De afgelopen jaren is er veel onderzoek gedaan naar veranderingen van het brein die samenhangen met het proces van veroudering. Hierbij moet met name worden gedacht aan neurodegeneratieve veranderingen zoals hersenatrofie (Raz et al., 1997; Resnick et al., 2003) of vasculaire veranderingen in de hersenen zoals cerebral small vessel disease (Pantoni & Garcia, 1995). De brede implementatie van nieuwe MRI-technieken zoals diffusion tensor imaging (DTI) heeft er bovendien toe geleid dat de integriteit van breinweefsels, met name de witte stof, op microstructureel niveau niet-invasief kan worden bestudeerd. De microstructurele integriteit van breinweefsel wordt minder met toenemende leeftijd (Pfefferbaum et al., 2000; Sullivan et al., 2001). Voor het merendeel van de beschreven ouderdomsgerelateerde veranderingen van het brein speelt bovendien erfelijkheid een belangrijke rol (Atwood et al., 2004; Carmelli et al., 1998; Chiang et al., 2011; Peper et al., 2007; Pfefferbaum et al., 2001). Genetische factoren zijn óók bepalend voor de menselijke levensverwachting (Herskind et al., 1996), waarbij voor buitengewone langlevendheid een clustering in families is aangetoond (Herskind et al., 1996; Skytthe et al., 2003).
Abstract
Background
Neurodegenerative changes and vascular damage of the brain are a common ageing phenomenon. This study aimed to determine whether the phenotype of familial longevity is marked by a relative preservation of brain tissue (micro)structure.
Methods
Participants were recruited from the Leiden Longevity Study. In total, 194 elderly offspring of nonagenarian siblings, who are enriched for familial factors of longevity, were contrasted with 176 environment and age-matched controls. All subjects underwent three Tesla MRI of the brain to study structural differences between both groups as a potential manifestation of genetically driven differences in biological age.
Results
No differences in whole brain, gray matter and white matter volume were found between offspring and control subjects. Left amygdalar volume of the offspring was larger compared with control subjects, but amygdalar volumes were not associated with chronological age in both groups. Concerning the presence of white matter lesions, offspring were less likely to have severe periventricular frontal caps and severe periventricular bands. Moreover, offspring were less likely to have frontal, temporal, and occipital subcortical white matter lesions. Prevalence of lacunar infarcts also was lower in offspring. Prevalence of microbleeds was not different between offspring and control subjects. Diffusion tensor imaging showed that offspring had relatively preserved white matter integrity when compared to control subjects, which was predominantly located in the callosal genu and, body and partly splenium.
Conclusions
Familial longevity is associated with preserved (micro)structure of predominantly the white matter. Future research needs to focus on how to translate this knowledge to the general population to make everybody live ‘healthier for longer.
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Literatuur
Alexander, A.L., Lee, J.E., Lazar, M. & Field, A.S. (2007). Diffusion tensor imaging of the brain. Neurotherapeutics, 4, 3, 316–329.
Altmann-Schneider, I., Craen, A.J. de, Slagboom, P.E., Westendorp, R.G., Buchem, M.A. van, Maier, A.B. & Grond, J. van der (2012). Brain tissue volumes in familial longevity: the Leiden Longevity Study. Aging Cell, 11, 6, 933–939.
Altmann-Schneider, I., Craen, A.J. de, Veer, I.M., Berg-Huysmans, A.A. van den, Slagboom, P.E., Westendorp, R.G., Buchem, M.A. van & Grond, J. van der (2013a). Preserved white matter integrity is a marker of familial longevity. Annals of Neurology.
Altmann-Schneider, I., Grond, J. van der, Slagboom, P.E., Westendorp, R.G., Maier, A.B., Buchem, M.A. van & Craen, A.J. de (2013b). Lower susceptibility to cerebral small vessel disease in human familial longevity: the Leiden Longevity Study. Stroke, 44, 1, 9–14.
Ashburner, J. & Friston, K.J. (2000). Voxel-based morphometry—the methods. Neuroimage, 11,6 Pt 1, 805–821.
Atwood, L.D., Wolf, P.A., Heard-Costa, N.L., Massaro, J.M., Beiser, A, D’Agostino, R.B. & DeCarli, C. (2004). Genetic variation in white matter hyperintensity volume in the Framingham Study. Stroke, 35, 7, 1609–1613.
Awad, I.A., Spetzler, R.F., Hodak, J.A., Awad, C.A. & Carey, R. (1986). Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. I. Correlation with age and cerebrovascular risk factors. Stroke, 17, 6, 1084–1089.
Bartzokis, G., Beckson, M., Lu, P.H., Nuechterlein, K.H., Edwards, N. & Mintz, J. (2001). Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study. Archives of General Psychiatry, 58, 5, 461–465.
Bartzokis, G., Cummings, J.L., Sultzer, D., Henderson, V.W., Nuechterlein, K.H. & Mintz, J. (2003). White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study. Archives of Neurology, 60, 3, 393–398.
Behrens, T.E., Berg, H.J., Jbabdi, S., Rushworth, M.F. & Woolrich, M.W. (2007). Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? Neuroimage, 34, 1, 144–155.
Behrens, T.E., Johansen-Berg, H., Woolrich, M.W., Smith, S.M., Wheeler- Kingshott, C.A., Boulby, P.A., Barker, G.J., Sillery, E.L., Sheehan, K., Ciccarelli, O., Thompson, A.J., Brady, J.M. & Matthews, P.M. (2003a). Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nature Neuroscience, 6, 7, 750–757.
Behrens, T.E., Woolrich, M.W., Jenkinson, M., Johansen-Berg, H., Nunes, R.G., Clare, S., Matthews, P.M., Brady, J.M. & Smith, S.M. (2003b). Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magnetic Resonance in Medicine, 50, 5, 1077–1088.
Bryan, R.N., Wells, S.W., Miller, T.J., Elster, A.D., Jungreis, C.A., Poirier, V.C., Lind, B.K. & Manolio, T.A. (1997). Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly–data from the Cardiovascular Health Study. Radiology, 202, 1, 47–54.
Carmelli, D., DeCarli, C., Swan, G.E., Jack, L.M., Reed, T., Wolf, P.A. & Miller, B.L. (1998). Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. Stroke, 29, 6, 1177–1181.
Chiang, M.C., McMahon, K.L., de Zubicaray, G.I., Martin, N.G., Hickie, I., Toga, A.W., Wright, M.J. & Thompson, P.M. (2011). Genetics of white matter development: a DTI study of 705 twins and their siblings aged 12 to 29. Neuroimage, 54, 3, 2308–2317.
Good, C.D., Johnsrude, I.S., Ashburner, J., Henson, R.N., Friston, K.J. & Frackowiak, R.S. (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage, 14,1 Pt 1, 21–36.
Griebe, M., Forster, A., Wessa, M., Rossmanith, C., Bazner, H., Sauer, T., Zohsel, K., Blahak, C., King, A.V., Linke, J., Hennerici, M.G., Gass, A. & Szabo, K. (2011). Loss of callosal fibre integrity in healthy elderly with age-related white matter changes. Journal of Neurology, Neurosurgery & Psychiatry, 258, 8, 1451–1459.
Herskind, A.M., McGue, M., Holm, N.V., Sorensen, T.I., Harvald, B. & Vaupel, J.W. (1996). The heritability of human longevity: a populationbased study of 2872 Danish twin pairs born 1870-1900. Human Genetics, 97, 3, 319–323.
Kuller, L.H., Arnold, A.M., Longstreth, W.T., Jr., Manolio, T.A., O’Leary, D.H., Burke, G.L., Fried, L.P. & 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, 9, 1307–1315.
Leritz, E.C., Shepel, J., Williams, V.J., Lipsitz, L.A., McGlinchey, R.E., Milberg, W.P. & Salat, D.H. (2013). Associations between T(1) white matter lesion volume and regional white matter microstructure in aging. Human Brain Mapping.
Mai, J.K., Paxinos, G. & Voss, T. (2008). Atlas of the human brain.
Marner, L., Nyengaard, J.R., Tang, Y. & Pakkenberg, B. (2003). Marked loss of myelinated nerve fibers in the human brain with age. Journal of Comparative Neurology, 462, 2, 144–152.
Mueller, E.A., Moore, M.M., Kerr, D.C., Sexton, G., Camicioli, R.M., Howieson, D.B., Quinn, J.F. & Kaye, J.A. (1998). Brain volume preserved in healthy elderly through the eleventh decade. Neurology, 51, 6, 1555–1562.
Pantoni, L. & Garcia, J.H. (1995). The significance of cerebral white matter abnormalities 100 years after Binswanger’s report. A review. Stroke, 26, 7, 1293–1301.
Peper, J.S., Brouwer, R.M., Boomsma, D.I., Kahn, R.S. & Hulshoff Pol, H.E. (2007). Genetic influences on human brain structure: a review of brain imaging studies in twins. Human Brain Mapping, 28, 6, 464–473.
Pfefferbaum, A., Sullivan, E.V. & Carmelli, D. (2001). Genetic regulation of regional microstructure of the corpus callosum in late life. Neuroreport, 12, 8, 1677–1681.
Pfefferbaum, A., Sullivan, E.V., Hedehus, M., Lim, K.O., Adalsteinsson, E. & Moseley, M. (2000). Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging. Magnetic Resonance in Medicine, 44, 2, 259–268.
Raz, N., Gunning, F.M., Head, D., Dupuis, J.H., McQuain, J., Briggs, S.D., Loken, W.J., Thornton, A.E. & Acker, J.D. (1997). Selective aging of the human cerebral cortex observed in vivo: differential vulnerability of the prefrontal gray matter. Cerebral Cortex, 7, 3, 268–282.
Resnick, S.M., Pham, D.L., Kraut, M.A., Zonderman, A.B. & Davatzikos, C. (2003). Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. Journal of Neuroscience, 23, 8, 3295–3301.
Roob, G., Schmidt, R., Kapeller, P., Lechner, A., Hartung, H.P. & Fazekas, F. (1999). MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology, 52, 5, 991–994.
Rozing, M.P., Houwing-Duistermaat, J.J., Slagboom, P.E., Beekman, M., Frolich, M., Craen, A.J. de, Westendorp, R.G. & Heemst, D. van (2010). Familial longevity is associated with decreased thyroid function. Journal of Clinical Endocrinology & Metabolism, 95, 11, 4979–4984.
Scheltens, P., Barkhof, F., Leys, D., Pruvo, J.P., Nauta, J.J., Vermersch, P., Steinling, M. & Valk, J. (1993). A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. Journal of Neurological Sciences, 114, 1, 7–12.
Schoenmaker, M., Craen, A.J. de, Meijer, P.H. de, Beekman, M., Blauw, G.J., Slagboom, P.E. & Westendorp, R.G. (2006). Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study. European Journal of Human Genetics, 14, 1, 79–84.
Skytthe, A., Pedersen, N.L., Kaprio, J., Stazi, M.A., Hjelmborg, J.V., Iachine, I., Vaupel, J.W. & Christensen, K. (2003). Longevity studies in GenomEUtwin. Twin Research, 6, 5, 448–454.
Smith, S.M., De Stefano, N., Jenkinson, M. & Matthews, P.M. (2001). Normalized accurate measurement of longitudinal brain change. Journal of Computer Assisted Tomography, 25, 3, 466–475.
Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E., Watkins, K.E., Ciccarelli, O., Cader, M.Z., Matthews, P.M. & Behrens, T.E. (2006). Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage, 31, 4, 1487–1505.
Smith, S.M., Jenkinson, M., Woolrich, M.W., Beckmann, C.F., Behrens, T.E., Johansen-Berg, H., Bannister, P.R., De, L.M., Drobnjak, I., Flitney, D.E., Niazy, R.K., Saunders, J., Vickers, J., Zhang, Y., De, S.N., Brady, J.M. & Matthews, P.M. (2004). Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage, 23, Suppl 1, S208–S219.
Smith, S.M., Zhang, Y., Jenkinson, M., Chen, J., Matthews, P.M., Federico, A. & De, S.N. (2002). Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage, 17, 1, 479–489.
Sullivan, E.V., Adalsteinsson, E., Hedehus, M., Ju, C., Moseley, M., Lim, K.O. & Pfefferbaum, A. (2001). Equivalent disruption of regional white matter microstructure in ageing healthy men and women. Neuroreport, 12, 1, 99–104.
Vaarhorst, A.A., Beekman, M., Suchiman, E.H., van Heemst, D., Houwing-Duistermaat, J.J., Westendorp, R.G., Slagboom, P.E. & Heijmans, B.T. (2011). Lipid metabolism in long-lived families: the Leiden Longevity Study. Age (Dordr.), 33, 2, 219–227.
Westendorp, R.G., Heemst, D. van, Rozing, M.P., Frolich, M., Mooijaart, S.P., Blauw, G.J., Beekman, M., Heijmans, B.T., Craen, A.J. de & Slagboom, P.E. (2009). Nonagenarian siblings and their offspring display lower risk of mortality and morbidity than sporadic nonagenarians: The Leiden Longevity Study. Journal of the American Geriatrics Society, 57, 9, 1634–1637.
Wijsman, C.A., Rozing, M.P., Streefland, T.C., Cessie, S. le, Mooijaart, S.P., Slagboom, P.E., Westendorp, R.G., Pijl, H. & Heemst, D. van (2011). Familial longevity is marked by enhanced insulin sensitivity. Aging Cell, 10, 1, 114–121.
Woolrich, M.W., Jbabdi, S., Patenaude, B., Chappell, M., Makni, S., Behrens, T., Beckmann, C., Jenkinson, M. & Smith, S.M. (2009). Bayesian analysis of neuroimaging data in FSL. Neuroimage, 45,1 Suppl, S173–S186.
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Mw. drs. I.E. Overwater, onderzoeker, afdelingen Neurologie, Neurowetenschappen en ENCORE expertisecentrum voor erfelijke neurocognitieve ontwikkelingsstoornissen, Erasmus MC Universitair Medisch Centrum, Rotterdam; drs. T. van der Vaart, onderzoeker, afdelingen Neurowetenschappen, Kindergeneeskunde en ENCORE expertisecentrum voor erfelijke neurocognitieve ontwikkelingsstoornissen, Erasmus MC Universitair Medisch Centrum, Rotterdam; m.vandervaart@erasmusmc.nl; mw. dr. M.C.Y. de Wit, neuroloogkinderneuroloog, afdelingen Neurologie en ENCORE expertisecentrum voor erfelijke neurocognitieve ontwikkelingsstoornissen, Erasmus MC Universitair Medisch Centrum, Rotterdam; mw. dr. R. Oostenbrink, kinderarts, afdelingen kindergeneeskunde en ENCORE expertisecentrum voor erfelijke neurocognitieve ontwikkelingsstoornissen, Erasmus MC Universitair Medisch Centrum, Rotterdam; prof. dr. Y. Elgersma, moleculair neurobioloog, afdelingen neurowetenschappen en ENCORE expertisecentrum voor erfelijke neurocognitieve ontwikkelingsstoornissen, Erasmus MC Universitair Medisch Centrum, Rotterdam
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Altmann-Schneider, I., van der Grond, J., van den Berg-Huysmans, A. et al. De Leiden Lang Leven Studie: weerspiegelt het brein een lang leven?. NEUROPRAXIS 17, 167–172 (2013). https://doi.org/10.1007/s12474-013-0031-y
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DOI: https://doi.org/10.1007/s12474-013-0031-y