Egocentric spatial orientation differences between Alzheimer's disease at early stages and mild cognitive impairment: a diagnostic aid.

Alzheimer's disease (AD) is a growing global crisis. Egocentric spatial orientation deteriorates with age and more significantly with AD. A simple and quick virtual reality (VR) localization and target finding technique is presented as a diagnostic aid to screen mild cognitive impairment (MCI) from AD. Spatial orientation data from 93 individuals (65 AD at a mild stage, 20 MCI, and 8 other dementia types) based on VR localization of a target on a landmark-less cubic 3-story building were analyzed. We hypothesize AD and MCI groups' performances are significantly different. AD and MCI spatial performances were statistically significantly (p < 0.001) different. These results plus the longitudinal tracking of three patients who developed AD over a period of 5 years suggest the proposed spatial tests may be used as a quick and simple clinical diagnostic aid to separate AD at early to mild stages from MCI.

Do Older and Young Adults Learn to Integrate Geometry While Navigating in an Environment of a Serious Game?

We evaluated the outcomes of an intervention using a serious game designed to be played on iPads for improving spatial reorientation by training users to integrate geometry of the environment, instead of relying solely on featural cues. Using data logged online through a clinical study of using this game, the effect of training among 16 older adults (69.3 ± 6.4 years, 4 males), who played the game repeatedly (self-administered) over a period of 8 weeks, was investigated. The game contains a hexagonal room with 3 objects, textured walls, and grids on the floor, which are removed one by one as the participant played the game. In each level, the room also rotates such that the viewpoint of the user is different from that of the previous level. Participants cannot play a higher level unless they make no mistake during the trials of the lower test level. In addition to data of older adults available from that clinical trial, we recruited 16 young adults (27.3 ± 5.6 years, 4 males) to play the game for 5 sessions and compared their results with those of the older adults. We evaluated the error type made in each test level and the scores for each session among older adults. Further, we compared the frequency of each error type between young and older adults during the test levels that a landmark adjacent to the target was removed over the first 5 sessions. The results of older adults' performance suggest they learned to make fewer mistakes over the sessions. Also, both young and older adults learned to integrate the geometrical cues rather than relying on the landmark cue adjacent to the target to find the target. Overall, the results indicate the designed hexagonal room game can enhance spatial cognition among all age groups of adults.

A Novel Program to Improve Cognitive Function in Individuals With Dementia Using Transcranial Alternating Current Stimulation (tACS) and Tutored Cognitive Exercises.

The effects of cognitive exercises on the healthy aging population is controversial. Transcranial alternating current stimulation (tACS) is considered a promising tool for modulating brain oscillation. Research is lacking on its long-lasting cognitive/therapeutic effect. This is the first pilot study to explore the effect of a regimen of cognitive exercises with and without tACS on older adults with dementia. The study groups were 28 individuals (age 56-83 years) enrolled into two groups: Exr Group, who received cognitive exercises only and the Exr + tACS Group who received tACS at 40 Hz simultaneously with cognitive exercises for a period of 4 consecutive weeks, 5 days/week, two 30 min-sessions/day; all the training sessions were tutored. The cognitive exercises were applied using the MindTriggers app. They were assessed at pre and post intervention and also one month after the end of trial (follow-up) with an independent assessment (WMS-IV) as the primary outcome measure. The results show significant cognitive improvement at post-intervention in both groups, while the Exr + tACS protocol lead to superior cognitive improvement at follow-up session. The most important outcomes of this study are: 1) The tutored repeated practice of the MindTriggers app exercises does significantly improve the cognitive functions of older adults with dementia and that that improvement lasts for at least one month after the end of the intervention, and 2) The application of tACS increases the positive effects of cognitive exercises with the positive effect lasting an even longer period of time than exercises alone; in other words we speculate that it may lead to long-term potentiation.

Older Adults Show Less Flexible Spatial Cue Use When Navigating in a Virtual Reality Environment Compared With Younger Adults.

Daily life requires accurate navigation, and thus better understanding of aging on navigational abilities is critical. Importantly, the use of spatial properties by older and younger adults remains unclear. During this study, younger and older human adults were presented with a virtual environment in which they had to navigate a series of hallways. The hallways provided 2 general types of spatial information: geometric, which included distance and directional turns along a learned route, and featural, which included landmarks situated along the route. To investigate how participants used these different cue types, geometric and/or landmark information was manipulated during testing trials. Data from 40 younger (20 women) and 40 older (20 women) adults were analyzed. Our findings suggest that (1) both younger and older adults relied mostly on landmarks to find their way, and (2) younger adults were better able to adapt to spatial changes to the environment compared with older adults.

Orientation in Virtual Reality Does Not Fully Measure Up to the Real-World.

Adult participants learned to reorient to a specific corner inside either a real or virtual rectangular room containing a distinct featural object in each corner. Participants in the virtual-reality (VR) condition experienced an immersive virtual version of the physical room using a head-mounted display (HMD) and customized manual wheelchair to provide self-movement. Following a disorientation procedure, people could reorient by using either the geometry of the room and/or the distinct features in the corners. Test trials in which the different spatial cues were manipulated revealed participants encoded features and geometry in both the real and VR rooms. However, participants in the VR room showed less facility with using geometry. Our results suggest caution must be taken when interpreting the nuances of spatial cue use in virtual environments. Reduced reliability of geometric cues in VR environments may result in greater reliance on feature cues than would normally be expected under similar real-world conditions.

Definite differences between in vitro actin-myosin sliding and muscle contraction as revealed using antibodies to myosin head.

Muscle contraction results from attachment-detachment cycles between myosin heads extending from myosin filaments and actin filaments. It is generally believed that a myosin head first attaches to actin, undergoes conformational changes to produce force and motion in muscle, and then detaches from actin. Despite extensive studies, the molecular mechanism of myosin head conformational changes still remains to be a matter for debate and speculation. The myosin head consists of catalytic (CAD), converter (CVD) and lever arm (LD) domains. To give information about the role of these domains in the myosin head performance, we have examined the effect of three site-directed antibodies to the myosin head on in vitro ATP-dependent actin-myosin sliding and Ca2+-activated contraction of muscle fibers. Antibody 1, attaching to junctional peptide between 50K and 20K heavy chain segments in the CAD, exhibited appreciable effects neither on in vitro actin-myosin sliding nor muscle fiber contraction. Since antibody 1 covers actin-binding sites of the CAD, one interpretation of this result is that rigor actin-myosin linkage is absent or at most a transient intermediate in physiological actin-myosin cycling. Antibody 2, attaching to reactive lysine residue in the CVD, showed a marked inhibitory effect on in vitro actin-myosin sliding without changing actin-activated myosin head (S1) ATPase activity, while it showed no appreciable effect on muscle contraction. Antibody 3, attaching to two peptides of regulatory light chains in the LD, had no significant effect on in vitro actin-myosin sliding, while it reduced force development in muscle fibers without changing MgATPase activity. The above definite differences in the effect of antibodies 2 and 3 between in vitro actin-myosin sliding and muscle contraction can be explained by difference in experimental conditions; in the former, myosin heads are randomly oriented on a glass surface, while in the latter myosin heads are regularly arranged within filament-lattice structures.

Usefulness of electromagnetic induction type of force transducer and actuator for myofibril mechanics.

A high performance device for measuring force and length change during myofibril contraction is fabricated. The principle of a device depends on the law of electromagnetic induction. Homogenized myofibrils were attached between two wires exposed in the uniform magnetic field by silicon adhesive under an inverted microscope. The purpose of this study is to examine performance whether the electromagnetic induction type of device actually works. Sensitivity and time resolution of force transducer was 50nN and 1ms respectively. Working displacement and time resolution of actuator as length transducer was 1-20 µm and 1.2 ms. We confirmed the performance of the device by showing appropriate force response to changes in length during myofibrils contraction, and possibility of application of the device to myofibril mechanics is discussed.