Background: White matter hyperintensities (WMH) increase cognitive impairment in patients with dementia. Objective: We investigated the impact of WMH on the neuropsychological profiles in patients with mild to moderate dementia. Methods: We consecutively recruited newly diagnosed patients with mild to moderate dementia across South Korea for 1 year. The participants completed neuropsychological tests, magnetic resonance imaging, and structured neurological evaluations. The patients were divided into 3 categories, i.e. minimal, moderate, and severe WMH groups, according to the proportional degree of WMH. Results: 289 patients were recruited; 140 (48.3%) for the minimal WMH group, 99 (34.2%) for the moderate group, and 50 (17.5%) for the severe group. Both advanced age and low general cognitive level were significant contributors to WMH in patients with dementia. After adjusting for age, the neuropsychological correlates of the proportional impact of WMH were frontal executive, language, and attention profiles. However, the only significant neuropsychological correlate was the recognition memory profile after adjusting for both age and general cognitive level simultaneously. Conclusion: The results suggest that the most significant neuropsychological profile impacting the burden of WMH in patients with mild to moderate dementia was the recognition memory profile, regardless of age and general cognitive function.

Keywords:
White matter hyperintensities, Neuropsychology of dementia, Alzheimerߣs disease, Subcortical vascular dementia
1.
Mathias JL, Burke J: Cognitive functioning in Alzheimer’s and vascular dementia: a meta-analysis. Neuropsychology 2009;23:411–423.
2.
Fernando MS, Ince PG: Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 2004;226:13–17.
3.
Bocti C, Swartz RH, Gao FQ, Sahlas DJ, Behl P, Black SE: A new visual rating scale to assess strategic white matter hyperintensities within cholinergic pathways in dementia. Stroke 2005;36:2126–2131.
4.
Van Dijk EJ, Prins ND, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM: Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan Study. Stroke 2008;39:2712–2719.
5.
Debette S, Markus HS: The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 2010;341:c3666.
6.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association Press, 1994.
7.
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.
8.
Kang Y, Na DL: Seoul Neuropsychological Screening Battery (SNSB). Seoul, Human Brain Research and Consulting Co, 2003.
9.
Kang Y, Na DL, Hahn S: A validity study on the Korean Mini-Mental State Examination (K-MMSE) in dementia patients. J Korean Neurol Assoc 1997;15:300–308.
10.
Collin C, Wade DT, Davies S, Horne V: The Barthel ADL Index: a reliability study. Int Disabil Stud 1988;10:61–63.
11.
Ku HM, Kim JH, Kwon EJ, Kim SH, Lee HS, Ko HJ: A study on the reliability and validity of Seoul-Instrumental Activities of Daily Living (S-IADL). J Korean Neuropsychiatr Assoc 2004;43:189–199.
12.
Fazekas F, Offenbacher H, Fuchs S, Schmidt R, Niederkorn K, Horner S, Lechner H: Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology 1988;38:1822–1825.
13.
Scheltens P, Barkhof F, Valk J, Algra PR, van der Hoop RG, Nauta J, Wolters EC: White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer’s disease. Evidence for heterogeneity. Brain 1992;115:735–748.
14.
Schmidt R, Ropele S, Enzinger C, Petrovic K, Smith S, Schmidt H, Matthews PM, Fazekas F: White matter lesion progression, brain atrophy, and cognitive decline: the Austrian stroke prevention study. Ann Neurol 2005;58:610–661.
15.
Longstreth WT Jr, Arnold AM, Beauchamp NJ Jr, Manolio TA, Lefkowitz D, Jungreis C, Hirsch CH, O’Leary DH, Furberg CD: 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.
16.
Kramer JH, Mungas D, Reed BR, Wetzel ME, Burnett MM, Miller BL, Weiner MW, Chui HC: Longitudinal MRI and cognitive change in healthy elderly. Neuropsychology 2007;21:412–418.
17.
Kalaria RN, Ballard C: Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1999;13(suppl 3):S115–S123.
18.
Shelley BP, Al Khabouri J: The spectrum of dementia: frequency, causes and clinical profile. A national referral hospital-based study in Oman. Dement Geriatr Cogn Disord 2007;24:280–287.
19.
Herrmann LL, Le Masurier M, Ebmeier KP: White matter hyperintensities in late life depression: a systematic review. J Neurol Neurosurg Psychiatry 2008;79:619–624.
20.
Beyer JL, Young R, Kuchibhatla M, Krishnan KR: Hyperintense MRI lesions in bipolar disorder: a meta-analysis and review. Int Rev Psychiatry 2009;21:394–409.
21.
Gräsel E, Cameron S, Lehrl S: What contribution can the Hachinski Ischemic Scale make to the differential diagnosis between multi-infarct dementia and primary degenerative dementia? Arch Gerontol Geriatr 1990;11:63–75.
22.
Erkinjuntti T: Subcortical ischemic vascular disease and dementia. Int Psychogeriatr 2003;15(suppl 1):23–26.
23.
Jacobs HI, Visser PJ, Van Boxtel MP, Frisoni GB, Tsolaki M, Papapostolou P, Nobili F, Wahlund LO, Minthon L, Frölich L, Hampel H, Soininen H, van de Pol L, Scheltens P, Tan FE, Jolles J, Verhey FR: The association between white matter hyperintensities and executive decline in mild cognitive impairment is network dependent. Neurobiol Aging 2010, E-pub ahead of print.
24.
Tullberg M, Fletcher E, DeCarli C, Mungas D, Reed BR, Harvey DJ, Weiner MW, Chui HC, Jagust WJ: White matter lesions impair frontal lobe function regardless of their location. Neurology 2004;63:246–253.
25.
Bowen BC, Barker WW, Loewenstein DA, Sheldon J, Duara R: MR signal abnormalities in memory disorder and dementia. AJR Am J Roentgenol 1990;154:1285–1292.
26.
Nordahl CW, Ranganath C, Yonelinas AP, Decarli C, Fletcher E, Jagust WJ: White matter changes compromise prefrontal cortex function in healthy elderly individuals. J Cogn Neurosci 2006;18:418–429.
27.
Brickman AM, Muraskin J, Zimmerman ME: Structural neuroimaging in Alzheimer’s disease: do white matter hyperintensities matter? Dialogues Clin Neurosci 2009;11:181–190.
28.
Traykov L, Baudic S, Thibaudet MC, Rigaud AS, Smagghe A, Boller F: Neuropsychological deficit in early subcortical vascular dementia: comparison to Alzheimer’s disease. Dement Geriatr Cogn Disord 2002;14:26–32.
29.
Tekin S, Cummings JL: Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53:647–654.
30.
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.
31.
O’Brien JT, Wiseman R, Burton EJ, Barber B, Wesnes K, Saxby B, Ford GA: Cognitive associations of subcortical white matter lesions in older people. Ann NY Acad Sci 2002;977:436–444.
32.
Selden NR, Gitelman DR, Salamon-Murayama N, Parrish TB, Mesulam MM: Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 1998;121:2249–2257.
33.
Sarter M, Bruno JP, Givens B: Attentional functions of cortical cholinergic inputs: what does it mean for learning and memory? Neurobiol Learn Mem 2003;80:245–256.
34.
Graef S, Schönknecht P, Sabri O, Hegerl U: Cholinergic receptor subtypes and their role in cognition, emotion, and vigilance control: an overview of preclinical and clinical findings. Psychopharmacology (Berl) 2011, E-pub ahead of print.
35.
Kövari E, Gold G, Herrmann FR, Canuto A, Hof PR, Michel JP, Bouras C, Giannakopoulos P: Cortical microinfarcts and demyelination significantly affect cognition in brain aging. Stroke 2004;35:410–414.
36.
Salat DH, Smith EE, Tuch DS, Benner T, Pappu V, Schwab KM, Gurol ME, Rosas HD, Rosand J, Greenberg SM: White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging. Stroke 2006;37:1759–1764.
37.
Greenberg SM, Gurol ME, Rosand J, Smith EE: Amyloid angiopathy-related vascular cognitive impairment. Stroke 2004;35(11 suppl 1):2616–2619.
38.
Bartzokis G, Lu PH, Mintz J: Human brain myelination and amyloid beta deposition in Alzheimer’s disease. Alzheimers Dement 2007;3:122–125.
39.
Roth AD, Ramírez G, Alarcón R, Von Bernhardi R: Oligodendrocytes damage in Alzheimer’s disease: beta amyloid toxicity and inflammation. Biol Res 2005;38:381–387.
40.
Erkinjuntti T: Diagnosis and management of vascular cognitive impairment and dementia. J Neural Transm Suppl 2002;91–109.
41.
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.
© 2011 S. Karger AG, Basel
2011
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.
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 government 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.
You do not currently have access to this content.