Vestibular contribution to path integration deficits in ‘at-genetic-risk’ for Alzheimer’s disease

Abstract

Path integration changes may precede a clinical presentation of Alzheimer disease by several years. Studies to date have focused on how grid cell changes affect path integration in preclinical AD. However, vestibular input is also critical for intact path integration. Here, we developed a naturalistic vestibular task that requires individuals to manually point an iPad device in the direction of their starting point following rotational movement, without any visual cues. Vestibular features were derived from the sensor data using feature selection. Completing machine learning models illustrate that the vestibular features accurately classified Apolipoprotein E4 carriers and non-carrier controls, mean age 62.7 years, with 65 to 79 percentage accuracy depending on task trial or algorithm. Our results demonstrate the cross-sectional role of the vestibular system in Alzheimer disease risk carriers and may explain individual phenotypic heterogeneity in path integration within this population.

A Cognitive-Motor Framework for Spatial Navigation in Aging and Alzheimer’s Disease

“…Likewise, path integration errors exhibited high sensitivity and specificity in differentiating between positive and negative biomarker status in the MCI group (AUC = .90), outperforming other 'gold-standard' cognitive tests of global cognition, episodic memory, and putative measures of allocentric navigation. Further analyses revealed that path integration errors in MCI due to AD were driven primarily by increased angular noise when encoding the rotation between legs of the outbound path as well as when estimating the correct heading of the inbound path (Castenaro et al, 2023; see also Chrastil & Warren, 2017;Coughlan et al, 2023;Newton et al, 2023).…”

“…Interestingly, the predictive efficacy of path integration tasks is most robust in the absence of external visual landmarks, suggesting that path integration errors associated with the earliest pathological changes in AD may emerge primarily from faulty or noisy vestibular inputs (Castenaro et al, 2023;Coughlan et al, 2023). A recent meta-analysis suggests that the predictive efficacy of spatial navigation to differentiate between relative AD risk status is most robust when using tasks that enable free ambulation during navigation with the full complement of body-based idiothetic cues (Plácido et al, 2022).…”

“…Because of the importance of vestibular cues to multisensory integration (Angelaki & Cullen, 2008;Cullen, 2014) and navigation (Coughlan et al, 2023;Stackman et al, 2002;Xie et al, 2017), difficulties navigating in immersive virtual reality or real-world environments would be one of the earliest signs of AD.…”