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Effect of beta‐amyloid and tau pathology on neural network segregation and episodic memory in aging
Author(s) -
Cassady Kaitlin,
Adams Jen.,
Maass Anne,
Harrison Theresa M.,
Baker Suzanne L.,
Jagust William J.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045474
Subject(s) - episodic memory , semantic memory , neuroscience , psychology , pathological , cognition , medicine , pathology
Background Functional alterations in large‐scale neural networks are consequences of both normal aging and Alzheimer’s disease (AD). Underlying pathological processes in both conditions are the accumulation of beta‐amyloid plaques (Aβ) and neurofibrillary tau tangles, which initially appear in the episodic memory system and track closely with memory loss. Aβ and tau aggregates in aging and AD may lead to memory loss through the disruption, or ‘dedifferentiation’, of episodic memory networks. Neural dedifferentiation refers to the finding that neural networks specialized for different cognitive functions become less segregated or ‘differentiated’ (i.e., reduced within‐ and increased between‐network connectivity) with age. Here, we investigated whether dedifferentiation in two distinct episodic memory networks (anterior‐temporal (AT); involved in object processing and posterior‐medial (PM); involved in scene processing) is associated with the accumulation of Aβ, tau and memory. Method We used resting state fMRI to measure functional connectivity (FC) in the AT and PM networks in older (OA; N=97, 76±6 years, 61F) and younger adults (YA; N=55, 25±4 years, 29F), and PIB‐PET (using threshold of 1.065 for PIB+/‐) to measure Aβ and FTP‐PET to measure tau in OA. We also collected cognitive data from OA. Episodic memory was measured with a composite z‐score of the California Verbal Learning Test and Visual Reproduction (short and long delay subtests of each). Result OA showed decreased segregation in AT and PM networks (decreased within‐network and increased between‐network FC) compared to YA. Furthermore, reduced segregation in the AT network was associated with higher levels of tau in AT regions whereas reduced segregation in the PM network was associated with higher levels of global Aβ. Finally, we found that PIB‐status moderates the association between mean segregation and episodic memory performance, such that less segregated networks correlated with better performance in PIB‐ OA while there was no association between segregation and performance in PIB+ OA. Conclusion These findings show that AD pathology disrupts the normal AT and PM networks in aging by decreasing within‐network and increasing between‐network FC. They also suggest a compensatory phase (in PIB‐ OA) followed by a dedifferentiation phase (in PIB+ OA) in the relationship between segregation and memory.