Public Health

Alzheimer's Disease (AD) pathology accumulates early in the medial temporal lobe (MTL), crucial for spatial navigation. As spatial navigation is among the first cognitive functions affected by AD, it may benefit from targeted behavioral interventions. We investigated the potential of a novel smartphone-assisted real-world wayfinding training, tailored for healthy older adults, to improve their spatial abilities and explored associations with hippocampal vascularization and AD biomarkers.

38 cognitively healthy older adults (62-84 years; 18 females) participated in a 3-week navigation training, using our smartphone application "Explore" (Figure 1). Training involved finding several locations displayed on a map in the medical campus area of Magdeburg, Germany, while GPS data were recorded. Pre- and post-training, participants underwent fMRI, performed a pointing task in a virtual campus version, and completed the VWLT. At pre-assessment, AD pathology was characterized by plasma sampling (Abeta1-42/1-40, Ptau217) and [18F]PI-2620 PET in a subsample. Hippocampal vascularization was assessed by 7T angiography. Performance in the virtual pointing task and a map drawing test was compared to a control group (n = 20) who performed a walking task of equal length without a navigational component. Additionally, changes in different mobile wayfinding performance indicators and their associations with AD biomarkers and hippocampal vascularization (i.e., mean distance of hippocampus to surrounding vessels) were examined.

Performance in the pointing task and map drawing, but not in the VWLT (p = .321), significantly improved due to the training (all p < .001; Figure 2A C). The control group showed no improvements in navigation. Training benefits were also evident in the mobile data (all p ≤.017; Figure 3A-E). Better wayfinding efficiency was associated with less vessel distance to hippocampus, r=.44, p = .012, and the number of orientation stops was negatively related to pTau217, r=-.38, p = .019 (Figure 3F).

We provide evidence that a remotely administered real-world wayfinding training enhances wayfinding abilities and improves spatial memory in older adults. Importantly, hippocampal vascularization may benefit wayfinding efficiency. Higher pTau217 was related to fewer orientation stops during navigation. As a next step, potential mediating effects between vascularization and AD pathology on wayfinding performance will be investigated.