Higher CSF Tau Levels Are Related to Hippocampal Hyperactivity and Object Mnemonic Discrimination in Older Adults

Research output: Contribution to journalArticle

Abstract

Mnemonic discrimination, the ability to distinguish similar events in memory, relies on subregions in the human medial temporal lobes (MTLs). Tau pathology is frequently found within the MTL of older adults and therefore likely to affect mnemonic discrimination, even in healthy older individuals. The MTL subregions that are known to be affected early by tau pathology, the perirhinal-transentorhinal region (area 35) and the anterior-lateral entorhinal cortex (alEC), have recently been implicated in the mnemonic discrimination of objects rather than scenes. Here we used an object-scene mnemonic discrimination task in combination with fMRI recordings and analyzed the relationship between subregional MTL activity, memory performance, and levels of total and phosphorylated tau as well as Aβ42/40 ratio in CSF. We show that activity in alEC was associated with mnemonic discrimination of similar objects but not scenes in male and female cognitively unimpaired older adults. Importantly, CSF tau levels were associated with increased fMRI activity in the hippocampus, and both increased hippocampal activity as well as tau levels were associated with mnemonic discrimination of objects, but again not scenes. This suggests that dysfunction of the alEC-hippocampus object mnemonic discrimination network might be a marker for tau-related cognitive decline.SIGNIFICANCE STATEMENT Subregions in the human medial temporal lobe are critically involved in episodic memory and, at the same time, affected by tau pathology. Impaired object mnemonic discrimination performance as well as aberrant activity within the entorhinal-hippocampal circuitry have been reported in earlier studies involving older individuals, but it has thus far remained elusive whether and how tau pathology is implicated in this specific impairment. Using task-related fMRI in combination with measures of tau pathology in CSF, we show that measures of tau pathology are associated with increased hippocampal activity and reduced mnemonic discrimination of similar objects but not scenes. This suggests that object mnemonic discrimination tasks could be promising markers for tau-related cognitive decline.

Details

Authors
  • David Berron
  • Arturo Cardenas-Blanco
  • Daniel Bittner
  • Coraline D. Metzger
  • Annika Spottke
  • Michael T. Heneka
  • Klaus Fliessbach
  • Anja Schneider
  • Stefan J. Teipel
  • Michael Wagner
  • Oliver Speck
  • Frank Jessen
  • Emrah Düzel
Organisations
External organisations
  • Otto von Guericke University Magdeburg
  • University Hospital Magdeburg
  • University Hospital Bonn
  • University of Bonn
  • University Hospital of Cologne
  • Universitätsmedizin Rostock
  • University College London
  • German Center for Neurodegenerative Diseases (DZNE) Magdeburg
  • German Center for Neurodegenerative Diseases (DZNE), Bonn
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • ageing, CSF, entorhinal cortex, fMRI, hippocampus, mnemonic discrimination
Original languageEnglish
Pages (from-to)8788-8797
Number of pages10
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume39
Issue number44
Publication statusPublished - 2019 Oct 30
Publication categoryResearch
Peer-reviewedYes