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.
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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25
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
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
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
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
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
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
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]
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
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
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
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
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
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
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
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
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.
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The authors declare that they have no conflict of interest.
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M. Griebe and A. Förster contributed equally to this study.
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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
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DOI: https://doi.org/10.1007/s00415-011-5956-6