Entorhinal-based Path Integration Selectively Predicts Midlife Risk of Alzheimer's Disease

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2024 Feb 29

PMID 38421123

Authors

Coco Newton

Marianna Pope

Catarina Rua

Richard Henson

Zilong Ji

Neil Burgess

Christopher T Rodgers

Matthias Stangl

Maria-Eleni Dounavi

Andrea Castegnaro

Ivan Koychev

Paresh Malhotra

Thomas Wolbers

Karen Ritchie

Craig W Ritchie

John OBrien

Li Su

Dennis Chan

Affiliations

Soon will be listed here.

Abstract

Introduction: Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)-based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD.

Methods: We compared immersive virtual reality (VR) PI ability to other cognitive domains in 100 asymptomatic midlife adults stratified by hereditary and physiological AD risk factors. In some participants, behavioral data were compared to 7T magnetic resonance imaging (MRI) measures of brain structure and function.

Results: Midlife PI impairments predicted both hereditary and physiological AD risk, with no corresponding multi-risk impairment in episodic memory or other spatial behaviors. Impairments associated with altered functional MRI signal in the posterior-medial EC.

Discussion: Altered PI may represent the transition point from at-risk state to disease manifestation in AD, prior to impairment in other cognitive domains.

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