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Alzheimer's disease and Down's syndrome: an in vivo MRI study

Published online by Cambridge University Press:  30 July 2008

F. Beacher ,
E. Daly ,
A. Simmons ,
V. Prasher ,
R. Morris ,
C. Robinson ,
S. Lovestone ,
K. Murphy  and
D. G. M. Murphy
F. Beacher
Affiliation:
Institute of Psychiatry, King's College, London, UK Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
E. Daly
Affiliation:
Institute of Psychiatry, King's College, London, UK Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
A. Simmons
Affiliation:
Institute of Psychiatry, King's College, London, UK Neuroimaging Research Group, Institute of Psychiatry, King's College, London, UK
V. Prasher
Affiliation:
Greenfields Monyhull Hospital, Kings Norton, Birmingham, UK
R. Morris
Affiliation:
Institute of Psychiatry, King's College, London, UK Department of Psychology, Institute of Psychiatry, King's College, London, UK
C. Robinson
Affiliation:
Greenfields Monyhull Hospital, Kings Norton, Birmingham, UK
S. Lovestone
Affiliation:
Institute of Psychiatry, King's College, London, UK Departments of Old Age Psychiatry and Neuroscience, Institute of Psychiatry, King's College, London, UK
K. Murphy
Affiliation:
Institute of Psychiatry, King's College, London, UK Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK College of Surgeons, Dublin, Ireland
D. G. M. Murphy*
Affiliation:
Institute of Psychiatry, King's College, London, UK Section of Brain Maturation, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK
*
*Address for correspondence: Dr D. G. M. Murphy, P50, Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. (Email: [email protected])
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Abstract

Background

Individuals with Down's syndrome (DS) are at high risk of developing Alzheimer's disease (AD). However, few studies have investigated brain anatomy in DS individuals with AD.

Method

We compared whole brain anatomy, as measured by volumetric magnetic resonance imaging (MRI), in DS individuals with and without AD. We also investigated whether volumetric differences could reliably classify DS individuals according to AD status. We used volumetric MRI and manual tracing to examine regional brain anatomy in 19 DS adults with AD and 39 DS adults without AD.

Results

DS individuals with AD had significantly smaller corrected volumes bilaterally of the hippocampus and caudate, and right amygdala and putamen, and a significantly larger corrected volume of left peripheral cerebrospinal fluid (CSF), compared to DS individuals without AD. The volume of the hippocampus and caudate nucleus correctly categorized 92% and 92% respectively of DS individuals without AD, and 75% and 80% respectively of DS individuals with AD.

Conclusions

DS individuals with AD have significant medial temporal and striatal volume reductions, and these may provide markers of clinical AD.

Keywords

Alzheimer's diseasecaudatedementiadiagnosisDown's syndromehippocampusmagnetic resonance imaging
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 4 , April 2009 , pp. 675 - 684
Copyright
Copyright © 2008 Cambridge University Press

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References

Aylward, EH, Li, Q, Habbak, QR, Warren, A, Pulsifer, MB, Barta, PE, Jerram, M, Pearlson, G (1997). Basal ganglia volume in adults with Down syndrome. Psychiatry Research 74, 73–82.CrossRefGoogle ScholarPubMed
Aylward, EH, Li, Q, Honeycutt, NA, Warren, AC, Pulsifer, MB, Barta, PE, Chan, MD, Smith, PD, Jerram, M, Pearlson, GD (1999). MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia. American Journal of Psychiatry 156, 564–568.CrossRefGoogle ScholarPubMed
Azari, NP, Horwitz, B, Pettigrew, KD, Grady, CL, Haxby, JV, Giacometti, KR, Schapiro, MB (1994). Abnormal pattern of cerebral glucose metabolic rates involving language areas in young adults with Down syndrome. Brain and Language 46, 1–20.CrossRefGoogle ScholarPubMed
Barta, PE, Dhingra, L, Royall, R, Schwartz, E (1997). Improving stereological estimates for the volume of structures identified in three-dimensional arrays of spatial data. Journal of Neuroscience Methods 75, 111–118.CrossRefGoogle ScholarPubMed
Beacher, F, Simmons, A, Daly, E, Prasher, V, Adams, C, Margallo-Lana, ML, Morris, R, Lovestone, S, Murphy, K, Murphy, DG (2005). Hippocampal myo-inositol and cognitive ability in adults with Down syndrome: an in vivo 1H-MRS study. Archives of General Psychiatry 62, 1360–1365.CrossRefGoogle Scholar
Blessed, G, Black, SE, Butler, T, Kay, DW (1991). The diagnosis of dementia in the elderly. A comparison of CAMCOG (the cognitive section of CAMDEX), the AGECAT program, DSM-III, the Mini-Mental State Examination and some short rating scales. British Journal of Psychiatry 159, 193–198.CrossRefGoogle ScholarPubMed
Busatto, GF, Garrido, GE, Almeida, OP, Castro, CC, Camargo, CH, Cid, CG, Buchpiguel, CA, Furuie, S, Bottino, CM (2003). A voxel-based morphometry study of temporal lobe gray matter reductions in Alzheimer's disease. Neurobiology of Aging 24, 221–231.CrossRefGoogle ScholarPubMed
Deb, S, Hare, M, Prior, L, Bhaumik, S (2007). Dementia screening questionnaire for individuals with intellectual disabilities. British Journal of Psychiatry 190, 440–444.CrossRefGoogle ScholarPubMed
Double, KL, Halliday, GM, Kril, JJ, Harasty, JA, Cullen, K, Brooks, WS, Creasey, H, Broe, GA (1996). Topography of brain atrophy during normal ageing and AD. Neurobiology of Aging 17, 513–521.CrossRefGoogle Scholar
Folin, M, Baiguera, S, Conconi, MT, Pati, T, Grandi, C, Parnigotto, PP, Nussdorfer, GG (2003). The impact of risk factors of Alzheimer's disease in the Down syndrome. International Journal of Molecular Medicine 11, 267–270.Google ScholarPubMed
Frisoni, GB, Testa, C, Zorzan, A, Sabattoli, F, Beltramello, A, Soininen, H, Laakso, MP (2002). Detection of grey matter loss in mild Alzheimer's disease with voxel based morphometry. Journal of Neurology, Neurosurgery and Psychiatry 73, 657–664.CrossRefGoogle ScholarPubMed
Hof, PR, Bouras, C, Perl, DP, Sparks, DL, Mehta, N, Morrison, JH (1995). Age-related distribution of neuropathologic changes in the cerebral cortex of patients with Down's syndrome. Archives of Neurology 52, 379–391.CrossRefGoogle ScholarPubMed
Hon, J, Huppert, FA, Holland, AJ, Watson, P (1999). Neuropsychological assessment of older adults with Down's syndrome: an epidemiological study using the Cambridge Cognitive Examination (CAMCOG). British Journal of Clinical Psychology 38, 155–165.CrossRefGoogle ScholarPubMed
Huppert, FA, Brayne, C, Gill, C, Paykel, ES, Beardsall, L (1995). CAMCOG – a concise neuropsychological test to assist dementia diagnosis: socio-demographic determinants in an elderly population sample. British Journal of Clinical Psychology 34, 529–541.CrossRefGoogle Scholar
Hyman, BT, Van Hoesen, GW, Damasio, AR (1990). Memory-related neural systems in Alzheimer's disease: an anatomic study. Neurology 40, 1721–1730.CrossRefGoogle ScholarPubMed
Karas, GB, Burton, EJ, Rombouts, SA, van Schijndel, RA, O'Brien, JT, Scheltens, P, McKeith, IG, Williams, D, Ballard, C, Barkhof, F (2003). A comprehensive study of gray matter loss in patients with Alzheimer's disease using optimized voxel-based morphometry. NeuroImage 18, 895–907.CrossRefGoogle ScholarPubMed
Kesslak, JP, Nagata, SF, Lott, I, Nalcioglu, O (1994). MRI analysis of age-related changes in the brains of individuals with DS. Neurology 44, 1039–1045.CrossRefGoogle Scholar
Krasuski, JS, Alexander, GE, Horwitz, B, Rapoport, SI, Schapiro, MB (2002). Relation of medial temporal volumes to age and memory function in nondemented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease. American Journal of Psychiatry 159, 74–81.CrossRefGoogle ScholarPubMed
Laakso, MP, Partanen, K, Riekkinen, P, Lehtovirta, M, Helkala, EL, Hallikainen, M, Hanninen, T, Vainio, P, Soininen, H (1996). Hippocampal volumes in Alzheimer's disease, Parkinson's disease with and without dementia, and in vascular dementia: an MRI study. Neurology 46, 678–681.CrossRefGoogle ScholarPubMed
Malamud, N (1972). Neuropathy of organic brain syndromes associated with ageing. In Advances in Behavioural Biology (ed. Gaitz, C. M.), pp. 63–87. Plenum Press: New York.Google Scholar
Marsden, CD (1982). The mysterious motor function of the basal ganglia: the Robert Wartenburge lecture. Neurology 32, 514–539.CrossRefGoogle ScholarPubMed
Miniszek, NA (1983). Development of Alzheimer disease in Down syndrome individuals. American Journal of Mental Deficiency 87, 377–385.Google ScholarPubMed
Murphy, DG, DeCarli, C, McIntosh, AR, Daly, E, Mentis, MJ, Pietrini, P, Szczepanik, J, Schapiro, MB, Grady, CL, Horwitz, B, Rapoport, SI (1996). Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonanceimaging and positron emission tomography study on the effect of ageing. Archives of General Psychiatry 53, 585–594.CrossRefGoogle Scholar
Packard, MG, Knowlton, BJ (2002). Learning and memory functions of the basal ganglia. Annual Review of Neuroscience 25, 563–593.CrossRefGoogle ScholarPubMed
Pearlson, GD, Breiter, SN, Aylward, EH, Warren, AC, Grygorcewicz, M, Frangou, S, Barta, PE, Pulsifer, MB (1998). MRI brain changes in subjects with Down syndrome with and without dementia. Developmental Medicine and Child Neurology 40, 326–334.Google ScholarPubMed
Pennanen, C, Kivipelto, M, Tuomainen, S, Hartikainen, P, Hänninen, T, Laakso, MP, Hallikainen, M, Vanhanen, M, Nissinen, A, Helkala, EL, Vainio, P, Vanninen, R, Partanen, K, Soininen, H (2004). Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiology of Aging 25, 303–310.CrossRefGoogle ScholarPubMed
Poldrack, RA, Prabhakaran, V, Seger, CA, Gabrieli, JD (1999). Striatal activation during acquisition of cognitive skill. Neuropsychology 13, 564–574.CrossRefGoogle ScholarPubMed
Prasher, VP, Farrer, MJ, Kessling, AM, Fisher, EM, West, RJ, Barber, PC, Butler, AC (1998). Molecular mapping of Alzheimer-type dementia in Down's syndrome. Annals of Neurology 43, 380–383.CrossRefGoogle ScholarPubMed
Prasher, V, Cumella, S, Natarajan, K, Rolfe, E, Shah, S, Haque, MS (2003). Magnetic resonance imaging, Down's syndrome and Alzheimer's disease: research and clinical implications. Journal of Intellectual Disabilities Research 47, 90–100.CrossRefGoogle ScholarPubMed
Raz, N, Torres, IJ, Briggs, SD, Spencer, WD, Thornton, AE, Loken, WJ, Gunning, FM, McQuain, JD, Driesen, NR, Acker, JD (1995). Selective neuroanatomical abnormalities in Down's syndrome and their cognitive correlates: evidence from MRI morphometry. Neurology 45, 356–366.CrossRefGoogle ScholarPubMed
Roizen, NJ, Patterson, D (2003). Down's syndrome. Lancet 361, 1281–1289.CrossRefGoogle ScholarPubMed
Rombouts, SA, Barkhof, F, Witter, MP, Scheltens, P (2000). Unbiased whole-brain analysis of gray matter loss in Alzheimer's disease. Neuroscience Letters 285, 231–233.CrossRefGoogle ScholarPubMed
Roth, M, Huppert, FA, Mountjoy, CQ, Tym, E (1998). The Revised Cambridge Examination for Mental Disorders of the Elderly. Cambridge University Press: Cambridge.Google Scholar
Simmons, A, Arridge, SR, Barker, GJ, Williams, SC (1996). Simulation of MRI cluster plots and application to neurological segmentation. Magnetic Resonance Imaging 14, 73–92.CrossRefGoogle ScholarPubMed
Squire, LR, Stark, CE, Clark, RE (2004). The medial temporal lobe. Annual Review of Neuroscience 27, 279–306.CrossRefGoogle ScholarPubMed
Sullivan, EV, Marsh, L, Mathalon, DH, Lim, KO, Pfefferbaum, A (1995). Age-related decline in MRI volumes of temporal lobe gray matter but not hippocampus. Neurobiology of Aging 16, 591–606.CrossRefGoogle Scholar
Teipel, SJ, Schapiro, MB, Alexander, GE, Krasuski, JS, Horwitz, B, Hoehne, C, Möller, HJ, Rapoport, SI, Hampel, H (2003). Relation of corpus callosum and hippocampal size to age in nondemented adults with Down's syndrome. American Journal of Psychiatry 160, 1870–1878.CrossRefGoogle ScholarPubMed
Teipel, SJ, Alexander, GE, Schapiro, MB, Möller, HJ, Rapoport, SI, Hampel, H (2004). Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry. Brain 127, 811–824.CrossRefGoogle ScholarPubMed
Tranel, D, Hyman, BT (1990). Neuropsychological correlates of bilateral amygdala damage. Archives of Neurology 47, 349–355.CrossRefGoogle ScholarPubMed
Visser, FE, Aldenkamp, AP, van Huffelen, AC, Kuilman, M, Overweg, J, van Wijk, J (1997). Prospective study of the Alzheimer-type dementia in institutionalized individuals with Down syndrome. American Journal of Mental Retardation 101, 400–412.Google ScholarPubMed
Wisniewski, KE, Wisniewski, HM, Wen, GY (1985). Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Annals of Neurology 17, 278–282.CrossRefGoogle ScholarPubMed
WHO (1992). The ICD-10 Classification of Mental and Behavioural Disorders. Clinical Descriptions and Diagnostic Guidelines. World Health Organization: Geneva.Google Scholar
Yamaguchi, S, Meguro, K, Shimada, M, Ishizaki, J, Yamadori, A, Sekita, Y (2002). Five-year retrospective changes in hippocampal atrophy and cognitive screening test performances in very mild Alzheimer's disease: the Tajiri Project. Neuroradiology 44, 43–48.CrossRefGoogle ScholarPubMed