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Tau, neural function, and episodic memory in the medial temporal lobe
Author(s) -
Berron David
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.037499
Subject(s) - perirhinal cortex , temporal lobe , entorhinal cortex , neuroscience , episodic memory , white matter , atrophy , hippocampus , hippocampal formation , psychology , pathology , cognition , medicine , magnetic resonance imaging , epilepsy , radiology
Background The human medial temporal lobe (MTL) is heavily connected with neocortical regions in the posterior‐medial and the anterior‐temporal system. In order to achieve successful memory functioning, those systems have to interact with each other as well as with the hippocampus. At the same time, subregions in the MTL are affected by neurofibrillary tangle (NFT) pathology in aging and Alzheimer's disease (AD) which is strongly associated with memory impairment. Method In three different samples of cognitively unimpaired (CU) individuals, we analyzed how tau pathology (measured using Tau PET and CSF pTau levels) was associated with altered resting‐state functional connectivity, task‐related functional activity, MTL subregional atrophy, white matter tract integrity and memory function. Result In the first sample (n=322 CU), we identified the sequence of MTL subregions being affected by tau accumulation. Tau accumulates early in the perirhinal cortex (Area 35) and was associated with memory function ‐ an effect that was partially mediated by anterior hippocampal atrophy. In the second sample (n=359 CU), we show that while entorhinal/perirhinal cortex functional connectivity with the anterior‐temporal system was predominantly reduced in beta amyloid (Ab) + vs. Ab‐ CU, functional connectivity with the posterior‐medial system was increasingly reduced with increasing levels of pTau in Ab+ CU. Reduced functional connectivity was both related to baseline memory and future cognitive decline, however, not significantly associated with entorhinal thickness or white matter tract integrity. Finally, we show in a third sample (n=22 CU) that increasing levels of pTau are related to increased hippocampal functional activity which are both individually associated with reduced performance in an object memory task. Conclusion Taken together, our results from three independent samples suggest that tau pathology affects memory function in early disease stages predominantly via aberrant MTL functional connectivity and activity rather than atrophy or degeneration of white matter tracts.