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Path integration selectively predicts midlife risk of Alzheimer's disease.

Charlotte Coco NewtonMarianna PopeCatarina RuaRichard HensonZilong JiNeil BurgessChristopher T RodgersMatthias StanglMaria-Eleni DounaviAndrea CastegnaroIvan KoychevParesh MalhotraThomas WolbersKaren RitchieCraig W RitchieJohn O'BrienLi SuDennis Channull null
Published in: bioRxiv : the preprint server for biology (2023)
The 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, we predicted that path integration impairment would represent the first behavioural change in adults at-risk of AD. Using immersive virtual reality, we found that midlife path integration impairments predicted both hereditary and physiological AD risk, with no corresponding impairment on tests of episodic memory or other spatial behaviours. Impairments related to poorer angular estimation and were associated with hexadirectional grid-like fMRI signal in the posterior-medial EC. These results indicate that altered path integration may represent the transition point from at-risk state to disease onset in AD, prior to impairment in other cognitive domains.
Keyphrases
  • virtual reality
  • induced apoptosis
  • functional connectivity
  • cognitive decline
  • cell therapy
  • oxidative stress
  • single cell
  • stem cells
  • bone marrow
  • cell cycle arrest
  • cell death
  • endoplasmic reticulum stress