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Vol. 35, No. 2, 2010
Issue release date: August 2010
Section title: Original Paper
Free Access
Neuroepidemiology 2010;35:117–122
(DOI:10.1159/000313443)

White Matter Hyperintensity and Cognitive Functioning in the Racial and Ethnic Minority Cohort of the Framingham Heart Study

Stavitsky K.a · Du Y.b · Seichepine D.a · Laudate T.M.a · Beiser A.b–d · Seshadri S.c, d · DeCarli C.e · Wolf P.A.c, d · Au R.c, d
aDepartment of Psychology, Boston University, bDepartment of Biostatistics, Boston University School of Public Health, and cDepartment of Neurology, Boston University School of Medicine, Boston, Mass., dFramingham Heart Study, Framingham, Mass., and eDepartment of Neurology and Center for Neuroscience, University of California, Davis, Sacramento, Calif., USA
email Corresponding Author

Abstract

Background: Previous studies have demonstrated an association between white matter hyperintensities (WMH) and cognitive performance primarily in Caucasian samples, limiting generalizability to other ethnic and racial groups. This study investigated the association of WMH and cognition in an ethnic and racial minority cohort (Omni) of the Framingham Heart Study and compared these results to the Caucasian (Offspring) cohort. Methods: Quantitative brain MRI and neuropsychological evaluations were performed on stroke- and dementia-free participants. Cognitive assessment included verbal memory, visuospatial memory and organization, language, and executive functioning. Linear regression models were conducted to assess the association between WMH and cognitive function. Results: The Omni group presented with demographic factors that significantly differed from those of the Offspring group: they were younger, but had more stroke risk factors such as hypertension. In the Offspring group, WMH volume was significantly associated with poorer performance on tests of executive function and visual organization. No significant associations between WMH and cognitive measures were found in the Omni group, but no differences (significant interaction terms) were seen between the regression coefficients. Conclusions: The Omni cohort had greater variability in factors that may mediate the association of WMH and cognition. More research is needed to investigate how stroke risk factors impact on the occurrence of WMH and its association with cognition in more diverse cohorts.

© 2010 S. Karger AG, Basel


  

Key Words

  • White matter hyperintensities
  • Cognition
  • Executive function
  • Framingham Heart Study
  • Magnetic resonance imaging
  • Cultural/ethnic diversity

References

  1. Cerhan JR, Folsom AR, Mortimer JA, Shahar E, Knopman DS, McGovern PG, Hays MA, Crum LD, Heiss G: Correlates of cognitive function in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Gerontology 1998;44:95–105.
  2. Elias MF, Sullivan LM, D’Agostino RB, Elias PK, Beiser A, Au R, Seshadri S, DeCarli C, Wolf PA: Framingham stroke risk profile and lowered cognitive performance. Stroke 2004;35:404–409.
  3. DeCarli C, Miller BL, Swan GE, Reed T, Wolf PA, Carmelli D: Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study. Arch Neurol 2001;58:643–647.
  4. Knopman D, Boland LL, Mosley T, Howard G, Liao D, Szklo M, McGovern P, Folsom AR: Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology 2001;56:42–48.
  5. Swan GE, Carmelli D, Larue A: Systolic blood pressure tracking over 25 to 30 years and cognitive performance in older adults. Stroke 1998;29:2334–2340.
  6. Kodl CT, Seaquist ER: Cognitive dysfunction and diabetes mellitus. Endocr Rev 2008;29:494–511.
  7. Pasquier F, Boulogne A, Leys D, Fontaine P: Diabetes mellitus and dementia. Diabetes Metab 2006;32:403–414.
  8. Solfrizzi V, Panza F, Colacicco AM, D’Introno A, Capurso C, Torres F, Grigoletto F, Maggi S, Del Parigi A, Reiman EM, Caselli RJ, Scafato E, Farchi G, Capurso A: Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology 2004;63:1882–1891.
  9. Au R, Massaro JM, Wolf PA, Young ME, Beiser A, Seshadri S, D’Agostino RB, DeCarli C: Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study. Arch Neurol 2006;63:246–250.
  10. Bigler ED, Lowry CM, Kerr B, Tate DF, Hessel CD, Earl HD, Miller MJ, Rice SA, Smith KH, Tschanz JT, Welsh-Bohmer K, Plassman B, Victoroff J: Role of white matter lesions, cerebral atrophy, and APOE on cognition in older persons with and without dementia: the Cache County, Utah, study of memory and aging. Neuropsychology 2003;17:339–352.
  11. Burton EJ, Kenny RA, O’Brien J, Stephens S, Bradbury M, Rowan E, Kalaria R, Firbank M, Wesnes K, Ballard C: White matter hyperintensities are associated with impairment of memory, attention, and global cognitive performance in older stroke patients. Stroke 2004;35:1270–1275.
  12. de Groot JC, de Leeuw FE, Oudkerk M, Hofman A, Jolles J, Breteler MM: Cerebral white matter lesions and subjective cognitive dysfunction: the Rotterdam Scan Study. Neurology 2001;56:1539–1545.
  13. DeCarli C, Reed T, Miller BL, Wolf PA, Swan GE, Carmelli D: Impact of apolipoprotein E epsilon4 and vascular disease on brain morphology in men from the NHLBI twin study. Stroke 1999;30:1548–1553.
  14. Gunning-Dixon FM, Raz N: Neuroanatomical correlates of selected executive functions in middle-aged and older adults: a prospective MRI study. Neuropsychologia 2003;41:1929–1941.
  15. 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.
  16. 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.
  17. Brickman AM, Zimmerman ME, Paul RH, Grieve SM, Tate DF, Cohen RA, Williams LM, Clark CR, Gordon E: Regional white matter and neuropsychological functioning across the adult lifespan. Biol Psychiatry 2006;60:444–453.
  18. Mensah GA, Mokdad AH, Ford ES, Greenlund KJ, Croft JB: State of disparities in cardiovascular health in the United States. Circulation 2005;111:1233–1241.
  19. Wright CB, Festa JR, Paik MC, Schmiedigen A, Brown TR, Yoshita M, DeCarli C, Sacco R, Stern Y: White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke 2008;39:800–805.
  20. Brickman AM, Schupf N, Manly JJ, Luchsinger JA, Andrews H, Tang MX, Reitz C, Small SA, Mayeux R, DeCarli C, Brown TR: Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan. Arch Neurol 2008;65:1053–1061.
  21. Birns J, Morris R, Jarosz J, Markus H, Kalra L: Ethnic differences in the cerebrovascular impact of hypertension. Cerebrovasc Dis 2008;25:408–416.
  22. Sacco RL, Wolf PA, Kannel WB, McNamara PM: Survival and recurrence following stroke. The Framingham study. Stroke 1982;13:290–295.
  23. Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A, D’Agostino RB, White LR: Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology 1992;42:115–119.
  24. Seshadri S, Wolf PA, Beiser A, Elias MF, Au R, Kase CS, D’Agostino RB, DeCarli C: Stroke risk profile, brain volume, and cognitive function: the Framingham Offspring Study. Neurology 2004;63:1591–1599.
  25. DeCarli C, Massaro J, Harvey D, Hald J, Tullberg M, Au R, Beiser A, D’Agostino R, Wolf PA: Measures of brain morphology and infarction in the Framingham Heart Study: establishing what is normal. Neurobiol Aging 2005;26:491–510.
  26. Williams LR, Hutchinson CE, Jackson A, Horan MA, Jones M, McInnes L, Rabbitt PM, Pendleton N: Clinical correlates of cerebral white matter hyperintensities in cognitively normal older adults. Arch Gerontol Geriatr 2010;50:127–131.

  

Author Contacts

Rhoda Au, PhD
Department of Neurology, Boston University School of Medicine
72 E. Concord Street, B608
Boston, MA 02118 (USA)
Tel. +1 617 638 5450, Fax +1 617 638 8086, E-Mail rhodaau@bu.edu

  

Article Information

Received: September 25, 2009
Accepted: April 8, 2010
Published online: June 15, 2010
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 3, Number of References : 26

  

Publication Details

Neuroepidemiology

Vol. 35, No. 2, Year 2010 (Cover Date: August 2010)

Journal Editor: Feigin V.L. (Auckland)
ISSN: 0251-5350 (Print), eISSN: 1423-0208 (Online)

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


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: Previous studies have demonstrated an association between white matter hyperintensities (WMH) and cognitive performance primarily in Caucasian samples, limiting generalizability to other ethnic and racial groups. This study investigated the association of WMH and cognition in an ethnic and racial minority cohort (Omni) of the Framingham Heart Study and compared these results to the Caucasian (Offspring) cohort. Methods: Quantitative brain MRI and neuropsychological evaluations were performed on stroke- and dementia-free participants. Cognitive assessment included verbal memory, visuospatial memory and organization, language, and executive functioning. Linear regression models were conducted to assess the association between WMH and cognitive function. Results: The Omni group presented with demographic factors that significantly differed from those of the Offspring group: they were younger, but had more stroke risk factors such as hypertension. In the Offspring group, WMH volume was significantly associated with poorer performance on tests of executive function and visual organization. No significant associations between WMH and cognitive measures were found in the Omni group, but no differences (significant interaction terms) were seen between the regression coefficients. Conclusions: The Omni cohort had greater variability in factors that may mediate the association of WMH and cognition. More research is needed to investigate how stroke risk factors impact on the occurrence of WMH and its association with cognition in more diverse cohorts.

© 2010 S. Karger AG, Basel


  

Author Contacts

Rhoda Au, PhD
Department of Neurology, Boston University School of Medicine
72 E. Concord Street, B608
Boston, MA 02118 (USA)
Tel. +1 617 638 5450, Fax +1 617 638 8086, E-Mail rhodaau@bu.edu

  

Article Information

Received: September 25, 2009
Accepted: April 8, 2010
Published online: June 15, 2010
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 3, Number of References : 26

  

Publication Details

Neuroepidemiology

Vol. 35, No. 2, Year 2010 (Cover Date: August 2010)

Journal Editor: Feigin V.L. (Auckland)
ISSN: 0251-5350 (Print), eISSN: 1423-0208 (Online)

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


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 9/25/2009
Accepted: 4/8/2010
Published online: 6/15/2010
Issue release date: August 2010

Number of Print Pages: 6
Number of Figures: 0
Number of Tables: 3

ISSN: 0251-5350 (Print)
eISSN: 1423-0208 (Online)

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


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. Cerhan JR, Folsom AR, Mortimer JA, Shahar E, Knopman DS, McGovern PG, Hays MA, Crum LD, Heiss G: Correlates of cognitive function in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Gerontology 1998;44:95–105.
  2. Elias MF, Sullivan LM, D’Agostino RB, Elias PK, Beiser A, Au R, Seshadri S, DeCarli C, Wolf PA: Framingham stroke risk profile and lowered cognitive performance. Stroke 2004;35:404–409.
  3. DeCarli C, Miller BL, Swan GE, Reed T, Wolf PA, Carmelli D: Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study. Arch Neurol 2001;58:643–647.
  4. Knopman D, Boland LL, Mosley T, Howard G, Liao D, Szklo M, McGovern P, Folsom AR: Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology 2001;56:42–48.
  5. Swan GE, Carmelli D, Larue A: Systolic blood pressure tracking over 25 to 30 years and cognitive performance in older adults. Stroke 1998;29:2334–2340.
  6. Kodl CT, Seaquist ER: Cognitive dysfunction and diabetes mellitus. Endocr Rev 2008;29:494–511.
  7. Pasquier F, Boulogne A, Leys D, Fontaine P: Diabetes mellitus and dementia. Diabetes Metab 2006;32:403–414.
  8. Solfrizzi V, Panza F, Colacicco AM, D’Introno A, Capurso C, Torres F, Grigoletto F, Maggi S, Del Parigi A, Reiman EM, Caselli RJ, Scafato E, Farchi G, Capurso A: Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology 2004;63:1882–1891.
  9. Au R, Massaro JM, Wolf PA, Young ME, Beiser A, Seshadri S, D’Agostino RB, DeCarli C: Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study. Arch Neurol 2006;63:246–250.
  10. Bigler ED, Lowry CM, Kerr B, Tate DF, Hessel CD, Earl HD, Miller MJ, Rice SA, Smith KH, Tschanz JT, Welsh-Bohmer K, Plassman B, Victoroff J: Role of white matter lesions, cerebral atrophy, and APOE on cognition in older persons with and without dementia: the Cache County, Utah, study of memory and aging. Neuropsychology 2003;17:339–352.
  11. Burton EJ, Kenny RA, O’Brien J, Stephens S, Bradbury M, Rowan E, Kalaria R, Firbank M, Wesnes K, Ballard C: White matter hyperintensities are associated with impairment of memory, attention, and global cognitive performance in older stroke patients. Stroke 2004;35:1270–1275.
  12. de Groot JC, de Leeuw FE, Oudkerk M, Hofman A, Jolles J, Breteler MM: Cerebral white matter lesions and subjective cognitive dysfunction: the Rotterdam Scan Study. Neurology 2001;56:1539–1545.
  13. DeCarli C, Reed T, Miller BL, Wolf PA, Swan GE, Carmelli D: Impact of apolipoprotein E epsilon4 and vascular disease on brain morphology in men from the NHLBI twin study. Stroke 1999;30:1548–1553.
  14. Gunning-Dixon FM, Raz N: Neuroanatomical correlates of selected executive functions in middle-aged and older adults: a prospective MRI study. Neuropsychologia 2003;41:1929–1941.
  15. 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.
  16. 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.
  17. Brickman AM, Zimmerman ME, Paul RH, Grieve SM, Tate DF, Cohen RA, Williams LM, Clark CR, Gordon E: Regional white matter and neuropsychological functioning across the adult lifespan. Biol Psychiatry 2006;60:444–453.
  18. Mensah GA, Mokdad AH, Ford ES, Greenlund KJ, Croft JB: State of disparities in cardiovascular health in the United States. Circulation 2005;111:1233–1241.
  19. Wright CB, Festa JR, Paik MC, Schmiedigen A, Brown TR, Yoshita M, DeCarli C, Sacco R, Stern Y: White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke 2008;39:800–805.
  20. Brickman AM, Schupf N, Manly JJ, Luchsinger JA, Andrews H, Tang MX, Reitz C, Small SA, Mayeux R, DeCarli C, Brown TR: Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan. Arch Neurol 2008;65:1053–1061.
  21. Birns J, Morris R, Jarosz J, Markus H, Kalra L: Ethnic differences in the cerebrovascular impact of hypertension. Cerebrovasc Dis 2008;25:408–416.
  22. Sacco RL, Wolf PA, Kannel WB, McNamara PM: Survival and recurrence following stroke. The Framingham study. Stroke 1982;13:290–295.
  23. Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A, D’Agostino RB, White LR: Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology 1992;42:115–119.
  24. Seshadri S, Wolf PA, Beiser A, Elias MF, Au R, Kase CS, D’Agostino RB, DeCarli C: Stroke risk profile, brain volume, and cognitive function: the Framingham Offspring Study. Neurology 2004;63:1591–1599.
  25. DeCarli C, Massaro J, Harvey D, Hald J, Tullberg M, Au R, Beiser A, D’Agostino R, Wolf PA: Measures of brain morphology and infarction in the Framingham Heart Study: establishing what is normal. Neurobiol Aging 2005;26:491–510.
  26. Williams LR, Hutchinson CE, Jackson A, Horan MA, Jones M, McInnes L, Rabbitt PM, Pendleton N: Clinical correlates of cerebral white matter hyperintensities in cognitively normal older adults. Arch Gerontol Geriatr 2010;50:127–131.