Franzmeier, Nicolai, Duezel, Emrah, Jessen, Frank, Buerger, Katharina, Levin, Johannes ORCID: 0000-0001-5092-4306, Duering, Marco, Dichgans, Martin, Haass, Christian, Suarez-Calvet, Marc ORCID: 0000-0002-2993-569X, Fagan, Anne M., Paumier, Katrina, Benzinger, Tammie, Masters, Colin L., Morris, John C., Perneczky, Robert, Janowitz, Daniel, Catak, Cihan, Wolfsgruber, Steffen, Wagner, Michael ORCID: 0000-0003-2589-6440, Teipel, Stefan, Kilimann, Ingo, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Rossor, Martin ORCID: 0000-0001-8215-3120, Jucker, Mathias, Chhatwal, Jasmeer, Spottke, Annika, Boecker, Henning, Brosseron, Frederic, Falkai, Peter ORCID: 0000-0003-2873-8667, Fliessbach, Klaus, Heneka, Michael T., Laske, Christoph, Nestor, Peter ORCID: 0000-0002-5860-5921, Peters, Oliver, Fuentes, Manuel, Menne, Felix, Priller, Josef ORCID: 0000-0001-7596-0979, Spruth, Eike J., Franke, Christiana, Schneider, Anja ORCID: 0000-0001-9540-8700, Kofler, Barbara, Westerteicher, Christine, Speck, Oliver ORCID: 0000-0002-6019-5597, Wiltfang, Jens ORCID: 0000-0003-1492-5330, Bartels, Claudia, Caballero, Miguel Angel Araque, Metzger, Coraline, Bittner, Daniel, Weiner, Michael, Lee, Jae-Hong, Salloway, Stephen, Danek, Adrian ORCID: 0000-0001-8857-5383, Goate, Alison, Schofield, Peter R., Bateman, Randall J. and Ewers, Michael (2018). Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease. Brain, 141. S. 1186 - 1201. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity x estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Franzmeier, NicolaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duezel, EmrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buerger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levin, JohannesUNSPECIFIEDorcid.org/0000-0001-5092-4306UNSPECIFIED
Duering, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dichgans, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haass, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suarez-Calvet, MarcUNSPECIFIEDorcid.org/0000-0002-2993-569XUNSPECIFIED
Fagan, Anne M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paumier, KatrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzinger, TammieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Masters, Colin L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morris, John C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perneczky, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janowitz, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Catak, CihanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolfsgruber, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Teipel, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilimann, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
Rossor, MartinUNSPECIFIEDorcid.org/0000-0001-8215-3120UNSPECIFIED
Jucker, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chhatwal, JasmeerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spottke, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boecker, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brosseron, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falkai, PeterUNSPECIFIEDorcid.org/0000-0003-2873-8667UNSPECIFIED
Fliessbach, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heneka, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laske, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nestor, PeterUNSPECIFIEDorcid.org/0000-0002-5860-5921UNSPECIFIED
Peters, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuentes, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menne, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Priller, JosefUNSPECIFIEDorcid.org/0000-0001-7596-0979UNSPECIFIED
Spruth, Eike J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, ChristianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, AnjaUNSPECIFIEDorcid.org/0000-0001-9540-8700UNSPECIFIED
Kofler, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westerteicher, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speck, OliverUNSPECIFIEDorcid.org/0000-0002-6019-5597UNSPECIFIED
Wiltfang, JensUNSPECIFIEDorcid.org/0000-0003-1492-5330UNSPECIFIED
Bartels, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caballero, Miguel Angel AraqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metzger, CoralineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bittner, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiner, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Jae-HongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salloway, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Danek, AdrianUNSPECIFIEDorcid.org/0000-0001-8857-5383UNSPECIFIED
Goate, AlisonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schofield, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bateman, Randall J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ewers, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-189848
DOI: 10.1093/brain/awy008
Journal or Publication Title: Brain
Volume: 141
Page Range: S. 1186 - 1201
Date: 2018
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2156
Language: English
Faculty: Faculty of Management, Economy and Social Sciences
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FUNCTIONAL CONNECTIVITY; HIPPOCAMPAL FUNCTION; IMAGING BIOMARKERS; PHYSICAL-ACTIVITY; MEMORY VARIANCE; WORKING-MEMORY; CORTICAL HUBS; BRAIN RESERVE; LOW-FREQUENCY; OLDER-ADULTSMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18984

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