[en] 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.
Disciplines :
Neurology
Author, co-author :
Berron, David ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, 39120 Magdeburg, Germany, david.berron@med.lu.se ; German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany ; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 223 62 Lund, Sweden
Cardenas-Blanco, Arturo ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, 39120 Magdeburg, Germany ; German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany
Bittner, Daniel; Department of Neurology, University Hospital Magdeburg, 39120 Magdeburg, Germany
Metzger, Coraline D; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, 39120 Magdeburg, Germany ; German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany ; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, 39120 Magdeburg, Germany
Spottke, Annika; Department of Neurology, University Hospital of Bonn, 53127 Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
HENEKA, Michael ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany ; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, 53127 Bonn, Germany
Fliessbach, Klaus; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany ; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, 53127 Bonn, Germany
Schneider, Anja; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany ; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, 53127 Bonn, Germany
Teipel, Stefan J; Department of Psychosomatic Medicine, Rostock University Medical Center, 18147 Rostock, Germany ; German Center for Neurodegenerative Diseases, 18147 Rostock, Germany
Wagner, Michael ; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany ; Department of Neurodegeneration and Geriatric Psychiatry, University of Bonn, 53127 Bonn, Germany
Speck, Oliver; German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany ; Department of Biomedical Magnetic Resonance, Otto-von-Guericke University, 39120 Magdeburg, Germany ; Leibniz Institute of Neurobiology, 39120 Magdeburg, Germany, and ; Center for Behavioral Brain Sciences, 39120 Magdeburg, Germany
Jessen, Frank; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany ; Department of Psychiatry, University Hospital Cologne, 50937 Cologne, Germany
Düzel, Emrah; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, 39120 Magdeburg, Germany ; German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany ; University College London, Institute of Cognitive Neuroscience, London WC1N 3AZ, United Kingdom ; Center for Behavioral Brain Sciences, 39120 Magdeburg, Germany
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