Subcortical ischemic vascular disease and cognition: A systematic review

Alves, Gilberto Sousa; Alves, Carlos Eduardo de Oliveira; Lanna, Maria Elisa; Moreira, Denise Madeira; Engelhardt, Eliasz; Laks, Jerson

doi:10.1590/S1980-57642009DN20200002

Abstract

Subcortical Ischemic Vascular Disease (SIVD) is underdiagnosed. This review investigates the relationship among SIVD severity, cognitive status and neuroimaging markers.

Methods:

Cohort, cross-sectional and case control studies were searched on ISI, Medline, Scielo, PsychoInfo and LILACS databases published between 1995 and 2006.

Results:

The most impaired cognitive domains were executive, attentional and memory retrieval mechanisms. These cognitive features were frequently associated to White Matter Lesions (WML).

Conclusions:

WML is an independent factor in cognitive decline. However, the threshold for this impact is not yet clearly established.

Key words:
neuropsychology; vascular dementia; cerebrovascular disorders; cognition

Resumo

A doença vascular isquêmica subcortical (DVIS) é uma condição ainda subdiagnosticada. Esta revisão investiga a relação entre a gravidade da DVIS, o status cognitivo e marcadores de neuroimagem.

Métodos:

Estudos de coorte, seccionais e casos-controles foram pesquisados nas bases de dados ISI, Medline, Scielo, PsychoInfo e LILACS entre 1995 e 2006.

Resultados:

Os domínios cognitivos mais comprometidos foram as funções executivas, a atenção e a recuperação da memória. Estes achados cognitivos estiveram frequentemente associados à presença de lesões em substância branca (LSB).

Conclusões:

As LSB constituem um fator de risco independente para o declínio cognitivo. Contudo, o limiar de impacto desta variável ainda não pôde ser claramente estabelecido.

Palavras-chave:
neuropsicologia; demência vascular; doença cerebrovascular; cognição

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

References

¹
Almkvist O, Wahlund LO, Andersson-Lundman G, Basun H, Backman L. White-matter hyperintensity and neuropsychological functions in dementia and healthy aging. Arch Neurol 1992;49:626-632.
²
Soderlund H, Nyberg L, Adolfsson R, Nilsson LG, Launer LJ. High prevalence of white matter hyperintensities in normal aging: Relation to blood pressure and cognition. Cortex 2003;39:1093-1105.
³
Paul RH, Haque O, Gunstad J, et al. Subcortical hyperintensities impact cognitive function among a select subset of healthy elderly. Arch Clin Neuropsychol 2005;20:697-704.
⁴
Chui H. Dementia due to subcortical ischaemic vascular disease. Clinical Cornerstone 2001;3:40-51.
⁵
Erkinjuntti T. Subcortical ischemic vascular disease and dementia. Int Psychogeriatr 2003;15(suppl 1):23-26.
⁶
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.
⁷
Erkinjuntti T, Inzitari D, Pantoni L, et al. 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: 262-72.
⁸
Pantoni L, Rossi R, Inzitari D, et al. Efficacy and safety of nimodipine in subcortical vascular dementia: A subgroup analysis of the Scandinavian multi-infarct dementia trial. J Neurol Sci 2000;175:124-134.
⁹
Brun A. Vascular burden of the white matter. Int Psychogeriatr 2003;15(suppl 1):53-58.
¹⁰
Ishii N, Nishihara Y, Imamura T. Why do frontal lobe symptoms predominate in vascular dementia with lacunes? Neurology 1986;36:340-345.
¹¹
Román GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426-436.
¹²
Wolfe N, Linn R, Babikian VL, Knoefel JE, Albert ML. Frontal systems impairment following multiple lacunar infarcts. Arch Neurol 1990;47:129-132.
¹³
Cummings JL. Frontal-subcortical circuits and human behavior. Arch Neurol 1993;50:873-880.
¹⁴
Román GC, Royall DR. Executive control function: a rational basis for the diagnosis of vascular dementia. Alzheimer Dis Assoc Disord 1999;13(suppl 3):69-80.
¹⁵
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;128:2034-2041.
¹⁶
Ferro JM, Madureira S. Age-related white matter changes and cognitive impairment. J Neurol Sci 2002;203-204:221-225.
¹⁷
Skoog I, Berg S, Johansson B, Palmertz B, Andreasson LA. The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year olds. Acta Neurol Scand 1996;93:142-148.
¹⁸
de Groot JC, de Leeuw FE, Oudkerk M, et al. Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol 2000;47:145-151
¹⁹
de Groot JC, de Leeuw F-E, Achten E, et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001;70:9-14.
²⁰
Moretti R, Torre P, Antonello RM, Cazzato G, Bava A, Manos PJ. Use of the ten-point clock test to compare executive functioning across 24 months in patients with subcortical vascular dementia. Percept Mot Skills 2005;100:207-216.
²¹
Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Frontal lobe dementia and subcortical vascular dementia: a neuropsychological comparison. Psychol Rep 2005;96:141-151.
²²
Libon DJ, Bogdanoff B, Bonavita J, et al. Dementia associated with periventricular and deep white matter alterations: a subtype of subcortical dementia. Arch Clin Neuropsychol 1997;12:239-250.
²³
Libon DJ, Bogdanoff B, Cloud BS, et al. Declarative and procedural learning, quantitative measures of the hippocampus, and subcortical white alterations in Alzheimer's disease and ischaemic vascular dementia. J Clin Exp Neuropsychol 1998;20:30-41.
²⁴
Moser DJ, Cohen RA, Paul RH, et al. Executive function and magnetic resonance imaging subcortical hyperintensities in vascular dementia. Neuropsychiatry Neuropsychol Behav Neurol 2001;14:89-92.
²⁵
Jokinen H, Kalska H, Mantyla R, et al. White matter hyperintensities as a predictor of neuropsychological deficits post-stroke. J Neurol Neurosurg Psychiatry 2005;76:1229-1233.
²⁶
Pohjasvaara T, Mantyla R, Ylikoski R, Kaste M, Erkinjuntti T. Clinical features of MRI-defined subcortical vascular disease. Alzheimer Dis Assoc Disord 2003;17:236-242.
²⁷
Kramer JH, Reed BR, Mungas D, Weiner MW, Chui HC. Executive dysfunction in subcortical ischaemic vascular disease. J Neurol Neurosurg Psychiatry 2002;72:217-220.
²⁸
Mok VC, Wong A, Lam WWM, et al. Cognitive impairment and functional outcome after stroke associated with small vessel disease. J Neurol Neurosurg Psychiatry 2004;75:560-566.
²⁹
Cloud BS, Swenson R, Malamut BL, et al. The Boston Revision of the Wechsler Memory Scale-Mental Control subtest. Presented at the 22nd annual meeting of the International Neuropsychological Society, Cincinnati, OH, 1994.
³⁰
O'Sullivan M, Morris RG, Markus HS. Brief cognitive assessment for patients with cerebral small vessel disease. J Neurol Neurosurg Psychiatry 2005;76:1140-1145.
³¹
Amberla K, Waljas M, Tuominen S, et al. Insidious cognitive decline in CADASIL. Stroke 2004;35:1598-1602.
³²
Peters N, Opherk C, Danek A, Ballard C, Herzog J, Dichgans M. The pattern of cognitive performance in CADASIL: a monogenic condition leading to subcortical ischemic vascular dementia. Am J Psychiatry 2005;162:2078-2085.
³³
Cohen RA, Paul RH, Ott BR, et al. The relationship of subcortical MRI hyperintensities and brain volume to cognitive function in vascular dementia. J Int Neuropsychol Soc 2002;8:743-752.
³⁴
Doddy RS, Massman PJ, Mawad M, Nance M. Cognitive consequences of subcortical magnetic resonance imaging changes in Alzheimer's disease: comparison to small vessel ischemic vascular dementia. Neuropsychiatry Neuropsychol Behav Neurol 1998;11:191-199.
³⁵
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.
³⁶
Galluzzi S, Sheu C-F, Zanetti O, Frisoni GB. Distinctive clinical features of mild cognitive impairment with subcortical cerebrovascular disease. Dement Geriatr Cogn Disord 2005;19:196-203.
³⁷
Tierney MC, Black SE, Szalai JP, et al. Recognition memory and verbal fluency differentiate probable Alzheimer disease from subcortical ischemic vascular Dementia. Arch Neurol 2001;58:1654-1659.
³⁸
Gainotti G, Marra C, Villa G. A double dissociation between accuracy and time of execution on attentional tasks in Alzheimer's disease and multi-infarct dementia. Brain 2001;124:731-738.
³⁹
Price CC, Jefferson AL, Merino JG, Heilman KM, Libon DJ. Subcortical vascular dementia: integrating neuropsychological and neuroradiologic data. Neurology 2005;65:376-382.
⁴⁰
Sabri O, Ringelstein EB, Hellwig D, et al. Neuropsychological impairment correlates with hypoperfusion and hypometabolism but not with severity of white matter lesions on MRI in patients with cerebral microangiopathy. Stroke 1999;30:556-566.
⁴¹
de Mendonça A, Ribeiro F, Guerreiro M, Palma T, Garcia C. Clinical significance of subcortical vascular disease in patients with mild cognitive impairment. Eur J Neurol 2005;12: 125-130.
⁴²
van Swieten JC, Staal S, Kappelle LJ, Derix MM, van Gijn J. Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts? J Neurol 1996;243:196-200.
⁴³
Reed BR, Eberling JL, Mungas D, Weiner M, Kramer JH, Jagust WJ. Effects of white matter lesions and lacunes on cortical function. Arch Neurol 2004;61:1545-1550.
⁴⁴
Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 1986;9:357-381.
⁴⁵
Takashima Y, Yao H, Koga H, et al. Frontal lobe dysfunction caused by multiple lacunar infarction in community dwelling elderly subjects. J Neurol Sci 2003;214:37-41.
⁴⁶
Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53:647-654.
⁴⁷
Perry RJ, Hodges JR. Attention and executive deficits in Alzheimer´s disease. A critical review. Brain 1999;122:383-404.
⁴⁸
Perry RJ, Watson P, Hodges JR. The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer´s disease: relation to episodic and semantic memory impairment. Neuropsychologia 2000;38:252-271.
⁴⁹
Pantoni L, Basile AM, Pracucci G, et al. Impact of age-related cerebral white matter changes on the transition to disability - the LADIS study: rationale, design and methodology. Neuroepidemiology 2005;24:51-62.
⁵⁰
Looi JCL, Sachdev OS. Vascular dementia as a frontal subcortical system dysfunction. Psychol Med 2000;30:997-1003.
⁵¹
Wolf H, Ecke GM, Bettin S, Dietrich J, Gertz HJ. Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study. Int J Geriatr Psychiatry 2000;15:803-812.
⁵²
Esiri MM. Which vascular lesions are of importance in vascular dementia? Ann NY Acad Sci 2000;903:239-243.
⁵³
Cummings JL. Frontal-subcortical circuits and human behavior. J Psychosom Res 1998;44:627-628.
⁵⁴
Filley CM. The behavioral neurology of cereral white matter. Neurology 1998;50:1535-1540.
⁵⁵
Fazekas F, Kleinert R, Offenbacher H, et al. Pathological correlates of incidental MRI white matter signal hyperintensities. Neurology 1993;43:1683-1689.
⁵⁶
Mesulam MM. Large-scale neurocognitive networks and distributed processing for attention, language and memory. Ann Neurol 1990;28:597-613.
⁵⁷
Ross ED, Hansel SL, Orbelo DM, Monnot M. Relationship of leukoaraiosis to cognitive decline and cognitive aging. Cogn Behav Neurol 2005;18:89-97.
⁵⁸
Garde E, Mortensen EL, Krabbe K, Rostrup E, Larsson HBW. Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: A longitudinal study. Lancet 2000;356:628-634.
⁵⁹
Pantoni L. Pathophysiology of age-related cerebral white matter changes. Cerebrovasc Dis 2002;13(suppl 2):7-10.
⁶⁰
Wen HM, Mok VC, Fan YH, et al. Effect of white matter changes on cognitive impairment in patients with lacunar infarcts. Stroke 2004;35:1826-1830.
⁶¹
Reed BR, Mungas DM, Kramer JH, et al. Profiles of neuropsychological impairment in autopsy-defined Alzheimer's disease and cerebrovascular disease. Brain 2007;130:731-739.

Publication Dates

Publication in this collection
Apr-Jun 2008

History

Received
14 Feb 2008
Accepted
06 May 2008

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹
Almkvist O, Wahlund LO, Andersson-Lundman G, Basun H, Backman L. White-matter hyperintensity and neuropsychological functions in dementia and healthy aging. Arch Neurol 1992;49:626-632.

[2] ²
Soderlund H, Nyberg L, Adolfsson R, Nilsson LG, Launer LJ. High prevalence of white matter hyperintensities in normal aging: Relation to blood pressure and cognition. Cortex 2003;39:1093-1105.

[3] ³
Paul RH, Haque O, Gunstad J, et al. Subcortical hyperintensities impact cognitive function among a select subset of healthy elderly. Arch Clin Neuropsychol 2005;20:697-704.

[4] ⁴
Chui H. Dementia due to subcortical ischaemic vascular disease. Clinical Cornerstone 2001;3:40-51.

[5] ⁵
Erkinjuntti T. Subcortical ischemic vascular disease and dementia. Int Psychogeriatr 2003;15(suppl 1):23-26.

[6] ⁶
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.

[7] ⁷
Erkinjuntti T, Inzitari D, Pantoni L, et al. 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: 262-72.

[8] ⁸
Pantoni L, Rossi R, Inzitari D, et al. Efficacy and safety of nimodipine in subcortical vascular dementia: A subgroup analysis of the Scandinavian multi-infarct dementia trial. J Neurol Sci 2000;175:124-134.

[9] ⁹
Brun A. Vascular burden of the white matter. Int Psychogeriatr 2003;15(suppl 1):53-58.

[10] ¹⁰
Ishii N, Nishihara Y, Imamura T. Why do frontal lobe symptoms predominate in vascular dementia with lacunes? Neurology 1986;36:340-345.

[11] ¹¹
Román GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426-436.

[12] ¹²
Wolfe N, Linn R, Babikian VL, Knoefel JE, Albert ML. Frontal systems impairment following multiple lacunar infarcts. Arch Neurol 1990;47:129-132.

[13] ¹³
Cummings JL. Frontal-subcortical circuits and human behavior. Arch Neurol 1993;50:873-880.

[14] ¹⁴
Román GC, Royall DR. Executive control function: a rational basis for the diagnosis of vascular dementia. Alzheimer Dis Assoc Disord 1999;13(suppl 3):69-80.

[15] ¹⁵
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;128:2034-2041.

[16] ¹⁶
Ferro JM, Madureira S. Age-related white matter changes and cognitive impairment. J Neurol Sci 2002;203-204:221-225.

[17] ¹⁷
Skoog I, Berg S, Johansson B, Palmertz B, Andreasson LA. The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year olds. Acta Neurol Scand 1996;93:142-148.

[18] ¹⁸
de Groot JC, de Leeuw FE, Oudkerk M, et al. Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol 2000;47:145-151

[19] ¹⁹
de Groot JC, de Leeuw F-E, Achten E, et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001;70:9-14.

[20] ²⁰
Moretti R, Torre P, Antonello RM, Cazzato G, Bava A, Manos PJ. Use of the ten-point clock test to compare executive functioning across 24 months in patients with subcortical vascular dementia. Percept Mot Skills 2005;100:207-216.

[21] ²¹
Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Frontal lobe dementia and subcortical vascular dementia: a neuropsychological comparison. Psychol Rep 2005;96:141-151.

[22] ²²
Libon DJ, Bogdanoff B, Bonavita J, et al. Dementia associated with periventricular and deep white matter alterations: a subtype of subcortical dementia. Arch Clin Neuropsychol 1997;12:239-250.

[23] ²³
Libon DJ, Bogdanoff B, Cloud BS, et al. Declarative and procedural learning, quantitative measures of the hippocampus, and subcortical white alterations in Alzheimer's disease and ischaemic vascular dementia. J Clin Exp Neuropsychol 1998;20:30-41.

[24] ²⁴
Moser DJ, Cohen RA, Paul RH, et al. Executive function and magnetic resonance imaging subcortical hyperintensities in vascular dementia. Neuropsychiatry Neuropsychol Behav Neurol 2001;14:89-92.

[25] ²⁵
Jokinen H, Kalska H, Mantyla R, et al. White matter hyperintensities as a predictor of neuropsychological deficits post-stroke. J Neurol Neurosurg Psychiatry 2005;76:1229-1233.

[26] ²⁶
Pohjasvaara T, Mantyla R, Ylikoski R, Kaste M, Erkinjuntti T. Clinical features of MRI-defined subcortical vascular disease. Alzheimer Dis Assoc Disord 2003;17:236-242.

[27] ²⁷
Kramer JH, Reed BR, Mungas D, Weiner MW, Chui HC. Executive dysfunction in subcortical ischaemic vascular disease. J Neurol Neurosurg Psychiatry 2002;72:217-220.

[28] ²⁸
Mok VC, Wong A, Lam WWM, et al. Cognitive impairment and functional outcome after stroke associated with small vessel disease. J Neurol Neurosurg Psychiatry 2004;75:560-566.

[29] ²⁹
Cloud BS, Swenson R, Malamut BL, et al. The Boston Revision of the Wechsler Memory Scale-Mental Control subtest. Presented at the 22nd annual meeting of the International Neuropsychological Society, Cincinnati, OH, 1994.

[30] ³⁰
O'Sullivan M, Morris RG, Markus HS. Brief cognitive assessment for patients with cerebral small vessel disease. J Neurol Neurosurg Psychiatry 2005;76:1140-1145.

[31] ³¹
Amberla K, Waljas M, Tuominen S, et al. Insidious cognitive decline in CADASIL. Stroke 2004;35:1598-1602.

[32] ³²
Peters N, Opherk C, Danek A, Ballard C, Herzog J, Dichgans M. The pattern of cognitive performance in CADASIL: a monogenic condition leading to subcortical ischemic vascular dementia. Am J Psychiatry 2005;162:2078-2085.

[33] ³³
Cohen RA, Paul RH, Ott BR, et al. The relationship of subcortical MRI hyperintensities and brain volume to cognitive function in vascular dementia. J Int Neuropsychol Soc 2002;8:743-752.

[34] ³⁴
Doddy RS, Massman PJ, Mawad M, Nance M. Cognitive consequences of subcortical magnetic resonance imaging changes in Alzheimer's disease: comparison to small vessel ischemic vascular dementia. Neuropsychiatry Neuropsychol Behav Neurol 1998;11:191-199.

[35] ³⁵
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.

[36] ³⁶
Galluzzi S, Sheu C-F, Zanetti O, Frisoni GB. Distinctive clinical features of mild cognitive impairment with subcortical cerebrovascular disease. Dement Geriatr Cogn Disord 2005;19:196-203.

[37] ³⁷
Tierney MC, Black SE, Szalai JP, et al. Recognition memory and verbal fluency differentiate probable Alzheimer disease from subcortical ischemic vascular Dementia. Arch Neurol 2001;58:1654-1659.

[38] ³⁸
Gainotti G, Marra C, Villa G. A double dissociation between accuracy and time of execution on attentional tasks in Alzheimer's disease and multi-infarct dementia. Brain 2001;124:731-738.

[39] ³⁹
Price CC, Jefferson AL, Merino JG, Heilman KM, Libon DJ. Subcortical vascular dementia: integrating neuropsychological and neuroradiologic data. Neurology 2005;65:376-382.

[40] ⁴⁰
Sabri O, Ringelstein EB, Hellwig D, et al. Neuropsychological impairment correlates with hypoperfusion and hypometabolism but not with severity of white matter lesions on MRI in patients with cerebral microangiopathy. Stroke 1999;30:556-566.

[41] ⁴¹
de Mendonça A, Ribeiro F, Guerreiro M, Palma T, Garcia C. Clinical significance of subcortical vascular disease in patients with mild cognitive impairment. Eur J Neurol 2005;12: 125-130.

[42] ⁴²
van Swieten JC, Staal S, Kappelle LJ, Derix MM, van Gijn J. Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts? J Neurol 1996;243:196-200.

[43] ⁴³
Reed BR, Eberling JL, Mungas D, Weiner M, Kramer JH, Jagust WJ. Effects of white matter lesions and lacunes on cortical function. Arch Neurol 2004;61:1545-1550.

[44] ⁴⁴
Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 1986;9:357-381.

[45] ⁴⁵
Takashima Y, Yao H, Koga H, et al. Frontal lobe dysfunction caused by multiple lacunar infarction in community dwelling elderly subjects. J Neurol Sci 2003;214:37-41.

[46] ⁴⁶
Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53:647-654.

[47] ⁴⁷
Perry RJ, Hodges JR. Attention and executive deficits in Alzheimer´s disease. A critical review. Brain 1999;122:383-404.

[48] ⁴⁸
Perry RJ, Watson P, Hodges JR. The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer´s disease: relation to episodic and semantic memory impairment. Neuropsychologia 2000;38:252-271.

[49] ⁴⁹
Pantoni L, Basile AM, Pracucci G, et al. Impact of age-related cerebral white matter changes on the transition to disability - the LADIS study: rationale, design and methodology. Neuroepidemiology 2005;24:51-62.

[50] ⁵⁰
Looi JCL, Sachdev OS. Vascular dementia as a frontal subcortical system dysfunction. Psychol Med 2000;30:997-1003.

[51] ⁵¹
Wolf H, Ecke GM, Bettin S, Dietrich J, Gertz HJ. Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study. Int J Geriatr Psychiatry 2000;15:803-812.

[52] ⁵²
Esiri MM. Which vascular lesions are of importance in vascular dementia? Ann NY Acad Sci 2000;903:239-243.

[53] ⁵³
Cummings JL. Frontal-subcortical circuits and human behavior. J Psychosom Res 1998;44:627-628.

[54] ⁵⁴
Filley CM. The behavioral neurology of cereral white matter. Neurology 1998;50:1535-1540.

[55] ⁵⁵
Fazekas F, Kleinert R, Offenbacher H, et al. Pathological correlates of incidental MRI white matter signal hyperintensities. Neurology 1993;43:1683-1689.

[56] ⁵⁶
Mesulam MM. Large-scale neurocognitive networks and distributed processing for attention, language and memory. Ann Neurol 1990;28:597-613.

[57] ⁵⁷
Ross ED, Hansel SL, Orbelo DM, Monnot M. Relationship of leukoaraiosis to cognitive decline and cognitive aging. Cogn Behav Neurol 2005;18:89-97.

[58] ⁵⁸
Garde E, Mortensen EL, Krabbe K, Rostrup E, Larsson HBW. Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: A longitudinal study. Lancet 2000;356:628-634.

[59] ⁵⁹
Pantoni L. Pathophysiology of age-related cerebral white matter changes. Cerebrovasc Dis 2002;13(suppl 2):7-10.

[60] ⁶⁰
Wen HM, Mok VC, Fan YH, et al. Effect of white matter changes on cognitive impairment in patients with lacunar infarcts. Stroke 2004;35:1826-1830.

[61] ⁶¹
Reed BR, Mungas DM, Kramer JH, et al. Profiles of neuropsychological impairment in autopsy-defined Alzheimer's disease and cerebrovascular disease. Brain 2007;130:731-739.

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