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Vol. 26, No. 4, 2008
Issue release date: October 2008
Dement Geriatr Cogn Disord 2008;26:314–322

Multi-Center Comparison of Medial Temporal Atrophy in Patients with Alzheimer’s Disease – Data from the ICTUS Study

Galluzzi S. · Talassi E. · Belussi M. · Scheltens P. · van de Pol L. · Nobili F. · Rodriguez G. · Froelich L. · Damian M. · Martinez-Lage P. · Gomez-Isla T. · Reynish E. · Ousset P.J. · Vellas B. · Frisoni G.B.
aLENITEM Laboratory of Epidemiology, Neuroimaging and Telemedicine and bPsychogeriatric Unit, IRCCS Centro S. Giovanni di Dio Fatebenefratelli, Brescia, cAfaR, Associazione Fatebenefratelli per la Ricerca, Rome, Italy; dAlzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands; eClinical Neurophysiology, Department of Endocrinological and Medical Sciences, University of Genoa, Italy; fDivision of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; gMemory Disturbances Unit, Neurology Department and hDepartment of Neurology and Neurosurgery, University Hospital of Navarra, University of Navarra, Pamplona, Spain; iInserm, U558, jUniversity Toulouse III, and kDepartment of Internal Medicine and Clinical Gerontology, Toulouse University Hospital, Toulouse, France

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Objective: To study multi-center variability of medial temporal lobe atrophy (MTA) in patients with Alzheimer’s disease (AD) recruited in a European observational study of AD. Methods: 117 mild to moderate AD patients from 5 European centers (Amsterdam, The Netherlands; Brescia and Genova, Italy; Mannheim, Germany; Pamplona, Spain) had magnetic resonance imaging scans performed as part of the routine diagnostic examination. MTA was assessed with the visual Scheltens scale. Results: AD patients from Brescia, Genova, Pamplona, and Mannheim had a mean 32% prevalence of no or borderline MTA vs. 62% of patients from Amsterdam (p = 0.002 for the difference between Amsterdam and all the other centers). The peculiar distribution of MTA in the Amsterdam patients may be attributable to younger age (70.7 ± 8.4 vs. 75.3 ± 6.8 years, p = 0.002), milder dementia severity (score 0.5 on the clinical dementia rating scale: 52 vs. 23%, p = 0.003), and less frequent depression (14 vs. 49%, p < 0.0005 in Amsterdam vs. all the other centers, respectively). Conclusion: Patients with probable AD recruited in different centers of Europe generally have similar MTA distribution, even if peculiar demographic and clinical findings might explain occasional differences. These results have implications for clinical trials in AD with biological markers as outcome measures.

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  1. Practice parameter for diagnosis and evaluation of dementia: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1994;44:2203–2206.
  2. Scheltens P, Fox N, Barkhof F, DeCarli C: Structural magnetic resonance imaging in the practical assessment of dementia: beyond exclusion. Lancet Neurol 2002;1:13–21.
  3. Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O’Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P: Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734–746.
  4. Jack CR Jr, Petersen RC, Xu YC, Waring SC, O’Brien PC, Tangalos EG, Smith GE, Ivnik RJ, Kokmen E: Medial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease. Neurology 1997;49:786–794.
  5. Scheltens P: Structural neuroimagings of Alzheimer’s disease and other dementias. Aging (Milano) 2001;13:203–209.
  6. Frisoni GB, Geroldi C, Beltramello A, Bianchetti A, Binetti G, Bordiga G, DeCarli C, Laakso MP, Soininen H, Testa C, Zanetti O, Trabucchi M: Radial width of the temporal horn: a sensitive measure in Alzheimer disease. Am J Neuroradiol 2002;23:35–47.
  7. Ashburner J, Csernansky JG, Davatzikos C, Fox NC, Frisoni GB, Thompson PM: Computer-assisted imaging to assess brain structure in healthy and diseased brains. Lancet Neurol 2003;2:79–88.
  8. Wang L, Swank JS, Glick IE, Gado MH, Miller MI, Morris JC, Csernansky JG: Changes in hippocampal volume and shape across time distinguish dementia of the Alzheimer type from healthy aging. Neuroimage 2003;20:667–682.
  9. Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, Kuiper M, Steinling M, Wolters EC, Valk J: 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;55:967–972.
  10. Bresciani L, Rossi R, Testa C, Geroldi C, Galluzzi S, Laakso MP, Beltramello A, Soininen H, Frisoni GB: Visual assessment of medial temporal atrophy on MR films in Alzheimer’s disease: comparison with volumetry. Aging Clin Exp Res 2005;17:8–13.
  11. Wahlund LO, Julin P, Johansson SE, Scheltens P: Visual rating and volumetry of the medial temporal lobe on magnetic resonance imaging in dementia: a comparative study. J Neurol Neurosurg Psychiatry 2000;69:630–635.
  12. Geroldi C, Rossi R, Calvagna C, Testa C, Bresciani L, Binetti G, Zanetti O, Frisoni GB: Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment. J Neurol Neurosurg Psychiatry 2006:77:1219–1222.
  13. DeCarli C, Frisoni GB, Clark CM, Harvey D, Grundman M, Petersen RC, Thal LJ, Jin S, Jack CR Jr, Scheltens P; Alzheimer’s Disease Cooperative Study Group: qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia. Arch Neurol 2007;64:108–115.
  14. Csernansky JG, Wang L, Miller JP, Galvin JE, Morris JC: Neuroanatomical predictors of response to donepezil therapy in patients with dementia. Arch Neurol 2005;62:1718–1722.
  15. Reynish E, Cortes F, Andrieu S, Cantet C, Olde Rikkert M, Melis R, Froelich L, Frisoni GB, Jönsson L, Visser PJ, Ousset PJ, Vellas B, ICTUS Study Group: The ICTUS study: a prospective longitudinal observational study of 1,380 AD patients in Europe. Study design and baseline characteristics of the cohort. Neuroepidemiology 2007;29:29–38.
  16. 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;34:939–944.
  17. 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;12:189–198.
  18. Rosen WG, Mohs RC, Davis KL: A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984;141:1356–1364.
  19. Morris JC: The clinical dementia rating: current version and scoring rules. Neurology 1993;43:2412–2414.
  20. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J: The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–2314.
  21. Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjögren M, Wallin A, Ader H, Leys D, Pantoni L, Pasquier F, Erkinjuntti T, Scheltens P; European Task Force on Age-Related White Matter Changes: a new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001;32:1318–1322.
  22. Frisoni GB, Testa C, Sabattoli F, Beltramello A, Soininen H, Laakso MP: Structural correlates of early and late onset Alzheimer’s disease: voxel-based morphometric study. J Neurol Neurosurg Psychiatry 2005;76:112–114.
  23. Shiino A, Watanabe T, Maeda K, Kotani E, Akiguchi I, Matsuda M: Four subgroups of Alzheimer’s disease based on patterns of atrophy using VBM and a unique pattern for early onset disease. Neuroimage 2006;33:17–26.
  24. Kemp PM, Holmes C, Hoffmann SMA, Bolt L, Holmes R, Rowden J, Fleming JS: Alzheimer’s disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia. J Neurol Neurosurg Psychiatry 2003;74:715–719.
  25. Lehtovirta M, Laasko MP, Soininen H, Helisalmi S, Mannermaa A, Helkala EL, Partanen K, Ryynänen M, Vainio P, Hartikainen P: Volumes of hippocampus, amygdale and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes. Neuroscience 1995;67:65–72.
  26. Van der Flier WM, Schoonenboom SN, Pijnenburg YA, Fox NP, Scheltens P: The effect of ApoE genotype on clinical phenotype in Alzheimer disease. Neurology 2006;67:526–527.
  27. Schott JM, Ridha BH, Crutch SJ, Healy DG, Uphill JB, Warrington EK, Rossor MN, Fox NC: Apolipoprotein ε genotype modifies the phenotype of Alzheimer disease. Arch Neurol 2006;63:155–156.
  28. Chui HC, Teng EL, Henderson VW, Moy AC: Clinical subtypes of dementia of the Alzheimer type. Neurology 1985;35:1544–1550.
  29. Janssen J, Hulshoff Pol HE, de Leeuw F-E, Schnack HG, Lampe IK, Kok RM, Kahn RS, Heeren TJ: Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression. J Neurol Neurosurg Psychiatry 2007;78:638–640.
  30. Hickie I, Naismith S, Ward PB, Turner K, Scott E, Mitchell P, Wilhelm K, Parker G: Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression. Br J Psychiatry 2005;186:197–202.
  31. Lee AL, Ogle WO, Sapolsky RM: Stress and depression: possible links to neuron death in the hippocampus. Bipolar Disord 2002;4:117–128.
  32. Sala M, Perez J, Soloff P, Ucelli di Nemi S, Caverzasi E, Soares JC, Brambilla P: Stress and hippocampal abnormalities in psychiatric disorders. Eur Neuropsychopharmacol 2004;14:393–405.
  33. Rapp MA, Schnaider-Beeri M, Grossman HT, Sano M, Perl DP, Purohit DP, Gorman JM, Haroutunian V: Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression. Arch Gen Psychiatry 2006;63:161–167.
  34. Greenwald BS, Kramer-Ginsberg E, Bogerts B, Ashtari M, Aupperle P, Wu H, Allen L, Zeman D, Patel M: Qualitative magnetic resonance imaging findings in geriatric depression. Possible link between later-onset depression and Alzheimer’s disease? Psychol Med 1997;27:421–431.
  35. Stern Y: Cognitive reserve and Alzheimer disease. Alzheimer Dis Assoc Disord 2006;20:112–117.
  36. Stern Y, Alexander GE, Prohovnik I, Mayeux R: Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer’s disease. Ann Neurol 1992;32:371–375.
  37. Stern Y, Alexander GE, Prohovnik I, Stricks L, Link B, Lennon MC, Mayeux R: Relationship between lifetime occupation and parietal flow: implications for a reserve against Alzheimer’s disease pathology. Neurology 1995;45:55–60.
  38. Alexander GE, Furey ML, Grady CL, Pietrini P, Brady DR, Mentis MJ, Schapiro MB: Association of premorbid intellectual function with cerebral metabolism in Alzheimer’s disease: implications for the cognitive reserve hypothesis. Am J Psychiatry 1997;154:165–172.
  39. Nagy Z, Esiri MM, Hindley NJ, Joachim C, Morris JH, King EM, McDonald B, Litchfield S, Barnetson L, Jobst KA, Smith AD: Accuracy of clinical operational diagnostic criteria for Alzheimer’s disease in relation to different pathological diagnostic protocols. Dement Geriatr Cogn Disord 1998;9:219–226.
  40. Varma AR, Snowden JS, Lloyd JJ, Talbot PR, Mann DM, Neary D: Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer’s disease and frontotemporal dementia. J Neurol Neurosurg Psychiatry 1999;66:184–188.
  41. Riekkinen P Jr, Soininen H, Helkala EL, Partanen K, Laakso M, Vanhanen M, Riekkinen P: Hippocampal atrophy, acute THA treatment and memory in Alzheimer’s disease. Neuroreport 1995;6:1297–1300.
  42. Jack CR Jr, Lowe VJ, Senjem ML, Weigand SD, Kemp BJ, Shiung MM, Knopman DS, Boeve BF, Klunk WE, Mathis CA, Petersen RC: 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain 2008;131:665–680.

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