# Predicting real world spatial disorientation in Alzheimer’s disease patients using virtual reality navigation tests

### Participant recruitment

A complete of 16 neighborhood residing AD sufferers in addition to 21 age and gender-matched wholesome controls have been recruited for this research (see Supplementary Materials for particulars on recruitment). All sufferers have been clinically identified with AD utilizing the Nationwide Institute of Neurological and Communicative Issues and Stroke and the Alzheimer’s Illness and Associated Issues Affiliation (NINCDS/ADRDA) diagnostic standards23.

All recruited individuals underwent an preliminary phone screening process to evaluate their eligibility for the research. Inclusion standards was being between 50 and 80 years of age, residing at house, and if within the affected person group, having a medical prognosis for AD and a household carer (relative/partner) that is aware of them effectively and is prepared to help within the research. The exclusion standards was having a earlier historical past of alcohol/substance abuse, prognosis of a psychiatric situation or every other important medical situations which may be prone to have an effect on participation within the research (head harm, imaginative and prescient loss, mobility points), and for the sufferers, prognosis of a comorbid neurological situation that isn’t associated to AD.

Signed knowledgeable consent was obtained from all individuals and in the event that they lacked psychological capability to provide knowledgeable consent, from their authorized guardians (relevant to sufferers solely) previous to present process the experimental protocol. Moral approval for this research was offered by the School of Drugs and Well being Sciences Analysis Ethics Committee on the College of East Anglia (FMH2017/18–123) in addition to the Nationwide Well being Service Well being Analysis Authority (challenge ID 205,788; 16/LO/1366). All experiments have been carried out in accordance with the related pointers and laws.

### Experimental protocol

All individuals underwent an experimental protocol which consisted of a VR spatial navigation testing session and a neighborhood spatial navigation testing session.

### VR navigation—digital grocery store take a look at

The Digital Grocery store Take a look at (VST) is a spatial navigation take a look at that assesses selfish orientation, allocentric orientation, and heading route. We selected this take a look at as because it has been utilized by earlier research to spotlight navigation impairments in AD sufferers, we needed to discover if affected person efficiency on this take a look at pertains to their spatial disorientation in the neighborhood25,27,28. In short, an iPad is used to indicate individuals 14 totally different movies (trials) lasting 20–40 s in length, of a purchasing trolley shifting round a digital grocery store, from a primary particular person perspective (Fig. 1a). The digital surroundings didn’t include any salient landmarks or options, and is designed to check spatial navigation talents with out tapping into episodic reminiscence, as any spatial illustration acquired throughout testing is on account of incidental encoding. In every video, individuals start at a set beginning location and observe a unique route, while making a collection of 90° turns, to achieve a selected vacation spot within the grocery store (first 7 trials = 20 s, 3 turns; remaining 7 trials = 40 s; 5 turns). On the finish of every trial, individuals are requested three units of inquiries to assess their selfish orientation (Fig. 1b), allocentric orientation (Fig. 1c), and heading route (Fig. 1d), respectively.

The VST has been described extensively in a earlier research25. Additional particulars of this take a look at are additionally given within the supplementary materials.

Within the wayfinding ranges, gamers are first proven a map containing the beginning location and site of numbered checkpoints. They’re instructed to review the map for so long as they want, and as soon as they’re prepared, they faucet on the display and the map disappears. Their job is to then navigate the boat (from a primary particular person perspective) to the checkpoints so as utilizing their reminiscence of the map (Fig. 2a). These ranges necessitate individuals to type and utilise a cognitive map for his or her wayfinding, and requires them to make use of extra of an allocentric versus an selfish navigation technique. The 2 final result variables for the wayfinding ranges are whole distance travelled to go to all of the checkpoints and whole length to finish the extent. In our evaluation nevertheless, we thought of wayfinding distance as representing extra the individuals’ navigation means in comparison with length, and subsequently we used this as our major measure for these ranges (see supplementary materials for particulars). On this research, the wayfinding ranges 6, 8, and 11 (which will increase in complexity) have been used, as these ranges have been proven to problem the navigation talents of individuals by a earlier research26. Every of those ranges had three checkpoints. Nonetheless, with most of the AD sufferers discovering degree 6 (i.e., the comparatively best degree) fairly difficult, the remaining ranges weren’t administered for them; therefore for the whole participant cohort, we used solely wayfinding efficiency on degree 6 for our evaluation.

Within the flare ranges, individuals aren’t supplied with a map and are merely requested to navigate the boat from their beginning location alongside varied bend/activates a river, till they discover a flare gun. As soon as the flare gun is discovered, the boat rotates by 180° clockwise and the individuals are requested to shoot the gun within the route of the place they assume the beginning location is, and are given three instructions to select from (proper, centre, left) (Fig. 2b). Primarily based on their response, individuals are awarded one, two, or three stars for his or her flare accuracy, with larger stars indicating larger accuracy. Much like the VST, this degree requires individuals to encode the beginning location in relation to their present place, and therefore measures their selfish orientation. Consistent with a earlier research26, the flare ranges 9 and 14 have been used and as well as, degree 19 was additionally used. These three ranges had just one 90° flip alongside the route. In an effort to problem the individuals to additional establish these with higher selfish orientation, a remaining difficult degree (i.e., degree 49) was administered which had 4 90° turns alongside the route. Flare accuracy for every degree was weighted for the entire variety of turns in that degree, and the entire flare accuracy throughout all ranges was the end result measure.

SHQ has been described extensively in a earlier research26,30. Additional particulars of this take a look at are additionally given within the supplementary materials.

The Detour Navigation Take a look at (DNT) is a novel real-world take a look at that we’re utilizing for the primary time, which checks the spatial navigation talents of individuals on an accompanied stroll in a naturalistic neighborhood setting, that can be a extremely acquainted surroundings (i.e., their very own neighbourhoods). We selected to make use of individuals’ personal neighbourhoods because the take a look at setting to precisely simulate the commonest RW scenario the place AD sufferers get misplaced in the neighborhood (i.e., throughout routine neighbourhood walks). An extra benefit of utilizing a neighbourhood setting is that it allows us to beat confounds of variations in spatial studying between controls and sufferers that might influence take a look at efficiency if navigation was assessed in an unfamiliar surroundings32.

On the finish of the VR navigation testing session, the individuals are requested to decide on and describe a well-recognized route (Route A) from their home to a landmark/location of their neighbourhood that they typically go to by foot, and this route is then marked by the experimenter on Google Maps. On a separate day, the individuals are visited at house and accompanied by the experimenter on Route A. As taking acquainted routes typically lends itself extra in the direction of the usage of selfish navigation33, this route allows us to evaluate the usage of this technique throughout navigation in the neighborhood. As soon as on the finish of Route A, the individuals are instructed to navigate again to their home utilizing the identical route. Unknown to the participant, on the first intersection on the way in which again, they’re requested to cease and discover an alternate, detour route (Route B) again house that doesn’t overlap in any respect (or if this isn’t doable, a route that overlaps as minimal as doable) with Route A. This job requires individuals to make use of their cognitive maps of their neighbourhoods, and lends itself extra in the direction of the usage of an allocentric navigation technique. An summary of the DNT is illustrated in Fig. 3.

On this job, we measured spatial disorientation exhibited by the individuals alongside these routes. Particularly, spatial disorientation is measured because the variety of—(a) flawed turns made and (b) moments of hesitation. A flawed flip is outlined as motion at an intersection (both straight or proper/left turns) onto a path that isn’t marked as a viable different route on the map or onto a part of the unique route. For the latter, exceptions are made the place the participant has no different different however to make use of a part of the unique path to get again house, during which case that is thought of as an appropriate overlap and therefore not marked as a flawed flip (eg. house situated at finish of a cul-de-sac). Individuals might make a complete of two consecutive flawed turns, at which level they’d be introduced again to the placement earlier than the primary flawed flip was made and inspired to strive once more. For the second variable, a second of hesitation was outlined because the participant both slowing down/stopping and looking out round to assist orientation or verbally admitting that they’re not sure about their whereabouts, in step with a earlier research21.

Total, for every participant the entire variety of flawed turns made and moments of hesitation have been summed for each unique/detour routes, and normalised for the respective whole route distance and whole route intersection quantity to provide a route disorientation rating. Moreover, for sufferers, a composite disorientation rating was calculated utilizing the formulation under:

$$mathrm{Composite, Disorientation, Rating}= frac{mathrm{Detour, Route, Disorientation, Rating}+1}{mathrm{Unique, Route, Disorientation, Rating}+1} .$$

Right here, a continuing of 1 was added to each unique/detour route disorientation scores to beat the division by zero downside, in instances the place a affected person exhibited no unique route disorientation (i.e., rating = 0). Therefore, a composite disorientation rating of 1 signifies that the affected person had no disorientation in both the unique or detour routes, a rating higher than 1 signifies extra disorientation on the detour than the unique route, and a rating lower than 1 signifies extra disorientation on the unique than detour route.

Particulars on the person routes (i.e., unique and detour) that each one individuals took, with respect to whole route distance and whole route intersection quantity, are offered within the supplementary materials.

### Information evaluation

The info evaluation was performed in 4 totally different steps utilizing RStudio software program package deal model 3.4.2 (https://www.R-project.org/)34. In step one, we investigated group variations in VR navigation by evaluating affected person efficiency on the VST (selfish orientation, allocentric orientation, and heading route) and SHQ (wayfinding and flare ranges) to that of controls. Within the second step, we assessed group variations in neighborhood navigation by evaluating affected person efficiency on the DNT (unique and detour route disorientation scores) to that of controls. To evaluate group variations within the VR and neighborhood navigation variables, t-tests and/or Wilcoxon Rank Sum checks have been used relying upon whether or not the variables had a standard/non-normal distribution.

Within the third evaluation step, we associated affected person efficiency on the VR navigation duties to that of their neighborhood navigation. Right here, we investigated whether or not any of the VR navigation variables (i.e., VST and SHQ variables) predict sufferers’ composite disorientation rating on the DNT utilizing linear regression fashions. Within the fourth and remaining evaluation step, we explored whether or not affected person efficiency on any of the VR navigation variables predict whether or not they’re at a excessive threat for spatial disorientation in the neighborhood. For this, we first divide the sufferers into excessive/low threat teams primarily based on their composite disorientation rating on the DNT. We then choose the VR navigation variables that considerably predicted DNT composite disorientation rating from step three, and assess how effectively these variables predict threat classification utilizing binomial logistic regression fashions. Steps three and 4 weren’t performed for the controls as we don’t count on controls to expertise disorientation in their very own neighbourhoods, and therefore aren’t involved in relating this final result measure with their VR navigation efficiency.