TY  - JOUR
AU  - Newton, Coco
AU  - Pope, Marianna
AU  - Rua, Catarina
AU  - Henson, Richard
AU  - Ji, Zilong
AU  - Burgess, Neil
AU  - Rodgers, Christopher T
AU  - Stangl, Matthias
AU  - Dounavi, Maria-Eleni
AU  - Castegnaro, Andrea
AU  - Koychev, Ivan
AU  - Malhotra, Paresh
AU  - Wolbers, Thomas
AU  - Ritchie, Karen
AU  - Ritchie, Craig W
AU  - O'Brien, John
AU  - Su, Li
AU  - Chan, Dennis
TI  - Entorhinal-based path integration selectively predicts midlife risk of Alzheimer's disease.
JO  - Alzheimer's and dementia
VL  - 20
IS  - 4
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2024-00349
SP  - 2779 - 2793
PY  - 2024
AB  - 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.
KW  - Adult
KW  - Humans
KW  - Alzheimer Disease: pathology
KW  - Entorhinal Cortex: pathology
KW  - Brain: pathology
KW  - Magnetic Resonance Imaging: methods
KW  - Alzheimer's disease (Other)
KW  - entorhinal cortex (Other)
KW  - path integration (Other)
KW  - preclinical (Other)
KW  - virtual reality (Other)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11032581
C6  - pmid:38421123
DO  - DOI:10.1002/alz.13733
UR  - https://pub.dzne.de/record/268845
ER  -