multi infarct dementia


Summary: Loss of higher cortical functions with retained awareness due to multiple cortical or subcortical CEREBRAL INFARCTION. Memory, judgment, attention span, and impulse control are often impaired, and may be accompanied by PSEUDOBULBAR PALSY; HEMIPARESIS; reflex abnormalities, and other signs of localized neurologic dysfunction. (From Adams et al., Principles of Neurology, 6th ed, p1060)

Top Publications

  1. Uchino M, Hirano T, Uyama E, Hashimoto Y. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and CADASIL-like disorders in Japan. Ann N Y Acad Sci. 2002;977:273-8 pubmed
    ..It was suspected that the incidence of CADASIL is not so rare in Japan. There were some families with CADASIL-like features, but without Notch3 mutations or GOM, suggesting the need for genetic analysis in the future. ..
  2. Collins C. Pathophysiology and classification of stroke. Nurs Stand. 2007;21:35-9 pubmed
    ..This article describes how different types of stroke present and outlines the likely outcome for patients for each type. ..
  3. Singhal S, Bevan S, Barrick T, Rich P, Markus H. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain. 2004;127:2031-8 pubmed
    ..This implies that modulating factors influence phenotype. Smoking appears to increase the risk of stroke, while high homocysteine levels are associated with an increased risk of migraine. ..
  4. Okawa M, Mishima K, Hishikawa Y, Hozumi S, Hori H, Takahashi K. Circadian rhythm disorders in sleep-waking and body temperature in elderly patients with dementia and their treatment. Sleep. 1991;14:478-85 pubmed
  5. Liebetrau M, Herzog J, Kloss C, Hamann G, Dichgans M. Prolonged cerebral transit time in CADASIL: a transcranial ultrasound study. Stroke. 2002;33:509-12 pubmed
    ..Studies comparing CADASIL subjects with other patient populations seem warranted to determine possible differences in CTT between different types of small-vessel disease. ..
  6. Yu J, Liu C, Zhang X, Han J. Acupuncture improved cognitive impairment caused by multi-infarct dementia in rats. Physiol Behav. 2005;86:434-41 pubmed
    ..Acupuncture as a potential clinic method in treating VD should be developed and investigated in the future. ..
  7. Rufa A, Dotti M, Frezzotti P, De Stefano N, Caporossi A, Federico A. Hemodynamic evaluation of the optic nerve head in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Arch Neurol. 2004;61:1230-3 pubmed
    ..Our results suggest that hemodynamic parameters are abnormal in the superficial nerve fiber layer of the optic nerve head of patients with CADASIL, especially in the temporal quadrants of the neuroretinal rim. ..
  8. Oberstein S. Diagnostic strategies in CADASIL. Neurology. 2003;60:2020; author reply 2020 pubmed
  9. de la Pena P, Bornstein B, Del Hoyo P, Fernandez Moreno M, Martin M, Campos Y, et al. Mitochondrial dysfunction associated with a mutation in the Notch3 gene in a CADASIL family. Neurology. 2001;57:1235-8 pubmed
    ..Mitochondrial dysfunction in patients with CADASIL may be an epiphenomenon, but results of this study suggest that the pathophysiology of the disease could include a defect in oxidative phosphorylation. ..

More Information


  1. Kristofikova Z, Kozmikova I, Hovorkova P, Ricny J, Zach P, Majer E, et al. Lateralization of hippocampal nitric oxide mediator system in people with Alzheimer disease, multi-infarct dementia and schizophrenia. Neurochem Int. 2008;53:118-25 pubmed publisher
    ..The volumetric asymmetry of the planum temporale as a marker of handedness is not probably simply linked to brain laterality at biochemical level but reflects alterations due to pathological processes. ..
  2. Molko N, Pappata S, Mangin J, Poupon F, LeBihan D, Bousser M, et al. Monitoring disease progression in CADASIL with diffusion magnetic resonance imaging: a study with whole brain histogram analysis. Stroke. 2002;33:2902-8 pubmed
    ..Thus, quantitative diffusion MRI can be used to monitor disease progression in CADASIL and possibly in other types of small-vessel brain disorders. ..
  3. Gridley T. Notch signaling and inherited disease syndromes. Hum Mol Genet. 2003;12 Spec No 1:R9-13 pubmed
    ..Mouse models for these three diseases have been developed, and are leading to novel insights into the pathology of these diseases in humans. ..
  4. De Luigi A, Fragiacomo C, Lucca U, Quadri P, Tettamanti M, Grazia De Simoni M. Inflammatory markers in Alzheimer's disease and multi-infarct dementia. Mech Ageing Dev. 2001;122:1985-95 pubmed
  5. Joutel A, Tournier Lasserve E. [Molecular basis and physiopathogenic mechanisms of CADASIL: a model of small vessel diseases of the brain]. J Soc Biol. 2002;196:109-15 pubmed
    ..Furthermore, they open new perspectives in the field of small-artery diseases of the brain and should help to further dissect their genetic etiologies and understand their pathogenic mechanisms. ..
  6. Joutel A, Dodick D, Parisi J, Cecillon M, Tournier Lasserve E, Bousser M. De novo mutation in the Notch3 gene causing CADASIL. Ann Neurol. 2000;47:388-91 pubmed
    ..Therefore, our finding suggests that CADASIL may be more frequent than anticipated. ..
  7. Arboleda Velasquez J, Lopera F, Lopez E, Frosch M, Sepulveda Falla D, Gutierrez J, et al. C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke. Neurology. 2002;59:277-9 pubmed
  8. Honda N, Machida K, Hosono M, Matsumoto T, Matsuda H, Oshima M, et al. Interobserver variation in diagnosis of dementia by brain perfusion SPECT. Radiat Med. 2002;20:281-9 pubmed
    ..MID, respectively). Considerable interobserver variation was present in BP-SPECT interpretation. BP-SPECT may be more effective for the evaluation of dementia than MRI when the same nuclear medicine physicians interpret both images. ..
  9. Walzl M. A promising approach to the treatment of multi-infarct dementia. Neurobiol Aging. 2000;21:283-7 pubmed
    ..These results can indicate the importance and influence of hemorheology on clinical symptoms in MID. ..
  10. Chabriat H, Pappata S, Ostergaard L, Clark C, Pachot Clouard M, Vahedi K, et al. Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking. Stroke. 2000;31:1904-12 pubmed
    ..This hypoperfusion appears to be related to the clinical severity. The significant effect of ACZ on CBF and CBV suggests that cerebral perfusion might be increased using pharmacological vasodilation in CADASIL. ..
  11. Mellies J, Calabrese P, Roth H, Gehlen W. [CADASIL. Clinical aspects, neuroradiology, genetics and diagnosis]. Fortschr Neurol Psychiatr. 1999;67:426-33 pubmed
    ..Frontal and subcortical hypoperfusion in demented individuals was demonstrated by SPECT-studies. The prevalence of CADASIL is still not known. To date there is no causative therapy. ..
  12. Solans Laque R, Bosch Gil J, Molina Catenario C, Ortega Aznar A, Alvarez Sabin J, Vilardell Tarres M. Stroke and multi-infarct dementia as presenting symptoms of giant cell arteritis: report of 7 cases and review of the literature. Medicine (Baltimore). 2008;87:335-44 pubmed publisher
    ..Additional antiplatelet or anticoagulant therapy should be evaluated according to the individual risk and benefit to the patient under care. ..
  13. Kalaria R, Kalimo H. Introduction: Non-atherosclerotic cerebrovascular disorders. Brain Pathol. 2002;12:337-42 pubmed
    ..The identification of novel genes associated with the hereditary forms of cerebrovascular disorders has been invaluable to understanding of the pathogenesis and management of sporadic disease. ..
  14. Chabriat H, Bousser M. CADASIL. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Adv Neurol. 2003;92:147-50 pubmed
  15. Erkinjuntti T, Rockwood K. Vascular dementia. Semin Clin Neuropsychiatry. 2003;8:37-45 pubmed
    ..Attempts to treat VaD had varying degrees of success, but it now appears that many forms of VCI might be preventable, especially with good control of vascular risk factors in middle age. ..
  16. Thijs V, Robberecht W, de Vos R, Sciot R. Coexistence of CADASIL and Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2003;74:790-2 pubmed
    ..Mutations in the APP, PSEN1, and PSEN2 genes were not identified. Neuropathological findings of Alzheimer's disease may be found in CADASIL patients. ..
  17. Robinson W, Galetta S, McCluskey L, Forman M, Balcer L. Retinal findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). Surv Ophthalmol. 2001;45:445-8 pubmed
    ..Although CADASIL is a systemic vascular disease affecting the entire arteriole tree, we are unaware of other reports describing the retinal findings observed in our patient. ..
  18. Ringelstein E, Mauckner A, Schneider R, Sturm W, Doering W, Wolf S, et al. Effects of enzymatic blood defibrination in subcortical arteriosclerotic encephalopathy. J Neurol Neurosurg Psychiatry. 1988;51:1051-7 pubmed
    ..The findings indicate that hyperviscosity in patients with SAE is merely an epiphenomenon. A potentially reversible, chronic penumbral state of the brain tissue apparently does not exist in SAE. ..
  19. Fan P, Liu Y, Zhang Z, Liu B, Ge W, Ye S, et al. [Serum apolipoprotein A I, B100 and E levels and apolipoprotein E polymorphism in patients with Alzheimer's disease and multiple infarction dementia in Chinese population]. Hua Xi Yi Ke Da Xue Xue Bao. 2001;32:389-91 pubmed
    ..ApoE4 might be a risk factor for AD and MID, and apo E2 might be a protective factor for AD. The serum apo A I and apoE levels were significantly decreased in patients with Alzheimer's disease and multiple infarction dementia. ..
  20. Besson J, Crawford J, Parker D, Smith F. Magnetic resonance imaging in Alzheimer's disease, multi-infarct dementia, alcoholic dementia and Korsakoff's psychosis. Acta Psychiatr Scand. 1989;80:451-8 pubmed
    ..The possible role of T1 measures in the pathophysiology of these disorders is discussed...
  21. Maeda K, Tanimoto K, Terada T, Shintani T, Kakigi T. Elevated urinary free cortisol in patients with dementia. Neurobiol Aging. 1991;12:161-3 pubmed
    ..Measurement of UFC might be a biological marker of dementia and may have a value in diagnosis of dementia. ..
  22. O LEARY D, Jyringi D, Sedler M. Childhood conduct problems, stages of Alzheimer's disease, and physical aggression against caregivers. Int J Geriatr Psychiatry. 2005;20:401-5 pubmed
    ..The rate of aggression seen in this clinical sample was much higher than the rate of physical aggression in a community sample of the elderly. ..
  23. Markus H, Martin R, Simpson M, Dong Y, Ali N, Crosby A, et al. Diagnostic strategies in CADASIL. Neurology. 2002;59:1134-8 pubmed
    ..GOM on skin biopsy is diagnostic but can be negative. Anterior temporal pole involvement on MRI is a useful diagnostic marker. ..
  24. Erkinjuntti T. Subcortical vascular dementia. Cerebrovasc Dis. 2002;13 Suppl 2:58-60 pubmed
    ..Subcortical VaD is expected to show a more predictable clinical picture, natural history, outcome and treatment responses. ..
  25. Moretti R, Torre P, Antonello R, Cazzato G. Behavioral alterations and vascular dementia. Neurologist. 2006;12:43-7 pubmed
    ..This opinion must be taken into account to find more suitable and tailored therapy to specific pathologies and not to a single, generic entity. ..
  26. Herrmann W, Stephan K, Gaede K, Apeceche M. A multicenter randomized double-blind study on the efficacy and safety of nicergoline in patients with multi-infarct dementia. Dement Geriatr Cogn Disord. 1997;8:9-17 pubmed
    ..Nicergoline was well tolerated and a similar number of adverse events were observed in both the placebo and the nicergoline group. ..
  27. Oberstein S, Bakker E, Ferrari M, Haan J. [From gene to disease; from Notch3 to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy]. Ned Tijdschr Geneeskd. 2001;145:359-60 pubmed
    ..CADASIL is caused by mutations in the Notch3 gene on chromosome 19. ..
  28. Fryxell K, Soderlund M, Jordan T. An animal model for the molecular genetics of CADASIL. (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). Stroke. 2001;32:6-11 pubmed
    ..In the case of CADASIL, the powerful genetic tools available in Drosophila: should help to facilitate future research. ..
  29. Katagai H, Yasui Furukori N, Kikuchi A, Kaneko S. Effective electroconvulsive therapy in a 92-year-old dementia patient with psychotic feature. Psychiatry Clin Neurosci. 2007;61:568-70 pubmed
    ..No cognitive side-effects were observed during and after the two ECT sessions. This demonstrates that ECT can be used as an alternative treatment when elderly dementia patients with psychotic feature cannot tolerate medication. ..
  30. Bondy B, Klages U, Muller Spahn F, Hock C. Cytosolic free [Ca2+] in mononuclear blood cells from demented patients and healthy controls. Eur Arch Psychiatry Clin Neurosci. 1994;243:224-8 pubmed
    ..However, there might be some difference in [Ca2+]i values between early- and late-onset AD, which could have pathophysiological importance. ..
  31. Manabe Y, Murakami T, Iwatsuki K, Narai H, Warita H, Hayashi T, et al. Nocturnal blood pressure dip in CADASIL. J Neurol Sci. 2001;193:13-6 pubmed
    ..01). This study suggests that a lower nocturnal blood pressure fall may be partly associated with incidence and/or worsening of deep white matter lesions in CADASIL. ..
  32. Nagasawa H, Kogure K, Kawashima K, Ido T, Itoh M, Hatazawa J. Effects of co-dergocrine mesylate (Hydergine) in multi-infarct dementia as evaluated by positron emission tomography. Tohoku J Exp Med. 1990;162:225-33 pubmed
    ..05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain. ..
  33. Rasquin S, Lodder J, Visser P, Lousberg R, Verhey F. Predictive accuracy of MCI subtypes for Alzheimer's disease and vascular dementia in subjects with mild cognitive impairment: a 2-year follow-up study. Dement Geriatr Cogn Disord. 2005;19:113-9 pubmed
    ..8-100%). The subtype 'multiple domain MCI' has high sensitivity in identifying people at risk for developing AD or VaD. The predictive accuracy of the MCI subtypes was similar for both AD and VaD. ..
  34. Schuff Werner P, Holdt B. Selective hemapheresis, an effective new approach in the therapeutic management of disorders associated with rheological impairment: mode of action and possible clinical indications. Artif Organs. 2002;26:117-23 pubmed
  35. Haritoglou C, Hoops J, Stefani F, Mehraein P, Kampik A, Dichgans M. Histopathological abnormalities in ocular blood vessels of CADASIL patients. Am J Ophthalmol. 2004;138:302-5 pubmed
  36. Verbeek M, Van Nostrand W, Otte Holler I, Wesseling P, de Waal R. Amyloid-beta-induced degeneration of human brain pericytes is dependent on the apolipoprotein E genotype. Ann N Y Acad Sci. 2000;903:187-99 pubmed
    ..The results of this study are in line with the observations that inheritance of the ApoE epsilon 4 allele increases the risk of developing Alzheimer's disease, and that the ApoE epsilon 2 allele has a relatively protective effect. ..
  37. Pola R, Gaetani E, Flex A, Aloi F, Papaleo P, Gerardino L, et al. -174 G/C interleukin-6 gene polymorphism and increased risk of multi-infarct dementia: a case-control study. Exp Gerontol. 2002;37:949-55 pubmed
    ..Our data support the hypothesis that IL-6 and inflammatory mechanisms are important in the pathophysiology of the vascular changes responsible for cognitive deterioration. ..
  38. Koponen H, Lepola U, Leinonen E. A long-term follow-up study of cerebrospinal fluid 5-hydroxyindoleacetic acid in delirium. Eur Arch Psychiatry Clin Neurosci. 1994;244:131-4 pubmed
    ..The 5-HIAA levels measured during the index admission correlated with the length of life after delirium suggesting that serotonergic dysfunction may have prognostic significance in delirious patients. ..
  39. Dehem J, Aerts P, De Man R, Brijs S, Debakker G, Provoost V. CADASIL disease in middle-aged nurse. JBR-BTR. 2003;86:152-3 pubmed
  40. Posada I, Garcia Morales I, Martinez M, Hoenicka J, Bermejo F. [CADASIL: a case with clinical, radiological, histological and genetic diagnoses]. Neurologia. 2003;18:229-33 pubmed
    ..Here we describe a patient with typical clinical symptoms, neuroimaging and pathology of CADASIL. C406T (Arg110Cys) mutation in notch3 gene was found. We comment on the clinical symptoms of different members of the patient's family. ..
  41. Small G. The role of neuroimaging in the diagnosis of vascular dementia. Acta Neurol Scand Suppl. 2002;178:10-4 pubmed
    ..Neuroimaging also provides information about location and size of vascular lesions that can lead to a better understanding of symptoms and may help guide therapy. ..
  42. Amberla K, Waljas M, Tuominen S, Almkvist O, Poyhonen M, Tuisku S, et al. Insidious cognitive decline in CADASIL. Stroke. 2004;35:1598-602 pubmed
    ..A deterioration of working memory and executive function was already observed in the prestroke phase, which means that cognitive decline may start insidiously before the first onset of symptomatic ischemic episodes. ..
  43. Lågas P, Juvonen V. Schizophrenia in a patient with cerebral autosomally dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL disease). Nord J Psychiatry. 2001;55:41-2 pubmed
    ..In this report we present the first patient in the world literature with CADASIL and schizophrenia and discuss the co-occurrence of these conditions in the light of the literature. ..
  44. Dichgans M. A new cause of hereditary small vessel disease: angiopathy of retina and brain. Neurology. 2003;60:8-9 pubmed
  45. Smith B, Henneberry J, Connolly T. Skin biopsy findings in CADASIL. Neurology. 2002;59:961 pubmed
  46. Iwamoto T, Umahara T. [Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)]. Nihon Rinsho. 2004;62 Suppl 4:174-9 pubmed
  47. Ito D, Tanahashi N, Murata M, Sato H, Saito I, Watanabe K, et al. Notch3 gene polymorphism and ischaemic cerebrovascular disease. J Neurol Neurosurg Psychiatry. 2002;72:382-4 pubmed
    ..65, p=0.311). In conclusion, the results indicate that T6746C polymorphism in the intracellular domain of the Notch3 gene is not associated with an increased risk for CVD. ..
  48. Dieu J, Veyckemans F. Perioperative management of a CADASIL type arteriopathy patient. Br J Anaesth. 2003;91:442-4 pubmed
    ..We used a balanced anaesthetic technique because it allows easier titration of the depth of anaesthesia with regard to mean arterial pressure. There is no contraindication to the use of loco-regional anaesthesia. ..
  49. Hensel A, Wolf H, Dieterlen T, Riedel Heller S, Arendt T, Gertz H. Morphometry of the amygdala in patients with questionable dementia and mild dementia. J Neurol Sci. 2005;238:71-4 pubmed
    ..There was no significant correlation between the longitudinal annual change in MMSE and the baseline amygdala volume in any of the three groups. ..
  50. Carlyle W, Ancill R, Sheldon L. Aggression in the demented patient: a double-blind study of loxapine versus haloperidol. Int Clin Psychopharmacol. 1993;8:103-8 pubmed
    ..Results demonstrated no significant difference regarding efficacy, but significantly fewer side effects with loxapine administration. The clinical and theoretical implications of these findings are discussed. ..
  51. Sanderson M, Wang J, Davis D, Lane M, Cornman C, Fadden M. Co-morbidity associated with dementia. Am J Alzheimers Dis Other Demen. 2002;17:73-8 pubmed
    ..There are distinct differences in comorbid conditions among dementia subtypes. Our research does not support previous studies that suggest a circulatory component to the development of Alzheimer's disease. ..
  52. Graham J, Potyk D. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: an unusual familial dementia. Report of a case and review of the literature. J Am Geriatr Soc. 2004;52:1036-7 pubmed
  53. Rubio A, Rifkin D, Powers J, Patel U, Stewart J, Faust P, et al. Phenotypic variability of CADASIL and novel morphologic findings. Acta Neuropathol. 1997;94:247-54 pubmed;alpha>B crystallin also seemed to be deposited extracellularly, which suggests that GOM also might be immunoreactive for alphaB crystallin. ..