Dementias pp 103-135 | Cite as

Lacunes in — the Knowledge of — Vascular Dementia

  • P. Martinez-Lage
  • V. Hachinski


A recent article on clinical-neuropathological correlations in multi-infarct dementia (MID) questions many assertions regarding the frequency and importance of MID [1]. Aiming to define neuropathological criteria for the diagnosis of MID, the authors searched for cases among the files of ten neuropathology departments in major medical centers involved in the CERAD program. After reviewing autopsies from patients with dementia, neuropathologists from four centers could not find even a single case in which cerebral infarction was “the only explanation of the clinical dementia.” The other six neuropathologists detected six valid cases … among 1929 patients with dementia! Even considering overly strict inclusion criteria and the biased interest of the ten centers in Alzheimer’s disease (AD), the quick conclusion is that “multi-infarct dementia unaccompanied by neuropathological evidence of Alzheimer’s disease is rare.” However, a second careful analysis of these unexpected numbers raises a number of questions regarding the concept of MID or vascular dementia (VD). At the pathological level the absence of commonly agreed upon diagnostic criteria is of concern. Lack of agreement may lead to a biased underestimation of the contribution of vascular lesions to cognitive impairment and dementia. The presence of senile plaques with or without neurofibrillary tangles in the brain of a patient with dementia and vascular lesions automatically excludes a diagnosis of VD in favor of AD. Paradoxically, when similar changes are present in a cognitively intact subject, establishing a diagnosis of AD may be too bold. This margin of uncertainty should be kept also for patients with vascular lesions, so that their relevance in the pathophysiology of cognitive decline and dementia can be investigated and clarified. Even when a case is labelled as mixed dementia, the responsibility for the clinical picture is heavily weighted towards the plausible degenerative rather than the vascular component. Observation, quantification and collection of neuropathological data may be laborious, but it is the interpretation and transformation of anatomical findings into clinical correlates that entails the highest difficulty and demands scientific rigor, inspiration, and open-mindedness. One of the most important sources of confusion and misunderstanding probably resides in the way clinical information is collected and classified.


Vascular Dementia Vascular Risk Factor Hippocampal Sclerosis Lacunar Infarct Vascular Cognitive Impairment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hulette C, Nochlin D, McKeel D, Morris JC, Mirra SS, et al (1997) Clinical-neuropathologic findings in multi-infarct dementia: a report of six autopsied cases. Neurology 48: 668–672PubMedCrossRefGoogle Scholar
  2. 2.
    Hachinski VC (1992) Preventable senility: a call for actions against vascular dementias. Lancet 340: 645–648PubMedCrossRefGoogle Scholar
  3. 3.
    Hachinski VC (1994) Vascular dementia: a radical redefinition. Dementia 5: 130–132PubMedGoogle Scholar
  4. 4.
    Hachinski VC, Bowler JV (1993) Vascular dementia. Neurology 43: 2159–2160PubMedCrossRefGoogle Scholar
  5. 5.
    Hébert R, Brayne C (1995) Epidemiology of vascular dementia. Neuroepidemiology 14: 240–257PubMedCrossRefGoogle Scholar
  6. 6.
    Jorm AF (1990) The epidemiology of Alzheimer’s disease and related disorders. Chapman and Hall, LondonGoogle Scholar
  7. 7.
    Bowler J, Hachinski VC (1996) History of the concept of vascular dementia: two opposing views on current definitions and criteria for vascular dementia. In: Prohovnik I, Wade J, Knezevic S, Tatemichi T, Erkinjuntti T (eds) Vascular dementia: current concepts. Wiley, Chichester, pp 1–24Google Scholar
  8. 8.
    Skoog I, Nilsson R, Palmertz B, et al (1993) A population-based study of dementia in 85-year-olds. N Engl J Med 328: 153–158PubMedCrossRefGoogle Scholar
  9. 9.
    Breteler MMB, van Swieten JC, Bolts ML, et al (1994) Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology 44: 1246–1252PubMedCrossRefGoogle Scholar
  10. 10.
    Martinez-Lage P, Manubens JM, Martinez-Lage JM, et al (1996) Vascular risk factors and cognitive performance in a non-demented elderly population. Neurology [Suppl] 1:A289Google Scholar
  11. 11.
    Breteler MMB, Claus JJ, Grobbee DE, et al (1994) Cardiovacular disease and distribution of cognitive function in elderly people: the Rotterdam Study. BMJ 308: 1604–1608PubMedCrossRefGoogle Scholar
  12. 12.
    Tatemichi TK, Sacktor N, Mayeux R (1994) Dementia associated with cerebrovascular disease, other degenerative diseases, and metabolic disorders. In: Terry RD, Katzman R, Bick KL (eds) Alzheimer’s disease. Raven, New York, pp 123–166Google Scholar
  13. 13.
    Pohjasvaara T, Erkinjuntti T, Vataja R, Kaste M (1997) Dementia three months after stroke. Baseline frequency and effect of different definitions of dementia in the Helsinki Stroke Aging. Memory Study (SAM) cohort. Stroke 28: 785–792PubMedCrossRefGoogle Scholar
  14. 14.
    Grace J, Nadler JD, White DA, et al (1995) Folstein vs Modified Mini-Mental State Examination in geriatric stroke. Stability, validity, and screening utility. Arch Neurol 52: 477–484PubMedCrossRefGoogle Scholar
  15. 15.
    Tatemichi TK, Desmond DW, Stern Y, et al (1994) Cognitive impairment after stroke: frequency, patterns, and relationship to functional disabilities. J Neurol Neurosurg Psychiatry 57: 202–207PubMedCrossRefGoogle Scholar
  16. 16.
    Tatemichi TK, Desmond DW (1996) Epidemiology of vascular dementia. In: Prohovnik I, Wade J, Knezevic S, Tatemichi T, Erkinjuntti T (eds) Vascular dementia: current concepts. Wiley, Chichester, p 40Google Scholar
  17. 17.
    Kokmen E, Whisnant JP, O’Fallon WM, et al (1996) Dementia after ischemic stroke: a population-based study in Rochester, Minnesota. Neurology 46: 154–159PubMedCrossRefGoogle Scholar
  18. 18.
    Pasquier F, Leys D (1997) Why are stroke patients prone to develop dementia? J Neurol 244: 135–142PubMedCrossRefGoogle Scholar
  19. 19.
    Rockwood K, Ebly E, Hachinski H, et al (1997) Presence and treatment of vascular risk factors in patients with vascular cognitive impairment. Arch Neurol 54: 33–39PubMedCrossRefGoogle Scholar
  20. 20.
    Martinez-Lage P, Hachinski VC (1998) Multi-infarct dementia. The vascular causes of cognitive impairment and dementia. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM (eds) Stroke: pathophysiology, diagnosis, and management, 3rd edn. Churchill Livingstone, New YorkGoogle Scholar
  21. 21.
    Moncayo J, Bogousslavsky J (1996) Vascular dementia: persisting controversies and questions. Eur J Neurol 3: 299–308CrossRefGoogle Scholar
  22. 22.
    Ladurner G, Iliff LD, Lechner H (1982) Clinical factors associated with dementia in ischaemic stroke. J Neurol Neurosurg Psychiatry 45: 97–101PubMedCrossRefGoogle Scholar
  23. 23.
    Loeb C, Gandolfo C, Bino G (1988) Intellectual impairment and cerebral lesions in multiple cerebral infarcts. A clinical-computed tomography study. Stroke 19: 560–565PubMedCrossRefGoogle Scholar
  24. 24.
    Tatemichi TK, Foulkes MA, Mohr JP, et al (1990) Dementia in stroke survivors in the Stroke Data Bank Cohort. Prevalence, incidence, risk factors, and computed tomographic findings. Stroke 21: 858–866PubMedCrossRefGoogle Scholar
  25. 25.
    Tatemichi TK, Desmond DW, Paik M, et al (1993) Clinical determinants of dementia related to stroke. Ann Neurol 33: 568–575PubMedCrossRefGoogle Scholar
  26. 26.
    Gorelick PB, Brody J, Cohen D, et al (1993) Risk factors for dementia associated with multiple cerebral infarcts. A case-control analysis in predominantly African-American hospital-based patients. Arch Neurol 50: 714–720PubMedCrossRefGoogle Scholar
  27. 27.
    Yoshitake T, Kiyohara W, Kato I, et al (1995) Incidence and risk factors of vascular dementia and Alzheimer’s disease in a defined elderly Japanese population: the Hisayama Study. Neurology 45: 1161–1168PubMedCrossRefGoogle Scholar
  28. 28.
    Lindsay J, Hebert R, Rockwood K (1997) The Canadian Study of Health and Aging. Risk factors for vascular dementia. Stroke 28: 526–530PubMedCrossRefGoogle Scholar
  29. 29.
    Moroney JT, Bagiella E, Desmond DW, et al (1995) Global hypoxic-ischemic events increase the risk of dementia after stroke. Ann Neurol 38: 290Google Scholar
  30. 30.
    Brun A (1994) Pathology and pathophysiology of cerebrovascular dementia: pure subgroups of obstructive and hypoperfusive etiology. Dementia 5: 145–147PubMedGoogle Scholar
  31. 31.
    Lopez OL, Rabin BS (1995) Alteraciones inmunológicas de 1a demencia vascular. In: Lopez Pousa S, Manubens JM, Rocca WA (eds) Epidemiología de 1a demencia vascular. Controversias en su tratamiento. JR Prous, Barcelona, pp 91–98Google Scholar
  32. 32.
    Caplan LR (1995) Binswanger’s disease-revisited. Neurology 45: 626–633PubMedCrossRefGoogle Scholar
  33. 33.
    Iwamoto T, Kubo H, Takasaki M (1995) Platelet activation in the cerebral circulation in different subtypes of ischemic stroke and Binswanger’s disease. Stroke 26: 52–56PubMedCrossRefGoogle Scholar
  34. 34.
    Bowler JV, Hachisnki VC (1994) Progress in the genetics of cerebrovascular disease: inherited subcortical arteriopathies. Stroke 25: 1696–1698PubMedCrossRefGoogle Scholar
  35. 35.
    Betard C, Robitaille Y, Gee M, et al (1994) ApoE allele frequencies in Alzheimer’s disease, Lewy body dementia, Alzheimer’s disease with cerebrovascular disease and vacular dementia. Neuroreport 5: 1893–1896PubMedCrossRefGoogle Scholar
  36. 36.
    American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington DCGoogle Scholar
  37. 37.
    World Health Organization (1993) The ICD-10 classification of mental and behavioural disorders. Diagnostic criteria for research. World Health Organization, GenevaGoogle Scholar
  38. 38.
    Roman GC, Tatemichi TK, Erkinjuntti T, et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43: 250–260PubMedCrossRefGoogle Scholar
  39. 39.
    Chui HC, Victoroff JI, Margolin D, et al (1992) Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer’s disease diagnostic and treatment centers. Neurology 42: 473–480PubMedCrossRefGoogle Scholar
  40. 40.
    Wallin A, Blennow K (1993) Heterogeneity of vascualr dementia: mechanisms and subgroups. J Geriatr Psychiatry Neurol 6: 177–185PubMedGoogle Scholar
  41. 41.
    Lopez OL, Larumbe MR, Becker JT, et al (1994) Reliability of NINDS-AIREN criteria for the diagnosis of vascular dementia. Neurology 44: 1240–1245PubMedCrossRefGoogle Scholar
  42. 42.
    Verhey FRJ, Lodder J, Rozendaal N, et al (1966) Comparison of seven sets of criteria used for the diagnosis of vascular dementia. Neuroepidemiology 15: 166–172CrossRefGoogle Scholar
  43. 43.
    Wetterling T, Kanitz R-D, Borgis K-J (1996) Comparison of different diagnostic criteria for vascular dementia (ADTCC, DSM-IV, ICD-10, NINDS-AIREN). Stroke 27: 30–36PubMedCrossRefGoogle Scholar
  44. 44.
    Villardita C (1992) Alzheimer’s disease compared with cerebrovascular dementia. Neuropsychological similarities and differences. Acta Neurol Scand 87: 299–308CrossRefGoogle Scholar
  45. 45.
    del Ser T, Bermejo F, Portera A, et al (1990) Vascular dementia. A clinicopathological study. Neurol Sci 96: 1–17CrossRefGoogle Scholar
  46. 46.
    Munoz DG (1991) The pathological basis of multi-infarct dementia. Alzheimer Dis Assoc Disord 5: 77–90PubMedCrossRefGoogle Scholar
  47. 47.
    Garcia JH, Brown GG (1992) Vascular dementia: neuropathologic alterations and metabolic brain changes. J Neurol Sci 109: 121–131PubMedCrossRefGoogle Scholar
  48. 48.
    Olsson Y, Brun A, Englund E (1996) Fundamental pathological lesions in vascular dementia. Acta Neurol Scand Suppl 168: 31–38PubMedCrossRefGoogle Scholar
  49. 49.
    Dickson DW, Davies P, Bevona C, et al (1994) Hippocampal sclerosis: a common pathological feature of dementia in very old (≥80 years of age) humans. Acta Neuropathol 88: 212–221PubMedCrossRefGoogle Scholar
  50. 50.
    Petito CK, Feldemann E, Pulsinelli WA, et al (1987) Delayed hipoocampal damage in humans following cardiorespiratory arrest. Neurology 37: 1281–1286PubMedCrossRefGoogle Scholar
  51. 51.
    Corey-Bloom J, Sabbagh MN, Bondi MW, et al (1997) Hippocampal sclerosis contributes 41 to dementia in the elderly. Neurology 48: 154–160PubMedCrossRefGoogle Scholar
  52. 52.
    Knopman DS, Mastri AR, Frey WHII, et al (1990) Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 40: 251–256PubMedCrossRefGoogle Scholar
  53. 53.
    Lassen NA (1982) Incomplete cerebral infarction-focal incomplete ischemie tissue necrosis not leading to emollision. Stroke 13: 522–523PubMedCrossRefGoogle Scholar
  54. 54.
    Garcia JH, Lassen NA, Weiller C, et al (1996) Ischemic stroke and incomplete infarction. Stroke 27: 761–765PubMedCrossRefGoogle Scholar
  55. 55.
    Bredesen DE (1995) Neural apoptosis. Ann Neurol 38: 839–851PubMedCrossRefGoogle Scholar
  56. 56.
    Matsushima K, Schmidt-Kastner R, Hakim AM (1996) Genes and cerebral ischemia: therapeutic perspectives. Cerbrovasc Disord 6: 119–127CrossRefGoogle Scholar
  57. 57.
    Gehrmann J, Banati RB, Wiessnert C, et al (1995) Reactive microglia in cerebral ischaemia: an early mediator of tissue damage? Neuropathol Appl Neurobiol 21: 277–289PubMedCrossRefGoogle Scholar
  58. 58.
    Yamanouchi H (1991) Loss of white matter oligodendrocytes and astrocytes in progressive subcortical vascular encephalopathy of Binswanger type. Acta Neurol Scand 83: 301–305PubMedCrossRefGoogle Scholar
  59. 59.
    Higashi T, Nishi S, Nakai ZA, et al (1995) Regulatory mechanisms of stress response in mammalian nervous system during cerebral ischaemia or after heat shock. Neuropathol Appl Neurobiol 21: 471–483CrossRefGoogle Scholar
  60. 60.
    Mesulam MM (1990) Large-scale neurocognitive networks and distributed processing for attention, language, and memory. Ann Neurol 28: 597–613PubMedCrossRefGoogle Scholar
  61. 61.
    Cummings JL, Benson DF (1992) Vascular dementias. In: Cummings JL, Benson DF (eds) Dementia: a clinical approach. Butterworth-Heinemann, Boston, pp 153–176Google Scholar
  62. 62.
    Meyer JS, Kawamura J, Terayama Y (1992) White matter lesions in the elderly. J Neurol Sci 110: 1–7PubMedCrossRefGoogle Scholar
  63. 63.
    Roman GC (1987) Senile dementia of the Binswanger type. A vascular form of dementia in the elderly. JAMA 258: 1782–1788PubMedCrossRefGoogle Scholar
  64. 64.
    Chimowitz MI, Awad IA, Furlan AJ (1989) Periventricular lesions on MRI. Facts and theories. Stroke 24: 7–12Google Scholar
  65. 65.
    Schmidt R, Fazekas F, Offenbacher H, et al (1993) Neuropsychologic correlates of MRI white matter hyperintsities: a study of 150 normal volunteers. Neurology 43: 2490–2494PubMedCrossRefGoogle Scholar
  66. 66.
    Fazekas F, Schmidt R, Offenbacher H, et al (1991) Prevalence of white matter and periventricular magnetic resonance hyperintesities in asymptomatic volunteers. J Neuroimaging 1: 27–30Google Scholar
  67. 67.
    Grafton ST, Sumi SM, Stimac GK, et al (1991) Comparison of postmortem magnetic resonance imaging and neuropathologic findings in the cerebral white matter. Arch Neurol 48: 293–298PubMedCrossRefGoogle Scholar
  68. 68.
    Leifer D, Buonanno FS, Richardson EP (1990) Clinicopathologic correlations of cranial magnetic resonance imaging of periventricular white matter. Neurology 40: 911–918PubMedCrossRefGoogle Scholar
  69. 69.
    Hachinski VC, Munoz DG (1991) Leuko-araiosis: an update. Bull Clin Neurosci 56: 24–33Google Scholar
  70. 70.
    Van Swieten JC, Kappelle LJ, Algra A, et al (1992) Hypodensity of the cerebral white matter in patients with transient ischemic attacks or minor stroke: the influence on the rate of subsequent stroke. Ann Neurol 32: 177–183PubMedCrossRefGoogle Scholar
  71. 71.
    van Zagten M, Boiten J, Kessels F, Lodder J (1996) Significant progression of white matter lesions and small deep (lacunar) infarcts in patients with stroke. Arch Neurol 53: 650–655PubMedCrossRefGoogle Scholar
  72. 72.
    Erkinjuntti T, Enavente O, Eliasziw M, et al (1996) Diffuse vacuolization (spongiosis) and arteriolosclerosis in the frontal white matter occurs in vascular dementia. Arch-Neurol 53: 325–332PubMedCrossRefGoogle Scholar
  73. 73.
    Tarvonen-Schröder S, Röyttä M, Räihä I, et al (1996) Clinical features of leuko-araiosis. J Neurol Neurosurg Psychiatry 60: 431–436PubMedCrossRefGoogle Scholar
  74. 74.
    Pullicino P, Benedict RHB, Capruso DX, et al (1996) Neuroimaging criteria for vascular dementia. Arch Neurol 53: 723–728PubMedCrossRefGoogle Scholar
  75. 75.
    Meyer JS, Ropgers RL, Mortel KF (1989) Multi-infarct dementia: demography, risk factors, and therapy. In: Ginsberg MD, Dietrich WD (eds) Cerebrovacular diseases. Raven, New York, pp 199–207Google Scholar
  76. 76.
    Mirsen T, Hachinski VC (1988) Epidemiology and classification of vascular and multi-infarct dementia. In: Meyer JS, Lechner H, Marshal J, Toole JF (eds) Vascular and multi-infarct dementia. Future, Mount Kisco, pp 61–76Google Scholar
  77. 77.
    Loeb C (1991) Vascular dementia: terminology and classification. In: Chopra JS, Jagannathan K, Sawhney IMS, Lechner H, Szendey GL (eds) Progress in cerebrovascular disease. Current concepts in stroke and vascular dementia. Elsevier Science, Amsterdam, pp 79–88Google Scholar
  78. 78.
    Ross GW, Cummings JL (1992) Vascular dementias. In: Thal LJ, Moos WH, Gamzu ER (eds) Cognitive disorders. Pathophysiology and treatment. Dekker, New York, pp 271–289Google Scholar
  79. 79.
    Erkinjuntti T (1987) Types of multi-infarct dementia. Acta Neurol Scand 75: 391–399PubMedCrossRefGoogle Scholar
  80. 80.
    Loeb C, Meyer JS (1996) Vascular dementia: still a debatable entity? J Neurol Sci 143: 31–40PubMedCrossRefGoogle Scholar
  81. 81.
    Hachinski VC, Lassen NA, Marshall J (1974) Multi-infarct dementia: a cause of mental deterioration in the elderly. Lancet 2: 207–210PubMedCrossRefGoogle Scholar
  82. 82.
    Freeman R, Bear D, Greenberg MS (1989) Behavioral disturbances in cerebrovascular disease. In: Toole JF (ed) Handbook of clinical neurology, vol 11 (55). Vascular diseases, part III. Elsevier Science, Amsterdam, pp 137–150Google Scholar
  83. 83.
    Arboix A, Marti-Vilalta JL (1992) Manifestaciones clínicas de los infartos isquémicos cerebrales de los “territorios frontera”. In: Matías-Guiu J, Martinez-Vila E, Marti-Vilalta JL (eds) Isquemia cerebral global. JR Prous, Barcelona, pp 33–39Google Scholar
  84. 84.
    Mahler ME, Cummings JL (1991) Behavioral neurology of multi-infarct dementia. Alzheimer Dis Assoc Disord 5: 122–130PubMedCrossRefGoogle Scholar
  85. 85.
    Castaigne P, Lhermitte F, Buge A, et al (1981) Paramedian thalamic and midbrain infarcts: clinical and neuropathological study. Ann Neurol 10: 127–148PubMedCrossRefGoogle Scholar
  86. 86.
    Tatemichi YK, Desmond DW, Prohovnik I, et al (1992) Confusion and memory loss from capsular genu infarction: a thalmocortical disconnection syndrome? Neurology 42: 1966–1979PubMedCrossRefGoogle Scholar
  87. 87.
    Caplan LR, Schmahmann JD, Kase CS, et al (1990) Caudate infarcts. Arch Neurol 47: 133–143PubMedCrossRefGoogle Scholar
  88. 88.
    Nakagawara J, Sperling B, Lassen NA (1997) Incomplete infarction of reperfused cortex may be quantitated with iomazenil. Stroke 28: 124–132PubMedCrossRefGoogle Scholar
  89. 89.
    Keith AJ, Jones KJ, Becker A, et al (1997) Preclinical diagnosis of Alzheimer’s disease with SPECT. Neurology 48: A207Google Scholar
  90. 90.
    Cummings JL (1993) Frontal-subcortical circuits and human behavior. Arch Neurol 50: 873–880PubMedCrossRefGoogle Scholar
  91. 91.
    Nichols FT III, Mohr JP (1986) Binswanger’s subacute arteriosclerotic encephalopathy. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM (eds) Stroke: pathophysiology, diagnosis, and management. Churchill Livingstone, New York, pp 875–885Google Scholar
  92. 92.
    Sulkava R, Erkinjuntti T (1987) Vascualr dementia due to cardiac arrhythmias and hypotension. Acta Neurol Scand 76: 123–128PubMedCrossRefGoogle Scholar
  93. 93.
    Chabriat H, Vahedi K, Iba-zizen MT, et al (1995) Clinical spectrum of CADASIL: a study of 7 families. Lancet 346: 934–939PubMedCrossRefGoogle Scholar
  94. 94.
    Sabbadini G, Francia A, Calandriello L, et al (1995) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Clinical, neuroimaging, pathological, and genetic study of a large Italian family. Brain 118: 207–215Google Scholar
  95. 95.
    Bousser MG, Tournier-Lasserve E (1994) Summary of the proceedings of the first International Workshop on CADASIL. Paris, 19-21 May 1993. Stroke 25: 704–707PubMedCrossRefGoogle Scholar
  96. 96.
    Joutel A, Corpechot C, Ducros A, et al (1996) Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 383: 707–710PubMedCrossRefGoogle Scholar
  97. 97.
    Boone KB, Miller BL, Lesser IM, et al (1992) Neuropsychological correlates of white matter lesions in healthy elderly subjects. A threshold effect. Arch Neurol 49: 549–554PubMedCrossRefGoogle Scholar
  98. 98.
    Ylikoski R, Ylikoski A, Erkinjuntti E, et al (1993) White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol 50: 818–824PubMedCrossRefGoogle Scholar
  99. 99.
    Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of old demented people. J Neurol Sci 11: 205–242PubMedCrossRefGoogle Scholar
  100. 100.
    Skoog I, Lernfeit B, Landahl S, et al (1996) 15-year follow-up study of blood pressure and dementia. Lancet 347: 1141–1145PubMedCrossRefGoogle Scholar
  101. 101.
    Ott A, Stolk RP, Hofman A, et al (1996) Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia 39: 1392–1397PubMedCrossRefGoogle Scholar
  102. 102.
    Ott A, Breteler MMB, de Bruyne MC, et al (1997) Atrial fibrillation and dementia in a population based study. The Rotterdam Study. Stroke 28: 316–321PubMedCrossRefGoogle Scholar
  103. 103.
    Olichney JM, Hansen LA, Hofstetter R, et al (1995) Cerebral infarction in Alzheimer’s disease is associated with severe amyloid angiopathy and hypertension. Arch Neurol 52: 702–708PubMedCrossRefGoogle Scholar
  104. 104.
    Snowdon DA, Greiner LH, Mortimer JA, et al (1997) Brain infarction and the clinical expression of Alzheimer’s disease. JAMA 277: 813–817PubMedCrossRefGoogle Scholar
  105. 105.
    Nagy Z, Esiri MM, Jobst KA, et al (1997) The effects of additional pathology on the cognitive deficit in Alzheimer disease. J Neuropathol Exp Neurol 56: 165–170PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 1999

Authors and Affiliations

  • P. Martinez-Lage
  • V. Hachinski

There are no affiliations available

Personalised recommendations