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Table of Contents
Vol. 19, No. 4, 2005
Issue release date: March 2005
Dement Geriatr Cogn Disord 2005;19:196–203
(DOI:10.1159/000083499)

Distinctive Clinical Features of Mild Cognitive Impairment with Subcortical Cerebrovascular Disease

Galluzzi S.a · Sheu C.-F.d · Zanetti O.b · Frisoni G.B.a, c
aLaboratory of Epidemiology and Neuroimaging, bAlzheimer’s Unit, IRCCS San Giovanni di Dio – FBF, Brescia, and cAFaR Associazione Fatebenefratelli per la Ricerca, Roma, Italy; dDepartment of Psychology, DePaul University, Chicago, Ill., USA
email Corresponding Author

Abstract

Background and Purpose: Patients with mild cognitive impairment and subcortical cerebrovascular disease (svMCI) can be isolated using criteria modified from those of Erkinjuntti et al. for subcortical vascular dementia and have poorer outcomes (cognitive deterioration, disability, institutionalization, and mortality). The aim of this study was to test which of the core (dysexecutive syndrome with relative sparing of memory, gait disorders and extrapyramidal signs) and supporting (urinary and behavioral symptoms) clinical features are most useful to recognize patients with svMCI and discriminate them from those with amnestic MCI (aMCI). Methods: Twenty-nine svMCI and 14 aMCI patients were seen in a memory clinic. Tests and scales assessing core and supporting features that independently contributed to the discrimination between svMCI and aMCI were identified with stepwise logistic regression analysis. The accuracy of the discrimination was estimated with area under the receiver operating characteristic curve and 95% confidence intervals (CIs). Results: The most accurate scales were the extrapyramidal sign scale by Richards et al. (0.75, 95% CI 0.61–0.89), letter fluency (0.75, 95% CI 0.61–0.90), irritability of the Neuropsychiatric Inventory and urinary dependence (0.66, 95% CI 0.49–0.82 for both), and digit span forward (0.59, 95% CI 0.41–0.77). The overall accuracy of a model compounding information from main and supporting features was 0.98, 95% CI 0.94–1.0. Conclusions: All the domains that are included in the clinical criteria for svMCI independently contribute to the identification of the condition. These criteria can be useful to recognize svMCI patients in clinical settings.


 goto top of outline Key Words

  • Mild cognitive impairment
  • Cerebrovascular disease
  • Subcortical vascular cognitive impairment
  • Small vessel disease

 goto top of outline Abstract

Background and Purpose: Patients with mild cognitive impairment and subcortical cerebrovascular disease (svMCI) can be isolated using criteria modified from those of Erkinjuntti et al. for subcortical vascular dementia and have poorer outcomes (cognitive deterioration, disability, institutionalization, and mortality). The aim of this study was to test which of the core (dysexecutive syndrome with relative sparing of memory, gait disorders and extrapyramidal signs) and supporting (urinary and behavioral symptoms) clinical features are most useful to recognize patients with svMCI and discriminate them from those with amnestic MCI (aMCI). Methods: Twenty-nine svMCI and 14 aMCI patients were seen in a memory clinic. Tests and scales assessing core and supporting features that independently contributed to the discrimination between svMCI and aMCI were identified with stepwise logistic regression analysis. The accuracy of the discrimination was estimated with area under the receiver operating characteristic curve and 95% confidence intervals (CIs). Results: The most accurate scales were the extrapyramidal sign scale by Richards et al. (0.75, 95% CI 0.61–0.89), letter fluency (0.75, 95% CI 0.61–0.90), irritability of the Neuropsychiatric Inventory and urinary dependence (0.66, 95% CI 0.49–0.82 for both), and digit span forward (0.59, 95% CI 0.41–0.77). The overall accuracy of a model compounding information from main and supporting features was 0.98, 95% CI 0.94–1.0. Conclusions: All the domains that are included in the clinical criteria for svMCI independently contribute to the identification of the condition. These criteria can be useful to recognize svMCI patients in clinical settings.

Copyright © 2005 S. Karger AG, Basel


 goto top of outline References
  1. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B: Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985–1992.
  2. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E: Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol 1999;56:303–308.
  3. Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, Rubin EH, Berg L: Mild cognitive impairment represents early-stage Alzheimer disease. Arch Neurol 2001;58:397–405.
  4. Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, Desmond DW: Limitations of clinical criteria for the diagnosis of vascular dementia in clinical trials. Is a focus on subcortical vascular dementia a solution? Ann NY Acad Sci 2000;903:262–272.
  5. Galluzzi S, Cimaschi L, Ferrucci L, Frisoni GB: Mild cognitive impairment: Clinical features and review of screening instruments. Aging (Milano) 2001;13:183–202.
  6. Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, Roman GC, Chui H, Desmond DW: Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm Suppl 2000;59:23–30.
  7. Frisoni GB, Galluzzi S, Bresciani L, Zanetti O, Geroldi C: Mild cognitive impairment with subcortical vascular features: Clinical characteristics and outcome. J Neurol 2002;249:1423–1432.
  8. Rockwood K, Brown M, Merry H, Sketris I, Fisk J: Vascular Cognitive Impairment Investigators of the Canadian Study of Health and Aging: Societal costs of vascular cognitive impairment in older adults. Stroke 2002;33:1605–1609.
  9. Fillit H, Hill J: The costs of vascular dementia. A comparison with Alzheimer’s disease. J Neurol Sci 2002;203–204:35–39.
  10. 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 1975;12:189–198.
  11. Morris JC: The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology 1993;43:2412–2414.
  12. Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, Russell RW, Symon L: Cerebral blood flow in dementia. Arch Neurol 1975;32:632–637.
  13. Novelli G, Papagno C, Capitani E, Laiacona M, Vallar G, Cappa SF: Tre test clinici di ricerca e produzione lessicale. Taratura su soggetti normali. Arch Psicol Neurol Psichiatr 1986;47:477–505.
  14. Heaton RK: Wisconsin Card Sorting Test Manual. Odessa, Psychological Assessment Resources Inc, 1981.
  15. Spinnler H, Tognoni G: Standardizzazione e taratura italiana di test neuropsicologici. Ital J Neurol Sci 1987;6(suppl 8):1–120.
  16. Orsini A, Grossi D, Capitani E, Laiacona M, Papagno C, Vallar G: Verbal and spatial immediate memory span: Normative data from 1,355 adults and 1,112 children. Ital J Neurol Sci 1987;8:539–548.
  17. Demakis GJ: A meta-analytic review of the sensitivity of the Wisconsin Card Sorting Test to frontal and lateralized frontal brain damage. Neuropsychology 2003;17:255–264.
  18. Hodges JR: Frontotemporal dementia (Pick’s disease): Clinical features and assessment. Neurology 2001;56(suppl 4):S6–S10.
  19. Tinetti ME: Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc 1986;34:119–126.
  20. Reuben DB, Siu AL: An objective measure of physical function of elderly outpatients. The Physical Performance Test. J Am Geriatr Soc 1990;38:1105–1112.
  21. Richards M, Marder K, Bell K, Dooneief G, Mayeux R, Stern Y: Interrater reliability of extrapyramidal signs in a group assessed for dementia. Arch Neurol 1991;48:1147–1149.
  22. Mahoney FI, Barthel DW: Functional evaluation: The Barthel Index. Md State Med J 1965;14:61–65.
  23. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J: The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–2314.
  24. Hanley JA, McNeil BJ: The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143:29–36.
  25. Zweig MH, Campbell G: Receiver-operating characteristic (ROC) plots: A fundamental evaluation tool in clinical medicine. Clin Chem 1993;39:561–577.
  26. Meyer JS, Xu G, Thornby J, Chowdhury MH, Quach M: Is mild cognitive impairment prodromal for vascular dementia like Alzheimer’s disease? Stroke 2002;33:1981–1985.
  27. Traykov L, Rigaud AS, Baudic S, Smagghe A, Boller F, Forette F: Apolipoprotein E varepsilon 4 allele frequency in demented and cognitively impaired patients with and without cerebrovascular disease. J Neurol Sci 2002;203–204:177–181.
  28. Pugh KG, Lipsitz LA: The microvascular frontal-subcortical syndrome of aging. Neurobiol Aging 2002;23:421–431.
  29. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–944.
  30. Ala TA, Frey WH 2nd: Validation of the NINCDS-ADRDA criteria regarding gait in the clinical diagnosis of Alzheimer disease. A clinicopathologic study. Alzheimer Dis Assoc Disord 1995;9:152–159.
  31. Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ, Buschke H: Abnormality of gait as a predictor of non-Alzheimer’s dementia. N Engl J Med 2002;347:1761–1768.
  32. Honig LS, Mayeux R: Natural history of Alzheimer’s disease. Aging (Milano) 2001;13:171–182.
  33. Cummings JL: Vascular subcortical dementias: clinical aspects. Dementia 1994;5:177–180.
  34. Sakakibara R, Hattori T, Uchiyama T, Yamanishi T: Urinary function in elderly people with and without leukoaraiosis: Relation to cognitive and gait function. J Neurol Neurosurg Psychiatry 1999;67:658–660.
  35. Kotsoris H, Barclay LL, Kheyfets S, Hulyalkar A, Dougherty J: Urinary and gait disturbances as markers for early multi-infarct dementia. Stroke 1987;18:138–141.
  36. Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S: Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: Results from the cardiovascular health study. JAMA 2002;288:1475–1483.
  37. Graham NL, Emery T, Hodges JR: Distinctive cognitive profiles in Alzheimer’s disease and subcortical vascular dementia. J Neurol Neurosurg Psychiatry 2004;75:61–71.
  38. Lafosse JM, Reed BR, Mungas D, Sterling SB, Wahbeh H, Jagust WJ: Fluency and memory differences between ischemic vascular dementia and Alzheimer’s disease. Neuropsychology 1997;11:514–522.
  39. Looi JC, Sachdev PS: Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999;53:670–678.
  40. Tierney MC, Black SE, Szalai JP, Snow WG, Fisher RH, Nadon G, Chui HC: Recognition memory and verbal fluency differentiate probable Alzheimer disease from subcortical ischemic vascular dementia. Arch Neurol 2001;58:1654–1659.
  41. Fein G, Di Sclafani V, Tanabe J, Cardenas V, Weiner MW, Jagust WJ, Reed BR, Norman D, Schuff N, Kusdra L, Greenfield T, Chui H: Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease. Neurology 2000;55:1626–1635.
  42. Mungas D, Jagust WJ, Reed BR, Kramer JH, Weiner MW, Schuff N, Norman D, Mack WJ, Willis L, Chui HC: MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer’s disease. Neurology 2001;57:2229–2235.
  43. Du AT, Schuff N, Laakso MP, Zhu XP, Jagust WJ, Yaffe K, Kramer JH, Miller BL, Reed BR, Norman D, Chui HC, Weiner MW: Effects of subcortical ischemic vascular dementia and AD on entorhinal cortex and hippocampus. Neurology 2002;58:1635–1641.
  44. Zekry D, Duyckaerts C, Moulias R, Belmin J, Geoffre C, Herrmann F, Hauw JJ: Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly. Acta Neuropathol (Berl) 2002;103:481–487.

 goto top of outline Author Contacts

Giovanni B. Frisoni, MD
Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio – FBF
via Pilastroni 4, IT–25125 Brescia (Italy)
Tel. +39 030 3501 361, Fax +39 027 0043 5727, E-Mail papers@centroAlzheimer.it http://www.centroAlzheimer.it


 goto top of outline Article Information

Accepted: August 8, 2004
Published online: January 25, 2005
Number of Print Pages : 8
Number of Figures : 1, Number of Tables : 3, Number of References : 44


 goto top of outline Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 19, No. 4, Year 2005 (Cover Date: Released March 2005)

Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420–8008 (print), 1421–9824 (Online)

For additional information: http://www.karger.com/dem


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background and Purpose: Patients with mild cognitive impairment and subcortical cerebrovascular disease (svMCI) can be isolated using criteria modified from those of Erkinjuntti et al. for subcortical vascular dementia and have poorer outcomes (cognitive deterioration, disability, institutionalization, and mortality). The aim of this study was to test which of the core (dysexecutive syndrome with relative sparing of memory, gait disorders and extrapyramidal signs) and supporting (urinary and behavioral symptoms) clinical features are most useful to recognize patients with svMCI and discriminate them from those with amnestic MCI (aMCI). Methods: Twenty-nine svMCI and 14 aMCI patients were seen in a memory clinic. Tests and scales assessing core and supporting features that independently contributed to the discrimination between svMCI and aMCI were identified with stepwise logistic regression analysis. The accuracy of the discrimination was estimated with area under the receiver operating characteristic curve and 95% confidence intervals (CIs). Results: The most accurate scales were the extrapyramidal sign scale by Richards et al. (0.75, 95% CI 0.61–0.89), letter fluency (0.75, 95% CI 0.61–0.90), irritability of the Neuropsychiatric Inventory and urinary dependence (0.66, 95% CI 0.49–0.82 for both), and digit span forward (0.59, 95% CI 0.41–0.77). The overall accuracy of a model compounding information from main and supporting features was 0.98, 95% CI 0.94–1.0. Conclusions: All the domains that are included in the clinical criteria for svMCI independently contribute to the identification of the condition. These criteria can be useful to recognize svMCI patients in clinical settings.



 goto top of outline Author Contacts

Giovanni B. Frisoni, MD
Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio – FBF
via Pilastroni 4, IT–25125 Brescia (Italy)
Tel. +39 030 3501 361, Fax +39 027 0043 5727, E-Mail papers@centroAlzheimer.it http://www.centroAlzheimer.it


 goto top of outline Article Information

Accepted: August 8, 2004
Published online: January 25, 2005
Number of Print Pages : 8
Number of Figures : 1, Number of Tables : 3, Number of References : 44


 goto top of outline Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 19, No. 4, Year 2005 (Cover Date: Released March 2005)

Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420–8008 (print), 1421–9824 (Online)

For additional information: http://www.karger.com/dem


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B: Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985–1992.
  2. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E: Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol 1999;56:303–308.
  3. Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, Rubin EH, Berg L: Mild cognitive impairment represents early-stage Alzheimer disease. Arch Neurol 2001;58:397–405.
  4. Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, Desmond DW: Limitations of clinical criteria for the diagnosis of vascular dementia in clinical trials. Is a focus on subcortical vascular dementia a solution? Ann NY Acad Sci 2000;903:262–272.
  5. Galluzzi S, Cimaschi L, Ferrucci L, Frisoni GB: Mild cognitive impairment: Clinical features and review of screening instruments. Aging (Milano) 2001;13:183–202.
  6. Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, Roman GC, Chui H, Desmond DW: Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm Suppl 2000;59:23–30.
  7. Frisoni GB, Galluzzi S, Bresciani L, Zanetti O, Geroldi C: Mild cognitive impairment with subcortical vascular features: Clinical characteristics and outcome. J Neurol 2002;249:1423–1432.
  8. Rockwood K, Brown M, Merry H, Sketris I, Fisk J: Vascular Cognitive Impairment Investigators of the Canadian Study of Health and Aging: Societal costs of vascular cognitive impairment in older adults. Stroke 2002;33:1605–1609.
  9. Fillit H, Hill J: The costs of vascular dementia. A comparison with Alzheimer’s disease. J Neurol Sci 2002;203–204:35–39.
  10. 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 1975;12:189–198.
  11. Morris JC: The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology 1993;43:2412–2414.
  12. Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, Russell RW, Symon L: Cerebral blood flow in dementia. Arch Neurol 1975;32:632–637.
  13. Novelli G, Papagno C, Capitani E, Laiacona M, Vallar G, Cappa SF: Tre test clinici di ricerca e produzione lessicale. Taratura su soggetti normali. Arch Psicol Neurol Psichiatr 1986;47:477–505.
  14. Heaton RK: Wisconsin Card Sorting Test Manual. Odessa, Psychological Assessment Resources Inc, 1981.
  15. Spinnler H, Tognoni G: Standardizzazione e taratura italiana di test neuropsicologici. Ital J Neurol Sci 1987;6(suppl 8):1–120.
  16. Orsini A, Grossi D, Capitani E, Laiacona M, Papagno C, Vallar G: Verbal and spatial immediate memory span: Normative data from 1,355 adults and 1,112 children. Ital J Neurol Sci 1987;8:539–548.
  17. Demakis GJ: A meta-analytic review of the sensitivity of the Wisconsin Card Sorting Test to frontal and lateralized frontal brain damage. Neuropsychology 2003;17:255–264.
  18. Hodges JR: Frontotemporal dementia (Pick’s disease): Clinical features and assessment. Neurology 2001;56(suppl 4):S6–S10.
  19. Tinetti ME: Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc 1986;34:119–126.
  20. Reuben DB, Siu AL: An objective measure of physical function of elderly outpatients. The Physical Performance Test. J Am Geriatr Soc 1990;38:1105–1112.
  21. Richards M, Marder K, Bell K, Dooneief G, Mayeux R, Stern Y: Interrater reliability of extrapyramidal signs in a group assessed for dementia. Arch Neurol 1991;48:1147–1149.
  22. Mahoney FI, Barthel DW: Functional evaluation: The Barthel Index. Md State Med J 1965;14:61–65.
  23. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J: The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–2314.
  24. Hanley JA, McNeil BJ: The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143:29–36.
  25. Zweig MH, Campbell G: Receiver-operating characteristic (ROC) plots: A fundamental evaluation tool in clinical medicine. Clin Chem 1993;39:561–577.
  26. Meyer JS, Xu G, Thornby J, Chowdhury MH, Quach M: Is mild cognitive impairment prodromal for vascular dementia like Alzheimer’s disease? Stroke 2002;33:1981–1985.
  27. Traykov L, Rigaud AS, Baudic S, Smagghe A, Boller F, Forette F: Apolipoprotein E varepsilon 4 allele frequency in demented and cognitively impaired patients with and without cerebrovascular disease. J Neurol Sci 2002;203–204:177–181.
  28. Pugh KG, Lipsitz LA: The microvascular frontal-subcortical syndrome of aging. Neurobiol Aging 2002;23:421–431.
  29. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–944.
  30. Ala TA, Frey WH 2nd: Validation of the NINCDS-ADRDA criteria regarding gait in the clinical diagnosis of Alzheimer disease. A clinicopathologic study. Alzheimer Dis Assoc Disord 1995;9:152–159.
  31. Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ, Buschke H: Abnormality of gait as a predictor of non-Alzheimer’s dementia. N Engl J Med 2002;347:1761–1768.
  32. Honig LS, Mayeux R: Natural history of Alzheimer’s disease. Aging (Milano) 2001;13:171–182.
  33. Cummings JL: Vascular subcortical dementias: clinical aspects. Dementia 1994;5:177–180.
  34. Sakakibara R, Hattori T, Uchiyama T, Yamanishi T: Urinary function in elderly people with and without leukoaraiosis: Relation to cognitive and gait function. J Neurol Neurosurg Psychiatry 1999;67:658–660.
  35. Kotsoris H, Barclay LL, Kheyfets S, Hulyalkar A, Dougherty J: Urinary and gait disturbances as markers for early multi-infarct dementia. Stroke 1987;18:138–141.
  36. Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S: Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: Results from the cardiovascular health study. JAMA 2002;288:1475–1483.
  37. Graham NL, Emery T, Hodges JR: Distinctive cognitive profiles in Alzheimer’s disease and subcortical vascular dementia. J Neurol Neurosurg Psychiatry 2004;75:61–71.
  38. Lafosse JM, Reed BR, Mungas D, Sterling SB, Wahbeh H, Jagust WJ: Fluency and memory differences between ischemic vascular dementia and Alzheimer’s disease. Neuropsychology 1997;11:514–522.
  39. Looi JC, Sachdev PS: Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999;53:670–678.
  40. Tierney MC, Black SE, Szalai JP, Snow WG, Fisher RH, Nadon G, Chui HC: Recognition memory and verbal fluency differentiate probable Alzheimer disease from subcortical ischemic vascular dementia. Arch Neurol 2001;58:1654–1659.
  41. Fein G, Di Sclafani V, Tanabe J, Cardenas V, Weiner MW, Jagust WJ, Reed BR, Norman D, Schuff N, Kusdra L, Greenfield T, Chui H: Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease. Neurology 2000;55:1626–1635.
  42. Mungas D, Jagust WJ, Reed BR, Kramer JH, Weiner MW, Schuff N, Norman D, Mack WJ, Willis L, Chui HC: MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer’s disease. Neurology 2001;57:2229–2235.
  43. Du AT, Schuff N, Laakso MP, Zhu XP, Jagust WJ, Yaffe K, Kramer JH, Miller BL, Reed BR, Norman D, Chui HC, Weiner MW: Effects of subcortical ischemic vascular dementia and AD on entorhinal cortex and hippocampus. Neurology 2002;58:1635–1641.
  44. Zekry D, Duyckaerts C, Moulias R, Belmin J, Geoffre C, Herrmann F, Hauw JJ: Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly. Acta Neuropathol (Berl) 2002;103:481–487.