Entorhinal Tau Predicts Hippocampal Activation and Memory Deficits in Alzheimer’s Disease

Article type: Research Article

Authors: Richter, Nils^{a; b; *} | Bischof, Gérard N.^{a; c} | Dronse, Julian^{a; b} | Nellessen, Nils^{a; b} | Neumaier, Bernd^{d; e} | Langen, Karl-Josef^f | Drzezga, Alexander^c | Fink, Gereon R.^{a; b} | van Eimeren, Thilo^{a; c} | Kukolja, Juraj^{a; b; g} | Onur, Oezguer A.^{a; b}

Affiliations: [a] Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany | [b] Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany | [c] Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany | [d] Nuclear Chemistry, Institute of Neuroscience and Medicine (INM-5), Research Center Jülich, Jülich, Germany | [e] Institute for Radiochemistry and Experimental Molecular Imaging, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany | [f] Medical Imaging Physics, Institute of Neuroscience and Medicine (INM-4), Research Center Jülich, Jülich, Germany | [g] Department of Neurology and Neurophysiology, Helios University Hospital Wuppertal, Wuppertal, Germany

Correspondence: [*] Correspondence to: Nils Richter, MD, Cognitive Neuroscie-nce, Institute for Neuroscience and Medicine, INM-3, Research Center Jülich, 52425 Jülich, Germany. Tel.: +49 0 2461 61 9173; Fax: +49 0 2461 61 1518; E-mail: n.richter@fz-juelich.de.

Abstract: Background:To date, it remains unclear how amyloid plaques and neurofibrillary tangles are related to neural activation and, consequently, cognition in Alzheimer’s disease (AD). Recent findings indicate that tau accumulation may drive hippocampal hyperactivity in cognitively normal aging, but it remains to be elucidated how tau accumulation is related to neural activation in AD. Objective:To determine whether the association between tau accumulation and hippocampal hyperactivation persists in mild cognitive impairment (MCI) and mild dementia or if the two measures dissociate with disease progression, we investigated the relationship between local tau deposits and memory-related neural activation in MCI and mild dementia due to AD. Methods:Fifteen patients with MCI or mild dementia due to AD underwent a neuropsychological assessment and performed an item memory task during functional magnetic resonance imaging. Cerebral tau accumulation was assessed using positron emission tomography and [18F]-AV-1451. Results:Entorhinal, but not global tau accumulation, was highly correlated with hippocampal activation due to visual item memory encoding and predicted memory loss over time. Neural activation in the posterior cingulate cortex and the fusiform gyrus was not significantly correlated with tau accumulation. Conclusion:These findings extend previous observations in cognitively normal aging, demonstrating that entorhinal tau continues to be closely associated with hippocampal hyperactivity and memory performance in MCI and mild dementia due to AD. Furthermore, data suggest that this association is strongest in medial temporal lobe structures. In summary, our data provide novel insights into the relationship of tau accumulation to neural activation and memory in AD.

Keywords: AV-1451, dementia, functional magnetic resonance imaging, mild cognitive impairment, positron emission tomography

DOI: 10.3233/JAD-200835

Journal: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1601-1614, 2020