Increased posterior default mode network activity and structural connectivity in young adult APOE-ε4 carriers: a multi-modal imaging investigation

Hodgetts, Carl J. ORCID: https://orcid.org/0000-0002-0339-2447, Shine, Jonathan P., Williams, Huw ORCID: https://orcid.org/0000-0002-4069-0259, Postans, Mark, Sims, Rebecca ORCID: https://orcid.org/0000-0002-3885-1199, WIlliams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Lawrence, Andrew D. ORCID: https://orcid.org/0000-0001-6705-2110 and Graham, Kim S. ORCID: https://orcid.org/0000-0002-1512-7667 2019. Increased posterior default mode network activity and structural connectivity in young adult APOE-ε4 carriers: a multi-modal imaging investigation. Neurobiology of Aging 73 , pp. 82-91. 10.1016/j.neurobiolaging.2018.08.026

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Abstract

Young adult APOE-ε4 carriers show increased activity in posterior regions of the default mode network (pDMN), but how this is related to structural connectivity is unknown. Thirty young adults (one half of whom were APOE-ε4 carriers; mean age 20 years) were scanned using both diffusion and functional magnetic resonance imaging. The parahippocampal cingulum bundle (PHCB)—which links the pDMN and the medial temporal lobe—was manually delineated in individual participants using deterministic tractography. Measures of tract microstructure (mean diffusivity and fractional anisotropy) were then extracted from these tract delineations. APOE-ε4 carriers had lower mean diffusivity and higher fractional anisotropy relative to noncarriers in PHCB, but not in a control tract (the inferior longitudinal fasciculus). Furthermore, PHCB microstructure was selectively associated with pDMN (and medial temporal lobe) activity during a scene discrimination task known to be sensitive to Alzheimer's disease. These findings are consistent with a lifespan view of Alzheimer's disease risk, where early-life, connectivity-related changes in specific, vulnerable “hubs” (e.g., pDMN) lead to increased neural activity. Critically, such changes may reflect reduced network efficiency/flexibility in APOE-ε4 carriers, which in itself may portend a faster decline in connectivity over the lifespan and ultimately trigger early amyloid-β deposition in later life.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Medicine Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information:	This is an open access article under the CCBY license
Publisher:	Elsevier
ISSN:	0197-4580
Funders:	Wellcome Trust
Date of First Compliant Deposit:	28 August 2018
Date of Acceptance:	16 August 2018
Last Modified:	05 Jan 2024 02:40
URI:	https://orca.cardiff.ac.uk/id/eprint/114398

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