Because of the significant risk associated with carrying two copies of APOE4, researchers began investigating the potential of treating APOE4 homozygotes (with Mild Cognitive Impairment [MCI], mild dementia, and moderate dementia due to Alzheimer’s) via intrathecal administration of AAVrh.10hAPOE2 (serotype rh.10 adeno-associated virus gene transfer vector expressing cDNA coding for human APOE2) directly to the central nervous system/cerebrospinal fluid. The goal of this approach is to increase the expression of APOE2 and overcome the harmful effects of APOE4.

In preclinical research, AAVrh.10hAPOE2 was tested with mice expressing human APP, PS1, and APOE4. Intracerebral delivery resulted in widespread brain expression of APOE2 as well as decreased beta-amyloid levels and amyloid deposition. Widespread expression of APOE2 was also observed in nonhuman primates two months after intraparenchymal, intracisternal, or intraventricular delivery of AAVrh.10hAPOE2.

In 2019, Weill Medical College of Cornell University began a Phase 1 trial, set to end in January 2024, evaluating LX1001 (AAVrh.10hAPOE2) in 15 volunteers who carry two APOE4 alleles, confirmed amyloid deposition, and a clinical diagnosis of MCI to moderate dementia. In March 2022, the FDA granted LX1001 Fast Track designation.

Improving and Accelerating Clinical Trials Assessing Gene Therapy for Alzheimer’s Disease

It is clear that gene therapy for Alzheimer’s disease is a promising area of clinical research, and advancements in neurosurgical techniques now enable reliable delivery of therapeutic vectors with real-time verification—yet several issues, such as the following, are hindering the ability to bring therapies to market quickly and help Alzheimer’s disease patients:

Using Augmented Reality for Dementia Diagnostics and Therapeutics

Healthcare is currently undergoing a digital transformation, generating a whole new approach to healthcare. Big data, mobile devices, wearable devices, and innovative artificial intelligence are changing the game, opening up a whole new paradigm in medicine.

This digital transformation will change the way we diagnose, monitor, and even treat symptoms of a breadth of diseases, including neurological diseases. For patients, this means being able to take their health into their own hands using new digital technologies, and for national healthcare systems, this means being able to utilize resources more efficiently while simultaneously improving patient engagement and patient outcomes.

Virtual and augmented reality for dementia are two of the newest additions to this digital revolution and have applications spanning the diagnostic and therapeutic spectrum.

Let’s take a closer look at how virtual and augmented reality are making their way into the neurological disease space.

Applications of Virtual and Augmented Reality for Dementia

According to Allied Market Research, the market for virtual and augmented reality in healthcare is expected to reach $2.4 billion by 2026. The growing demand for new, innovative diagnostic and therapeutic techniques, alongside increased awareness surrounding applications of virtual and augmented realities technologies, is quickly bringing immersive technologies into the neurological disease space.

Highly personalized, patient-oriented medicine is now within reach and includes augmented reality for supporting dementia patients with everyday tasks and managing behavioral symptoms of dementia, psychological need-based virtual reality experiences, and artificial intelligence to diagnose Alzheimer’s disease.

Neurocognitive Training Through Augmented Reality

Neurocognitive deterioration in patients with dementia, particularly those with dementia caused by Alzheimer’s disease, is known to negatively impact patients’ abilities to complete complex Activities of Daily Living (ADLs), such as shopping for groceries, navigating routines, and preparing drinks and meals. The ADL capacity of a dementia patient greatly influences their ability to live and function independently.

In an effort to find an avenue for patients to practice and potentially improve upon these activities to remain independent, researchers have begun investigating using virtual and augmented reality for dementia patients.

In a 2019 study, researchers aimed to analyze the feasibility and usability of a head-mounted Microsoft HoloLens to support patients with Alzheimer’s disease in executing the ADL of tea making. While executing this task, patients received three-dimensional dynamic holographs of the sub-steps required to complete the task.

Although they did not find that the guidance and support provided by augmented reality reduced errors or improved success rates, the overall acceptability of this application was high. Researchers concluded that the biggest impediment was the bulky hardware, and overall, the paradigm of augmented support is generally working, but the implementation itself needs improvement (e.g. through an improved user interface).

Virtual Reality for Mild Cognitive Impairment and Dementia

Virtual reality-based interventions are also making their mark in research and clinical trials. Over the last few years, researchers have investigated the potential of virtual reality to improve balance and reduce fall risk, reduce aggressive behaviors, and improve overall interactions and behaviors with caregivers.

Balance, gait, and fall risk: A 2019 pilot study aimed to assess the feasibility, patient experience, and effects of a novel sensor-based balance training program using an interactive virtual user interface for patients with Mild Cognitive Impairment (MCI). The training included weight shifting and virtual obstacle crossing. When measuring post-intervention effects of the patients with MCI, they found that sway and fear of falling were reduced, indicating this method is beneficial for improving postural control.

Behavioral and psychological symptoms of dementia (BPSD): A 2021 study aimed to develop a virtual reality intervention program for dementia patients in nursing homes to reduce BPSD and assess the program’s feasibility. Surveys and questionnaires were utilized to identify specific activities that alleviated BPSD among patients. Patients used arm motions in their virtual environment to choose the virtual location to visit and interact with. The study demonstrated the feasibility, safety, and patient satisfaction of the program and warrants further research to determine if the program can be utilized to reduce BPSD in dementia patients.

Altoida’s mission is to accelerate and improve drug development, neurological disease research, and patient care. To learn more about our precision-neurology platform and app-based medical device, contact us!

APOE Allele	Genetic Significance
APOE2	APOE2 is relatively rare and may provide individuals with some level of protection against Alzheimer’s disease. Experts estimate that carrying two APOE2 alleles (or one APOE2 and one APOE3) may reduce the risk of developing Alzheimer’s by up to 40%. Typically, if an individual with this allele does develop Alzheimer’s, the development of the disease occurs later in life compared to an individual with the APOE4 allele.
APOE3	APOE3 is the most common APOE allele and is currently believed to play no role in increasing or decreasing the risk of developing Alzheimer’s disease.
APOE4	APOE4 is believed to increase the risk of developing Alzheimer’s disease and is associated with an earlier onset of the disease. Approximately 25% of people carry a single copy of APOE4, and 2% to 3% of people carry two copies. Individuals with one copy have an increased risk of developing Alzheimer’s. The presence of two copies is a stronger indicator that an individual may develop the disease. More specifically, carrying one copy of APOE4 may increase Alzheimer’s risk by two to three times, while carrying two copies may increase risk by up to 12 times.