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.
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.
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.
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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This post is Copyright: 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 O’Brien,
Li Su,
Dennis Chan,
for the PREVENT Dementia Research Programme | February 29, 2024

Wiley: Alzheimer’s & Dementia: Table of Contents