Vascular cognitive impairment

CONTINUUM Lifelong Learning in Neurology

Volumn 13, Issue 2, 2007, Pages 109-143

  Chui, Helena C ^a   Brown, Nancy Nielsen ^b  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b WESTERN UNIVERSITY OF HEALTH SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMITRIPTYLINE; ANTIHYPERTENSIVE AGENT; APOLIPOPROTEIN E; CHOLINESTERASE INHIBITOR; CITICOLINE; DONEPEZIL; GALANTAMINE; GINKGO BILOBA EXTRACT; INDAPAMIDE; MEMANTINE; NICERGOLINE; NIMODIPINE; NOTCH3 RECEPTOR; OXIRACETAM; PENTOXIFYLLINE; PERINDOPRIL; PIRACETAM; PLACEBO; PROPENTOFYLLINE; TRIFLUSAL;

ALZHEIMER DISEASE; AMNESIA; ANTERIOR CEREBRAL ARTERY; ANTICHOLINERGIC EFFECT; APATHY; ARTERIOSCLEROSIS; BINSWANGER ENCEPHALOPATHY; BRAIN ATHEROSCLEROSIS; BRAIN ATROPHY; BRAIN CORTEX; BRAIN INFARCTION; BRAIN INJURY; CADASIL; CEREBROVASCULAR DISEASE; CLINICAL TRIAL; COGNITIVE DEFECT; COHORT ANALYSIS; COMORBIDITY; COMPUTER ASSISTED TOMOGRAPHY; DAILY LIFE ACTIVITY; DEPRESSION; DIAGNOSTIC ACCURACY; DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; HIPPOCAMPUS; HUMAN; HYPERTENSION; LEFT HEMISPHERE; LEUKOARAIOSIS; MINI MENTAL STATE EXAMINATION; MORTALITY; MULTIINFARCT DEMENTIA; NEUROPATHOLOGY; NEUROPSYCHOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOLOGY; PHENOTYPE; PROGNOSIS; REVIEW; RISK FACTOR; SIDE EFFECT; STATISTICAL SIGNIFICANCE; STROKE; UNSPECIFIED SIDE EFFECT; VERBAL MEMORY; WHITE MATTER;

EID: 34247270240     PISSN: 10802371     EISSN: None     Source Type: Journal    
DOI: 10.1212/01.CON.0000267238.15122.b6     Document Type: Review

References (68)

1. ▶ Agüero-Torres H, Fratiglioni L, Guo Z, et al. Prognostic factors in very old demented adults: a seven-year follow-up from a population-based survey in Stockholm. J Am Geriatr Soc 1998;46:444-452. Comparison of rate of cognitive decline in Alzheimer's disease (AD) and multi-infarct dementia in a community-based survey.
2. ▶ Agüero-Torres H, Fratiglioni L, Guo Z, et al. Mortality from dementia in advanced age: a 5-year follow-up study of incident dementia cases. J Clin Epidmiol 1999;52:737-743. Comparison of mortality between AD and multi-infarct dementia in a community-based survey.
3. ▶ American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington DC: American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for vascular dementia.
4. ▶ Bennett DA, Wilson RS, Gilley DW, Fox JH. Clinical diagnosis of Binswanger's disease. J Neurol Neurosurg Psychiatry 1990;53:961-965. Clinical criteria for Binswanger syndrome.
5. ▶ Chui HC. Vascular dementia, a new beginning: shifting focus from clinical phenotype to ischemic brain injury. Neurol Clin 2000;18:951-978. Review of vascular dementia and its conceptual basis.
6. ▶ Chui HC. Neuropathology lessons in vascular dementia. Alzheimer Dis Assoc Disord 2005;19:45-52. Review of autopsy studies including the Nun Study, Oxford Project to Investigate Memory and Aging (OPTIMA) Study, Honolulu Asia Aging Study, Religious Order Study, and Ischemic Vascular Dementia Program project.
7. ▶ Chui HC, Victoroff JI, Margolin D, et al. Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer Disease Diagnostic and Treatment Centers. Neurology 1992;42(3 pt 1):473-480. Alzheimer Disease Diagnostic and Treatment Centers (ADDTC) clinical criteria for probable and possible ischemic vascular dementia.
8. ▶ Chui HC, Zarow C, Mack WJ, et al. Cognitive impact of subcortical vascular and Alzheimer's disease pathology. Ann Neurol 2006;60:677-687. In 79 autopsy cases from a mixed sample with subcortical vascular dementia, AD, and normal aging, vascular brain injury and hippocampal sclerosis contribute independently to cognitive impairment, but their effects are overwhelmed by increasing AD. APOE4 was associated with AD but not cerebrovascular disease pathology.
9. ▶ D'Agostino RB, Wolf PA, Belanger AJ, Kannel WB. Stroke risk profile: adjustment for antihypertensive medication. The Framingham Study. Stroke 1994;25:40-43. Sequel to Wolf and colleagues, 1991, refining risk points assigned for blood pressure in patients treated for hypertension.
10. ▶ de Leeuw FE, de Groot JC, Oudkerk M, et al. Hypertension and cerebral white matter lesions in a prospective cohort study. Brain 2002;125(pt 4): 765-772. Subjects with successfully treated hypertension had only moderately increased rates of subcortical white matter lesions and periventricular white matter lesions (relative risk [RR] 3.3; 95% confidence interval [CI] 1.3 to 8.4; and 2.6; 95% CI 1.0 to 6.8, respectively) compared with normotensive subjects. For poorly controlled hypertensives, these RRs were 8.4 (95% CI 3.1 to 22.6) and 5.8 (95% CI 2.1 to 16.0), respectively.
11. ▶ Desmond DW, Moroney JT, Paik MC, et al. Frequency and clinical determinants of dementia after ischemic stroke. Neurology 2000;54: 1124-1131. The authors diagnosed dementia in 119 (26.3%) of the 453 patients. Regarding dementia subtypes, 68 (57.1%) of the 119 patients were diagnosed with vascular dementia, 46 (38.7%) patients were diagnosed with AD with concomitant stroke, and 5 (4.2%) patients were diagnosed with dementia for other reasons.
12. ▶ Desmond DW, Moroney JT, Sano M, Stern Y. Recovery of cognitive function after stroke. Stroke 1996;27:1798-1803. Improvement in generalized cognitive function may be evident 1 year after stroke (n = 151) in association with left hemisphere infarction and severe hemispheral syndromes, while it may be compromised by diabetes, possibly because of an increased burden of cerebrovascular disease.
13. ▶ Desmond DW, Moroney JT, Sano M, Stern Y. Incidence of dementia after ischemic stroke: results of a longitudinal study. Stroke 2002;33: 2254-2260. Longitudinal study of 334 ischemic stroke patients without dementia at baseline and 241 stroke-free controls. The RR of dementia associated with stroke was 3.83 (95% CI 2.14 to 6.84). Cerebral hypoxia or ischemia were independently related to incident dementia (RR 4.40; 95% CI 2.20 to 8.85).
14. ▶ Erkinjuntti T, Inzitari D, Pantoni L, et al. Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm Suppl 2000;59:23-30. Clinical criteria for subcortical vascular dementia.
15. ▶ Erkinjuntti T, Kurz A, Gauthier S, et al. Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet 2002;359:1283-1290. Positive randomized, double-blind, placebo-controlled trial of 24 mg of galantamine in vascular dementia.
16. ▶ Fitzpatrick AL, Kuller LH, Ives DG, et al. Incidence and prevalence of dementia in the Cardiovascular Health Study. J Am Geriatr Soc 2004; 52:195-204. Incidence rates of dementia and dementia subtypes in 3602 Cardiovascular Health Study participants, including 2865 white and 492 African American participants free of dementia, who were followed for an average of 5.4 years.
17. ▶ Forette F, Seux ML, Staessen JA, et al. Systolic Hypertension in Europe Investigators. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002;162:2046-2052. Erratum in Arch Intern Med 2003;163:241. Additional 2-year open-label follow-up of over 2400 subjects initially enrolled in a double-blind, randomized, controlled study, which continues to show beneficial effects on cognition of treating elderly persons with systolic hypertension.
18. ▶ Freels S, Nyenhuis DL, Gorelick PB. Predictors of survival in African American patients with AD, VaD, or stroke without dementia. Neurology 2002;59:1146-1153. Proportional hazards regression models were used to analyze risk of death in 113 patients with AD (53 deaths), 79 patients with vascular dementia (31 deaths), and 56 patients with stroke without dementia (14 deaths).
19. ▶ Gold G, Bouras C, Canuto A, et al. Clinicopathological validation study of four sets of clinical criteria for vascular dementia. Am J Psychiatry 2002;159:82-87. Sensitivity and specificity were assessed by comparing the clinical with the neuropathologic diagnosis of 89 autopsied patients with dementia from a geriatric and psychiatric hospital.
20. ▶ Greenberg SM, Eng JA, Ning M, et al. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 2004;35:1415-1420. Ninety-four consecutive survivors of primary lobar intracerebral hemorrhage (age 55 or older) underwent gradient-echo MRI at presentation. The total number of hemorrhages at baseline predicted risk of future symptomatic intracerebral hemorrhage (3-year cumulative risks 14%, 17%, 38%, and 51% for subjects with 1, 2, 3 to 5, or 6 or greater baseline hemorrhages, P=.003).
21. ▶ Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke - Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220-2241. Recommendations to standardize clinical, neuropsychological, imaging, and pathologic assessment of vascular cognitive impairment.
22. ▶ Hachinski VC, Iliff LD, Zilhka E, et al. Cerebral blood flow in dementia. Arch Neurol 1975;32:632-637. Classic paper describing the Hachinski Ischemic Score.
23. ▶ Howard G, Prineas R, Moy C, et al. Racial and geographic differences in awareness, treatment, and control of hypertension: the REasons for Geographic And Racial Differences in Stroke Study. Stroke 2006;37: 1171-1178. Hypertension awareness, treatment, and control were measured in the REasons for Geographic And Racial Differences in Stroke study, a national population-based cohort of black and white participants aged greater than 45 years (n = 11,701).
24. ▶ Ishiko A, Shimizu A, Nagata E, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): a hereditary cerebrovascular disease, which can be diagnosed by skin biopsy electron microscopy. Am J Dermatopathol 2005; 27:131-134. Electron microscopic features of CADASIL on skin biopsy.
25. ▶ Ivan CS, Seshadri S, Beiser A, et al. Dementia after stroke: the Framingham Study. Stroke 2004;35:1264-1268. Comparison of 212 subjects who were free of dementia and sustained subsequent first stroke with 1060 age- and sex-matched, stroke- and dementia-free controls. Dementia developed in 19.3% of cases and 11.0% of controls. Baseline stroke doubled the risk of dementia (hazard ratio: 2.0; 95% CI 1.5 to 3.1).
26. ▶ Kaye J. Treatment of vascular dementia. In: Qizilbash N, Schneider LS, Chui H, et al, editors. Evidence-based dementia practice. Oxford, UK: Blackwell Science, 2002:589-607. Evidence-based review of treatments for vascular dementia.
27. ▶ Knopman D, Rocca WA, Cha RH, et al. Survival study of vascular dementia in Rochester, Minnesota. Arch Neurol 2003;60:85-90. Retrospective review of 479 patients with incident dementia and 479 referent subjects. Patients with vascular dementia had a higher RR of death (RR 2.7; 95% CI 1.9 to 3.9) than patients with dementia overall (RR 1.8; 95% CI 1.6 to 2.1) or patients with AD (RR 1.4; 95% CI 1.2 to 1.7).
28. ▶ Knopman DS, Rocca WA, Cha RH, et al. Incidence of vascular dementia in Rochester, Minn, 1985-1989. Arch Neurol 2002;59:1605-1610. The records-linkage system of the Rochester Epidemiology Project was used to ascertain incident cases of dementia.
29. ▶ Korf ES, Wahlund LO, Visser PJ, Scheltens P. Medial temporal lobe atrophy on MRI predicts dementia in patients with mild cognitive impairment. Neurology 2004;63:94-100. Provides semiquantitative rating scale for hippocampal atrophy.
30. ▶ Lesnik Oberstein SA, van den Boom R, van Buchem MA, et al, Dutch CADASIL Research Group. Cerebral microbleeds in CADASIL. Neurology 2001;57: 1066-1070. Cerebral microbleeds visualized by T2*-weighted gradient echo MRI were present in 31% of symptomatic CADASIL mutation carriers, predominantly in the thalamus.
31. ▶ Longstreth WT Jr, Arnold AM, Beauchamp NJ Jr, et al. Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke 2005;36:56-61. Of 1919 subjects with repeat MRI approximately 5 years later, 538 (28%) showed worsening of white matter grade by 1 grade. Participants with worsening grade experienced greater decline on the modified Mini-Mental State Examination and Digit Symbol Substitution Test.
32. ▶ Longstreth WT Jr, Dulberg C, Manolio TA, et al. Incidence, manifestations, and predictors of brain infarcts by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke 2002;33:2376-2382. Incident MRI-defined infarcts were observed in 17% of elderly subjects followed over 5 years. Most are small, subcortical, and associated with subtle cognitive decline but not recognized as a TIA or stroke.
33. ▶ Lopez OL, Kuller LH, Becker JT, et al. Classification of vascular dementia in the Cardiovascular Health Study Cognition Study. Neurology 2005; 64:1539-1547. The Cardiovascular Health Study classified 480 incident cases between 1994 and 1999 among 3608 participants using different diagnostic criteria.
34. ▶ Manolio TA, Kronmal RA, Burke GL, et al. Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study. Stroke 1994;25:318-327. Provides semiquantitative rating scale for severity of cerebral atrophy.
35. ▶ Moroney JT, Bagiella E, Desmond DW, et al. Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias. Neurology 1997;49:1096-1105. Receiver-operator characteristic curves were used in a meta-analysis of 312 autopsied cases to identify the best cutoffs of the Hachinski Ischemic Score to differentiate multi-infarct dementia, AD, and mixed dementia.
36. ▶ Mungas D, Harvey D, Reed BR, et al. Longitudinal volumetric MRI change and rate of cognitive decline. Neurology 2005;65:565-571. Associations between baseline and change in quantitative MRI measures of cortical gray matter, hippocampi, white matter hyperintensities, and lacunes and change in executive and memory ability in a mixed sample of subcortical vascular dementia, AD, and normal aging.
37. ▶ Mungas D, Jagust WJ, Reed BR, et al. MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer disease. Neurology 2001;57:2229-2235. Associations between quantitative MRI volumes of cortical gray matter, hippocampi, white matter hyperintensities, lacunes, and neuropsychological testing in a mixed sample of subcortical vascular dementia, AD, and normal aging.
38. ▶ Nyenhuis DL, Gorelick PB, Freels S, Garron DC. Cognitive and functional decline in African Americans with VaD, AD, and stroke without dementia. Neurology 2002;58:56-61. Comparison of rates of cognitive and functional decline in African American patients diagnosed at baseline with vascular dementia (n = 79), AD (n = 113), or stroke without dementia (n = 56) and followed for up to 7 years with annual neuropsychological and other examinations.
39. ▶ Orgogozo JM, Rigaud AS, Stoffler A, et al. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke 2002;33:1834-1839. After 28 weeks, the memantine-treated group showed a 2.0-point difference in the Alzheimer Disease Assessment Scale, cognitive subscale, compared with the placebo group in this double-blind, randomized, controlled trial (n = 288).
40. ▶ O'Sullivan M, Jarosz JM, Martin RJ, et al. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 2001;56:628-634. Scores for hyperintensities of the MRI-measured temporal white matter and external capsule-insula region were significantly higher in 20 patients with CADASIL compared with 20 patients with sporadic leukoaraiosis.
41. ▶ O'Sullivan M, Lythgoe DJ, Pereira AC, et al. Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis. Neurology 2002;59:321-326. Cerebral blood flow of normal-appearing white matter was reduced in periventricular regions for patients with leukoaraiosis and history of lacunar stroke compared with normal controls, suggesting that hypoperfusion may be an early feature in the development of periventricular lesions.
42. 2 P<.01) and Global Deterioration Scale (P<.05).
43. ▶ Peila R, White LR, Masaki K, et al. Reducing the risk of dementia: efficacy of long-term treatment of hypertension. Stroke 2006;37:1165-1170. Risk of dementia with greater than 12 years of antihypertensive treatment was lower compared with never-treated hypertensives (HR for dementia = 0.40; 95% CI 0.22 to 0.75).
44. ▶ Pohjasvaara T, Erkinjuntti T, Ylikoski R, et al. Clinical determinants of poststroke dementia. Stroke 1998;29:75-81. Poststroke dementia was observed in 31.8% of 337 patients with ischemic stroke. Correlates of dementia were dysphasia (odds ratio [OR] 5.6), major dominant stroke syndrome (OR 5.0), history of prior cerebrovascular disease (OR 2.0), and low educational level (OR 1.1).
45. ▶ Prins ND, van Dijk EJ, den Heijer T, et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 2005;128(pt 9):2034-2041. Among 832 subjects followed for a mean of 5.2 years, increasing severity of periventricular white matter lesions and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in information processing speed and executive function.
46. ▶ Pullicino PM, Miller LL, Alexandrov AV, Ostrow PT. Infraputaminal "lacunes." Clinical and pathological correlations. Stroke 1995;26:1598-1602. Differentiates giant dilated perivascular spaces from lacunar infarcts.
47. ▶ Ravaglia G, Forti P, Maioli F, et al. Incidence and etiology of dementia in a large elderly Italian population. Neurology 2005;64:1525-1530. Among a dementia-free cohort of 937 subjects followed for 4 years, the incidence rates per 1000 person years were 37.8 (95% CI 30.0 to 47.7) for dementia, 23.8 (95% CI 17.3 to 31.7) for AD, and 11.0 (95% CI 7.2 to 16.9) for vascular dementia.
48. ▶ Rocca WA, Kokmen E. Frequency and distribution of vascular dementia. Alzheimer Dis Assoc Disord 1999;13(suppl 3):9-14. Review of international incidence rates of vascular dementia.
49. ▶ Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250-260. National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) clinical criteria for probable and possible vascular dementia.
50. ▶ Sachdev PS, Brodaty H, Valenzuela MJ, et al. The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients. Neurology 2004a;62:912-919. Neuropsychological testing was performed in 170 patients with stroke or TIA and compared with 96 age-matched normal controls.
51. ▶ Sachdev PS, Brodaty H, Valenzuela MJ, et al. Progression of cognitive impairment in stroke patients. Neurology 2004b;63:1618-1623. Patients (n = 128) had a mean decline of 0.83 (SD 2.2) points on the Mini-Mental State Examination compared with an increase of 0.76 (1.3) in controls (n = 78) (P<.0001).
52. ▶ Schneider JA, Bienias JL, Wilson RS, et al. The apolipoprotein E epsilon4 allele increases the odds of chronic cerebral infarction [corrected] detected at autopsy in older persons. Stroke 2005;36:954-959. Erratum in Stroke 2005;36:1353. After controlling for age and sex in 214 autopsied subjects, APOE ε4 increased the odds of cerebral infarction by 2.3-fold (95% CI 1.2 to 4.2), even after accounting for amyloid angiopathy.
53. ▶ Schneider LS. Increased mortality associated with cholinesterase inhibitors in VCI. International Alzheimer Association Conference. Madrid, Spain. June 2006. A meta-analysis showed increased mortality (OR 1.44) in the donepezil-treated group in two of three vascular dementia clinical trials.
54. ▶ Seshadri S, Beiser A, Kelly-Hayes M, et al. The lifetime risk of stroke: estimates from the Framingham Study. Stroke 2006;37:345-350. Participants in the original Framingham cohort (n = 4897) who were stroke- and dementia-free at 55 years of age were followed for up to 51 years. For women, the lifetime risks for stroke and AD were similar (namely, 1 in 5), whereas for men, the lifetime risk for stroke was 1 in 6 and for AD was 1 in 10. Participants with normal blood pressure (less than 120/80 mm Hg) had half the lifetime risk of stroke compared with those with high blood pressure (140/90 mm Hg or greater).
55. ▶ Sudlow C, Martinez Gonzalez NA, Kim J, Clark C. Does apolipoprotein E genotype influence the risk of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage? Systematic review and meta-analyses of 31 studies among 5,961 cases and 17,965 controls. Stroke 2006;37:364-370. Meta-analysis of 31 studies with 5961 cases and 17, 965 controls. Small increases in OR were found between ε4 allele and ischemic stroke (OR 1.11; 95% CI 1.01 to 1.22. However, the association between ε4 and ischemic stroke disappeared when analyses were limited to only 11 large studies (more than 200 cases) or studies without control-selection bias.
56. ▶ Tournier-Lasserve E, Iba-Zizen MT, Romero N, Bousser MG. Autosomal dominant syndrome with stroke like-episodes and leukoencephalopathy. Stroke 1991;22:1297-1302. Initial description of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
57. ▶ Tzourio C, Anderson C, Chapman N, et al. Progress Collaborative Group. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 2003;163:1069-1075. In the PROGRESS trial, 6105 subjects with previous stroke or TIA were randomized to perindopril plus or minus indapamide versus placebo and followed for 3.9 years.
58. ▶ van Straaten EC, Fazekas F, Rostrup E, et al, LADIS Group. Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study. Stroke 2006;37:836-840. Comparison of visual rating and volumetric measures of MRI white matter hyperintensities in 618 elderly community-dwelling subjects.
59. ▶ Vermeer SE, den Heijer T, Koudstaal PJ, et al, Rotterdam Scan Study. Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2003a;34:392-396. New silent infarcts occurred in 14% of 668 subjects after mean 3.4 years follow-up and were associated with the same risk factors for stroke.
60. ▶ Vermeer SE, Koudstaal PJ, Oudkerk M, et al. Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2002;33:21-25. Silent infarcts were found in 24% of 1077 elderly subjects and were associated with hypertension but not diabetes or smoking.
61. ▶ Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003b;348:1215-1222. Silent infarcts at baseline more than doubled the risk of dementia, and incident silent infarcts increased the rate of cognitive decline.
62. ▶ Viswanathan A, Chabirat H. Cerebral microhemorrhage. Stroke 2006;37:550-555. A review of microhemorrhages visualized by gradient-echo or T2*-weighted MRI: pathophysiology, prevalence, and clinical implications.
63. ▶ Wilkinson D, Doody R, Helme R, et al. Donepezil 308 Study Group. Donepezil in vascular dementia: a randomized, placebo-controlled study. Neurology 2003;61:479-486. Randomized, double-blind, placebo-controlled, 24-week studies of donepezil among subjects with probable vascular dementia (n = 616).
64. ▶ Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke 1991;22:312-318. Original description of Framingham Stroke Risk Profile, later modified by D'Agostino and colleagues (1994) for treated blood pressure levels.
65. ▶ World Health Organization. International statistical classification of diseases. 10th revision. Geneva: World Health Organization, 1993. International Statistical Classification of Diseases, 10th Revision diagnosis of vascular dementia.
66. ▶ Yamanouchi H. Loss of white matter oligodendrocytes and astrocytes in progressive subcortical vascular encephalopathy of Binswanger type. Acta Neurol Scand 1991;83:301-305. Pathologic study of Binswanger encephalopathy.
67. ▶ Yip AG, McKee AC, Green RC, et al. APOE, vascular pathology, and the AD brain. Neurology 2005;65:259-265. APOE ε4 is associated with small vessel arteriolosclerosis, microinfarcts of the deep nuclei, neuritic senile plaque density, and amyloid angiopathy in patients with autopsy-proven AD.
68. ▶ Zarow C, Vinters HV, Ellis WG, et al. Correlates of hippocampal neuron number in Alzheimer's disease and ischemic vascular dementia. Ann Neurol 2005;57:896-903. The total number of CA-1 hippocampal neurons was estimated in 28 autopsy cases using unbiased stereology. Number of neurons was significantly less in AD compared with ischemic vascular dementia (P<.02), with greatest loss of neurons seen in two cases with combined AD and hippocampal sclerosis. Number of neurons correlated with MRI-measured hippocampal volume, regardless of underlying type of pathology.