to have significant Alzheimer disease pathology with cholinergic deficits in the nucleus basalis of Meynert.[7] Vascular cognitive disorder (VCD) is a new term used to describe a particular constellation of cognitive and functional impairment spectrum that ranges from vascular cognitive impairment (VCI) to subcortical vascular dementia, poststroke dementia, and mixed dementia.[3] Epidemiology

Frequency

International

Vascular dementia is the second most common cause of dementia in the United States and Europe, but it is the most common form in some parts of Asia.

The prevalence rate of vascular dementia is 1.5% in Western countries and approximately 2.2% in Japan.

In Japan, vascular dementia accounts for 50% of all dementias that occur in individuals older than 65 years.

In Europe, vascular dementia and mixed dementia account for approximately 20% and 40% of cases, respectively.

In Latin America, 15% of all dementias are vascular.

In community-based studies in Australia, the prevalence rate for vascular and mixed dementia is 13% and 28%, respectively.

The prevalence rate of dementia is 9 times higher in patients who have had a stroke than in controls. One year after a stroke, 25% of patients develop new-onset dementia. Within 4 years following a stroke, the relative risk of incident dementia is 5.5%.

Mortality/Morbidity

In patients with dementia who have had a stroke, the increase in mortality is significant. The 5-year survival rate is 39% for patients with vascular dementia compared with 75% for age-matched controls.[8] Vascular dementia is associated with a higher mortality rate than AD, presumably because of the coexistence of other atherosclerotic diseases.

Study on causes of death in patients with dementia showed that circulatory system disorders (eg, ischemic heart disease) is the most common immediate cause of death in vascular dementia, followed by respiratory system diseases (eg, pneumonia).[9] A study of hospitalization rates in patients with dementia showed that persons who developed different types of incident dementia, including vascular dementia, were found to have an increased risk of hospitalization, including hospitalization for ambulatory care-sensitive conditions.[10] Sex

The prevalence of vascular dementia is higher in men than in women.

Age

Incidence increases with age.

References

1. Zhang-Nunes SX, Maat-Schieman ML, van Duinen SG, Roos RA, Frosch MP, Greenberg SM. The cerebral beta-amyloid angiopathies: hereditary and sporadic. Brain Pathol. Jan 2006;16(1):30-9. [Medline].

2. Schmidtke K, Hull M. Cerebral small vessel disease: how does it progress?. J Neurol Sci. Mar 15 2005;229-230:13-20. [Medline].

3. Jellinger KA. The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol (Berl). Apr 2007;113(4):349-88. [Medline].

4. Delano-Wood L, Abeles N, Sacco JM, Wierenga CE, Horne NR, Bozoki A. Regional white matter pathology in mild cognitive impairment: differential influence of lesion type on neuropsychological functioning. Stroke. Mar 2008;39(3):794-9. [Medline].

5. Jurasic MJ, Popovic IM, Morovic S, Trkanjec Z, Seric V, Demarin V. Can beta stiffness index be proposed as risk factor for dementia?. Journal of Neurological Sciences. In press.

6. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA. Mar 12 1997;277(10):813-7. [Medline].

7. Roman GC, Kalaria RN. Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia. Neurobiol Aging. Dec 2006;27(12):1769-85. [Medline].

8. Brodaty H, McGilchrist C, Harris L, Peters KE. Time until institutionalization and death in patients with dementia. Role of caregiver training and risk factors. Arch Neurol. Jun 1993;50(6):643-50. [Medline].

9. Brunnstrom HR, Englund EM. Cause of death in patients with dementia disorders. Eur J Neurol. Apr 2009;16(4):488-92. [Medline].

10. Phelan EA, Borson S, Grothaus L, Balch S, Larson EB. Association of incident dementia with hospitalizations. JAMA. Jan 11 2012;307(2):165-72. [Medline].

11. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. Nov 1975;12(3):189-98. [Medline].

12. American Psychiatric Association. Diagnosis and Statistical Manual of Mental Disorders. Fourth Edition. Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Press; 2000.

13. Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. Apr 1983;17:37-49.

14. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in Dementia. Biol Psychiatry. Feb 1 1988;23(3):271-84. [Medline].

15. Schneider B, Maurer K, Frolich L. [Dementia and suicide]. Fortschr Neurol Psychiatr. Apr 2001;69(4):164-9. [Medline].

16. Price CC, Jefferson AL, Merino JG, Heilman KM, Libon DJ. Subcortical vascular dementia: integrating neuropsychological and neuroradiologic data. Neurology. Aug 9 2005;65(3):376-82. [Medline]. [Full Text].

17. Rusanen M, Kivipelto M, Quesenberry CP Jr, Zhou J, Whitmer RA. Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia. Arch Intern Med. Oct 25 2010;[Medline].

18. Roman GC. The epidemiology of vascular dementia. Handbook of Clinical Neurology. 2008;vol. 89(3rd series):639-658.

19. Nagata K, Maruya H, Yuya H, et al. Can PET data differentiate Alzheimer's disease from vascular dementia?. Ann N Y Acad Sci. Apr 2000;903:252-61. [Medline].

20. Starkstein SE, Sabe L, Vazquez S, et al. Neuropsychological, psychiatric, and cerebral blood flow findings in vascular dementia and Alzheimer's disease. Stroke. Mar 1996;27(3):408-14. [Medline].

21. Amenta F, Lanari A, Mignini F, Silvestrelli G, Traini E, Tomassoni D. Nicardipine use in cerebrovascular disease: A review of controlled clinical studies. Journal of the Neurological Sciences. In press.

22. Seitz DP, Adunuri N, Gill SS, et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. Feb 16 2011;2:CD008191. [Medline].

23. Meeuwsen EJ, Melis RJ, Van Der Aa GC, Golke-Willemse GA, De Leest BJ, Van Raak FH, et al. Effectiveness of dementia follow-up care by memory clinics or general practitioners: randomised controlled trial. BMJ. May 15 2012;344:e3086. [Medline]. [Full Text].

24. Vercambre MN, Grodstein F, Manson JE, Stampfer MJ, Kang JH. Physical activity and cognition in women with vascular conditions. Arch Intern Med. Jul 25 2011;171(14):1244-50. [Medline]. [Full Text].

25. Shprecher D and Mehta L. The syndrome of delayed post- hypoxic leukoencephalopathy. Neurorehabilitation. 2010;26:65-72.

26. American Psychiatric Association. Practice guideline for the treatment of patients with Alzheimer's disease and other dementias of late life. American Psychiatric Association. Am J Psychiatry. May 1997;154(5 Suppl):1-39. [Medline].

27. Ballard C, McKeith I, O'Brien J, et al. Neuropathological substrates of dementia and depression in vascular dementia, with a particular focus on cases with small infarct volumes. Dement Geriatr Cogn Disord. Mar-Apr 2000;11(2):59-65. [Medline].

28. Caplan LR. Binswanger's disease--revisited. Neurology. Apr 1995;45(4):626-33. [Medline].

29. Chabriat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet. Oct 7 1995;346(8980):934-9. [Medline].

30. Chui HC. Vascular dementia, a new beginning: shifting focus from clinical phenotype to ischemic brain injury. Neurol Clin. 2001;18:951-77.

31. Cummings JL. Vascular subcortical dementias: clinical aspects. Dementia. May-Aug 1994;5(3-4):177-80. [Medline].

32. Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet. Apr 13 2002;359(9314):1283-90. [Medline].

33. European Dementia Study. European Pentoxifylline Multi-Infarct Dementia Study. Eur Neurol. 1996;36(5):315-21. [Medline].

34. Fagerstrom KO. Reducing the weight gain after stopping smoking. Addict Behav. 1987;12(1):91-3. [Medline].

35. Grilli M, Pizzi M, Memo M, Spano P. Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science. Nov 22 1996;274(5291):1383-5. [Medline].

36. Hachinski VC, Bowler JV. Vascular dementia. Neurology. Oct 1993;43(10):2159-60; discussion 2160-1. [Medline].

37. Hebert R, Brayne C. Epidemiology of vascular dementia. Neuroepidemiology. 1995;14(5):240-57. [Medline].

38. in't Veld BA, Ruitenberg A, Hofman A, Stricker BH, Breteler MM. Antihypertensive drugs and incidence of dementia: the Rotterdam Study. Neurobiol Aging. May-Jun 2001;22(3):407-12. [Medline].

39. Kalaria RN. The role of cerebral ischemia in Alzheimer's disease. Neurobiol Aging. Mar-Apr 2000;21(2):321-30. [Medline].

40. Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol. Nov 1997;42(5):776-82. [Medline].

41. Meyer JS, Huang J, Chowdhury MH. MRI confirms mild cognitive impairments prodromal for Alzheimer's, vascular and Parkinson-Lewy body dementias. J Neurol Sci. Jun 15 2007;257(1-2):97-104. [Medline].

42. Meyer JS, Rogers RL, McClintic K, et al. Randomized clinical trial of daily aspirin therapy in multi-infarct dementia. A pilot study. J Am Geriatr Soc. Jun 1989;37(6):549-55. [Medline].

43. Moretti R, Torre P, Antonello RM. Rivastigmine in subcortical vascular dementia: a randomized, controlled, open 12-month study in 208 patients. Am J Alzheimers Dis Other Demen. Sep-Oct 2003;18(5):265-72. [Medline].

44. Moretti R, Torre P, Antonello RM, et al. Rivastigmine in vascular dementia. Expert Opin Pharmacother. Jun 2004;5(6):1399-410. [Medline].

45. Nelson NW. Differential diagnosis of Alzheimer's dementia and vascular dementia. Dis Mon. Mar 2007;53(3):148-51. [Medline].

46. Premkumar DR, Cohen DL, Hedera P, Friedland RP, Kalaria RN. Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. Am J Pathol. Jun 1996;148(6):2083-95. [Medline].

47. Sadowski M, Pankiewicz J, Scholtzova H, Li YS, Quartermain D, Duff K, et al. Links between the pathology of Alzheimer's disease and vascular dementia. Neurochem Res. Jun 2004;29(6):1257-66. [Medline].

48. Skoog I. Status of risk factors for vascular dementia. Neuroepidemiology. 1998;17(1):2-9. [Medline].

49. Vascular Dementia Conference. Summary of the 1st International Conference on the Development of Drug Treatment for Vascular Dementia. Alzheimer Dis Assoc Disorders. Dec 1999;13, Supplement 3:S1-S206.

50. Wetterling T, Kanitz RD, Borgis KJ. Comparison of different diagnostic criteria for vascular dementia (ADDTC, DSM-IV, ICD-10, NINDS-AIREN). Stroke. Jan 1996;27(1):30-6. [Medline].

51. Wilkinson D, Doody R, Helme R. Donepezil in vascular dementia: a randomized, placebo-controlled study. Neurology. Aug 26 2003;61(4):479-86. [Medline].

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