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Vol. 20, No. 4, 2005
Issue release date: September 2005
Section title: Original Research Article
Dement Geriatr Cogn Disord 2005;20:238–244
(DOI:10.1159/000087343)

A Volumetric Magnetic Resonance Imaging Study of the Amygdala in Frontotemporal Lobar Degeneration and Alzheimer’s Disease

Whitwell J.L.a, b · Sampson E.L.a, c · Watt H.C.a, d · Harvey R.J.a, e · Rossor M.N.a, f · Fox N.C.a
aDementia Research Centre, Institute of Neurology, University College London, London, UK; bDepartment of Diagnostic Radiology, Mayo Clinic, Rochester, Minn., USA; cDepartment of Mental Health Sciences, Royal Free and University College Medical School, London, UK; dMedical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK; eDepartment of Clinical and Biomedical Science, University of Melbourne, Melbourne, Australia; fDivision of Neuroscience and Psychological Medicine, Imperial College London, London, UK
email Corresponding Author

Abstract

The amygdala is severely atrophied at post-mortem in frontotemporal lobar degeneration (FTLD), and may contribute to the prominent behavioural changes that are early features of FTLD. The aim of this study was to assess amygdala atrophy using MRI in the main syndromic variants of FTLD and Alzheimer’s disease (AD). Brain and amygdala volumes, adjusted for intracranial volume, were measured on 46 clinically diagnosed FTLD patients [22 frontal variant FTD (FTD), 14 semantic dementia (SD), 10 progressive non-fluent aphasia (PNFA)], 20 AD patients, and 17 controls. While severe amygdala atrophy was present in both FTLD (41% smaller than controls on the left; 33% on the right) and in AD (22% on the left; 19% on the right), the FTLD group had significantly greater amygdala atrophy (z = 3.21, p = 0.001 left, z = 2.50, p = 0.01 right) and left/right asymmetry (z = 2.03, p = 0.04) than AD. Amygdala atrophy was greater in SD than FTD, PNFA and AD (p < 0.02 for all). Highly asymmetrical atrophy was present in SD, greater on the left (z = 3.23, p = 0.001), and to a lesser extent in PNFA. Despite an overlap between clinical and radiological features of FTLD and AD, marked amygdala atrophy points towards a diagnosis of FTLD, with left greater than right atrophy suggestive of one of the language variants.

© 2005 S. Karger AG, Basel


  

Key Words

  • Magnetic resonance imaging
  • Amygdala
  • Frontotemporal lobar degeneration
  • Alzheimer’s disease

References

  1. Harvey RJ, Skelton-Robinson M, Rossor MN: The prevalence and causes of dementia in people under the age of 65 years. J Neurol Neurosurg Psychiatry 2003;74:1206–1209.
  2. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF: Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546–1554.
  3. Cummings JL, Duchen LW: Kluver-Bucy syndrome in Pick disease: clinical and pathologic correlations. Neurology 1981;31:1415–1422.
  4. Tranel D, Hyman BT: Neuropsychological correlates of bilateral amygdala damage. Arch Neurol 1990;47:349–355.
  5. Snowden JS, Bathgate D, Varma A, Blackshaw A, Gibbons ZC, Neary D: Distinct behavioural profiles in frontotemporal dementia and semantic dementia. J Neurol Neurosurg Psychiatry 2001;70:323–332.
  6. Rosen H, Perry R, Murphy J, Kramer JH, Mychack P, Schuff N, Weiner M, Levenson RW, Miller BL: Emotion comprehension in the temporal variant of frontotemporal dementia. Brain 2002;125:2286–2295.
  7. Mummery CJ, Patterson K, Price CJ, Ashburner J, Frackowiak RSJ, Hodges JR: A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory. Ann Neurol 2000;47:36–45.
  8. Chan D, Fox NC, Scahill RI, Crum WR, Whitwell J, Leschziner G, Rossor AM, Stevens JM, Cipolotti L, Rossor MN: Patterns of temporal lobe atrophy in semantic dementia and Alzheimer’s disease. Ann Neurol 2001;49:433–442.
  9. Galton CJ, Patterson K, Graham KS, Lambon-Ralph MA, Williams G, Antoun N, Sahakian BJ, Hodges JR: Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia. Neurology 2001;57:216–225.
  10. Rosen HJ, Gorno-Tempini ML, Goldman WP, Perry R, Schuff N, Weiner M, Feiwell R, Kramer JH, Miller BL: Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002;58:198–208.
  11. Boccardi M, Pennanen C, Laakso M, Testa C, Geroldi C, Soininen H, Frisoni GB: Amygdaloid atrophy in frontotemporal dementia and Alzheimer’s disease. Neurosci Lett 2002;335:139–143.
  12. Dickson DW: Neuropathology of Pick’s disease. Neurology 2001;56(suppl 4):S16–S20.
  13. Burns A, Jacoby R, Levy R: Psychiatric phenomena in Alzheimer’s disease. IV. Disorders of behaviour. Br J Psychiatry 1990;157:86–94.
  14. Cuenod CA, Denys A, Michot JL, Jehenson P, Forette F, Kaplan D, Syrota A, Boller F: Amygdala atrophy in Alzheimer’s disease: an in vivo magnetic resonance imaging study. Arch Neurol 1993;50:941–945.
  15. Laakso MP, Partanen K, Lehtovirta M, Hallikainen M, Hanninen T, Vainio P, Riekkinen P Sr, Soininen H: MRI of amygdala fails to diagnose early Alzheimer’s disease. Neuroreport 1995;27:2414–2418.
  16. Folstein M, Folstein S, McHughs P: The ‘Mini mental state’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  17. 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.
  18. Freeborough PA, Fox NC, Kitney RI: Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. Comput Methods Programs Biomed 1997;53:15–25.
  19. Whitwell JL, Crum WR, Watt HC, Fox NC: Normalization of cerebral volumes by use of intracranial volume: implications for longitudinal quantitative MR imaging. Am J Neuroradiol 2001;22:1483–1489.
  20. Laakso MP, Soininen H, Partanen K, Helkala EL, Hartikainen P, Vainio P, Hallikainen M, Hanninen T, Riekkinen PJ: Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer’s disease: correlation with memory functions. J Neural Transm 1995;9:73–86.
  21. Abe K, Ukita H, Yanagihara T: Imaging in primary progressive aphasia. Neuroradiology 1997;39:556–559.
  22. Rosen HJ, Kramer JH, Gorno-Tempini ML, Schuff N, Weiner M, Miller B: Patterns of cerebral atrophy in primary progressive aphasia. Am J Geriatr Psychiatry 2002;10:89–97.
  23. Turner RS, Kenyon LC, Trojanowski JQ, Gonatas N, Grossman M: Clinical, neuroimaging, and pathologic features of progressive nonfluent aphasia. Ann Neurology 1996;39:166–173.
  24. Adolphs R, Tranel D, Damasio H, Damasio A: Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature 1994;372:669–672.
  25. Bozeat S, Gregory CA, Ralph MA, Hodges JR: Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer’s disease? J Neurol Neurosurg Psychiatry 2000;69:178–186.
  26. Thompson SA, Patterson K, Hodges JR: Left/right asymmetry of atrophy in semantic dementia: behavioral-cognitive implications. Neurology 2003;61:1196–1203.
  27. Lui W, Miller BL, Kramer JH, Rankin K, Wyss-Coray C, Gearhart R, Phengrasamy L, Weiner M, Rosen HJ: Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology 2004;62:742–748.

    External Resources

  28. Boxer A, Rankin K, Miller B, Schuff N, Weiner M, Gorno-Tempini ML, Rosen HJ: Cinguloparietal atrophy distinguishes Alzheimer disease from semantic dementia. Arch Neurol 2003;60:949–956.
  29. Boccardi M, Laakso MP, Bresciani L, Galluzzi S, Geroldi C, Beltramello A, Soininen H, Frisoni GB: The MRI pattern of frontal and temporal brain atrophy in fronto-temporal dementia. Neurobiol Aging 2003;24:95–103.

  

Author Contacts

Prof. Nick Fox
Dementia Research Centre, National Hospital for Neurology and Neurosurgery
8–11 Queen Square, London WC1N 3BG (UK)
Tel. +44 207 829 8773, Fax +44 207 676 2066
E-Mail nfox@dementia.ion.ucl.ac.uk

  

Article Information

Accepted: June 2, 2005
Published online: August 5, 2005
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 3, Number of References : 29

  

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 20, No. 4, Year 2005 (Cover Date: Released September 2005)

Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420–8008 (print), 1421–9824 (Online)

For additional information: http://www.karger.com/dem


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

The amygdala is severely atrophied at post-mortem in frontotemporal lobar degeneration (FTLD), and may contribute to the prominent behavioural changes that are early features of FTLD. The aim of this study was to assess amygdala atrophy using MRI in the main syndromic variants of FTLD and Alzheimer’s disease (AD). Brain and amygdala volumes, adjusted for intracranial volume, were measured on 46 clinically diagnosed FTLD patients [22 frontal variant FTD (FTD), 14 semantic dementia (SD), 10 progressive non-fluent aphasia (PNFA)], 20 AD patients, and 17 controls. While severe amygdala atrophy was present in both FTLD (41% smaller than controls on the left; 33% on the right) and in AD (22% on the left; 19% on the right), the FTLD group had significantly greater amygdala atrophy (z = 3.21, p = 0.001 left, z = 2.50, p = 0.01 right) and left/right asymmetry (z = 2.03, p = 0.04) than AD. Amygdala atrophy was greater in SD than FTD, PNFA and AD (p < 0.02 for all). Highly asymmetrical atrophy was present in SD, greater on the left (z = 3.23, p = 0.001), and to a lesser extent in PNFA. Despite an overlap between clinical and radiological features of FTLD and AD, marked amygdala atrophy points towards a diagnosis of FTLD, with left greater than right atrophy suggestive of one of the language variants.

© 2005 S. Karger AG, Basel


  

Author Contacts

Prof. Nick Fox
Dementia Research Centre, National Hospital for Neurology and Neurosurgery
8–11 Queen Square, London WC1N 3BG (UK)
Tel. +44 207 829 8773, Fax +44 207 676 2066
E-Mail nfox@dementia.ion.ucl.ac.uk

  

Article Information

Accepted: June 2, 2005
Published online: August 5, 2005
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 3, Number of References : 29

  

Publication Details

Dementia and Geriatric Cognitive Disorders

Vol. 20, No. 4, Year 2005 (Cover Date: Released September 2005)

Journal Editor: Chan-Palay, V. (New York, N.Y.)
ISSN: 1420–8008 (print), 1421–9824 (Online)

For additional information: http://www.karger.com/dem


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Received: 6/2/2005
Published online: 9/12/2005
Issue release date: September 2005

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 3

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Harvey RJ, Skelton-Robinson M, Rossor MN: The prevalence and causes of dementia in people under the age of 65 years. J Neurol Neurosurg Psychiatry 2003;74:1206–1209.
  2. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF: Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546–1554.
  3. Cummings JL, Duchen LW: Kluver-Bucy syndrome in Pick disease: clinical and pathologic correlations. Neurology 1981;31:1415–1422.
  4. Tranel D, Hyman BT: Neuropsychological correlates of bilateral amygdala damage. Arch Neurol 1990;47:349–355.
  5. Snowden JS, Bathgate D, Varma A, Blackshaw A, Gibbons ZC, Neary D: Distinct behavioural profiles in frontotemporal dementia and semantic dementia. J Neurol Neurosurg Psychiatry 2001;70:323–332.
  6. Rosen H, Perry R, Murphy J, Kramer JH, Mychack P, Schuff N, Weiner M, Levenson RW, Miller BL: Emotion comprehension in the temporal variant of frontotemporal dementia. Brain 2002;125:2286–2295.
  7. Mummery CJ, Patterson K, Price CJ, Ashburner J, Frackowiak RSJ, Hodges JR: A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory. Ann Neurol 2000;47:36–45.
  8. Chan D, Fox NC, Scahill RI, Crum WR, Whitwell J, Leschziner G, Rossor AM, Stevens JM, Cipolotti L, Rossor MN: Patterns of temporal lobe atrophy in semantic dementia and Alzheimer’s disease. Ann Neurol 2001;49:433–442.
  9. Galton CJ, Patterson K, Graham KS, Lambon-Ralph MA, Williams G, Antoun N, Sahakian BJ, Hodges JR: Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia. Neurology 2001;57:216–225.
  10. Rosen HJ, Gorno-Tempini ML, Goldman WP, Perry R, Schuff N, Weiner M, Feiwell R, Kramer JH, Miller BL: Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002;58:198–208.
  11. Boccardi M, Pennanen C, Laakso M, Testa C, Geroldi C, Soininen H, Frisoni GB: Amygdaloid atrophy in frontotemporal dementia and Alzheimer’s disease. Neurosci Lett 2002;335:139–143.
  12. Dickson DW: Neuropathology of Pick’s disease. Neurology 2001;56(suppl 4):S16–S20.
  13. Burns A, Jacoby R, Levy R: Psychiatric phenomena in Alzheimer’s disease. IV. Disorders of behaviour. Br J Psychiatry 1990;157:86–94.
  14. Cuenod CA, Denys A, Michot JL, Jehenson P, Forette F, Kaplan D, Syrota A, Boller F: Amygdala atrophy in Alzheimer’s disease: an in vivo magnetic resonance imaging study. Arch Neurol 1993;50:941–945.
  15. Laakso MP, Partanen K, Lehtovirta M, Hallikainen M, Hanninen T, Vainio P, Riekkinen P Sr, Soininen H: MRI of amygdala fails to diagnose early Alzheimer’s disease. Neuroreport 1995;27:2414–2418.
  16. Folstein M, Folstein S, McHughs P: The ‘Mini mental state’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  17. 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.
  18. Freeborough PA, Fox NC, Kitney RI: Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. Comput Methods Programs Biomed 1997;53:15–25.
  19. Whitwell JL, Crum WR, Watt HC, Fox NC: Normalization of cerebral volumes by use of intracranial volume: implications for longitudinal quantitative MR imaging. Am J Neuroradiol 2001;22:1483–1489.
  20. Laakso MP, Soininen H, Partanen K, Helkala EL, Hartikainen P, Vainio P, Hallikainen M, Hanninen T, Riekkinen PJ: Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer’s disease: correlation with memory functions. J Neural Transm 1995;9:73–86.
  21. Abe K, Ukita H, Yanagihara T: Imaging in primary progressive aphasia. Neuroradiology 1997;39:556–559.
  22. Rosen HJ, Kramer JH, Gorno-Tempini ML, Schuff N, Weiner M, Miller B: Patterns of cerebral atrophy in primary progressive aphasia. Am J Geriatr Psychiatry 2002;10:89–97.
  23. Turner RS, Kenyon LC, Trojanowski JQ, Gonatas N, Grossman M: Clinical, neuroimaging, and pathologic features of progressive nonfluent aphasia. Ann Neurology 1996;39:166–173.
  24. Adolphs R, Tranel D, Damasio H, Damasio A: Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature 1994;372:669–672.
  25. Bozeat S, Gregory CA, Ralph MA, Hodges JR: Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer’s disease? J Neurol Neurosurg Psychiatry 2000;69:178–186.
  26. Thompson SA, Patterson K, Hodges JR: Left/right asymmetry of atrophy in semantic dementia: behavioral-cognitive implications. Neurology 2003;61:1196–1203.
  27. Lui W, Miller BL, Kramer JH, Rankin K, Wyss-Coray C, Gearhart R, Phengrasamy L, Weiner M, Rosen HJ: Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology 2004;62:742–748.

    External Resources

  28. Boxer A, Rankin K, Miller B, Schuff N, Weiner M, Gorno-Tempini ML, Rosen HJ: Cinguloparietal atrophy distinguishes Alzheimer disease from semantic dementia. Arch Neurol 2003;60:949–956.
  29. Boccardi M, Laakso MP, Bresciani L, Galluzzi S, Geroldi C, Beltramello A, Soininen H, Frisoni GB: The MRI pattern of frontal and temporal brain atrophy in fronto-temporal dementia. Neurobiol Aging 2003;24:95–103.