Reliability of functional magnetic resonance imaging associative encoding memory paradigms in non-demented elderly adults.
Functional magnetic resonance imaging (fMRI) holds significant potential to aid in the development of early interventions to improve memory function, and to assess longitudinal change in memory systems in aging and early Alzheimer's disease (AD). However, the test-retest reliability of hippocampal activation and of "beneficial" deactivation in the precuneus has yet to be fully established during memory encoding tasks in older subjects. Using a mixed block and event-related face-name associative encoding paradigm, we assessed the reliability of hippocampal activation and default network deactivation over a 4- to 6-week interscan interval in 27 older individuals who were cognitively normal [Clinical Dementia Rating (CDR) Scale = 0; n = 18] or mildly impaired (CDR = 0.5; n = 9). Reliability was assessed in whole brain maps and regions of interest using both a full-task paradigm of six functional runs as well as an abbreviated paradigm of the first two functional runs, which would be advantageous for use in clinical trials. We found reliable hippocampal signal response across both block- and event-related designs in the right hippocampus. Comparable reliability in hippocampal activation was found in the full and the abbreviated paradigm. Similar reliability in hippocampal activation was observed across both CDR groups overall, but the CDR 0.5 group was more variable in left hippocampal activity. Task-related deactivation in the precuneus demonstrated much greater variability than hippocampal activation in all analyses. Overall, these results are encouraging for the utility of fMRI in "Proof of Concept" clinical trials investigating the efficacy of potentially therapeutic agents for treatment of age-related memory changes, cognitive impairment, and early AD.
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Deepti
D
Putcha
Kelly
K
O'Keefe
Pete
P
LaViolette
Jackie
J
O'Brien
Doug
D
Greve
Dorene M
DM
Rentz
Joseph
J
Locascio
Alireza
A
Atri
Reisa
R
Sperling
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D015203:Reproducibility of Results
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):321-5
8552630
Neuropsychologia. 2006;44(14):2836-45
16879844
J Cogn Neurosci. 2003 Oct 1;15(7):935-45
14628755
Neuroimage. 2004 Nov;23(3):921-7
15528092
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2181-6
18238903
Ann Neurol. 2004 Jul;56(1):27-35
15236399
Hum Brain Mapp. 2001 Nov;14(3):129-39
11559958
Neuroimage. 2009 Oct 1;47(4):1678-90
19539034
Neuroimage. 2005 May 1;25(4):1112-23
15850729
Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8660-5
8710927
Neurobiol Aging. 2010 May;31(5):839-52
18674847
Neurobiol Aging. 2007 Feb;28(2):238-47
16434125
Neuroimage. 2006 Feb 1;29(3):1000-6
16139527
J Cogn Neurosci. 2002 Nov 15;14(8):1200-14
12495526
J Magn Reson Imaging. 2003 Apr;17(4):463-71
12655586
Am J Geriatr Psychiatry. 2008 Apr;16(4):283-92
18378553
Radiology. 2007 Oct;245(1):224-35
17885190
J Intern Med. 2004 Sep;256(3):183-94
15324362
J Neurol Neurosurg Psychiatry. 2008 Jun;79(6):630-5
17846109
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):455-60
11756667
Cereb Cortex. 2008 Aug;18(8):1856-64
18063564
BMC Med. 2006 Jan 13;4:1
16412236
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1837-41
1542680
Cereb Cortex. 2009 Mar;19(3):733-44
18653664
Brain. 2005 Apr;128(Pt 4):773-87
15705615
Psychol Aging. 2009 Dec;24(4):792-808
20025396
J Cogn Neurosci. 1999 Jan;11(1):80-95
9950716
Brain. 2003 Jan;126(Pt 1):43-56
12477696
Nat Rev Neurosci. 2001 Oct;2(10):685-94
11584306
Psychopharmacol Bull. 1988;24(4):523-9
3074313
Neurology. 2010 Jun 15;74(24):1969-76
20463288
Psychol Bull. 1979 Mar;86(2):420-8
18839484
AJNR Am J Neuroradiol. 1997 Aug;18(7):1317-22
9282862
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82
11209064
Neurobiol Aging. 2006 Nov;27(11):1604-12
16226349
Alzheimer Dis Assoc Disord. 2010 Jan-Mar;24(1):28-36
19571734
J Neurosci. 2009 Oct 7;29(40):12686-94
19812343
Hippocampus. 2007;17(11):1071-80
17604351
Nat Rev Neurosci. 2003 Nov;4(11):863-72
14595398
Neuroimage. 2005 Mar;25(1):253-66
15734360
J Cogn Neurosci. 2007 Jun;19(6):1021-32
17536972
Neurobiol Aging. 2009 May;30(5):717-30
17963998
Neurology. 2005 Feb 8;64(3):501-8
15699382
Science. 1998 Aug 21;281(5380):1185-7
9712581
Am J Psychiatry. 2001 Jun;158(6):955-8
11384907
Biol Psychiatry. 2010 Mar 15;67(6):584-7
19833321
J Neurosci. 2006 Oct 4;26(40):10222-31
17021177
J Cogn Neurosci. 2003 Apr 1;15(3):394-408
12729491
Neuroimage. 2008 Aug 1;42(1):196-206
18538585
Hum Brain Mapp. 2000 Mar;9(3):156-64
10739366
J Neurol Neurosurg Psychiatry. 2003 Jan;74(1):44-50
12486265
Brain Res Bull. 2001 Feb;54(3):287-98
11287133
Neurology. 2003 Aug 26;61(4):500-6
12939424
Neuroimage. 2003 Oct;20(2):1400-10
14568509
Ann N Y Acad Sci. 2008 Mar;1124:1-38
18400922
Hum Brain Mapp. 2009 Dec;30(12):4033-47
19492301
Brain Lang. 2002 Mar;80(3):421-37
11896650
Neuroimage. 2004 Mar;21(3):1000-8
15006667
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14504-9
14608034
J Neurosci. 2006 Jan 11;26(2):381-8
16407533
Neurology. 2005 Aug 9;65(3):404-11
16087905
N Engl J Med. 2000 Aug 17;343(7):450-6
10944562
Neuron. 2009 Jul 30;63(2):178-88
19640477
Neuron. 2007 Dec 6;56(5):924-35
18054866
Hum Brain Mapp. 2003 Jan;18(1):42-52
12454911
Neuroimage. 2008 Jun;41(2):311-22
18411061
J Cogn Neurosci. 2006 Feb;18(2):227-41
16494683
Science. 1998 Aug 21;281(5380):1188-91
9712582