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Principal component analysis of FDG PET in amnestic MCI

  • Flavio NobiliEmail author
  • Dario Salmaso
  • Silvia Morbelli
  • Nicola Girtler
  • Arnoldo Piccardo
  • Andrea Brugnolo
  • Barbara Dessi
  • Stig A. Larsson
  • Guido Rodriguez
  • Marco Pagani
Original Article

Abstract

Purpose

The purpose of the study is to evaluate the combined accuracy of episodic memory performance and 18F-FDG PET in identifying patients with amnestic mild cognitive impairment (aMCI) converting to Alzheimer’s disease (AD), aMCI non-converters, and controls.

Methods

Thirty-three patients with aMCI and 15 controls (CTR) were followed up for a mean of 21 months. Eleven patients developed AD (MCI/AD) and 22 remained with aMCI (MCI/MCI). 18F-FDG PET volumetric regions of interest underwent principal component analysis (PCA) that identified 12 principal components (PC), expressed by coarse component scores (CCS). Discriminant analysis was performed using the significant PCs and episodic memory scores.

Results

PCA highlighted relative hypometabolism in PC5, including bilateral posterior cingulate and left temporal pole, and in PC7, including the bilateral orbitofrontal cortex, both in MCI/MCI and MCI/AD vs CTR. PC5 itself plus PC12, including the left lateral frontal cortex (LFC: BAs 44, 45, 46, 47), were significantly different between MCI/AD and MCI/MCI. By a three-group discriminant analysis, CTR were more accurately identified by PET-CCS + delayed recall score (100%), MCI/MCI by PET-CCS + either immediate or delayed recall scores (91%), while MCI/AD was identified by PET-CCS alone (82%). PET increased by 25% the correct allocations achieved by memory scores, while memory scores increased by 15% the correct allocations achieved by PET.

Conclusion

Combining memory performance and 18F-FDG PET yielded a higher accuracy than each single tool in identifying CTR and MCI/MCI. The PC containing bilateral posterior cingulate and left temporal pole was the hallmark of MCI/MCI patients, while the PC including the left LFC was the hallmark of conversion to AD.

Keywords

18F-FDG PET Episodic memory Mild cognitive impairment Alzheimer’s disease 

Notes

Acknowledgments

This study complies with the current Italian laws and received ethical approval.

We thank Dr. Giampiero Villavecchia for supervising PET acquisition and Dr. Alessandra Piccini for performing ApoE evaluation.

References

  1. 1.
    Cummings JL, Doody R, Clark C. Disease-modifying therapies for Alzheimer disease: challenges to early intervention. Neurology 2007;69:1622–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Dubois B, Feldman HH, Jacova C, DeKosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734–46.PubMedCrossRefGoogle Scholar
  3. 3.
    Bennett DA, Wilson RS, Schneider JA, Evans DA, Beckett LA, Aggarwal NT, et al. Natural history of mild cognitive impairment in older persons. Neurology 2002;59:198–205.PubMedGoogle Scholar
  4. 4.
    Loewenstein DA, Acevedo A, Agron J, Duara R. Stability of neurocognitive impairment in different subtypes of mild cognitive impairment. Dement Geriatr Cogn Disord 2007;23:82–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256:183–94.PubMedCrossRefGoogle Scholar
  6. 6.
    Feldman HH, Jacova C. Mild cognitive impairment. Am J Geriatr Psychiatry 2005;13:645–55.PubMedCrossRefGoogle Scholar
  7. 7.
    Sarazin M, Berr C, De Rotrou J, Fabrigoule C, Pasquier F, Legrain S, et al. Amnestic syndrome of the medial temporal type identifies prodromal AD. A longitudinal study. Neurology 2007;69:1859–67.PubMedCrossRefGoogle Scholar
  8. 8.
    Fossati P, Harvey PO, Le BG, Ergis AM, Jouvent R, Allilaire JF. Verbal memory performance of patients with a first depressive episode and patients with unipolar and bipolar recurrent depression. J Psychiatr Res 2004;38:137–44.PubMedCrossRefGoogle Scholar
  9. 9.
    Pasquier F, Grymonprez L, Lebert F, Van der Linden M. Memory impairment differs in frontotemporal dementia and Alzheimer’s disease. Neurocase 2001;7:161–71.PubMedCrossRefGoogle Scholar
  10. 10.
    Anchisi D, Borroni B, Franceschi F, Kerrouche N, Kalbe E, Beuthien-Beumann B, et al. Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease. Arch Neurol 2005;62:1728–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Visser PJ, Scheltens P, Verhey FRJ, Schmand B, Launer LJ, Jolles J, et al. Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment. J Neurol 1999;246:477–85.PubMedCrossRefGoogle Scholar
  12. 12.
    Mosconi L, Perani D, Sorbi S, Herholz K, Nacmias B, Holthoff V, et al. MCI conversion to dementia and the APOE genotype. A prediction study with FDG-PET. Neurology 2004;63:2332–40.PubMedGoogle Scholar
  13. 13.
    Chetelat G, Eustache F, Viader F, De La Sayette V, Pelerin A, Mezegne F, et al. FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment. Neurocase 2005;11:14–25.PubMedCrossRefGoogle Scholar
  14. 14.
    Mosconi L, Tsui WH, Pupi A, De Santi S, Drzezga A, Minoshima S, et al. 18F-FDG PET database of longitudinally confirmed healthy elderly individuals improves detection of mild cognitive impairment and Alzheimer’s disease. J Nucl Med 2007;48:1129–34.PubMedCrossRefGoogle Scholar
  15. 15.
    Drzezga A, Lautenschlager N, Siebner H, Riemenschneider M, Willoch F, Minoshima S, et al. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer’s disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 2003;30:1104–13.PubMedCrossRefGoogle Scholar
  16. 16.
    Hunt A, Schönknecht P, Henze M, Seidl U, Haberkorn U, Schröder J. Reduced cerebral glucose metabolism in patients at risk for Alzheimer’s disease. Psychiatry Res: Neuroimaging 2007;155:147–54.PubMedCrossRefGoogle Scholar
  17. 17.
    Whalley LJ. Brain ageing and dementia: what makes the difference? Br J Psychiatry 2002;181:369–71.PubMedCrossRefGoogle Scholar
  18. 18.
    Vandenberghe R, Tournoy J. Cognitive aging and Alzheimer’s disease. Postgrad Med J 2005;81:343–52.PubMedCrossRefGoogle Scholar
  19. 19.
    Dringenberg HC. Alzheimer’s disease: more than a “cholinergic disorder”—evidence that cholinergic–monoaminergic interactions contribute to EEG slowing and dementia. Behav Brain Res 2000;115:235–49.PubMedCrossRefGoogle Scholar
  20. 20.
    Folstein MF, Folstein SE, McHugh PR. “Mini-Mental State”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98.PubMedCrossRefGoogle Scholar
  21. 21.
    Katz S, Downs TD, Cash HR, Grotz RC. Progress in development of the index of ADL. Gerontologist 1970;10:20–30.PubMedGoogle Scholar
  22. 22.
    Lawton MP, Brody EM. Assessment of older people; self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–86.PubMedGoogle Scholar
  23. 23.
    Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–14.PubMedGoogle Scholar
  24. 24.
    Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 1992;55:967–72.PubMedCrossRefGoogle Scholar
  25. 25.
    Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001;32:1318–22.PubMedGoogle Scholar
  26. 26.
    Masur DM, Fuld PA, Blau AD, Thal LJ, Levin HS, Aronson MK. Distinguishing normal and demented elderly with selective reminding test. J Clin Exp Neuropsychol 1989;11:615–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Carlesimo GA, Caltagirone C, Gainotti G. The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analysis of cognitive impairment. The group for the standardization of the Mental Deterioration Battery. Eur Neurol 1996;36:378–84.PubMedCrossRefGoogle Scholar
  28. 28.
    Spinnler H, Tognoni G. Standardizzazione e taratura Italiana di test neuropsicologici. Ital J Neurol Sci 1987;6(Suppl. 8):1–120.Google Scholar
  29. 29.
    Barbarotto R, Laiacona M, Frosio R, Vecchio M, Farinato A, Capitani E. A normative study on visual reaction times and two Stroop colour-word tests. Ital J Neurol Sci 1998;19:161–70.PubMedCrossRefGoogle Scholar
  30. 30.
    Watson YI, Arfken CL, Birge SJ. Clock completion: an objective screening test for dementia. J Am Geriatr Soc 1993;41:1235–40.PubMedGoogle Scholar
  31. 31.
    Amodio P, Wenin H, Del Piccolo F, Mapelli D, Montagnese S, Pellegrini A, et al. Variability of trail making test, symbol digit test and line trait test in normal people. A normative study taking into account age-dependent decline and sociobiological variables. Aging Clin Exp Res 2002;14:117–31.PubMedGoogle Scholar
  32. 32.
    Knopman DS, Boeve BF, Parisi JE, Dickson DW, Smith GE, Ivnik RJ. Antemortem diagnosis of frontotemporal lobar degeneration. Ann Neurol 2005;57:480–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Loeb C, Gandolfo C. Diagnostic evaluation of degenerative and vascular dementia. Stroke 1983;14:399–401.PubMedGoogle Scholar
  34. 34.
    McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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 1984;34:939–44.PubMedGoogle Scholar
  35. 35.
    Bartenstein P, Asenbaum S, Catafau A, Halldin C, Pilowski L, Pupi A, et al. European Association of Nuclear Medicine procedure guidelines for brain imaging using [18F]FDG. Eur J Nucl Med 2002;29:BP43–BP48.Google Scholar
  36. 36.
    Greitz T, Bohm C, Holte S, Eriksson L. A computerized brain atlas: construction, anatomical content, and some applications. J Comput Assist Tomog 1991;15:26–38.CrossRefGoogle Scholar
  37. 37.
    Thurfjell L, Bohm C, Bengtsson E. CBA—an atlas based software tool used to facilitate the interpretation of neuroimaging data. Comput Methods Programs Biomed 1995;4:51–71.CrossRefGoogle Scholar
  38. 38.
    Andersson JLR, Thurfjell L. Implementation and validation of a fully automatic system for intra- and inter-individual registration of PET brain scans. J Comput Assist Tomogr 1997;21:136–44.PubMedCrossRefGoogle Scholar
  39. 39.
    Poulin P, Zakzanis KK. In vivo neuroanatomy of Alzheimer’s disease: evidence from structural and functional brain imaging. Brain Cogn 2002;49:220–5.PubMedGoogle Scholar
  40. 40.
    Van Heertum RL, Tikofsky RS. Positron emission tomography and single photon emission computed tomography brain imaging in the evaluation of Dementia. Semin Nucl Med 2003;33:77–85.PubMedCrossRefGoogle Scholar
  41. 41.
    Pett MA, Lackey NR, Sullivan JJ. Making sense of factor analysis in health care research: a practical guide. London: Sage; 2003.Google Scholar
  42. 42.
    Rodriguez G, Nobili F, Copello F, Vitali P, Gianelli MV, Taddei G, et al. 99mTc-HMPAO regional cerebral blood flow and quantitative electroencephalography in Alzheimer’s disease: a correlative study. J Nucl Med 1999;40:522–9.PubMedGoogle Scholar
  43. 43.
    Pagani M, Salmaso D, Rodriguez G, Nardo D, Larsson SA, Nobili F. Principal component analysis in mild and moderate Alzheimer’s Disease. Psychiatry Res: Neuroimaging; in press.Google Scholar
  44. 44.
    Varrone A, Pagani M, Salvatore E, Salmaso D, Sansone V, Amboni M, et al. Identification by [99mTc]ECD SPECT of anterior cingulate hypoperfusion in progressive supranuclear palsy, in comparison with Parkinson’s disease. Eur J Nucl Med Mol Imaging 2007;34:1071–81.PubMedCrossRefGoogle Scholar
  45. 45.
    Scarmeas N, Habeck CG, Zarahn E, Anderson KE, Park A, Hilton J, et al. Covariance PET patterns in early Alzheimer’s disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance. NeuroImage 2004;23:35–45.PubMedCrossRefGoogle Scholar
  46. 46.
    Salmon E, Kerrouche N, Perani D, Lekeu F, Holthoff V, Beuthien-Baumann B, et al. On the multivariate nature of brain metabolic impairment in Alzheimer’s disease. Neurobiol Aging 2007; July 23; epub ahead of print.Google Scholar
  47. 47.
    Mosconi L, De Santi S, Brys M, Tsui WH, Pirraglia E, Glodzik-Sobanska L, et al. Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. Biol Psychiatry 2008;63:609–18.PubMedCrossRefGoogle Scholar
  48. 48.
    Liddell BJ, Paul RH, Arns M, Gordon N, Kukla M, Rowe D, et al. Rates of decline distinguish Alzheimer’s disease and mild cognitive impairment relative to normal aging: integrating cognition and brain function. J Integr Neurosci 2007;6:141–74.PubMedCrossRefGoogle Scholar
  49. 49.
    Kantarci K, Jack CR Jr. Neuroimaging in Alzheimer disease: an evidence-based review. Neuroimaging Clin N Am 2003;13:197–209.PubMedCrossRefGoogle Scholar
  50. 50.
    Mesulam MM, Shaw P, Mash D, et al. Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum. Ann Neurol 2004;55:815–28.PubMedCrossRefGoogle Scholar
  51. 51.
    Blennow K, De Leon M, Zetterberg H. Alzheimer’s disease. Lancet 2006;368:387–403.PubMedCrossRefGoogle Scholar
  52. 52.
    Drzezga A, Grimmer T, Riemenschneider M, Lautenschlager N, Siebner H, Alexopoulus P, et al. Prediction of individual clinical outcome in MCI by means of genetic assessment and 18F-FDG PET. J Nucl Med 2005;46:1625–32.PubMedGoogle Scholar
  53. 53.
    DeCarli C. Mild cognitive impairment: diagnosis, prognosis, aetiology, and treatment. Lancet Neurol 2003;2:15–21.PubMedCrossRefGoogle Scholar
  54. 54.
    de Leon MJ, Convit A, Wolf OT, Tarshish CY, DeSanti S, Rusinek H. Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-D-glucosey positron-emission tomography (FDG PET). Proc Natl Acad Sci USA 2001;98:10966–71.PubMedCrossRefGoogle Scholar
  55. 55.
    Chetelat G, Landeau B, Eustache F, Mezenge F, Viader F, de la Sayette V, et al. Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: A longitudinal MRI study. NeuroImage 2005;27:934–46.PubMedCrossRefGoogle Scholar
  56. 56.
    Ringman JM, O’Neill J, Geschwind D, Medina L, Apostolova LG, Rodriguez Y, et al. Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer’s disease mutations. Brain 2007;130:1767–76.PubMedCrossRefGoogle Scholar
  57. 57.
    Braak H, Braak E. Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol (Berl) 1996;92:197–201.CrossRefGoogle Scholar
  58. 58.
    Bartzokis G, Sultzer D, Lu PH, Nuechterlein KH, Mintz J, Cummings JL. Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical “disconnection” in aging and Alzheimer’s disease. Neurobiol Aging 2004;25:843–51.PubMedCrossRefGoogle Scholar
  59. 59.
    Cabeza R, Nyberg L. Imaging cognition. II. An empirical review of 275 PET and fMRI studies. J Cogn Neurosci 2000;12:1–47.PubMedCrossRefGoogle Scholar
  60. 60.
    Simic G, Bexheti S, Kelovic Z, Kos M, Grbic K, Hof PR, et al. Hemispheric asymmetry, modular variability and age-related changes in the human entorhinal cortex. Neuroscience 2005;130:911–925.PubMedCrossRefGoogle Scholar
  61. 61.
    Mosconi L, Tsui WH, De Santi S, Li J, Rusinek H, Convit A, et al. Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis. Neurology 2005;64:1860–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Flavio Nobili
    • 1
    • 2
    • 3
    Email author
  • Dario Salmaso
    • 4
    • 5
  • Silvia Morbelli
    • 6
  • Nicola Girtler
    • 1
    • 2
    • 3
  • Arnoldo Piccardo
    • 7
  • Andrea Brugnolo
    • 1
    • 2
    • 3
  • Barbara Dessi
    • 1
    • 2
    • 3
  • Stig A. Larsson
    • 8
  • Guido Rodriguez
    • 1
    • 2
    • 3
  • Marco Pagani
    • 4
    • 5
    • 8
  1. 1.Clinical Neurophysiology, Department of Endocrinological and Medical SciencesUniversity of GenoaGenoaItaly
  2. 2.Alzheimer Evaluation UnitS. Martino HospitalGenoaItaly
  3. 3.Head–Neck DepartmentS. Martino HospitalGenoaItaly
  4. 4.Institute of Cognitive Sciences and TechnologiesCNRRomeItaly
  5. 5.Institute of Cognitive Sciences and TechnologiesCNRPaduaItaly
  6. 6.Nuclear Medicine Unit, Department of Internal MedicineUniversity of GenoaGenoaItaly
  7. 7.Nuclear Medicine Unit, Department of Imaging DiagnosticsGalliera HospitalGenoaItaly
  8. 8.Department of Nuclear MedicineKarolinska HospitalStockholmSweden

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