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000139950 0247_ $$2doi$$a10.1093/brain/awy053
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000139950 037__ $$aDZNE-2020-06272
000139950 041__ $$aEnglish
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000139950 1001_ $$aChhatwal, Jasmeer P$$b0
000139950 245__ $$aPreferential degradation of cognitive networks differentiates Alzheimer's disease from ageing.
000139950 260__ $$aOxford$$bOxford Univ. Press$$c2018
000139950 264_1 $$2Crossref$$3online$$bOxford University Press (OUP)$$c2018-03-07
000139950 264_1 $$2Crossref$$3print$$bOxford University Press (OUP)$$c2018-05-01
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000139950 520__ $$aConverging evidence from structural, metabolic and functional connectivity MRI suggests that neurodegenerative diseases, such as Alzheimer's disease, target specific neural networks. However, age-related network changes commonly co-occur with neuropathological cascades, limiting efforts to disentangle disease-specific alterations in network function from those associated with normal ageing. Here we elucidate the differential effects of ageing and Alzheimer's disease pathology through simultaneous analyses of two functional connectivity MRI datasets: (i) young participants harbouring highly-penetrant mutations leading to autosomal-dominant Alzheimer's disease from the Dominantly Inherited Alzheimer's Network (DIAN), an Alzheimer's disease cohort in which age-related comorbidities are minimal and likelihood of progression along an Alzheimer's disease trajectory is extremely high; and (ii) young and elderly participants from the Harvard Aging Brain Study, a cohort in which imaging biomarkers of amyloid burden and neurodegeneration can be used to disambiguate ageing alone from preclinical Alzheimer's disease. Consonant with prior reports, we observed the preferential degradation of cognitive (especially the default and dorsal attention networks) over motor and sensory networks in early autosomal-dominant Alzheimer's disease, and found that this distinctive degradation pattern was magnified in more advanced stages of disease. Importantly, a nascent form of the pattern observed across the autosomal-dominant Alzheimer's disease spectrum was also detectable in clinically normal elderly with clear biomarker evidence of Alzheimer's disease pathology (preclinical Alzheimer's disease). At the more granular level of individual connections between node pairs, we observed that connections within cognitive networks were preferentially targeted in Alzheimer's disease (with between network connections relatively spared), and that connections between positively coupled nodes (correlations) were preferentially degraded as compared to connections between negatively coupled nodes (anti-correlations). In contrast, ageing in the absence of Alzheimer's disease biomarkers was characterized by a far less network-specific degradation across cognitive and sensory networks, of between- and within-network connections, and of connections between positively and negatively coupled nodes. We go on to demonstrate that formalizing the differential patterns of network degradation in ageing and Alzheimer's disease may have the practical benefit of yielding connectivity measurements that highlight early Alzheimer's disease-related connectivity changes over those due to age-related processes. Together, the contrasting patterns of connectivity in Alzheimer's disease and ageing add to prior work arguing against Alzheimer's disease as a form of accelerated ageing, and suggest multi-network composite functional connectivity MRI metrics may be useful in the detection of early Alzheimer's disease-specific alterations co-occurring with age-related connectivity changes. More broadly, our findings are consistent with a specific pattern of network degradation associated with the spreading of Alzheimer's disease pathology within targeted neural networks.
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000139950 650_7 $$2NLM Chemicals$$a2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
000139950 650_7 $$2NLM Chemicals$$aAniline Compounds
000139950 650_7 $$2NLM Chemicals$$aThiazoles
000139950 650_7 $$00Z5B2CJX4D$$2NLM Chemicals$$aFluorodeoxyglucose F18
000139950 650_2 $$2MeSH$$aAdult
000139950 650_2 $$2MeSH$$aAged
000139950 650_2 $$2MeSH$$aAged, 80 and over
000139950 650_2 $$2MeSH$$aAging
000139950 650_2 $$2MeSH$$aAlzheimer Disease: complications
000139950 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000139950 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000139950 650_2 $$2MeSH$$aAniline Compounds: pharmacokinetics
000139950 650_2 $$2MeSH$$aBrain Mapping
000139950 650_2 $$2MeSH$$aCognition Disorders: diagnostic imaging
000139950 650_2 $$2MeSH$$aCognition Disorders: etiology
000139950 650_2 $$2MeSH$$aFemale
000139950 650_2 $$2MeSH$$aFluorodeoxyglucose F18: pharmacokinetics
000139950 650_2 $$2MeSH$$aHumans
000139950 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000139950 650_2 $$2MeSH$$aMale
000139950 650_2 $$2MeSH$$aMiddle Aged
000139950 650_2 $$2MeSH$$aModels, Neurological
000139950 650_2 $$2MeSH$$aNeural Pathways: diagnostic imaging
000139950 650_2 $$2MeSH$$aNeural Pathways: drug effects
000139950 650_2 $$2MeSH$$aPositron-Emission Tomography
000139950 650_2 $$2MeSH$$aThiazoles: pharmacokinetics
000139950 7001_ $$aSchultz, Aaron P$$b1
000139950 7001_ $$aJohnson, Keith A$$b2
000139950 7001_ $$aHedden, Trey$$b3
000139950 7001_ $$aJaimes, Sehily$$b4
000139950 7001_ $$aBenzinger, Tammie L S$$b5
000139950 7001_ $$aJack, Clifford$$b6
000139950 7001_ $$aAnces, Beau M$$b7
000139950 7001_ $$aRingman, John M$$b8
000139950 7001_ $$aMarcus, Daniel S$$b9
000139950 7001_ $$aGhetti, Bernardino$$b10
000139950 7001_ $$aFarlow, Martin R$$b11
000139950 7001_ $$0P:(DE-2719)2810712$$aDanek, Adrian$$b12$$udzne
000139950 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b13$$udzne
000139950 7001_ $$0P:(DE-2719)9000355$$aYakushev, Igor$$b14$$udzne
000139950 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b15$$udzne
000139950 7001_ $$aKoeppe, Robert A$$b16
000139950 7001_ $$aGalasko, Douglas R$$b17
000139950 7001_ $$aXiong, Chengjie$$b18
000139950 7001_ $$aMasters, Colin L$$b19
000139950 7001_ $$aSchofield, Peter R$$b20
000139950 7001_ $$aKinnunen, Kirsi M$$b21
000139950 7001_ $$aSalloway, Stephen$$b22
000139950 7001_ $$aMartins, Ralph N$$b23
000139950 7001_ $$aMcDade, Eric$$b24
000139950 7001_ $$aCairns, Nigel J$$b25
000139950 7001_ $$aBuckles, Virginia D$$b26
000139950 7001_ $$aMorris, John C$$b27
000139950 7001_ $$aBateman, Randall$$b28
000139950 7001_ $$0P:(DE-HGF)0$$aSperling, Reisa A$$b29$$eCorresponding author
000139950 7001_ $$aNetwork, Dominantly Inherited Alzheimer$$b30
000139950 77318 $$2Crossref$$3journal-article$$a10.1093/brain/awy053$$b : Oxford University Press (OUP), 2018-03-07$$n5$$p1486-1500$$tBrain$$v141$$x0006-8950$$y2018
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000139950 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5917745
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