, Volume 57, Issue 4, pp 401–411 | Cite as

Age effects on cortical thickness in young Down’s syndrome subjects: a cross-sectional gender study

  • Andrea RomanoEmail author
  • Marta Moraschi
  • Riccardo Cornia
  • Alessandro Bozzao
  • Olga Gagliardo
  • Laura Chiacchiararelli
  • Cristina Iani
  • Giacomo Stella
  • Giorgio Albertini
  • Alberto Pierallini
Functional Neuroradiology



The aim of this study was to determine differences in the characteristic pattern of age-related cortical thinning in men and women with Down’s syndrome (DS) by means of MRI and automatic cortical thickness measurements and a cross-sectional design, in a large cohort of young subjects.


Eighty-four subjects with DS, 30 females (11–35 years, mean age ± SD = 22.8 ± 5.9) and 54 males (11–35 years, mean age ± SD = 21.5 ± 6.5), were examined using a 1.5-T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package. For all subjects participating in the study, the Pearson product-moment correlation coefficient between age and mean cortical thickness values has been evaluated.


A significant negative correlation between cortical thickness and age was found in female DS subjects, predominantly in frontal and parietal lobes, bilaterally. In male DS subjects, a significant negative correlation between cortical thickness and age was found in the right fronto-temporal lobes and cingulate regions. Whole brain mean cortical thickness values were significantly negative correlated with age only in female DS subjects.


Females with Down’s syndrome showed a strong correlation between cortical thickness and age, already in early age. We suggest that the cognitive impairment due to hormonal deficit in the postmenopausal period could be emphasized by the early structural decline of gray matter in female DS subjects.


Gender Down’s syndrome MRI Free-surfer Aging 


Ethical standards and patient consent

We declare that all human and animal studies have been approved by our Institutional Ethics Committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.

Conflict of interest

We declare that we have no conflict of interest.


  1. 1.
    Krasuski JS, Alexander GE, Horwitz B, Rapoport SI, Schapiro MB (2002) Relation of medial temporal lobe volumes to age and memory function in non demented adults with Down’s syndrome: implications for the prodromal phase of Alzheimer’s disease. Am J Psychiatry 159:74–81CrossRefPubMedGoogle Scholar
  2. 2.
    Cenini G, Dowling ALS, Beckett TL, Barone E, Mancuso C, Murphy MP, Levine H 3rd, Lott IT, Schmitt FA, Butterfield DA, Head E (2012) Association between frontal cortex oxidative damage and beta-amyloid as a function of age in Down syndrome. Biochim Biophys Acta 1822:130–138CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Beacher F, Daly E, Simmons A, Prasher V, Morris R, Robinson C, Lovestone S, Murphy K, Murphy DG (2010) Brain anatomy and ageing in non-demented adults with Down’s syndrome: an in vivo MRI study. Psychol Med 40:611–619CrossRefPubMedGoogle Scholar
  4. 4.
    Head E, Silverman W, Patterson D, Lott IT (2012) Aging and down syndrome. Curr Gerontol Geriatr Res 2010:1–6CrossRefGoogle Scholar
  5. 5.
    Teipel SJ, Alexander GE, Shapiro MB, Moller HS, Rapoport SI, Hampel H (2004) Age-related cortical grey matter reductions in non-demented Down’s syndrome adults determined by MRI voxel-based morphometry. Brain 127:811–824CrossRefPubMedGoogle Scholar
  6. 6.
    Mann DM (1998) The pathological association between Down syndrome and Alzheimer disease. Mech Ageing Dev 43:99–136CrossRefGoogle Scholar
  7. 7.
    Smigielska-Kuzia J, Bockowski L, Sobaniec W, Sendrowski K, Olchowik B, Cholewa M, Lukasiewicz A, Lebkowska U (2011) A volumetric magnetic resonance imaging study of brain structures in children with Down syndrome. Neurol Neurochir Pol 45:363–369PubMedGoogle Scholar
  8. 8.
    Beacher F, Daly E, Simmons A, Prasher V, Morris R, Robinson C, Lovestone S, Murphy K, Murphy DG (2009) Alzheimer’s disease and Down’s syndrome: an in vivo MRI study. Psychol Med 39:675–684CrossRefPubMedGoogle Scholar
  9. 9.
    Carducci F, Onorati P, Condoluci C, Di Gennaro G, Quarato PP, Pierallini A, Sarà M, Miano S, Cornia R, Albertini G (2013) Whole-brain voxel-based morphometry study of children and adolescents with Down syndrome. Funct Neurol 28:19–28PubMedCentralPubMedGoogle Scholar
  10. 10.
    Long X, Liao W, Jiang C, Liang D, Qiu B, Zhang L (2012) Healthy aging: an automatic analysis of global and regional morphological alterations of human brain. Acad Radiol 19:785–793CrossRefPubMedGoogle Scholar
  11. 11.
    Lemaitre H, Goldman AL, Sambataro F, Verchinski BA, Meyer-Lindenbarg A, Weimberger D, Mattay VS (2012) Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiol Aging 33:617.e1–617.e9CrossRefGoogle Scholar
  12. 12.
    Ruigrok ANV, Salimi-Khorshidi G, Lai MC, Baron-Cohen S, Lombardo MV, Tait RJ, Suckling J (2014) A meta-analysis of sex differences in human brain structure. Neurosci Biobehav Rev 39:34–50CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Fjell AM, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B, Dale AM, Walhovd KB (2009) Minute effects of sex on the ageing brain: a multi-sample MRI-study of healthy aging and Alzheimer’s disease. J Neurosci 29:8774–8783CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Schupf N, Pang D, Patel BN, Silverman W, Schubert R, Lai F, Kline JK, Stern Y, Ferin M, Tycko B, Mayeux R (2003) Onset of dementia is associated with age at menopause in women with Down’s syndrome. Ann Neurol 54:433–438CrossRefPubMedGoogle Scholar
  15. 15.
    White NS, Alkire MT, Haier RJ (2003) A voxel-based morphometric study of non demented adults with Down syndrome. Neuroimage 20:393–403CrossRefPubMedGoogle Scholar
  16. 16.
    Hasboun D, Chantome M, Zouaoui A, Sahel M, Deladoeuille M, Sourour N, Duyme M, Baulac M, Marsault C, Dormont D (1996) MR determination of hippocampal volume: comparison of three methods. AJNR Am J Neuroradiol 17:1091–1098PubMedGoogle Scholar
  17. 17.
    Pruessner JC, Li LM, Serles W, Pruessner M, Collins DL, Kabani N, Lupien S, Evans AC (2000) Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cereb Cortex 10:433–442CrossRefPubMedGoogle Scholar
  18. 18.
    Chan D, Fox NC, Scahill RI, Crum WR, Whitwell JL, Leschziner G, Rossor AM, Stevens JM, Cipolotti L, Rossor MN (2001) Patterns of temporal lobe atrophy in semantic dementia and Alzheimer’s disease. Ann Neurol 49:433–442CrossRefPubMedGoogle Scholar
  19. 19.
    Fischl B, Sereno MI, Dale AM (1999) Cortical surface-based analysis. II. Inflation, flattening and a surface-based coordinate system. Neuroimage 9:195–207CrossRefPubMedGoogle Scholar
  20. 20.
    Dale AM, Fischl B, Sereno MI (1999) Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9:179–194CrossRefPubMedGoogle Scholar
  21. 21.
    Fischl B, Dale AM (2000) Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A 97:11050–11055CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Rosas HD, Liu AK, Hersch S, Glessner M, Ferrante RJ, Salat DH, van der Kouwe A, Jenkins BG, Dale AM, Fischl B (2002) Regional and progressive thinning of the cortical ribbon in Huntington’s disease. Neurology 58:695–701CrossRefPubMedGoogle Scholar
  23. 23.
    Kuperberg GR, Broome MR, McGuire PK, David AS, Eddy M, Ozawa F, Goff D, West WC, Williams SC, van der Kouwe A, Salat DH, Dale AM, Fischl B (2003) Regionally localized thinning of the cerebral cortex in schizophrenia. Arch Gen Psychiatry 60:878–888CrossRefPubMedGoogle Scholar
  24. 24.
    Salat DH, Buckner RL, Snyder AZ, Greve DN, Desikan RS, Busa E, Morris JC, Dale AM, Fischl B (2004) Thinning of the cerebral cortex in aging. Cereb Cortex 14:721–730CrossRefPubMedGoogle Scholar
  25. 25.
    Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I (2001) Controlling the false discovery rate in behavior genetic research. Behav Brain Res 125:279–284CrossRefPubMedGoogle Scholar
  26. 26.
    Pinter JD, Eliez S, Schmitt JE, Capone GT, Reiss AL (2010) Neuroanatomy of Down’s syndrome: a high-resolution MRI study. Am J Psychiatry 158:1659–1665CrossRefGoogle Scholar
  27. 27.
    Lott IT, Dierssen M (2010) Cognitive deficits and associated neurological complications in individuals with Down’s syndrome. Lancet Neurol 9:623–633CrossRefPubMedGoogle Scholar
  28. 28.
    Teipel SJ, Schapiro MB, Alexander GE, Krasuski JS, Horwitz B, Hoehne C, Moller HJ, Rapoport SI, Hampel H (2003) Relation of corpus callosum and hippocampal size to age in non demented adults with Down’s syndrome. Am J Psychiatry 160:1870–1878CrossRefPubMedGoogle Scholar
  29. 29.
    Contestabile A, Fila T, Ceccarelli C, Bonasoni P, Bonapace L, Santini D, Bartesaghi R, Ciani E (2007) Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with Down syndrome and in Ts65Dn mice. Hippocampus 17:665–678CrossRefPubMedGoogle Scholar
  30. 30.
    Escorial S, Romàn FJ, Martìnez K, Burgaleta M, Karama S, Colom R (2014) Sex differences in neocortical structure and cognitive performance: a surface-based morphometry study. Neuroimage 104:355–365CrossRefPubMedGoogle Scholar
  31. 31.
    Schupf N, Kapell D, Nightingale B, Rodriguez A, Tycko B, Mayeux R (1998) Earlier onset of Alzheimer’s disease in men with Down syndrome. Neurology 50:991–995CrossRefPubMedGoogle Scholar
  32. 32.
    Lai F, Williams RS (1989) A prospective study of Alzheimer disease in Down syndrome. Arch Neurol 46:849–853CrossRefPubMedGoogle Scholar
  33. 33.
    Lee JH, Gurney S, Pang D, Temkin A, Park N, Janicki SC, Zigmen WB, Silverman W, Tycko B, Schupf N (2012) Polymorphisms in HSD17B1: early onset and increased risk of Alzheimer’s disease in women with Down syndrome. Curr Gerontol Geriatr Res 2012:1–8CrossRefGoogle Scholar
  34. 34.
    Zhao Q, Lee JH, Pang D, Temkin A, Park N, Janicki SC, Zigman WB, Silverman W, Tycko B, Schupf N (2011) Estrogen receptor-beta variants are associated with increased risk of Alzheimer’s disease in women with Down syndrome. Dement Geriatr Cogn Disord 32:241–249CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Hof PR, Bouras C, Perl DP, Sparks DL, Mehta N, Morrison JH (1995) Age-related distribution of neuropathologic changes in the cerebral cortex of patients with Down’s syndrome. Quantitative regional analysis and comparison with Alzheimer’s disease. Arch Neurol 52:379–391CrossRefPubMedGoogle Scholar
  36. 36.
    Teipel SJ, Hampel H (2006) Neuroanatomy of Down syndrome in vivo: a model of preclinical Alzheimer’s disease. Behav Genet 36:405–415CrossRefPubMedGoogle Scholar
  37. 37.
    Karlsen AS, Pakkenberg B (2011) Total numbers of neurons and glial cells in cortex and basal ganglia of ages brains with Down syndrome—a stereological study. Cereb Cortex 21:2519–2524CrossRefPubMedGoogle Scholar
  38. 38.
    Lott IT (2012) Antioxidants in Down syndrome. Biochim Biophys Acta 1822:657–663CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Koran ME, Hohman TJ, Edwards CM, Vega JN, Pryweller JR, Slosky LE, Crockett G, Villa de Rey L, Meda SA, Dankner N, Avery SN, Blackford JU, Dykens EM, Thornton-Wells TA (2014) Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development. J Neurodev Disord 6:8CrossRefPubMedCentralPubMedGoogle Scholar
  40. 40.
    Anderson JS, Nielsen JA, Ferguson MA, Burback MC, Cox ET, Dai L, Gerig G, Edgin JO, Korenberg JR (2013) Abnormal brain synchrony in Down syndrome. Neuroimage Clin 2:703–715CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Han X, Jovicich J, Salat D, van der Kouwe A, Quinn B, Czanner S, Busa E, Pacheco J, Albert M, Killiany R, Maguire P, Rosas D, Makris N, Dale A, Dickerson B, Fischl B (2006) Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer. Neuroimage 32:180–194CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Andrea Romano
    • 1
    Email author
  • Marta Moraschi
    • 1
  • Riccardo Cornia
    • 2
  • Alessandro Bozzao
    • 3
  • Olga Gagliardo
    • 3
  • Laura Chiacchiararelli
    • 4
  • Cristina Iani
    • 5
  • Giacomo Stella
    • 2
  • Giorgio Albertini
    • 6
  • Alberto Pierallini
    • 7
  1. 1.San Raffaele Foundation Rome, Rehabilitation Facility Ceglie MessapicaMerit Project RBNE08E8CZRomeItaly
  2. 2.Department of Education and Human SciencesUniversity of Modena and Reggio EmiliaEmilia-RomagnaItaly
  3. 3.NESMOS, Department of Neuroradiology, S. Andrea HospitalUniversity SapienzaRomeItaly
  4. 4.Department of Medical Physics, S. Andrea HospitalUniversity SapienzaRomeItaly
  5. 5.Department of Communication and EconomyUniversity of Modena and Reggio EmiliaEmilia-RomagnaItaly
  6. 6.Department of PaediatricsIRCSS San Raffaele PisanaRomeItaly
  7. 7.Department of RadiologyIRCSS San Raffaele PisanaRomeItaly

Personalised recommendations