Where are we now with neurotech for Alzheimer’s disease and dementia?

Just over 7 years ago the U.S. launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, an innovative effort to explore, develop and treat conditions of the human brain. Since then there has been about $1.3 billion dedicated through the National Institutes of Health to develop new tools, diagnostics and treatments for conditions of the brain and central nervous system. Today, there is a consortium of brain research initiatives around the world to build a collective understanding of this precious human organ. Conditions such as Alzheimer’s disease and dementia plague our aging population and is now migrating to younger and younger adults. June is Alzheimer’s disease awareness month. In this posting, we will explore what we currently know about neurotechnologies applicable to this condition and some of the promising research.

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Anyone who has had a family member, spouse or friend with Alzheimer’s disease or dementia understands the hidden challenges and daily struggles for the person living with the condition as well as caregivers and support systems around those individuals. More broadly, there is a societal impact with nearly 5.8 million Americans living with Alzheimer’s disease. Women are more prevalent to be afflicted with the disease while those of African-American and Hispanic descents are also highly susceptible to the disease. Medicare’s and Medicaid’s costs to care for individuals with Alzheimer’s disease and other dementias are projected to grow to $770 billion by 2050.

This societal impact coupled with the collaborative research efforts like the BRAIN initiative have reaped innovative research discoveries and commercialization developments in the field of neurotechnology. This not only includes potential treatments for those living with the condition but also tools for early diagnosis or preventative measures.

What does neurotech have to offer now?

For so many progressive neurological conditions, early diagnosis is pivotal to drive treatment, therapies and quality of life. Neurotech tools are currently available to aid in that diagnosis. Technologies using electroencephalogram (EEG) technology is one modality. Evoke Neuroscience offers a device that uses computational EEG and ERP (event related potentials) to reveal functional alterations in the electrophysiology of neurons that are present during the earliest stages of Alzheimer’s disease, before symptoms even appear. Other device companies using EEG as diagnostic tools include Neuronetrix, ANT, EGI (Philips) and Compumedics. These devices can be accessed through a physician and can help them detect mild cognitive impairments, differentiate dementia from pseudo-dementia, and evaluate cognition.

Another assessment tool being developed by Winterlight Labs uses tablet-based software to monitor cognitive decline based on speech analysis. Based in Toronto, the software company’s tool takes inputs while the person talks into a tablet device. Using linguistics and artificial intelligence, the software identifies a biomarker related to dementia and Alzheimer’s disease.

Other noninvasive approaches are also available for AD treatment. A cortical enhancing technology uses transcranial magnetic stimulation (TMS) combined with cognitive training to induce long-term potentiation in brain regions affected by AD. One such technology is a tool to help treat or slow the progression of AD or dementia. Brainsway offers a clinical treatment using deep transcranial magnetic stimulation (TMS) of the brain. This is a widely available treatment for drug resistent depression and pain. It is showing potential with AD and dementia but not specifically approved yet. Another neurotech company is developing a transcranial electromagnetic treatment device designed to break-up small abnormal amyloid and tau oligomers that are thought to initiate and propagate the AD process.

There are also home-based cognitive training programs that could help with prevention. These are technologies and software products that exploit cortical plasticity principles to aid individuals with cognitive impairment. Neofect Cognition is one cognitive program that helps people to benefit from brain activation and dementia prevention. It is an online interactive tool for either attention training or memory exercises.

Other efforts seek to develop noninvasive optical stimulation to restore gamma oscillation, which in turn activates the microglia cells to remove beta amyloid plaques in the brain. The amyloid plaques are considered to play a key role in the progression of Alzheimer’s disease. An example is a company based in Israel, NeuroAudit, who is developing brain stimulation tools.

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Under development are some promising technologies

Several startup neurotechnology firms are investigating neuromodulation therapy as a treatment for Alzheimer’s disease. Deep brain stimulation (DBS) therapies for Alzheimer’s disease and mild cognitive impairments is one option. Andres Lozano at the University of Toronto originated the concept of treating memory disorders using DBS. The primary target is the fornix. In 2015, investigators affiliated with Functional Neuromodulation reported results from the ADvance study of DBS of the fornix for treatment of mild Alzheimer’s disease. They reported that treatment with DBS suggested clinical benefit at 12 months in patients aged 65 or older. Though the slowing of clinical decline as measured by cognitive testing was not statistically significant, there was a significant improvement in glucose metabolism in key memory circuits between treatment and control arms of the study.

Following this study, two research teams and one neurotech startup firm have been investigating different brain targets and therapeutic approaches to treating the disorder. Dan Rizzuto’s team at Penn State has reported positive results using cortical stimulation of the lateral temporal lobe to improve memory in people with Alzheimer’s disease. Rizzuto has spun off a commercial firm, Nia Therapeutics, to further develop the technology. Rizzuto described his team’s strategy of only delivering stimulation during periods of bad memory performance. Delivering stimulation during good memory period actually interferes with recall. Their research team identified an electrocorticography (ECoG) biomarker based on the presence of both high frequency and low frequency oscillation to characterize good versus bad memory states and uses that indicator to drive stimulation.

Another research team at Ohio State’s Wexner Medical Center reported positive results from stimulation of the frontal lobes in three patients with Alzheimer’s disease. Reporting in the Journal of Alzheimer’s Disease, Douglas Scharre and colleagues from the Neurological Institute at Wexner found that DBS targeting frontal brain regions can reduce the overall performance decline typically seen in people with mild or early stage Alzheimer’s. “The frontal lobes are responsible for our abilities to solve problems, organize and plan, and utilize good judgments. By stimulating this region of the brain, the Alzheimer’s subjects cognitive and daily functional abilities as a whole declined more slowly than Alzheimer’s patients in a matched comparison group not being treated with DBS,” said Dr. Scharre. All three study participants showed improvement. One subject was not doing any meal preparation when she entered the study in 2013, but after two years of DBS, she could independently initiate preparations of a simple meal, assemble ingredients, and cook the meal.

Here are some additional clinical trials that involve neurotech interventional treatments and with results posted online. More information about these trials and results are available on Clinicaltrials.gov

  • Effect of Repetitive Transcranial Magnetic Stimulation on Language in Alzheimer’s Disease. This study was sponsored by the New York Memory Services organzation and aimed to investigate the efficacy of targeted repetitive transcranial magnetic stimulation (rTMS) on expressive language in people with Alzheimer’s disease (AD). In rTMS, magnetic pulses are used to non-invasively stimulate focal areas of cortex of about a square centimeter in area. Identifier is NCT00814697
  • Effects of Transcranial Direct Current Stimulation on the Apathy of Alzheimer’s Disease. This study was sponsored by the University of Sao Paulo and was investigating the effects of repeated transcranial direct current stimulation for the treatment of apathy in moderate Alzheimer’s disease in patients selected from an outpatient clinics in São Paulo, Brazil. Identifier is NCT01481558
  • Effects of a Combined Transcranial Magnetic Stimulation (TMS) and Cognitive Training in Alzheimer’s Patients. This study was sponsored by Beth Israel Deaconess Medical Center with Neuronix Ltd. The aims were to investigate the potential benefits of combining cognitive training (mental exercises) together with transcranial magnetic stimulation (TMS) to see if this can make a difference in the condition of people with Alzheimer’s disease. Identifier is NCT01504958
  • Enhancing Spatial Navigation Using Non-Invasive Brain Stimulation. This study was sponsored by the VA Office of Research and Development. It aimed to examine whether non-invasive brain stimulation, specifically transcranial direct current stimulation, can improve allocentric navigation in healthy older adults and patients with mild cognitive impairment. Identifier is NCT01958437
  • The Effect of rTMS Treatment on Alzheimer’s and Sleep Quality. Sponsored at the University of Manitoba, this study aimed to determine whether repetitive transcranial magnetic stimulation (rTMS) could be potentially used as a treatment for Alzheimer’s disease. rTMS is a technique that stimulates the brain by rapidly switching a magnetic field in a coil placed over your head. Identifier is NCT01894620
  • Efficacy of 1072nm Infrared Stimulation on Executive Functioning in Dementia. This study was sponsored by the Quietmind Foundation in collaboration with Maculume Limited. The study was to assess the effect of 1072nm infrared (IR) phototherapy on the behavioral and cognitive symptoms associated with early and mid-stage dementia. Identifier is NCT01059877

Currently, there is no cure for dementia or Alzheimer’s disease but better diagnostic tools can help to detect the conditions earlier than when symptoms become apparent. Plus, promising neurotech treatments could lead the way to improve quality of life today and open a path to a cure tomorrow.

Neurotech Network offers free resources and a directory of devices specifically for Alzheimer’s disease and dementia. Check out our resource page here.

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The content for this article was provided by Neurotech Network. The source of references include the World Health Organization, Alzheimer’s Association and clinicaltrials.gov.

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