title: Is verbal episodic memory in elderly with amyloid deposits preserved through altered neuronal function?
abstract: A potential mechanism that enables intellectual preservation in cognitively normal elderly that harbor beta-amyloid (Aβ) pathology is heightened cerebral glucose metabolism. To investigate cross-sectional inter-relationships between Aβ, glucose metabolism, and cognition, 81 subjects (mean age: 75 ± 7 years) underwent [(11)C]Pittsburgh Compound-B and [(18)F]fluorodeoxyglucose positron emission tomography scans and neuropsychological testing. They were divided into low-Aβ (n = 53), intermediate-Aβ (n = 13) and high-Aβ (n = 15) groups as defined by their global cortical [(11)C]PIB retention. Glucose metabolism was assessed using a MetaROI mask that covers metabolically critical regions in Alzheimer's disease (AD) (i.e., posterior cingulate and bilateral angular and inferior temporal gyri). Previously validated factor scores for verbal and visual episodic memory, semantic memory, working memory, and executive functioning were used to evaluate cognitive performances. Greater Aβ deposition in the precuneus was associated with higher metabolic activity (at trend level) and lower visual episodic memory scores. Glucose metabolism did not correlate with cognition across all subjects. However, heightened metabolic activity was associated with better verbal episodic memory performance in subjects with elevated amyloid levels. This preliminary study suggests that neural compensation, as a manifestation of brain reserve, enables elderly supposedly on the path to AD, at least temporarily, to preserve cognitive function.
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, the Netherlands Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands r.ossenkoppele@vumc.nl.
authors.forename: Rik
authors.initials: R
authors.lastname: Ossenkoppele
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Cindee
authors.initials: C
authors.lastname: Madison
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Hwamee
authors.initials: H
authors.lastname: Oh
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Miranka
authors.initials: M
authors.lastname: Wirth
authors.affiliation: Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D003430:Cross-Sectional Studies; D056344:Executive Function / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D061212:Memory, Episodic; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012660:Semantics; D013067:Speech Perception / Q000502:physiology*; D014796:Visual Perception / Q000502:physiology
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: PET; [11C]PIB; [18F]FDG; aging; beta-amyloid; cognition; glucose metabolism
references.citation: Neuroreport. 2002 Dec 20;13(18):2425-8
references.pmid: 12499842
references.citation: Science. 2009 Nov 13;326(5955):1005-7
references.pmid: 19779148
references.citation: Alzheimer Dis Assoc Disord. 2006 Apr-Jun;20(2):112-7
references.pmid: 16772747
references.citation: Alzheimers Dement. 2013 Nov;9(6):687-698.e1
references.pmid: 23474040
references.citation: J Comput Assist Tomogr. 1995 Jul-Aug;19(4):541-7
references.pmid: 7622680
references.citation: Brain. 2007 Nov;130(Pt 11):2837-44
references.pmid: 17928318
references.citation: N Engl J Med. 2012 Aug 30;367(9):795-804
references.pmid: 22784036
references.citation: Alzheimer Dis Assoc Disord. 1999 Oct-Dec;13(4):226-31
references.pmid: 10609672
references.citation: Neurology. 2010 Mar 9;74(10):807-15
references.pmid: 20147655
references.citation: Neuroimage. 2012 Jan 16;59(2):1152-60
references.pmid: 21884802
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7209-14
references.pmid: 19357304
references.citation: J Cereb Blood Flow Metab. 2005 Nov;25(11):1528-47
references.pmid: 15944649
references.citation: Ann Neurol. 2011 Jun;69(6):1032-42
references.pmid: 21437929
references.citation: Ann Neurol. 2004 Mar;55(3):306-19
references.pmid: 14991808
references.citation: Lancet Neurol. 2012 Nov;11(11):1006-12
references.pmid: 23079557
references.citation: Ann Neurol. 1999 Mar;45(3):358-68
references.pmid: 10072051
references.citation: Arch Neurol. 2008 Nov;65(11):1509-17
references.pmid: 19001171
references.citation: Cereb Cortex. 2012 Aug;22(8):1813-23
references.pmid: 21945849
references.citation: Neuroimage. 2003 Nov;20(3):1894-8
references.pmid: 14642499
references.citation: Neuroimage. 2002 Nov;17(3):1394-402
references.pmid: 12414279
references.citation: J Cereb Blood Flow Metab. 2001 Oct;21(10):1133-45
references.pmid: 11598490
references.citation: Ann Neurol. 2010 Mar;67(3):353-64
references.pmid: 20373347
references.citation: Neurology. 2012 Jan 24;78(4):232-40
references.pmid: 22189452
references.citation: Arch Neurol. 2011 May;68(5):644-9
references.pmid: 21555640
references.citation: Neurobiol Aging. 2010 Aug;31(8):1275-83
references.pmid: 20472326
references.citation: Ann Neurol. 2012 Oct;72(4):578-86
references.pmid: 23109153
references.citation: Neuroimage. 2011 Feb 1;54(3):1887-95
references.pmid: 20965254
references.citation: Brain. 2011 Jun;134(Pt 6):1635-46
references.pmid: 21490054
references.citation: J Neurosci. 2005 Aug 24;25(34):7709-17
references.pmid: 16120771
references.citation: Ann Neurol. 2012 Nov;72(5):730-8
references.pmid: 23280791
references.citation: Ann Neurol. 2010 Jan;67(1):122-31
references.pmid: 20186853
references.citation: Neurobiol Aging. 2012 Dec;33(12):2746-55
references.pmid: 22429886
references.citation: Ann Neurol. 2010 Mar;67(3):317-24
references.pmid: 20373343
references.citation: Arch Neurol. 2009 Dec;66(12):1469-75
references.pmid: 20008650
references.citation: Neurology. 2012 Feb 7;78(6):387-95
references.pmid: 22302550
references.citation: Ann Neurol. 2012 Jun;71(6):765-75
references.pmid: 22488240
references.citation: Brain. 2009 May;132(Pt 5):1310-23
references.pmid: 19042931
references.citation: Neuropsychologia. 2011 Jul;49(9):2776-83
references.pmid: 21689670
references.citation: Neurology. 2003 Apr 22;60(8):1374-7
references.pmid: 12707450
references.citation: J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40
references.pmid: 8784228
references.citation: Neurology. 2012 Oct 16;79(16):1645-52
references.pmid: 23071163
references.citation: Neurology. 2012 Oct 16;79(16):1636-44
references.pmid: 22786606
references.citation: Arch Neurol. 2012 Jun;69(6):709-13
references.pmid: 22529247
references.citation: J Neurosci. 2009 Nov 25;29(47):14770-8
references.pmid: 19940172
references.citation: J Neurosci. 2012 Dec 12;32(50):18227-33
references.pmid: 23238736
references.citation: Ann Neurol. 2011 Jan;69(1):181-92
references.pmid: 21280088
references.citation: Nat Neurosci. 2011 Jun;14(6):750-6
references.pmid: 21532579
references.citation: Neurology. 2006 Jun 27;66(12):1837-44
references.pmid: 16801647
references.citation: Arch Neurol. 2009 Dec;66(12):1476-81
references.pmid: 20008651
references.citation: Eur J Nucl Med Mol Imaging. 2012 Jun;39(6):990-1000
references.pmid: 22441582
references.citation: Lancet Neurol. 2010 Jan;9(1):119-28
references.pmid: 20083042
references.citation: Neurobiol Aging. 2011 Jul;32(7):1207-18
references.pmid: 19660834
references.citation: Ann Neurol. 2011 Nov;70(5):857-61
references.pmid: 22162065
references.citation: Trends Cogn Sci. 2011 Nov;15(11):520-6
references.pmid: 21983147
references.citation: Cereb Cortex. 2009 Mar;19(3):497-510
references.pmid: 18632739
references.citation: N Engl J Med. 2000 Aug 17;343(7):450-6
references.pmid: 10944562
references.citation: Annu Rev Psychol. 2009;60:173-96
references.pmid: 19035823
references.citation: Alzheimers Dement. 2011 May;7(3):280-92
references.pmid: 21514248