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In vivo demonstration of amyloid burden in posterior cortical atrophy: a case series with PET and CSF findings

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Abstract

Our objective was to evaluate amyloid deposition in posterior cortical atrophy (PCA), using both cerebrospinal fluid (CSF) biomarker analysis and amyloid imaging. Five PCA patients, selected based on their neuropsychological profile and atrophic changes in posterior regions on MRI, underwent CSF analysis. CSF amyloid-beta 1–42, total tau, and phosphorylated tau at threonine 181 levels were determined. They also had positron emission tomography (PET) with Pittsburgh Compound B ([11C]PIB). [11C]PIB ratio images were assessed with visual, regional and voxel-based analyses and compared to eight typical Alzheimer's disease (AD) patients and eight controls. The biological profile in the five PCA patients, resulting from CSF and [11C]PIB images analysis, was consistent with AD. Individual comparisons of PCA patients’ [11C]PIB images with the AD group with Statistical Parametric Mapping (SPM) revealed a distinctive posterior uptake in four out of the five patients showing increased amyloid deposition in occipital, temporal, and/or parietal regions. ROI group analysis showed a tendency for higher amyloid deposition in occipital and temporal regions. However, this pattern was not found with SPM group analysis when the global level of [11C]PIB uptake was used as a covariate. Our results indicate that amyloid burden can be demonstrated in vivo in PCA suggesting a diagnosis of AD. PCA patients may present a higher global amyloid load than AD that was not related to age at onset, disease severity, disease duration, or educational level in our study. Combined CSF and PET biomarkers seem helpful for in vivo diagnosis of this focal syndrome with underlying AD pathology.

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References

  1. Benson DF, Davis RJ, Snyder BD (1988) Posterior cortical atrophy. Arch Neurol 45(7):789–793

    PubMed  CAS  Google Scholar 

  2. Tang-Wai DF et al (2004) Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy. Neurology 63(7):1168–1174

    PubMed  CAS  Google Scholar 

  3. Renner JA et al (2004) Progressive posterior cortical dysfunction: a clinicopathologic series. Neurology 63(7):1175–1180

    PubMed  CAS  Google Scholar 

  4. McMonagle P et al (2006) The cognitive profile of posterior cortical atrophy. Neurology 66(3):331–338

    Article  PubMed  Google Scholar 

  5. Formaglio M et al (2009) Homonymous hemianopia and posterior cortical atrophy. Rev Neurol (Paris) 165(3):256–62

    Google Scholar 

  6. Whitwell JL et al (2007) Imaging correlates of posterior cortical atrophy. Neurobiol Aging 28(7):1051–1061

    Article  PubMed  Google Scholar 

  7. Nestor PJ et al (2003) The topography of metabolic deficits in posterior cortical atrophy (the visual variant of Alzheimer’s disease) with FDG-PET. J Neurol Neurosurg Psychiatry 74(11):1521–1529

    Article  PubMed  CAS  Google Scholar 

  8. Schmidtke K, Hull M, Talazko J (2005) Posterior cortical atrophy: variant of Alzheimer’s disease? A case series with PET findings. J Neurol 252(1):27–35

    Article  PubMed  Google Scholar 

  9. Alladi S et al (2007) Focal cortical presentations of Alzheimer’s disease. Brain 130(Pt 10):2636–2645

    Article  PubMed  CAS  Google Scholar 

  10. Hof PR et al (1997) Atypical form of Alzheimer’s disease with prominent posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways. Vision Res 37(24):3609–3625

    Article  PubMed  CAS  Google Scholar 

  11. Hulstaert F et al (1999) Improved discrimination of AD patients using beta-amyloid(1–42) and tau levels in CSF. Neurology 52(8):1555–1562

    PubMed  CAS  Google Scholar 

  12. Shaw LM et al (2009) Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol 65(4):403–413

    Article  PubMed  CAS  Google Scholar 

  13. Mathis CA et al (2002) A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. Bioorg Med Chem Lett 12(3):295–298

    Article  PubMed  CAS  Google Scholar 

  14. Klunk WE et al (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55(3):306–319

    Article  PubMed  CAS  Google Scholar 

  15. Engler H et al (2006) Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 129(Pt 11):2856–2866

    Article  PubMed  Google Scholar 

  16. Bacskai BJ et al (2007) Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. Arch Neurol 64(3):431–434

    Article  PubMed  Google Scholar 

  17. Lockhart A et al (2007) PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Brain 130(Pt 10):2607–2615

    Article  PubMed  CAS  Google Scholar 

  18. Ikonomovic MD et al (2008) Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 131(Pt 6):1630–1645

    Article  PubMed  Google Scholar 

  19. Folstein MFFS, McHugh PR (1975) Mini-mental state. A pratical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  PubMed  CAS  Google Scholar 

  20. Morris JC (1993) The clinical dementia rating (CDR): current version and scoring rules. Neurology 43(11):2412–2414

    PubMed  CAS  Google Scholar 

  21. McKhann G et al (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34(7):939–944

    PubMed  CAS  Google Scholar 

  22. Grober E, Buschke H (1987) Genuine memory deficits in dementia. Dev Psychol 3:13–36

    Google Scholar 

  23. Delis D et al (1987) The California Verbal Learning Test (research Ždition). Psychological corporation, New York

  24. Cardebat DDB, Puel M, Goulet P, Joanette Y (1990) Formal and semantic lexial evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level. Acta Neurol Belg 90:207–217

    PubMed  CAS  Google Scholar 

  25. Bachy-Langedock N (1989) Batterie d’examen des troubles en denomination, Editest, Bruxelles

  26. Stroop (1935) Studies of interferences in serial verbal reactions. J Exp Psychol 18:643–662

    Article  Google Scholar 

  27. Reitan RM, Wolfson D (2004) The Trail Making Test as an initial screening procedure for neuropsychological impairment in older children. Arch Clin Neuropsychol 19(2):281–288

    Article  PubMed  Google Scholar 

  28. Rapport LJ, Millis SR, Bonello PJ (1998) Validation of the Warrington theory of visual processing and the visual object and space perception battery. J Clin Exp Neuropsychol 20(2):211–220

    Article  PubMed  CAS  Google Scholar 

  29. Sunderland T et al (1989) Clock drawing in Alzheimer’s disease. A novel measure of dementia severity. J Am Geriatr Soc 37(8):725–729

    PubMed  CAS  Google Scholar 

  30. Hansson O et al (2006) Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 5(3):228–234

    Article  PubMed  CAS  Google Scholar 

  31. Tapiola T et al (2009) Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66(3):382–389

    Article  PubMed  Google Scholar 

  32. Mattsson N et al (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. Jama 302(4):385–393

    Article  PubMed  CAS  Google Scholar 

  33. Lopresti BJ et al (2005) Simplified quantification of Pittsburgh Compound B amyloid imaging PET studies: a comparative analysis. J Nucl Med 46(12):1959–1972

    PubMed  CAS  Google Scholar 

  34. Hammers A et al (2003) Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp 19(4):224–247

    Article  PubMed  Google Scholar 

  35. Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26(3):839–851

    Article  PubMed  Google Scholar 

  36. Kambe T et al (2010) Posterior cortical atrophy with [11C] Pittsburgh compound B accumulation in the primary visual cortex. J Neurol 257(3):469–71

    Google Scholar 

  37. Migliaccio R et al (2009) Clinical syndromes associated with posterior atrophy: early age at onset AD spectrum. Neurology 73(19):1571–1578

    Article  PubMed  CAS  Google Scholar 

  38. Tenovuo O et al (2008) Posterior cortical atrophy: a rare form of dementia with in vivo evidence of amyloid-beta accumulation. J Alzheimers Dis 15(3):351–355

    PubMed  CAS  Google Scholar 

  39. Ng SY et al (2007) Evaluating atypical dementia syndromes using positron emission tomography with carbon 11 labeled Pittsburgh Compound B. Arch Neurol 64(8):1140–1144

    Article  PubMed  Google Scholar 

  40. Grimmer T et al (2009) Clinical severity of Alzheimer’s disease is associated with PIB uptake in PET. Neurobiol Aging 30(12):1902–1909

    Article  PubMed  CAS  Google Scholar 

  41. Edison P et al (2007) Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 68(7):501–508

    Article  PubMed  CAS  Google Scholar 

  42. Kemppainen NM et al (2007) PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 68(19):1603–1606

    Article  PubMed  CAS  Google Scholar 

  43. Rabinovici GD et al (2010) Increased metabolic vulnerability in early-onset Alzheimer’s disease is not related to amyloid burden. Brain 133(Pt 2): p 512–28

    Google Scholar 

  44. Forsberg A et al (2008) PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 29(10):1456–1465

    Article  PubMed  CAS  Google Scholar 

  45. Gomperts SN et al (2008) Imaging amyloid deposition in Lewy body diseases. Neurology 71(12):903–910

    Article  PubMed  CAS  Google Scholar 

  46. Edison P et al (2008) Amyloid load in Parkinson’s disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry 79(12):1331–1338

    Article  PubMed  CAS  Google Scholar 

  47. Pike KE et al (2007) Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease. Brain 130(Pt 11):2837–2844

    Article  PubMed  Google Scholar 

  48. Villemagne VL et al (2008) Abeta deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer’s disease. Neuropsychologia 46(6):1688–1697

    Article  PubMed  CAS  Google Scholar 

  49. Baumann TP et al (2010) CSF-Tau and CSF-Abeta(1–42) in posterior cortical atrophy. Dement Geriatr Cogn Disord 29(6):530–533

    Google Scholar 

  50. Strozyk D et al (2003) CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60(4):652–656

    PubMed  CAS  Google Scholar 

  51. Roher AE et al (2009) Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer’s disease. Biomarkers 14(7):493–501

    Article  PubMed  CAS  Google Scholar 

  52. Koopman K et al (2009) Improved discrimination of autopsy-confirmed Alzheimer’s disease (AD) from non-AD dementias using CSF P-tau(181P). Neurochem Int 55(4):214–218

    Article  PubMed  CAS  Google Scholar 

  53. Mulder C et al (2010) Amyloid-beta(1-42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease. Clin Chem 56(2):248–53

    Google Scholar 

  54. Hort J et al (2010) Use of cerebrospinal fluid biomarkers in diagnosis of dementia across Europe. Eur J Neurol 17(1):90–6

    Google Scholar 

  55. Engelborghs S et al (2008) Diagnostic performance of a CSF-biomarker panel in autopsy-confirmed dementia. Neurobiol Aging 29(8):1143–1159

    Article  PubMed  Google Scholar 

  56. Iqbal K et al (2005) Subgroups of Alzheimer’s disease based on cerebrospinal fluid molecular markers. Ann Neurol 58(5):748–757

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Maïté Formaglio.

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Formaglio, M., Costes, N., Seguin, J. et al. In vivo demonstration of amyloid burden in posterior cortical atrophy: a case series with PET and CSF findings. J Neurol 258, 1841–1851 (2011). https://doi.org/10.1007/s00415-011-6030-0

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  • DOI: https://doi.org/10.1007/s00415-011-6030-0

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