1. Path integration deficits related to Alzheimer's disease pathology in clinically normal older adults.
- Author
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Colmant, Lise, Boyer, Emilien, Gérard, Thomas, Bierbrauer, Anne, Kunz, Lukas, Sleegers, Kristel, Axmacher, Nikolai, Lefèvre, Philippe, and Hanseeuw, Bernard J
- Abstract
Background: The entorhinal cortex (EC) is the first cortical region affected by tauopathy in Alzheimer's disease (AD) and is implicated in path integration. In early stages of AD, path integration deficits could be present, even before overt memory deficits. Furthermore, path integration deficits are found among older individuals at risk for AD, such as APOE ε4 carriers. We investigated whether this deficit was related to AD pathology or to APOE genotype using a pure path integration task, the "Apple Game" (Bierbrauer et al. 2020). Method: Participants navigated through a virtual arena and were asked to drop a basket to its initial location after visiting one intermediate location. We recruited 175 clinically normal participants (MMSE>24/30, median age = 65). We genotyped the APOE gene and classified participants as ε4 carriers (n = 60) or non‐carriers (n = 115). We measured the plasma ratio of Aβ42 and Aβ40 using Simoa. We defined a threshold of Aβ42/Aβ40 with a gaussian mixture model to classify participants as Aβ+ (Aβ42/Aβ40<0.047, n = 54) or Aβ‐ (Aβ42/Aβ40> = 0.047, n = 121). We analyzed path integration performance depending on APOE genotype and amyloid status with a linear mixed model including age as covariate. A subset of participants (n = 49) underwent a second generation Tau‐PET (18F‐MK‐6240). Task performance was related to EC tauopathy using a linear mixed model. Results: The path integration performance was lower among older individuals Aβ+ compared to Aβ‐ (Fig.1, p = 0.04). There was no APOE effect after taking Aβ into account. This indicates that path integration performance was more related to Aβ pathology than to APOE genotype. In participants with Tau‐PET, we observed that the angular error, a component of the task performance, increased with the EC Tau signal (Fig.2, p = 0.05). Conclusion: We detected a path integration deficit among clinically normal older individuals that depended on Aβ. Furthermore, path integration performance was related to tauopathy in the EC, possibly reflecting impairment of grid cells. These observations suggest that path integration deficits observed in older individuals carrying an APOE ε4 allele are related to incipient AD pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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