While Understanding of Alzheimer's is Evolving, Countless Unanswered Questions Remain

Speaking at the Pri-Med West meeting in Anaheim, California, Gary Small, MD, a Professor of Aging and the Director of Geriatric Psychiatry at UCLA’s Brain Research Institute started off with an easy humor.

“How many of you heard me speak before?” he asked, eliciting a large show of hands, before following that up with “How many of you can’t remember?” He cracked that some redundancy might be good, given the importance of repetition in maintaining memory.

The session was geared around dementia, which according to Dr. Small is any cognitive impairment that can interfere with daily life. Citing that 70% of dementia cases are actually Alzheimer’s, his speech circled around two questions: do we have any control over our brain health as we age, and if we do, is it possible to forestall symptoms of Alzheimer’s?

In terms of longer lifespans due to medical developments and the inevitable increase in dementia prevalence for a population living longer, he said that “we are victims of our own success.” It is currently believed that 5 million Americans currently have Alzheimer’s; by 2050, he says, there’ll be nearly 15 million Americans with it.

There is inherent difficulty in correctly predicting and diagnosing Alzheimer’s, since, as Small colossally understates, biopsies are quite invasive. There are genetic factors that may tie in, but there remain no definite methods. The presence of the APOE-4 allele in one’s genetics may predict an increased risk of developing the disease, but he cautions against using it, or other potentially related genes like TOMM-40 and TREM2, as predictive tests. Those with the genes present but who live healthy lifestyles are still less likely to develop Alzheimer’s than those without them who live less mindfully.

Understanding, however, has still improved in recent years. It is now known that the onset of Alzheimer’s follows a remarkably consistent pattern, with the disease’s signature “plaques and tangles” beginning to accumulate in the brain and invade it from the bottom up.

Small maintains that there is no “gold standard” assessment in diagnosing the condition, but that a battery of tests may hone in on a good diagnosis. Knowledge of genetic predisposition, lifestyle, symptoms, and then MRIs and blood tests in combination can give clinicians enough ammunition to make the proper call.

Differentially diagnosing dementia and depression can also be difficult, as many times patients will come into an office carrying symptoms of both, and it’s possible that the conditions may feed each other. The frustration of Alzheimer’s can spur depression, and stress is widely considered a risk factor for Alzheimer’s.

Treatment itself also remains murky. If the three most important words in real estate are “location, location, location,” Small says, the three most important for Alzheimer’s management and prevention are “timing, timing, and timing.” As it stands, the drugs developed for the condition have largely been symptomatic, referring to those approved in the late 1990’s and early 2000’s like tacrine and memantine. Cholinesterase inhibitors like tacrine and donepezil can also carry a host of adverse effects, and they have a hearty list of potentially problematic drug interactions.

The focus of Alzheimer’s science today is increasingly, as Small believes it should be, on actual disease-modifying drugs. There’s plenty of research going on in the space of monoclonal anti-amyloid antibodies for prevention, though “whether that works or not, I don’t know,” Small says. There is even work on insulin nasal sprays, he says, due to a link between Alzheimers and diabetes, and his team is trying to get into work around using focused ultrasound waves.

With a range of innovative potential treatments, he says, many are using biomarkers to try to understand what does and does not have an impact. “Even the biomarker research can be complex,” he says, though, since often times the biomarkers that science currently has don’t actually correspond with symptoms themselves: “‘The good news is, your scan looks great, the bad news is, you won’t remember this conversation.’ We want to develop a surrogate marker where there’s actually tracking of the test in the treatment.”

In the meantime, the best advice he seemed to hold was to live well. Exercise is essential, and mental exercise may be an intriguing developing field. Computer and mobile games could emerge as a key tool, according to Small: “There are certain computer games that have actually been shown to boost mental acuity,” he said. Scientists at UC San Francisco have found that you can teach a 70 year old after a few weeks to operate within a game at the same level as an untrained 20 year old. He also mentioned, to a series of hushed gasps, that surgeons who play video games have been found to make less operating mistakes.

Caring for Alzheimer’s patients remains tricky, and often takes a toll on those responsible for it. “There is a tremendous caregiver burden,” he says, “When a full-time caregiver comes in the office, think depression. At least 50% of them develop clinical depression.”

For his own part, Small says his team at UCLA is doing what they can. “We’re doing studies trying to fight inflammation in methods that are non-toxic, using curcumin…we’re doing double-blind, placebo-controlled studies to try to understand this,” citing that in India, where much turmeric (from which curcumin is derived) is consumed, there are lower rates of Alzheimer’s.

Concluding, he says “I think we’ve come a distance in terms of better diagnostic and treatment strategies and we’re really helping a lot of people today…but while we’re waiting for the science to catch up, it’s clear that there’s so much we all can do to try to stave off symptoms of dementia and Alzheimer’s.” Half of all cases of the condition, he said, stem from behavioral patterns that can be modified.