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Deep versus Periventricular White Matter Lesions and Cognitive Function in a Community Sample of Middle-Aged Participants

Published online by Cambridge University Press:  12 June 2012

Juan José Soriano-Raya
Affiliation:
Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain
Júlia Miralbell
Affiliation:
Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain
Elena López-Cancio
Affiliation:
Stroke Unit, Department of Neurosciences, Germans Trias i Pujol University Hospital, Autonomous University of Barcelona, Badalona, Barcelona, Spain
Núria Bargalló
Affiliation:
Radiology Department, Image Diagnosis Center, Hospital Clinic, Barcelona, Spain August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
Juan Francisco Arenillas
Affiliation:
Stroke Unit, Department of Neurology, Hospital Clínico Universitario, Valladolid, Spain
Maite Barrios
Affiliation:
Department of Methodology of Behavioral Sciences, University of Barcelona, Barcelona, Spain
Cynthia Cáceres
Affiliation:
Stroke Unit, Department of Neurosciences, Germans Trias i Pujol University Hospital, Autonomous University of Barcelona, Badalona, Barcelona, Spain
Pere Toran
Affiliation:
Primary Healthcare Research Support Unit Metropolitana Nord, ICS-IDIAP Jordi Gol, Mataró, Barcelona, Spain Primary Healthcare Centre Gatassa, Mataró, Barcelona, Spain
Maite Alzamora
Affiliation:
Primary Healthcare Research Support Unit Metropolitana Nord, ICS-IDIAP Jordi Gol, Mataró, Barcelona, Spain Primary Healthcare Centre Riu Nord-Riu Sud, Santa Coloma de Gramenet, Barcelona, Spain
Antoni Dávalos
Affiliation:
Stroke Unit, Department of Neurosciences, Germans Trias i Pujol University Hospital, Autonomous University of Barcelona, Badalona, Barcelona, Spain
Maria Mataró*
Affiliation:
Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain Institute for Brain, Cognition and Behavior (IR3C), University of Barcelona, Barcelona, Spain
*
Correspondence and reprint requests to: Maria Mataró, Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Passeig de la Vall d'Hebron 171, 08035 Barcelona, Spain. E-mail: [email protected]

Abstract

The association of cerebral white matter lesions (WMLs) with cognitive status is not well understood in middle-aged individuals. Our aim was to determine the specific contribution of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) to cognitive function in a community sample of asymptomatic participants aged 50 to 65 years. One hundred stroke- and dementia-free adults completed a comprehensive neuropsychological battery and brain MRI protocol. Participants were classified according to PVH and DWMH scores (Fazekas scale). We dichotomized our sample into low grade WMLs (participants without or with mild lesions) and high grade WMLs (participants with moderate or severe lesions). Analyses were performed separately in PVH and DWMH groups. High grade DWMHs were associated with significantly lower scores in executive functioning (−0.45 standard deviations [SD]), attention (−0.42 SD), verbal fluency (−0.68 SD), visual memory (−0.52 SD), visuospatial skills (−0.79 SD), and psychomotor speed (−0.46 SD). Further analyses revealed that high grade DWMHs were also associated with a three- to fourfold increased risk of impaired scores (i.e.,<1.5 SD) in executive functioning, verbal fluency, visuospatial skills, and psychomotor speed. Our findings suggest that only DWMHs, not PVHs, are related to diminished cognitive function in middle-aged individuals. (JINS, 2012, 18, 1–12)

Type
Research Articles
Copyright
Copyright © The International Neuropsychological Society 2012

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References

Alzamora, M.T., Baena-Díez, J.M., Sorribes, M., Forés, R., Toran, P., Vicheto, M., Arenillas, J.F. (2007). Peripheral Arterial Disease study (PERART): Prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality. BMC Public Health, 7, 348.CrossRefGoogle ScholarPubMed
Alzamora, M.T., Sorribes, M., Heras, A., Vila, N., Vicheto, M., Fores, R., Pera, G. (2008). Ischemic stroke incidence in Santa Coloma de Gramenet (ISISCOG), Spain. A community-based study. BMC Neurology, 8, 5.CrossRefGoogle Scholar
Andersson, T. (2010). What do white matter hyperintensities really represent? Stroke, 41, 574.CrossRefGoogle ScholarPubMed
Artiola, L., Hermosillo, D., Heaton, R.K., Pardee, R.E. (1999). Manual de normas y procedimientos para la batería neuropsicológica en español. Tucson, AZ: M Press.Google Scholar
Basile, A.M., Pantoni, L., Pracucci, G., Asplund, K., Chabriat, H., Erkinjuntti, T., Inzitari, D. (2006). Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study. Cerebrovascular Diseases, 21, 315322.CrossRefGoogle ScholarPubMed
Bombois, S., Debette, S., Delbeuck, X., Bruandet, A., Lepoittevin, S., Delmaire, C., Pasquier, F. (2007). Prevalence of subcortical vascular lesions and association with executive function in mild cognitive impairment subtypes. Stroke, 38, 25952597.CrossRefGoogle ScholarPubMed
Boone, K.B., Miller, B.L., Lesser, I.M., Mehringer, C.M., Hill-Gutierrez, E., Goldberg, M.A., Berman, N.G. (1992). Neuropsychological correlates of white-matter lesions in healthy elderly participants. A threshold effect. Archives of Neurology, 49, 549554.CrossRefGoogle Scholar
Bowler, J.V., Hachinski, V. (2003). Vascular cognitive impairment—a new concept. In: J.V. Bowler & V. Hachinski (Eds.), Vascular cognitive impairment: Preventable dementia. New York: Oxford University Press.CrossRefGoogle Scholar
Bracco, L., Piccini, C., Moretti, M., Mascalchi, M., Sforza, A., Nacmias, B., Sorbi, S. (2005). Alzheimer's disease: Role of size and location of white matter changes in determining cognitive deficits. Dementia and Geriatric Cognitive Disorders, 20, 358366.CrossRefGoogle ScholarPubMed
Burns, J.M., Church, J.A., Johnson, D.K., Xiong, C., Marcus, D., Fotenos, A.F., Buckner, R.L. (2005). White matter lesions are prevalent but differentially related with cognition in aging and early Alzheimer disease. Archives of Neurology, 62, 18701876.CrossRefGoogle ScholarPubMed
Chen, X., Wen, W., Anstey, K.J., Sachdev, P.S. (2009). Prevalence, incidence, and risk factors of lacunar infarcts in a community sample. Neurology, 73, 266272.CrossRefGoogle Scholar
Cohen, R.A., Paul, R.H., Ott, B.R., Moser, D.J., Zawacki, T.M., Stone, W., Gordon, N. (2002). The relationship of subcortical MRI hyperintensities and brain volume to cognitive function in vascular dementia. Journal of the International Neuropsychological Society, 8, 743752.CrossRefGoogle ScholarPubMed
Conners, C.K. (1995). Conners’ Continuous Performance Test. Toronto: Multi-Health Systems Inc.Google Scholar
Debette, S., Bombois, S., Bruandet, A., Delbeuck, X., Lepoittevin, S., Delmaire, C., Pasquier, F. (2007). Subcortical hyperintensities are associated with cognitive decline in patients with mild cognitive impairment. Stroke, 38, 29242930.CrossRefGoogle ScholarPubMed
Debette, S., Markus, H.S. (2010). The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: Systematic review and meta-analysis. BMJ, 341, c3666. doi:10.1136/bmj.c3666CrossRefGoogle ScholarPubMed
De Groot, J.C., De Leeuw, F.E., Oudkerk, M., Van Gijn, J., Hofman, A., Jolles, J., Breteler, M.M. (2000). Cerebral white matter lesions and cognitive function: The Rotterdam scan study. Annals of Neurology, 47, 145151.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
De Leeuw, F.E., de Groot, J.C., Achten, E., Oudkerk, M., Ramos, L.M., Heijboer, R., Breteler, M.M. (2001). Prevalence of cerebral white matter lesions in elderly people: A population based magnetic resonance imaging study. The Rotterdam Scan Study. Journal of Neurology, Neurosurgery, and Psychiatry, 70, 914.CrossRefGoogle Scholar
DeCarli, C., Murphy, D.G., Tranh, M., Grady, C.L., Haxby, J.V., Gillette, J.A., Rapoport, S.I. (1995). The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology, 45, 20772084.CrossRefGoogle ScholarPubMed
Delano-Wood, L., Abeles, N., Sacco, J.M., Wierenga, C.E., Horne, N.R., Bozoki, A. (2008). Regional white matter pathology in mild cognitive impairment: Differential influence of lesion type on neuropsychological functioning. Stroke, 39, 794799.CrossRefGoogle ScholarPubMed
Desmond, D. (2002). Cognition and white matter lesions. Cerebrovascular Diseases 2002, 13(Suppl. 2), 5357.CrossRefGoogle ScholarPubMed
Enzinger, C., Fazekas, F., Ropele, S., Schmidt, R. (2007). Progression of cerebral white matter lesions -- clinical and radiological considerations. Journal of the Neurological Sciences, 257, 510.CrossRefGoogle ScholarPubMed
Fazekas, F., Barkhof, F., Wahlund, L.O., Pantoni, L., Erkinjuntti, T., Scheltens, P., Schmidt, R. (2002). CT and MRI rating of white matter lesions. Cerebrovascular Diseases, 13(Suppl. 2), 3136.CrossRefGoogle ScholarPubMed
Fazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A. (1987). MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR American Journal of Roentgenology, 149, 351356.CrossRefGoogle ScholarPubMed
Fazekas, F., Enzinger, C., Ropele, S., Schmidt, R. (2009). White matter changes. In L. O. Wahlund, T. Erkinjuntti, & S. Gauthier (Eds.), Vascular cognitive impairment in clinical practice. New York: Cambridge University Press.Google Scholar
Fazekas, F., Kleinert, R., Offenbacher, H., Payer, F., Schmidt, R., Kleinert, G., Lechner, H. (1991). The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR American Journal of Neuroradiology, 12, 915921.Google ScholarPubMed
Fazekas, F., Kleinert, R., Offenbacher, H., Schmidt, R., Kleinert, G., Payer, F., Lechner, H. (1993). Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology, 43, 16831689.CrossRefGoogle ScholarPubMed
Fazekas, F., Schmidt, R., Scheltens, P. (1998). Pathophysiologic mechanisms in the development of age-related white matter changes of the brain. Dementia and Geriatric Cognitive Disorders, 9(Suppl. 1), 25.CrossRefGoogle ScholarPubMed
Fernando, M.S., O'Brien, J.T., Perry, R.H., English, P., Forster, G., McMeekin, W., Ince, P.G. (2004). Comparison of the pathology of cerebral white matter with post-mortem magnetic resonance imaging (MRI) in the elderly brain. Neuropathology and Applied Neurobiology, 30, 385395.CrossRefGoogle ScholarPubMed
Fernando, M.S., Simpson, J.E., Matthews, F., Brayne, C., Lewis, C.E., Barber, R., Ince, P.G. (2006). White matter lesions in an unselected cohort of the elderly: Molecular pathology suggests origin from chronic hypoperfusion injury. Stroke, 37, 13911398.CrossRefGoogle Scholar
Folstein, M.F., Folstein, S.E., McHugh, P.R. (1975). “Mini Mental State”: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatry Research, 12, 189198.CrossRefGoogle ScholarPubMed
Frisoni, G.B., Galluzzi, S., Pantoni, L., Filippi, M. (2007). The effect of white matter lesions on cognition in the elderly--small but detectable. Nature Clinical Practice. Neurology, 3, 620627.CrossRefGoogle ScholarPubMed
Golden, C.J. (1978). Stroop color and word test. Chicago, IL: Stoelting Company.Google Scholar
Gouw, A.A., Van der Flier, W.M., van Straaten, E.C., Barkhof, F., Ferro, J.M., Baezner, H., Scheltens, P. (2006). LADIS Study Group. Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: The LADIS study. Journal of Neurology, 253, 11891196.CrossRefGoogle Scholar
Graham, N.L., Emery, T., Hodges, J.R. (2004). Distinctive cognitive profiles in Alzheimer's disease and subcortical vascular dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 75, 6171.Google ScholarPubMed
Hachinski, V., Iadecola, C., Petersen, R.C., Breteler, M.M., Nyenhuis, D.L., Black, S.E., Leblanc, G.G. (2006). National institute of neurological disorders and stroke–Canadian stroke network vascular cognitive impairment harmonization standards. Stroke, 37, 22202241.CrossRefGoogle ScholarPubMed
Hachinski, V.C., Potter, P., Merskey, H. (1987). Leuko-araiosis. Archives of Neurology, 44, 2123.CrossRefGoogle ScholarPubMed
Hunt, A.L., Orrison, W.W., Yeo, R.A., Haaland, K.Y., Rhyne, R.L., Garry, P.J., Rosenberg, G.A. (1989). Clinical significance of white matter lesions in the elderly. Neurology, 39, 14701474.CrossRefGoogle ScholarPubMed
Inzitari, D. (2000). Age-related white matter changes and cognitive impairment. Annals of Neurology, 47, 141143.3.0.CO;2-6>CrossRefGoogle ScholarPubMed
Inzitari, D., Cadelo, M., Marranci, M.L., Pracucci, G., Pantoni, L. (1997). Vascular deaths in elderly neurological patients with leukoaraiosis. Journal of Neurology, Neurosurgery, and Psychiatry, 62, 177181.CrossRefGoogle ScholarPubMed
Jokinen, H., Kalska, H., Mäntylä, R., Ylikoski, R., Hietanen, M., Pohjasvaara, T., Erkinjuntti, T. (2005). White matter hyperintensities as a predictor of neuropsychological deficits post-stroke. Journal of Neurology, Neurosurgery, and Psychiatry, 75, 12291233.CrossRefGoogle Scholar
Junqué, C., Pujol, J., Vendrell, P., Bruna, O., Jódar, M., Ribas, J.C., Marti-Vilalta, J.L. (1990). Leuko-araiosis on magnetic resonance imaging and speed of mental processing. Archives of Neurology, 47, 151156.CrossRefGoogle ScholarPubMed
Kim, K.W., MacFall, J.R., Payne, M.E. (2008). Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biological Psychiatry, 64, 273280.CrossRefGoogle ScholarPubMed
Kongs, S.K., Thompson, L.L., Iverson, G.L., Heaton, R.K. (2000). Wisconsin Card Sorting Test-64 Card Version. Professional manual. Lutz, FL: Psychological Assessment Resources.Google Scholar
Kuller, L.H., Arnold, A.M., Longstreth, W.T. Jr., , Manolio, T.A., O'Leary, D.H., Burke, G.L., Newman, A.B. (2007). White matter grade and ventricular volume on brain MRI as markers of longevity in the Cardiovascular Health Study. Neurobiology of Aging, 28, 13071315.CrossRefGoogle ScholarPubMed
Kuller, L.H., Longstreth, W.T. Jr., Arnold, A.M., Bernick, C., Bryan, R.N., Beauchamp, N.J. Jr. (2004). White matter hyperintensity on cranial magnetic resonance imaging: A predictor of stroke. Stroke, 35, 18211825.CrossRefGoogle ScholarPubMed
Leaper, S.A., Murray, A.D., Lemmon, H.A., Staff, R.T., Deary, I.J., Crawford, J.R., Whalley, L.J. (2001). Neuropsychologic correlates of brain white matter lesions depicted on MR images: 1921 Aberdeen Birth Cohort. Radiology, 221, 5155.CrossRefGoogle ScholarPubMed
Lezak, M.D., Howieson, D.B., Loring, D.W. (2004). Neuropsychological assessment. New York: Oxford University Press.Google Scholar
Linortner, P., Fazekas, F., Schmidt, R., Ropele, S., Pendl, B., Petrovic, K., Enzinger, C. (2010). White matter hyperintensities alter functional organization of the motor system. Neurobiology of Aging, 33, 197. e1–e9.Google ScholarPubMed
Longstreth, W.T. Jr., Arnold, A.M., Beauchamp, N.J. Jr., Manolio, T.A., Lefkowitz, D., Jungreis, C., Furberg, C.D. (2005). Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: The Cardiovascular Health Study. Stroke, 36, 5661.CrossRefGoogle ScholarPubMed
Longstreth, W.T. Jr., Manolio, T.A., Arnold, A., Burke, G.L., Bryan, N., Jungreis, C.A., Fried, L. (1996). Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people: The Cardiovascular Health Study. Stroke, 27, 12741282.CrossRefGoogle ScholarPubMed
López-Cancio, E., Dorado, L., Millán, M., Reverté, S., Suñol, A., Massuet, A., Arenillas, J.F. (2011). The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): Rationale and design. BMC Neurology, 11, 22. doi:10.1186/1471-2377-11-22.CrossRefGoogle ScholarPubMed
Mosley, T.H. Jr., Knopman, D.S., Catellier, D.J., Bryan, N., Hutchinson, R.G., Grothues, C.A., Szklo, M. (2005). Cerebral MRI findings and cognitive functioning: The Atherosclerosis Risk in Communities study. Neurology, 64, 20562062.CrossRefGoogle ScholarPubMed
O'Brien, J.T., Erkinjuntti, T., Reisberg, B., Roman, G., Sawada, T., Pantoni, L., DeKosky, S.T. (2003). Vascular cognitive impairment. Lancet Neurology, 2, 8998.CrossRefGoogle ScholarPubMed
Pantoni, L. (2002). Pathophysiology of age-related cerebral white matter changes. Cerebrovascular Diseases, 13(Suppl. 2), 710.CrossRefGoogle ScholarPubMed
Pantoni, L., Basile, A.M., Pracucci, G., Asplund, K., Bogousslavsky, J., Chabriat, H., Inzitari, D. (2005). Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: Rationale, design and methodology. Neuroepidemiology, 24, 5162.CrossRefGoogle ScholarPubMed
Pantoni, L., Poggesi, A., Inzitari, D. (2007). The relation between white-matter lesions and cognition. Current Opinion in Neurology, 20, 390397.CrossRefGoogle ScholarPubMed
Prins, N.D., van Dijk, E.J., den Heijer, T., Vermeer, S.E., Jolles, J., Koudstaal, P.J., Breteler, M.M. (2005). Cerebral small-vessel disease and decline in information and processing speed, executive function and memory. Brain, 128, 20342041.CrossRefGoogle ScholarPubMed
Prins, N.D., van Dijk, E.J., den Heijer, T., Vermeer, S.E., Koudstaal, P.J., Oudkerk, M., Breteler, M.M. (2004). Cerebral white matter lesions and the risk of dementia. Archives of Neurology, 61, 15311534.CrossRefGoogle ScholarPubMed
Ruff, R.M., Parker, S.B. (1993). Gender- and age-specific changes in motor speed and eye-hand coordination in adults: Normative values for the finger tapping and grooved pegboard tests. Perceptual and Motor Skills, 76, 12191230.CrossRefGoogle ScholarPubMed
Sachdev, P.S., Brodaty, H., Valenzuela, M.J., Lorentz, L., Looi, J.C., Wen, W., Zagami, A.S. (2004). The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients. Neurology, 62, 912919.CrossRefGoogle ScholarPubMed
Sachdev, P.S., Wen, W., Christensen, H., Jorm, A.F. (2005). White matter hyperintensities are related to physical disability and poor motor function. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 362367.CrossRefGoogle ScholarPubMed
Scarabino, T., Nemore, F., Giannatempo, G.M., Bertolino, A., Di Salle, F., Salvolini, U. (2003). 3.0 T magnetic resonance in neuroradiology. European Journal of Radiology, 48, 154164.CrossRefGoogle ScholarPubMed
Schmidt, R., Enzinger, C., Ropele, S., Schmidt, H., Fazekas, F. (2006). Subcortical vascular cognitive impairment: Similarities and differences with multiple sclerosis. Journal of the Neurological Sciences, 245, 37.CrossRefGoogle ScholarPubMed
Schmidt, R., Fazekas, F., Offenbacher, H., Dusek, T., Zach, E., Reinhart, B., Schumacher, M. (1993). Neuropsychologic correlates of MRI white matter hyperintensities: A study of 150 normal volunteers. Neurology, 43, 24902494.CrossRefGoogle ScholarPubMed
Schmidt, R., Grazer, A., Enzinger, C., Ropele, S., Homayoon, N., Pluta-Fuerst, A., Fazekas, F. (2011). MRI-detected white matter lesions: Do they really matter? Journal of Neural Transmission, 118, 673681.CrossRefGoogle ScholarPubMed
Schmidt, R., Ropele, S., Enzinger, C., Petrovic, K., Smith, S., Schmidt, H., Fazekas, F. (2005). White matter lesion progression, brain atrophy, and cognitive decline: The Austrian Stroke Prevention Study. Annals of Neurology, 58, 610616.CrossRefGoogle ScholarPubMed
Schmidt, R., Schmidt, H., Fazekas, F., Schumacher, M., Niederkorn, K., Kapeller, P., Kostner, G.M. (1997). Apolipoprotein E polymorphism and silent microangiopathy-related cerebral damage. Results of the Austrian Stroke Prevention Study. Stroke, 28, 951956.CrossRefGoogle ScholarPubMed
Sheikh, J.I., Yesavage, J.A. (1986). Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version. Clinical Gerontologist: The Journal of Aging and Mental Health, 5, 165173.Google Scholar
Smith, S.M., Zhang, Y., Jenkinson, M., Chen, J., Matthews, P.M., Federico, A., De Stefano, N. (2002). Accurate, robust and automated longitudinal and cross-sectional brain change analysis. Neuroimage, 17, 479489.CrossRefGoogle ScholarPubMed
Steingart, A., Hachinski, V.C., Lau, C., Fox, A.J., Diaz, F., Cape, R., Merskey, H. (1987). Cognitive and neurologic findings in participants with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis). Archives of Neurology, 44, 3235.CrossRefGoogle Scholar
Stenset, V., Hofoss, D., Berstad, A.E., Negaard, A., Gjerstad, L., Fladby, T. (2008). White matter lesion subtypes and cognitive deficits in patients with memory impairment. Dementia and Geriatric Cognitive Disorders, 26, 424431.CrossRefGoogle ScholarPubMed
Strauss, E., Sherman, E., Spreen, O. (2006). A compendium of neuropsychological tests (3rd ed.). New York: Oxford University Press.Google Scholar
Tombaugh, T.N. (2004). Trail Making Test A and B: Normative data stratified by age and education. Archives of Clinical Neuropsychology, 19, 203214.CrossRefGoogle Scholar
Tunstall-Pedoe, H., Kuulasmaa, K., Mähönen, M., Tolonen, H., Ruokokoski, E., Amouyel, P. (1999). Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease. Lancet, 353, 15471557.CrossRefGoogle ScholarPubMed
Van der Flier, W.M., van Straaten, E.C., Barkhof, F., Verdelho, A., Madureira, S., Pantoni, L., Scheltens, P. (2005). Small vessel disease and general cognitive function in nondisabled elderly. The LADIS Study. Stroke, 36, 21162120.CrossRefGoogle ScholarPubMed
Van Dijk, E.J., Prins, N.D., Vermeer, S.E., Koudstaal, P.J., Breteler, M.M. (2002). Frequency of white matter lesions and silent lacunar infarcts. Journal of Neural Transmission. Supplementum, 62, 2539.CrossRefGoogle Scholar
Van Swieten, J.C., van den Hout, J.H., van Ketel, B.A., Hijdra, A., Wokke, J.H., van Gijn, J. (1991). Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain, 114, 761774.CrossRefGoogle ScholarPubMed
Vannorsdall, T.D., Waldstein, S.R., Kraut, M., Pearlson, G.D., Schretlen, D.J. (2009). White matter abnormalities and cognition in a community sample. Archives of Clinical Neuropsychology, 24, 209217.CrossRefGoogle Scholar
Verdelho, A., Madureira, S., Ferro, J.M., Basile, A.M., Chabriat, H., Erkinjuntti, T., Inzitari, D. (2007). Differential impact of cerebral white matter changes, diabetes, hypertension and stroke on cognitive performance among non-disabled elderly. The LADIS study. Journal of Neurology, Neurosurgery, and Psychiatry, 78, 13251330.CrossRefGoogle ScholarPubMed
Vernooij, M.W., Ikram, M.A., Tanghe, H.L., Vincent, A.J., Hofman, A., Krestin, G.P., van der Lugt, A. (2007). Incidental findings on brain MRI in the general population. New England Journal of Medicine, 357, 18211828.CrossRefGoogle ScholarPubMed
Wallin, A., Fladby, T. (2010). Do white matter hyperintensities on MRI matter clinically? BMJ, 341, c3400. doi:10.1136/bmj.c3400CrossRefGoogle ScholarPubMed
Wardlaw, J.M., Lewis, S.C., Keir, S.L., Dennis, M.S., Shenkin, S. (2006). Cerebral microbleeds are associated with lacunar stroke defined clinically and radiologically, independently of white matter lesions. Stroke, 37, 26332636.CrossRefGoogle ScholarPubMed
Wechsler, D. (1997a). WAIS-III: Administration and scoring manual. San Antonio, TX: The Psychological Corporation.Google Scholar
Wechsler, D. (1997b). Wechsler Memory Scale—Third Edition manual. San Antonio, TX: The Psychological Corporation.Google Scholar
Wen, W., Sachdev, P. (2004). The topography of white matter hyperintensities on brain MRI in healthy 60- to 64-year-old individuals. Neuroimage, 22, 144154.CrossRefGoogle ScholarPubMed
Wen, W., Sachdev, P.S., Chen, X., Anstey, K. (2006). Gray matter reduction is correlated with white matter hyperintensity volume: A voxel-based morphometric study in a large epidemiological sample. Neuroimage, 29, 10311039.CrossRefGoogle Scholar
Yamauchi, H., Fukuda, H., Oyanagi, C. (2002). Significance of white matter high intensity lesions as a predictor of stroke from arteriolosclerosis. Journal of Neurology, Neurosurgery, and Psychiatry, 78, 576582.CrossRefGoogle Scholar
Ylikoski, R., Ylikoski, A., Erkinjuntti, T., Sulkava, R., Raininko, R., Tilvis, R. (1993). White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Archives of Neurology, 50, 818824.CrossRefGoogle ScholarPubMed