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Altered default-mode network activation in mild cognitive impairment compared with healthy aging

  • Diagnostic Neuroradiology
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Abstract

Introduction

Rapidly increasing aging of the world’s population is causing a heightened prevalence of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The global burden, caused by this, is tremendous. In order to slow down the progression of the disease and preserve quality of life as much as possible, early identification of subjects at risk is indispensable within this framework.

Methods

In the present study, we combined independent component analysis and statistical parametric analysis to identify and compare the default-mode network (DMN) in healthy elderly and patients with MCI, with a special interest for hippocampal and lateral temporal involvement.

Results

Functional results indicated reduced cortical activation in the DMN for MCI patients, compared with age- and education-matched healthy elderly controls, mainly in the retrosplenial region/posterior cingulate cortex, left hippocampus, and bilateral inferior and middle frontal areas. Increased activation for patients was observed in the medial prefrontal and bilateral middle temporal/angular cortex. Lateral temporal involvement in the DMN was in both the elderly control samples, and the patient group detected and suggested a slightly increased activation, more right than left, in middle temporal areas in the MCI patients, compared with healthy elderly.

Conclusion

Results are discussed with reference to the existing literature on early pathological changes in MCI and AD and subsequent compensation mechanisms in resting state and memory circuits.

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References

  1. Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL, de Leon M, Feldman H, Ganguli M, Hampel H, Scheltens P, Tierney MC, Whitehouse P, Winblad B, IPAEC (2006) Mild cognitive impairment. Lancet 367:1262–1270

    Article  PubMed  Google Scholar 

  2. Gustavson A, Scensson M et al (2011) Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21:718–779

    Article  Google Scholar 

  3. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3:186–191

    Article  PubMed  Google Scholar 

  4. Petersen RC, Smith GE, Ivnik RJ, Tangalos EG, Schaid DJ, Thibodeau SN, Kokmen E, Waring SC, Kurland LT (1995) Apolipoprotein-E status as a predictor of the development of Alzheimer’s disease in memory-impaired individuals. JAMA 273:1274–1278

    Article  PubMed  CAS  Google Scholar 

  5. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985–1992

    Article  PubMed  CAS  Google Scholar 

  6. Bondi MW, Wierenga CE (2007) Use of functional magnetic resonance imaging in the early identification of Alzheimer’s disease. Neuropsychol Rev 17:127–143

    Article  PubMed  Google Scholar 

  7. Calhoun VD, Adali T, Pearlson GD, Pekar JJ (2001) A method for making group inferences from functional MRI data using independent component analysis. Hum Brain Mapp 14:140–151

    Article  PubMed  CAS  Google Scholar 

  8. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82:239–259

    Article  PubMed  CAS  Google Scholar 

  9. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network—anatomy, function, and relevance to disease. J Cogn Neurosci 1124:1–38

    Google Scholar 

  10. Damoiseaux JS, Greicius MD (2009) Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity. Brain Struct Funct 213:525–533

    Article  PubMed  Google Scholar 

  11. Raichle ME, Macleod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci USA 98:676–682

    Article  PubMed  CAS  Google Scholar 

  12. Damoiseaux JS, Rombouts SARB, Barkhof F, Scheltens P, Stam CJ, Smith SM, Beckmann CF (2006) Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA 103:13848–13853

    Article  PubMed  CAS  Google Scholar 

  13. Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: Evidence from functional MRI. Proc Natl Acad Sci USA 101:4637–4642

    Article  PubMed  CAS  Google Scholar 

  14. Rombouts SARB, Barkhof F, Goekoop R, Stam CJ, Scheltens P (2005) Altered resting state networks in mild cognitive impairment and mild Alzheimer’s disease: an fMRI study. Hum Brain Mapp 26:231–239

    Article  PubMed  Google Scholar 

  15. Qi ZG, Wu X, Wang ZQ, Zhang N, Dong HQ, Yao L, Li KC (2010) Impairment and compensation coexist in amnestic MCI default mode network. Neuroimage 50:48–55

    Article  PubMed  Google Scholar 

  16. Sorg C, Riedl V, Muhlau M, Calhoun VD, Eichele T, Laer L, Drzezga A, Forstl H, Kurz A, Zimmer C, Wohlschlager AM (2007) Selective changes of resting-state networks in individuals at risk for Alzheimer’s disease. Proc Natl Acad Sci USA 104:18760–18765

    Article  PubMed  CAS  Google Scholar 

  17. Ojemann GA, Schoenfield-McNeill J, Corina D (2009) The roles of human lateral temporal cortical neuronal activity in recent verbal memory encoding. Cereb Cortex 19:197–205

    Article  PubMed  Google Scholar 

  18. Sperling RA, Bates JF, Chua EF, Cocchiarella AJ, Rentz DM, Rosen BR, Schacter DL, Albert MS (2003) FMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease. J Neurol Neurosurg Psychiatry 74:44–50

    Article  PubMed  CAS  Google Scholar 

  19. Machulda MM (2003) Comparison of memory fMRI response among normal, MCI, and Alzheimer’s patients. Neurology 61:1164–1164 (vol 61, pg 500, 2003)

    Article  Google Scholar 

  20. Small SA, Perera GM, DeLaPaz R, Mayeux R, Stern Y (1999) Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer’s disease. Ann Neurol 45:466–472

    Article  PubMed  CAS  Google Scholar 

  21. Dickerson BC, Salat DH, Greve DN, Chua EF, Rand-Giovannetti E, Rentz DM, Bertram L, Mullin K, Tanzi RE, Blacker D, Albert MS, Sperling RA (2005) Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65:404–411

    Article  PubMed  CAS  Google Scholar 

  22. Johnson SC, Schmitz TW, Moritz CH, Meyerand ME, Rowley HA, Alexander AL, Hansen KW, Gleason CE, Carlsson CM, Ries ML, Asthana S, Chen K, Reiman EM, Alexander GE (2006) Activation of brain regions vulnerable to Alzheimer’s disease: the effect of mild cognitive impairment. Neurobiol Aging 27:1604–1612

    Article  PubMed  CAS  Google Scholar 

  23. Greicius MD, Supekar K, Menon V, Dougherty RF (2009) Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex 19:72–78

    Article  PubMed  Google Scholar 

  24. Hedden T, Van Dijk KRA, Becker JA, Mehta A, Sperling RA, Johnson KA, Buckner RL (2009) Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. J Neurosci 29:12686–12694

    Article  PubMed  CAS  Google Scholar 

  25. Wang L, Zang YF, He Y, Liang M, Zhang XQ, Tian LX, Wu T, Jiang TZ, Li KC (2006) Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: evidence from resting state fMRI. Neuroimage 31:496–504

    Article  PubMed  Google Scholar 

  26. Bai F, Zhang ZJ, Yu H, Shi YM, Yuan YG, Zhu WL, Zhang XR, Qian Y (2008) Default-mode network activity distinguishes amnestic type mild cognitive impairment from healthy aging: a combined structural and resting-state functional MRI study. Neurosci Lett 439:111–115

    Article  Google Scholar 

  27. Wang K, Liang M, Wang L, Tian LX, Zhang XQ, Li KC, Jiang TZ (2007) Altered functional connectivity in early Alzheimer’s disease: a resting-state fMRI study. Hum Brain Mapp 28:967–978

    Article  PubMed  Google Scholar 

  28. Grady CL, McIntosh AR, Beig S, Keightley ML, Burian H, Black SE (2003) Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer’s disease. J Neurosci 23:986–993

    PubMed  CAS  Google Scholar 

  29. Oldfield RC (1971) Assessment and analysis of handedness—Edinburgh Inventory. Neuropsychologia 9:97

    Article  PubMed  CAS  Google Scholar 

  30. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST (2001) Practice parameter: early detection of dementia: Mild cognitive impairment (an evidence-based review)—report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56:1133–1142

    Article  PubMed  CAS  Google Scholar 

  31. Morris JC (1993) The clinical dementia rating (CDR)—current version and scoring rules. Neurology 43:2412–2414

    Article  PubMed  CAS  Google Scholar 

  32. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL (1982) A new clinical-scale for the staging of dementia. Br J Psychiatry 140:566–572

    Article  PubMed  CAS  Google Scholar 

  33. Miatton M, Wolters M, Lannoo E, Vingerhoets G (2004) Updated and extended Flemish normative data of commonly used neuropsychological tests. Psychol Belg 44:189–216

    Google Scholar 

  34. Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. Neuroimage 11:805–821

    Article  PubMed  CAS  Google Scholar 

  35. Stevens MC, Kiehl KA, Pearlson G, Calhoun VD (2007) Functional neural circuits for mental timekeeping. Hum Brain Mapp 28:394–408

    Article  PubMed  Google Scholar 

  36. Petrella JR, Sheldon FC, Prince SE, Calhoun VD, Doraiswamy PM (2011) Default mode network connectivity in stable vs progressive mild cognitive impairment. Neurology 76:511–517

    Article  PubMed  CAS  Google Scholar 

  37. Jin M, Pelak VS, Cordes D (2012) Aberrant default mode network in subjects with amnestic mild cognitive impairment using resting-state functional MRI. Magn Reson Imaging 30:48–61

    Article  PubMed  Google Scholar 

  38. Grady CL, Furey ML, Pietrini P, Horwitz B, Rapoport SI (2001) Altered functional connectivity and impaired short-term memory in Alzheimer’s disease. Brain 124:739–756

    Article  PubMed  CAS  Google Scholar 

  39. Schwindt GC, Black SE (2009) Functional imaging studies of episodic memory in Alzheimer’s disease: a quantitative meta-analysis. Neuroimage 45:181–190

    Article  PubMed  Google Scholar 

  40. Collie A, Maruff P (2000) The neuropsychology of preclinical Alzheimer’s disease and mild cognitive impairment. Neurosci Biobehav Rev 24:365–374

    Article  PubMed  CAS  Google Scholar 

  41. Bai F, Liao W, Watson DR, Shi YM, Wang Y, Yue CX, Teng YH, Wu D, Yuan YG, Jia JP, Zhang ZJ (2011) Abnormal whole-brain functional connection in amnestic mild cognitive impairment patients. Behav Brain Res 216:666–672

    Article  PubMed  Google Scholar 

  42. Wang Z, Yan C, Zhao C, Qi Z, Zhou W, Lu J, He Y, Li K (2011) Spatial patterns of intrinsic brain activity in mild cognitive impairment and Alzheimer’s disease: a resting-state functional MRI study. Hum Brain Mapp 32:1720–1740

    Article  PubMed  Google Scholar 

  43. Smith CD, Umberger GH, Manning EL, Slevin JT, Wekstein DR, Schmitt FA, Markesbery WR, Zhang Z, Gerhardt GA, Kryscio RJ, Gash DM (1999) Critical decline in fine motor hand movements in human aging. Neurology 53:1458–1461

    Article  PubMed  CAS  Google Scholar 

  44. Agosta F, Rocca MA, Pagani E, Absinta M, Magnani G, Marcone A, Falautano M, Comi G, Gorno-Tempini ML, Filippi M (2010) Sesorimotor network rewiring in mild cognitive impairment and Alzheimer’s disease. Hum Brain Mapp 31:515–525

    PubMed  Google Scholar 

  45. Karas GB, Burton EJ, Rombouts SARB, van Schijndel RA, O’Brien JT, Scheltens P, McKeith IG, Williams D, Ballard C, Barkhof FA (2003) Comprehensive study of gray matter loss in patients with Alzheimer’s disease using optimized voxel-based morphometry. Neuroimage 18:895–907

    Article  PubMed  CAS  Google Scholar 

  46. Karas GB, Scheltens P, Rombouts SARB, Visser PJ, van Schijndel RA, Fox NC, Barkhof F (2004) Global and local gray matter loss in mild cognitive impairment and Alzheimer’s disease. Neuroimage 23:708–716

    Article  PubMed  CAS  Google Scholar 

  47. Chetelat G, Landeau B, Eustache F, Mezenge F, Viader F, de la Sayette V, Desgranges B, Baron JC (2005) Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. Neuroimage 27:934–946

    Article  PubMed  CAS  Google Scholar 

  48. Whitwell JL, Shiung MM, Przybelski SA, Weigand SD, Knopman DS, Boeve BF, Petersen RC, Jack CR (2008) MRI patterns of atrophy associated with progression to AD in amnestic mild cognitive impairment. Neurology 70:512–520

    Article  PubMed  CAS  Google Scholar 

  49. Sluimer JD, van der Flier WM, Karas GB, van Schijndel R, Barnes J, Boyes RG, Cover KS, Olabarriaga SD, Fox NC, Scheltens P, Vrenken H, Barkhof F (2009) Accelerating regional atrophy rates in the progression from normal aging to Alzheimer’s disease. Eur Radiol 19:12826–12833

    Article  Google Scholar 

  50. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington DC, pp 157–158, text rev

    Google Scholar 

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Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium

    Frederick De Vogelaere, Patrick Santens & Paul Boon

  2. Department of Radiology, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium

    Erik Achten

  3. Laboratory for Neuropsychology, Ghent University, Ghent, Belgium

    Guy Vingerhoets

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  1. Frederick De Vogelaere
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  2. Patrick Santens
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  4. Paul Boon
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  5. Guy Vingerhoets
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Correspondence to Frederick De Vogelaere.

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De Vogelaere, F., Santens, P., Achten, E. et al. Altered default-mode network activation in mild cognitive impairment compared with healthy aging. Neuroradiology 54, 1195–1206 (2012). https://doi.org/10.1007/s00234-012-1036-6

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  • DOI: https://doi.org/10.1007/s00234-012-1036-6

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