title: Why looking at the whole hippocampus is not enough-a critical role for anteroposterior axis, subfield and activation analyses to enhance predictive value of hippocampal changes for Alzheimer's disease diagnosis.
abstract: The hippocampus is one of the earliest affected brain regions in Alzheimer's disease (AD) and its dysfunction is believed to underlie the core feature of the disease-memory impairment. Given that hippocampal volume is one of the best AD biomarkers, our review focuses on distinct subfields within the hippocampus, pinpointing regions that might enhance the predictive value of current diagnostic methods. Our review presents how changes in hippocampal volume, shape, symmetry and activation are reflected by cognitive impairment and how they are linked with neurogenesis alterations. Moreover, we revisit the functional differentiation along the anteroposterior longitudinal axis of the hippocampus and discuss its relevance for AD diagnosis. Finally, we indicate that apart from hippocampal subfield volumetry, the characteristic pattern of hippocampal hyperactivation associated with seizures and neurogenesis changes is another promising candidate for an early AD biomarker that could become also a target for early interventions.
authors.affiliation: Centre for the Cellular Basis of Behaviour, Department of Neuroscience, Institute of Psychiatry, King's College London London, UK.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Maruszak
authors.affiliation: Centre for the Cellular Basis of Behaviour, Department of Neuroscience, Institute of Psychiatry, King's College London London, UK.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Thuret
keywords: Alzheimer’s disease; dorsal hippocampus; hippocampal asymmetry; hippocampal shape; hippocampal volume; hippocampus; hyperactivation; ventral hippocampus
references.citation: Neuropsychopharmacology. 2011 Oct;36(11):2169-86
references.pmid: 21734652
references.citation: Neurobiol Aging. 2001 Mar-Apr;22(2):177-86
references.pmid: 11182467
references.citation: Hippocampus. 2006;16(11):946-58
references.pmid: 16983649
references.citation: J Neural Transm Suppl. 1998;54:97-106
references.pmid: 9850918
references.citation: Hippocampus. 2013 Dec;23(12):1246-58
references.pmid: 23804525
references.citation: Neurology. 2000 Jul 12;55(1):134-6
references.pmid: 10891924
references.citation: Arch Neurol. 2011 Aug;68(8):1040-8
references.pmid: 21825241
references.citation: Acta Neuropathol. 2002 Apr;103(4):363-9
references.pmid: 11904756
references.citation: J Alzheimers Dis. 2014;38(1):11-38
references.pmid: 23948932
references.citation: Nat Rev Neurosci. 2010 May;11(5):339-50
references.pmid: 20354534
references.citation: Neurology. 2003 May 13;60(9):1495-500
references.pmid: 12743238
references.citation: Arch Neurol. 2009 Nov;66(11):1385-92
references.pmid: 19901171
references.citation: PLoS One. 2013;8(4):e59586
references.pmid: 23560052
references.citation: J Alzheimers Dis. 2012;30(2):355-65
references.pmid: 22414571
references.citation: Hippocampus. 2009 Nov;19(11):1055-64
references.pmid: 19309039
references.citation: Arch Neurol. 2006 May;63(5):693-9
references.pmid: 16682538
references.citation: Hippocampus. 2009 Jun;19(6):558-64
references.pmid: 19405132
references.citation: Acta Neuropathol. 1991;82(4):239-59
references.pmid: 1759558
references.citation: Hippocampus. 2012 Feb;22(2):292-8
references.pmid: 21049483
references.citation: Neuroreport. 2001 Oct 8;12(14):3019-22
references.pmid: 11568629
references.citation: Cold Spring Harb Perspect Med. 2012 Apr;2(4):a006213
references.pmid: 22474610
references.citation: Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006189
references.pmid: 22229116
references.citation: Neuroimage. 2012 Jan 16;59(2):1315-23
references.pmid: 21889995
references.citation: J Neurol Neurosurg Psychiatry. 2008 Jun;79(6):630-5
references.pmid: 17846109
references.citation: Neuron. 2010 Jan 14;65(1):7-19
references.pmid: 20152109
references.citation: J Comp Neurol. 1977 Mar 1;172(1):49-84
references.pmid: 65364
references.citation: Epilepsia. 2004 Jul;45(7):751-6
references.pmid: 15230697
references.citation: Alzheimer Dis Assoc Disord. 2012 Jan-Mar;26(1):17-27
references.pmid: 22343374
references.citation: Ann Neurol. 2005 Jun;57(6):896-903
references.pmid: 15929035
references.citation: Lancet Neurol. 2006 Oct;5(10):828-34
references.pmid: 16987729
references.citation: Radiology. 2010 Aug;256(2):598-606
references.pmid: 20656843
references.citation: Hippocampus. 2014 Mar;24(3):257-69
references.pmid: 24132937
references.citation: Nat Rev Neurol. 2010 Feb;6(2):67-77
references.pmid: 20139996
references.citation: Neurobiol Aging. 2007 Dec;28(12):1889-903
references.pmid: 16997428
references.citation: PLoS One. 2013 Sep 26;8(9):e76001
references.pmid: 24086677
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2367-72
references.pmid: 20133882
references.citation: Science. 2008 Sep 19;321(5896):1686-9
references.pmid: 18802001
references.citation: Neurology. 2007 Mar 13;68(11):828-36
references.pmid: 17353470
references.citation: Arch Neurol. 2011 Oct;68(10):1257-66
references.pmid: 21670386
references.citation: Neuroscience. 2013 Nov 12;252:234-52
references.pmid: 23973415
references.citation: PLoS One. 2008 Aug 13;3(8):e2935
references.pmid: 18698410
references.citation: Neurology. 2010 Oct 19;75(16):1415-22
references.pmid: 20944075
references.citation: Neuroscience. 2000;95(3):721-5
references.pmid: 10670438
references.citation: Neuron. 2011 May 26;70(4):582-8
references.pmid: 21609817
references.citation: Hum Brain Mapp. 2009 Sep;30(9):2766-88
references.pmid: 19172649
references.citation: Brain. 2009 Apr;132(Pt 4):1067-77
references.pmid: 19251758
references.citation: Lancet Neurol. 2013 Feb;12(2):207-16
references.pmid: 23332364
references.citation: Brain. 2009 May;132(Pt 5):1310-23
references.pmid: 19042931
references.citation: Neuroimage. 2004 Aug;22(4):1754-66
references.pmid: 15275931
references.citation: Epilepsy Behav. 2009 Jan;14(1):118-20
references.pmid: 18782632
references.citation: Prog Brain Res. 2007;163:601-13
references.pmid: 17765740
references.citation: Neuroimage. 2009 Oct 1;47(4):1476-86
references.pmid: 19463957
references.citation: Brain. 2008 Dec;131(Pt 12):3266-76
references.pmid: 18988639
references.citation: Neuroimage Clin. 2013 Aug 14;3:155-62
references.pmid: 24179859
references.citation: Neuroimage. 2013 Feb 1;66:50-70
references.pmid: 23142652
references.citation: Arch Neurol. 2009 Dec;66(12):1447-55
references.pmid: 20008648
references.citation: AJNR Am J Neuroradiol. 2011 Oct;32(9):1658-61
references.pmid: 21835940
references.citation: JAMA. 2002 Sep 25;288(12):1475-83
references.pmid: 12243634
references.citation: Neurology. 2010 Jun 15;74(24):1969-76
references.pmid: 20463288
references.citation: Neuron. 2011 May 26;70(4):589-96
references.pmid: 21609818
references.citation: Lancet Neurol. 2010 Nov;9(11):1118-27
references.pmid: 20934914
references.citation: Science. 2012 Oct 5;338(6103):72-5
references.pmid: 23042885
references.citation: PLoS One. 2013 Nov 15;8(11):e80513
references.pmid: 24260406
references.citation: Hippocampus. 2008;18(1):5-10
references.pmid: 17924531
references.citation: Hum Brain Mapp. 2014 May;35(5):2359-71
references.pmid: 24039001
references.citation: Cereb Cortex. 2005 Nov;15(11):1676-89
references.pmid: 15703252
references.citation: Cereb Cortex. 2007 Nov;17(11):2491-506
references.pmid: 17204820
references.citation: Dement Geriatr Cogn Disord. 2012;34(2):96-111
references.pmid: 22922821
references.citation: Proc Natl Acad Sci U S A. 2004 May 4;101(18):7141-6
references.pmid: 15118092
references.citation: PLoS One. 2011;6(11):e27262
references.pmid: 22073301
references.citation: Arch Neurol. 2004 Aug;61(8):1290-3
references.pmid: 15313849
references.citation: Neurobiol Aging. 2004 Mar;25(3):303-10
references.pmid: 15123335
references.citation: Epilepsia. 2008 Jun;49 Suppl 5:19-25
references.pmid: 18522597
references.citation: Alzheimers Dement. 2011 Sep;7(5):532-9
references.pmid: 21889116
references.citation: Neurology. 2002 Mar 12;58(5):750-7
references.pmid: 11889239
references.citation: Neuropsychiatr Dis Treat. 2013;9:1443-55
references.pmid: 24092982
references.citation: J Alzheimers Dis. 2012;31(1):85-99
references.pmid: 22504319
references.citation: Curr Opin Neurobiol. 2011 Dec;21(6):929-34
references.pmid: 22079495
references.citation: Int J Geriatr Psychiatry. 2011 Feb;26(2):166-72
references.pmid: 21229599
references.citation: Nat Genet. 2012 Apr 15;44(5):552-61
references.pmid: 22504417
references.citation: J Neurol Neurosurg Psychiatry. 2000 Jan;68(1):93-6
references.pmid: 10601411
references.citation: JAMA Neurol. 2014 Jan;71(1):11-22
references.pmid: 24276092
references.citation: Neurobiol Aging. 2006 Dec;27(12):1751-6
references.pmid: 16309795
references.citation: Dement Geriatr Cogn Disord. 2008;25(2):115-26
references.pmid: 18087152
references.citation: Dement Geriatr Cogn Disord. 2007;23(6):382-9
references.pmid: 17389798
references.citation: PLoS One. 2013 Aug 12;8(8):e71354
references.pmid: 23951142
references.citation: Neuroimage. 2005 Dec;28(4):1033-42
references.pmid: 16084115
references.citation: Neuroimage. 2011 Aug 15;57(4):1331-42
references.pmid: 21640840
references.citation: Neuroimage. 2013 Feb 1;66:28-35
references.pmid: 23128076
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1381-6
references.pmid: 12552120
references.citation: J Int Neuropsychol Soc. 2004 Sep;10(5):664-78
references.pmid: 15327714
references.citation: Neurobiol Aging. 2012 Apr;33(4):825.e25-36
references.pmid: 21782287
references.citation: Trends Cogn Sci. 2013 May;17(5):230-40
references.pmid: 23597720
references.citation: Neuroimage. 2007 May 15;36(1):8-18
references.pmid: 17434756
references.citation: Proc Natl Acad Sci U S A. 2012 May 29;109(22):8740-5
references.pmid: 22592800
references.citation: Neuron. 2011 Dec 22;72(6):931-7
references.pmid: 22196329
references.citation: Brain. 2006 May;129(Pt 5):1229-39
references.pmid: 16627465
references.citation: Alzheimers Dement. 2008 Jul;4(4):265-70
references.pmid: 18631977
references.citation: Trends Neurosci. 2011 Oct;34(10):515-25
references.pmid: 21788086
references.citation: Eur Neurol. 1993;33(6):403-8
references.pmid: 8307060
references.citation: PLoS One. 2013 May 17;8(5):e64318
references.pmid: 23691195
references.citation: Acta Psychiatr Scand. 2009 Apr;119(4):252-65
references.pmid: 19236314
references.citation: J Cogn Neurosci. 2013 Nov;25(11):1908-25
references.pmid: 23806136
references.citation: Neuroimage. 2010 Jul 1;51(3):1242-52
references.pmid: 20338246
references.citation: Neuroimage. 2009 Mar;45(1 Suppl):S3-15
references.pmid: 19041724
references.citation: Science. 1998 Aug 21;281(5380):1185-7
references.pmid: 9712581
references.citation: Neurobiol Aging. 2004 Oct;25(9):1205-12
references.pmid: 15312966
references.citation: Ann Neurol. 2010 Dec;68(6):865-75
references.pmid: 21194156
references.citation: Curr Alzheimer Res. 2009 Aug;6(4):347-61
references.pmid: 19689234
references.citation: Trends Neurosci. 2002 Jun;25(6):295-301
references.pmid: 12086747
references.citation: Neuroimage. 2011 May 1;56(1):212-9
references.pmid: 21272654
references.citation: Neuron. 2012 May 10;74(3):467-74
references.pmid: 22578498
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9944-9
references.pmid: 23716653
references.citation: Nat Rev Neurol. 2012 Mar 13;8(4):189-202
references.pmid: 22410582
references.citation: Clinics (Sao Paulo). 2011;66 Suppl 1:45-54
references.pmid: 21779722
references.citation: Neurology. 2009 Apr 28;72(17):1519-25
references.pmid: 19398707
references.citation: Development. 2011 Oct;138(20):4351-62
references.pmid: 21880781
references.citation: Neuroimage. 2005 Apr 15;25(3):783-92
references.pmid: 15808979
references.citation: Int J Alzheimers Dis. 2011;2011:535816
references.pmid: 21760988
references.citation: Br Med Bull. 2012 Sep;103(1):89-114
references.pmid: 22833570
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7209-14
references.pmid: 19357304
references.citation: Lancet. 1994 Sep 17;344(8925):769-72
references.pmid: 7916070
references.citation: Front Aging Neurosci. 2013 Aug 27;5:43
references.pmid: 23986699
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3017-22
references.pmid: 21282661
references.citation: J Neurosci. 2011 Nov 30;31(48):17680-8
references.pmid: 22131428
references.citation: Proc Natl Acad Sci U S A. 2011 May 24;108(21):8873-8
references.pmid: 21555581
references.citation: J Neurosci. 2005 Sep 21;25(38):8680-5
references.pmid: 16177036
references.citation: Hippocampus. 2010 Oct;20(10):1124-5
references.pmid: 20848611
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42
references.pmid: 15070770
references.citation: Neurology. 2001 Dec 26;57(12):2223-8
references.pmid: 11756601
references.citation: Psychiatry Res. 2012 Jan 30;201(1):48-53
references.pmid: 22285719
references.citation: Front Neurosci. 2012 Dec 13;6:179
references.pmid: 23248580
references.citation: Hum Brain Mapp. 2010 Sep;31(9):1339-47
references.pmid: 20839293
references.citation: Hippocampus. 1998;8(6):608-19
references.pmid: 9882018
references.citation: Epilepsia. 2011 Jan;52 Suppl 1:39-46
references.pmid: 21214538
references.citation: Neurology. 2005 Aug 9;65(3):404-11
references.pmid: 16087905
references.citation: Dement Geriatr Cogn Disord. 2005;19(5-6):338-44
references.pmid: 15785035
references.citation: N Engl J Med. 2000 Aug 17;343(7):450-6
references.pmid: 10944562
references.citation: Alzheimer Dis Assoc Disord. 2012 Oct-Dec;26(4):314-21
references.pmid: 22156755
references.citation: Neurology. 2009 Dec 1;73(22):1899-905
references.pmid: 19846828
references.citation: Biochem Soc Trans. 2011 Aug;39(4):902-9
references.pmid: 21787321
references.citation: Nature. 2011 Apr 28;472(7344):466-70
references.pmid: 21460835
references.citation: Neurology. 2002 Jun 25;58(12):1791-800
references.pmid: 12084879
references.citation: Alzheimers Dement. 2011 May;7(3):280-92
references.pmid: 21514248
references.citation: Neuroimage. 2010 Nov 1;53(2):506-14
references.pmid: 20600996
references.citation: Neurobiol Aging. 2010 Jul;31(7):1077-88
references.pmid: 18814937
references.citation: J Neurosci. 2013 May 22;33(21):8926-36
references.pmid: 23699504
references.citation: Hippocampus. 2011 Sep;21(9):968-79
references.pmid: 20865732