August 5, 2016
The Huffington Post
Howard Fillit, MD

Last week, I headed to Toronto for the Alzheimer’s Association International Conference, which brings together leaders in research, caregiving, and advocacy. While there, I checked in with several of the researchers being funded by my organization, the Alzheimer’s Drug Discovery Foundation (ADDF), and attended many of the more than 100 scientific presentations on the schedule. I returned with optimism about the drugs in development to treat Alzheimer’s and what we can do now to help prevent it. These three trends were my takeaways from the conference.

1. Prevention is an important focus for researchers in the fight against Alzheimer’s. 
Some of the most exciting findings presented in Toronto came from researchers working on the ACTIVE study, the largest trial of “brain training” methods ever conducted. Using computerized “brain training games” developed by Posit Science, the researchers found that elderly people who received one specific type of training, called “speed of processing,” had significantly less cognitive decline and lower risk of dementia over a 10-year period than those receiving no training at all. This is the first study to show that a brain training game reduces your odds of developing dementia. The training also positively impacted daily life, demonstrating that it had a clinically meaningful effect. We don’t yet know “the mechanism of action” (i.e., what’s happening in the brains of people who play the game that protects it from dementia and decline), so future research should focus on finding out. Still, the ACTIVE study reinforces the importance of continuing to challenge yourself and remain mentally active throughout life.

In other prevention news, scientists from the preDIVA study, conducted over six years and led by scientists at the Academic Medical Center in Amsterdam (Netherlands), presented strong evidence showing that patients who lowered their risk of heart disease (through blood pressure medication and heart-healthy lifestyle changes) also slowed cognitive aging and reduced their risk of dementia. Additional research was presented on the benefits of aerobic exercise and high-quality sleep, and the cognitive risks of insomnia and sleep apnea. One study by researchers from multiple Korean institutions found that young and middle-aged individuals who did not sleep well had a higher risk of increased beta-amyloid proteins in their brains as they age. This is another area of research that should be further explored. Overall, the findings presented suggest that certain interventions can delay dementia and slow cognitive aging, which is good news for us all. The ADDF’s website has more information on the prevention of cognitive aging and dementia.

2. New treatments for Alzheimer’s are on the horizon and the pipeline of drugs in development is more diverse than it’s ever been. 
Although the first Phase 3 study of a drug that targets tau (from TauRx) had disappointing results, other types of anti-tau therapeutics are moving forward. These include immunotherapy “vaccines” (i.e., monoclonal antibodies) that are demonstrating safety and efficacy in early-stage studies, such as the Phase 1 study of C2N 8E12. Another drug in Phase 1 trials, MK-8719 from the biotech Alectos, in partnership with Merck, inhibits an enzyme that stimulates the production of tau tangles. (The ADDF provided early funding to scientists developing this drug at Simon Fraser University.) Some of these drugs are being tested against devastating and rare neurodegenerative diseases in which tau also plays a role, such as progressive supranuclear palsy (PSP). Other promising classes of potential Alzheimer’s drugs that reported results at the conference target systemic inflammation, neuroinflammation, genetics, epigenetics, mitochondrial dysfunction and neuronal energy failure, and vascular disease. It is encouraging to see so much diversity in research approaches. The ADDF was an early funder of many of these diverse therapies because we believe that Alzheimer’s is a complex disease and requires a multi-faceted approach to effectively treat it. I’m encouraged to see others now investing in these innovative drug targets.

Most of the other Alzheimer’s drugs in Phase 3 trials target beta-amyloid plaques, and some of these made news as well. Two drug classes—BACE inhibitors and immunotherapies using monoclonal antibodies—are moving forward. Early results are promising, and showing few side effects. Roche’s gantenerumab, an amyloid-focused immunotherapy, has completed a Phase 3 trial, with encouraging results on a number of measures in early Alzheimer’s. A 15-year post-mortem follow up on Elan Pharmaceuticals’ AN1792, the first amyloid immunotherapy for Alzheimer’s, found that beta-amyloid was cleared from the brains of a significant percentage of these patients. A number of studies of inhibitors of beta secretase (BACE), an enzyme that aids in the creation of beta-amyloid, also demonstrated promise. One of these BACE1 inhibitors, Janssen’s JNJ-54861911, was shown in its first clinical trial to reduce markers of beta-amyloid in the blood and spinal fluid of a significant number of patients with early Alzheimer’s. One or more of these drugs could be available to patients within the next two years.

3. New types of brain imaging are advancing that will enable both earlier and more accurate diagnoses of neurodegenerative diseases. 
Until recently, MRI and beta-amyloid PET imaging (which the ADDF supported) were the only types of brain imaging available to test for the presence of Alzheimer’s and related dementias. Now, several researchers, including Dr. Neil Vasdev at Massachusetts General Hospital, are developing PET imaging for tau, the brain protein that forms the “tangles” common in Alzheimer’s disease. And others are developing MRI contrast agents to better visualize beta-amyloid plaques. New MRI imaging techniques have also advanced our knowledge about vascular cognitive impairment and enabled better diagnosis for this common contributing factor to dementia in older people.

These advances are critically needed. Though Alzheimer’s remains the most common cause of dementia, we now know that some people diagnosed with it actually have other disorders. These include hippocampal sclerosis, suspected non-Alzheimer’s pathophysiology (SNAP), primary age-related tauopathy (PART), vascular dementia, and multiple forms of frontotemporal dementia. Accurately diagnosing patients allows for earlier and better treatment and means that clinical trials of promising drugs can enroll the right patients.