Skip to main content

Advertisement

SpringerLink
Log in

Loss of callosal fibre integrity in healthy elderly with age-related white matter changes

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Age-related white matter changes (ARWMC) appear to correspond to a continuum from normal functioning to clinically overt neurological syndromes. Disturbance of the structural integrity of cerebral fibre tracts—the so-called cerebral network—by ARWMC might be one explanation for this development. From 3 T magnetic resonance imaging (MRI) data of 34 healthy elderly subjects (60–82 years) we calculated the lesion volume of ARWMC and the area of the corpus callosum (CC). Gait, balance and cognition were assessed. We compared these findings in those with mild (n = 22) and advanced (n = 12) ARWMC and performed tract-based spatial statistics (TBSS) to analyze white matter structural integrity. In subjects with advanced ARWMC, TBSS showed a significant decrease of fractional anisotropy (FA) in several large tracts of the white matter including the CC; total CC, CC2 and CC5 areas were significantly smaller. Despite these morphological changes, tests of gait, balance and cognition as measured by the Mini-Mental State Examination (MMSE) were in the normal range for both groups; only the Montreal Cognitive Assessment (MoCA) detected executive and language dysfunction in those with advanced ARWMC. Loss of tissue integrity and atrophy of the CC secondary to spatially remote lesions in the peri- and paraventricular white matter in ARWMC appear to be already detectable in healthy elderly individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Reference

  1. Ay H, Arsava EM, Rosand J, Furie KL, Singhal AB, Schaefer PW, Wu O, Gonzalez RG, Koroshetz WJ, Sorensen AG (2008) Severity of leukoaraiosis and susceptibility to infarct growth in acute stroke. Stroke 39:1409–1413

    Article  PubMed  Google Scholar 

  2. Baezner H, Blahak C, Poggesi A, Pantoni L, Inzitari D, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Langhorne P, O’brien J, Scheltens P, Visser MC, Wahlund LO, Waldemar G, Wallin A, Hennerici MG (2008) Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology 70:935–942

    Article  PubMed  CAS  Google Scholar 

  3. Baezner H, Hennerici M (2005) From trepidant abasia to motor network failure–gait disorders as a consequence of subcortical vascular encephalopathy (SVE): review of historical and contemporary concepts. J Neurol Sci 229–230:81–88

    Article  PubMed  Google Scholar 

  4. Bhadelia RA, Price LL, Tedesco KL, Scott T, Qiu WQ, Patz S, Folstein M, Rosenberg I, Caplan LR, Bergethon P (2009) Diffusion tensor imaging, white matter lesions, the corpus callosum, and gait in the elderly. Stroke 40:3816–3820

    Article  PubMed  Google Scholar 

  5. Blahak C, Baezner H, Pantoni L, Poggesi A, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Langhorne P, O’brien J, Visser MC, Wahlund LO, Waldemar G, Wallin A, Inzitari D, Hennerici MG (2009) Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study. J Neurol Neurosurg Psychiatry 80:608–613

    Article  PubMed  CAS  Google Scholar 

  6. Breteler MM, van Swieten JC, Bots ML, Grobbee DE, Claus JJ, van den Hout JH, van Harskamp F, Tanghe HL, de Jong PT, van Gijn J (1994) Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology 44:1246–1252

    PubMed  CAS  Google Scholar 

  7. de Leeuw FE, de Groot JC, Achten E, Oudkerk M, Ramos LM, Heijboer R, Hofman A, Jolles J, van Gijn J, Breteler MM (2001) Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 70:9–14

    Article  PubMed  Google Scholar 

  8. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 149:351–356

    PubMed  CAS  Google Scholar 

  9. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  PubMed  CAS  Google Scholar 

  10. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB (1995) Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 332:556–561

    Article  PubMed  CAS  Google Scholar 

  11. Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB (1994) A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 49:M85–M94

    PubMed  CAS  Google Scholar 

  12. Guttmann CR, Benson R, Warfield SK, Wei X, Anderson MC, Hall CB, Abu-Hasaballah K, Mugler JP III, Wolfson L (2000) White matter abnormalities in mobility-impaired older persons. Neurology 54:1277–1283

    PubMed  CAS  Google Scholar 

  13. Hofer S, Frahm J (2006) Topography of the human corpus callosum revisited—comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage 32:989–994

    Article  PubMed  Google Scholar 

  14. Jokinen H, Kalska H, Mantyla R, Pohjasvaara T, Ylikoski R, Hietanen M, Salonen O, Kaste M, Erkinjuntti T (2006) Cognitive profile of subcortical ischaemic vascular disease. J Neurol Neurosurg Psychiatry 77:28–33

    Article  PubMed  CAS  Google Scholar 

  15. Jokinen H, Kalska H, Ylikoski R, Madureira S, Verdelho A, van der Flier WM, Scheltens P, Barkhof F, Visser MC, Fazekas F, Schmidt R, O’brien J, Waldemar G, Wallin A, Chabriat H, Pantoni L, Inzitari D, Erkinjuntti T (2009) Longitudinal cognitive decline in subcortical ischemic vascular disease—the LADIS Study. Cerebrovasc Dis 27:384–391

    Article  PubMed  Google Scholar 

  16. Jokinen H, Ryberg C, Kalska H, Ylikoski R, Rostrup E, Stegmann MB, Waldemar G, Madureira S, Ferro JM, van Straaten EC, Scheltens P, Barkhof F, Fazekas F, Schmidt R, Carlucci G, Pantoni L, Inzitari D, Erkinjuntti T (2007) Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study. J Neurol Neurosurg Psychiatry 78:491–496

    Article  PubMed  Google Scholar 

  17. Lee DY, Fletcher E, Martinez O, Zozulya N, Kim J, Tran J, Buonocore M, Carmichael O, DeCarli C (2010) Vascular and degenerative processes differentially affect regional interhemispheric connections in normal aging, mild cognitive impairment, and Alzheimer disease. Stroke 41:1791–1797

    Article  PubMed  Google Scholar 

  18. Madden DJ, Whiting WL, Huettel SA, White LE, MacFall JR, Provenzale JM (2004) Diffusion tensor imaging of adult age differences in cerebral white matter: relation to response time. Neuroimage 21:1174–1181

    Article  PubMed  Google Scholar 

  19. Moretti M, Carlucci G, Di Carlo A, Fonda C, Prieto M, Mugnai S, Bracco L, Piccini C, Pracucci G, Inzitari D (2005) Corpus callosum atrophy is associated with gait disorders in patients with leukoaraiosis. Neurol Sci 26:61–66

    Article  PubMed  CAS  Google Scholar 

  20. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699

    Article  PubMed  Google Scholar 

  21. Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25

    Article  PubMed  Google Scholar 

  22. O’Sullivan M, Jones DK, Summers PE, Morris RG, Williams SC, Markus HS (2001) Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline. Neurology 57:632–638

    PubMed  Google Scholar 

  23. Pantoni L, Poggesi A, Basile AM, Pracucci G, Barkhof F, Chabriat H, Erkinjuntti T, Ferro JM, Hennerici M, O’brien J, Schmidt R, Visser MC, Wahlund LO, Waldemar G, Wallin A, Inzitari D (2006) Leukoaraiosis predicts hidden global functioning impairment in nondisabled older people: the LADIS (Leukoaraiosis and Disability in the Elderly) Study. J Am Geriatr Soc 54:1095–1101

    Article  PubMed  Google Scholar 

  24. Poggesi A, Pracucci G, Chabriat H, Erkinjuntti T, Fazekas F, Verdelho A, Hennerici M, Langhorne P, O’brien J, Scheltens P, Visser MC, Crisby M, Waldemar G, Wallin A, Inzitari D, Pantoni L (2008) Urinary complaints in nondisabled elderly people with age-related white matter changes: the Leukoaraiosis and Disability (LADIS) study. J Am Geriatr Soc 56:1638–1643

    Article  PubMed  Google Scholar 

  25. Rosano C, Brach J, Longstreth WT Jr, Newman AB (2006) Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults. Neuroepidemiology 26:52–60

    Article  PubMed  Google Scholar 

  26. Ryberg C, Rostrup E, Sjostrand K, Paulson OB, Barkhof F, Scheltens P, van Straaten EC, Fazekas F, Schmidt R, Erkinjuntti T, Wahlund LO, Basile AM, Pantoni L, Inzitari D, Waldemar G (2008) White matter changes contribute to corpus callosum atrophy in the elderly: the LADIS study. AJNR Am J Neuroradiol 29:1498–1504

    Article  PubMed  CAS  Google Scholar 

  27. Ryberg C, Rostrup E, Stegmann MB, Barkhof F, Scheltens P, van Straaten EC, Fazekas F, Schmidt R, Ferro JM, Baezner H, Erkinjuntti T, Jokinen H, Wahlund LO, O’brien J, Basile AM, Pantoni L, Inzitari D, Waldemar G (2007) Clinical significance of corpus callosum atrophy in a mixed elderly population. Neurobiol Aging 28:955–963

    Article  PubMed  CAS  Google Scholar 

  28. Sala S, Agosta F, Pagani E, Copetti M, Comi G, Filippi M (2010) Microstructural changes and atrophy in brain white matter tracts with aging. Neurobiol Aging [Epub ahead of print]

  29. Salat DH, Tuch DS, Greve DN, van der Kouwe AJ, Hevelone ND, Zaleta AK, Rosen BR, Fischl B, Corkin S, Rosas HD, Dale AM (2005) Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiol Aging 26:1215–1227

    Article  PubMed  CAS  Google Scholar 

  30. Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:1487–1505

    Article  PubMed  Google Scholar 

  31. Srikanth V, Phan TG, Chen J, Beare R, Stapleton JM, Reutens DC (2010) The location of white matter lesions and gait—a voxel-based study. Ann Neurol 67:265–269

    Article  PubMed  Google Scholar 

  32. Sullivan EV, Adalsteinsson E, Hedehus M, Ju C, Moseley M, Lim KO, Pfefferbaum A (2001) Equivalent disruption of regional white matter microstructure in ageing healthy men and women. Neuroreport 12:99–104

    Article  PubMed  CAS  Google Scholar 

  33. Sullivan EV, Adalsteinsson E, Pfefferbaum A (2006) Selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking. Cereb Cortex 16:1030–1039

    Article  PubMed  Google Scholar 

  34. Tadic SD, Griffiths D, Murrin A, Schaefer W, Aizenstein HJ, Resnick NM (2010) Brain activity during bladder filling is related to white matter structural changes in older women with urinary incontinence. Neuroimage 51:1294–1302

    Article  PubMed  Google Scholar 

  35. Vernooij MW, Ikram MA, Vrooman HA, Wielopolski PA, Krestin GP, Hofman A, Niessen WJ, van der LA, Breteler MM (2009) White matter microstructural integrity and cognitive function in a general elderly population. Arch Gen Psychiatry 66:545–553

    Article  PubMed  Google Scholar 

  36. Wakana S, Jiang H, Nagae-Poetscher LM, van Zijl PC, Mori S (2004) Fiber tract-based atlas of human white matter anatomy. Radiology 230:77–87

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study (M.W., A.V.K, and J.L.) was supported by a grant from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG), SFB 636/C6.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurology, UniversitätsMedizin Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Martin Griebe, Alex Förster, Christina Rossmanith, Hansjörg Bäzner, Tamara Sauer, Kathrin Zohsel, Christian Blahak, Michael G. Hennerici, Achim Gass & Kristina Szabo

  2. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, 68159, Mannheim, Germany

    Michèle Wessa, Andrea V. King & Julia Linke

Authors
  1. Martin Griebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alex Förster
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michèle Wessa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christina Rossmanith
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hansjörg Bäzner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tamara Sauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kathrin Zohsel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christian Blahak
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrea V. King
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Julia Linke
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michael G. Hennerici
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Achim Gass
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kristina Szabo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Griebe.

Additional information

M. Griebe and A. Förster contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Griebe, M., Förster, A., Wessa, M. et al. Loss of callosal fibre integrity in healthy elderly with age-related white matter changes. J Neurol 258, 1451–1459 (2011). https://doi.org/10.1007/s00415-011-5956-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-011-5956-6

Keywords

Search

Navigation