New Directions for AD Treatment—An Update

As scientists close in on this devastating disease, some research suggests there may be steps you can take to decrease your risk.

The search for ways to prevent and treat Alzheimer’s disease (AD) has been a long and arduous process. Although progress is being made in many areas, years of research still have not produced therapies that can stop or reverse the steady advance of this mind-wrecking neurodegenerative disease.

Yet scientists are accruing valuable knowledge about the characteristics of AD. New approaches are targeting not only the production and buildup of toxic proteins in the brain, but also the genetic changes associated with AD, the damaging effects of inflammation that accompanies the disease process, and even dietary and other lifestyle factors believed to be involved in AD risk and disease progression. Among these findings, there are some that point to steps individuals might take to help protect their brains against this disease.

“Our understanding of Alzheimer’s disease is growing, thanks in part to brain imaging technology, and there are several ongoing research projects that appear to be especially promising,” says Massachusetts General Hospital (MGH) geriatric psychiatrist Jennifer Gatchel, MD, PhD, an Instructor in Psychiatry at Harvard Medical School.

“However, we have not yet found proven strategies to prevent this disease, nor do we have therapies that can stop the damage AD wreaks on brain cells nor reverse that damage once it occurs. The development of new drugs and therapies is a time-consuming process that requires careful evaluation of the safety and efficacy of each approach. Fortunately, some of what we are learning suggests that there may be steps individuals can take on their own to help lower their AD risk.”

WHAT YOU CAN DO

For more information on Alzheimer’s disease studies and clinical trials, visit the following websites:

The National Institutes on Aging’s Alzheimer’s Disease Education and Referral Center, Clinical Trials, at http://bit.ly/1VgSoHA

Alzheimer’s Association, Clinical Trials for Alzheimer’s Disease and Dementia, at
http://bit.ly/1dRZCv5

CenterWatch, Alzheimer’s Disease Clinical Trials, at http://bit.ly/2no4Mf0

Three DIY Strategies

Three interesting studies suggest that a combination of lifestyle changes and mental stimulation may help decrease vulnerability to AD. The studies, summarized on page 7, involve strategies that individuals might adopt to help improve their resistance to cognitive decline:

1. The Metabolic Enhancement for Neurodegeneration (MEND) program combines various lifestyle approaches to address early signs of AD. In a small study, 10 participants with memory loss were treated with a personalized plan, which involved improving sleep; consuming a low-glycemic, low-inflammatory, low-grain diet rich in antioxidants; if needed, taking supplements of certain vitamins (B-12, D3 and K2), omega-3 fatty acids, and the spice curcumin; getting regular physical activity; lowering stress levels; and engaging in activities that provided brain stimulation, among other factors. Brain scans and neuropsychological testing revealed “unprecedented” improvements over the course of two years in all of the participants, many of whom regained normal cognitive functioning, according to a report published June 12, 2016 in the journal Aging. If confirmed by larger studies, the findings suggest that such a combined approach may reverse damage associated with early AD.

2. The FINGER study: This study involved 1,260 older participants who were in danger of cognitive decline. Half of participants worked closely with a medical team to maintain a healthy diet, engage in regular brain training and physical exercise programs that included both muscle and cardiovascular training, and manage metabolic and vascular risk factors through regular blood tests, and other means. The other half of the participants received health advice only. Over two years, the intervention group maintained stable cognitive performance or improved, while the control group declined, according to a report in the June 6, 2015 issue of The Lancet.

3. Processing speed training was used in a long-term study in which older adults participated in 10 to 14 brain-training sessions designed to boost processing speed and lasting an hour or slightly longer. The results suggest that such training may protect the brain for years. Those who engaged in the training experienced a 48 percent reduction in dementia risk over 10 years compared to those who received no training, according to a paper presented at the 2016 Alzheimer’s Association International Conference in Toronto. “Double Decision,” the cognitive training program used in the study is available on BrainHQ.com for $96. Free speed-of-processing games are also available online (examples: www.brain-improvement-tip.com/braingames, and www.wikihow.com/Increase-Your-Brain’s-Processing-Speed).

Drugs in the Pipeline

Drug therapies under development usually focus on one aspect of the complex interplay of factors involved in AD, in the hope of disturbing the processes that ultimately end in dementia. The following are some of the more promising new approaches now in the drug-development pipeline:

The BACE1 inhibitor: Now in Phase III trials, this drug aims to interfere with the formation in the brain of toxic beta-amyloid plaque, a hallmark of AD. Although the drug proved ineffective for people with mild-to-moderate AD, its developers hope that it will work in people in the very early, or prodromal, stage of the disease.

Aducamumab: Rather than preventing amyloid plaque formation, this drug is designed to remove plaque that has already built up in the brain. According to a report in the Aug. 31, 2016 issue of Nature, the medication, which involves the use of an antibody (or passive vaccine) against amyloid that is derived from healthy people who may have natural AD resistance, not only successfully removed amyloid, but also improved cognition in participants with early-stage AD. Side effects of the drug can be serious, however, and include small hemorrhages and swelling in the brain. Larger Phase III trials are now in progress in an effort to find the right balance between drug benefits and side effects.

AbbVie-8E12: This drug is an antibody that targets tau, the tangled brain fibers that, with beta-amyloid, are a hallmark of AD. AbbVie-8E12 is one of the few drugs in trials that targets tau. It is now in Phase II trials.

Riluzole: This drug has already been used safely in the treatment of amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and animal studies suggest it may help prevent neuronal loss associated with aging and disease. The drug addresses the abnormal accumulation of the neurotransmitter glutamate between neurons—which has been shown to damage brain circuitry—by promoting changes in genes that restore to youthful levels molecules responsible for clearing glutamate, along with genes critical for brain plasticity and communication among brain cells. The drug’s developers believe that the use of Riluzole in the early stages of AD might prevent or at least retard disease progression that leads to widespread irreversible neuronal loss and significant cognitive dysfunction. Human trials are currently under way.

Etanercept: Currently in Phase II human trials, this arthritis drug has been repurposed to target and reduce inflammation that aggravates and accelerates dementia and brain degeneration. The drug has a proven safety record, and an early pilot study in which cognitive decline effectively ceased in participants receiving the drug suggests it may help slow the progress of AD. MMM

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