Where Do We Stand in the Clinical Care of Alzheimer's Disease?

According to 2013 data from the Alzheimer’s Association, an estimated 5.2 million Americans have Alzheimer’s disease (AD). In the absence of a cure for this debilitating disease, much of the recent clinical research has focused on making earlier and more precise diagnoses, increasing tolerability of pharmacological treatment, and finding alternative therapies to improve quality of life. Clinical Geriatrics ^® ( CG) had the opportunity to interview Freddi Segal-Gidan, PA, PhD, Director and Principal Investigator, Rancho/University of Southern California Alzheimer’s Disease Center, about the current state of diagnosing and symptomatically treating patients with AD.

CG: In 2011, the National Institute on Aging/Alzheimer’s Association workgroups updated the clinical diagnostic criteria of AD from what had been outlined in 1984. What are the important changes in these criteria, and to what extent have these guidelines been applied in diagnosis and treatment of AD in your clinic?

Segal-Gidan: These new criteria reflect the advances in our understanding about the underlying biology and pathophysiology of AD and increased understanding of the clinical cours e. We now recognize there is a long and silent preclinical phase to AD with subtle, early changes involving both personality and cognition that were previously disregarded or not recognized. These changes have already taken hold in academic medical settings, and they are beginning to occur in community-based clinical settings.

There is increasing discussion of biomarkers, cerebrospinal fluid (CSF) analysis, and positron emission tomography (PET) scan with patients and family who present for diagnostic evaluation. The limiting factor to incorporating biomarkers in the diagnosis for many is the cost. Neither a CSF analysis nor PET imaging with Amyvid, a scanning agent, are routinely covered by medical insurance. Currently, treatment options are limited, but biomarkers may become more important in direct treatment options in the future.

The diagnosis of mild neurocognitive disorder was added in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Does this addition represent a new area of concern and treatment?

In our practice, we have long recognized that there is a spectrum of cognitive decline from normal to dementia that includes an intermediary stage, clinically called mild cognitive impairment (MCI). During the past decade, we have seen an increasing number of people present for evaluation who fall within this area of cognitive decline, either with no functional loss or loss that does not meet the criteria of dementia per neuropsychological testing. The advantage of early recognition of cognitive decline, such as MCI, is that it provides opportunity for patients to be directly involved in their care and in decision-making for future care needs. Increasingly, we also begin medications, such as acetylcholinesterase inhibitors, in patients with MCI, as the literature has shown that starting these drugs earlier may provide greater benefit. The other importance of MCI is that research studies, especially drug trials, are increasingly focused on patients with MCI in the hope that therapies may be more successful if started earlier. On the negative side, recognition of MCI/mild neurocognitive disorder means that individuals may actually have an increasingly longer course of disease and decline as we expand our definition, meaning that this diagnosis could lead to premature withdrawal from the workforce and have negative psychological consequences (ie, increased anxiety, depression, stigma), which are often reported by patients with AD and other dementias.

There seems to be a growing interest in the use of socially assistive robotics in the care of persons with Alzheimer’s and dementia, but the data evaluating their use are limited. Some robots can provide social aid (ie, playing music, reciting books); some can be used to provide cognitive games; and some can encourage mild forms of exercise. Can you briefly speak to what the literature shows regarding the potential for socially assistive robotics in this care setting?

I have followed the literature on the use of robots with keen interest.  I am most familiar with the work done by Dr. Maja Mataric at the Center for Robotics and Embedded Systems (CRES) at USC, who has researched the use of robotics in exercise with older adults.  This work is exciting and very promising, but I not aware of its movement outside of the research laboratory into practice. I am fascinated, but less familiar with the actual research, on the use of robots in group living situations (assisted living and skilled nursing facilities) as social aids.  Most of the work seems directed toward robots as substitutes for humans in repetitive tasks that often can become boring for the provider with the goal that the provider’s time (a most precious commodity) can be better utilized.  The initial concern was acceptance of the robots, but with improved design this has been successfully addressed. The biggest limitation at present I believe is cost, both initial investment and maintenance.   

Dietary and herbal supplements and medical foods are being marketed as AD prophylaxis, but data guiding the safety and efficacy of these products are lacking since the FDA does not regulate them. Do you recommend any supplements or medical foods to your patients?

In our practice, we focus primarily on evidence-based recommendations, for which there are none that support the use of any particular supplement or medical food, that I am aware of. However, we also recognize the widespread use of dietary and herbal supplements and the strong desire among patients and families to try anything given the limited pharmacologic treatment options currently available. The advantage is that most supplements and medical foods do not cause any harm, except to the pocketbook. I become most concerned when people are spending significant money out of pocket on these products, so I try to have frank discussions with them on what is reasonable as far as use, cost, and expectations. We recommend against gingko biloba for most older adults due to the concern for increased risk of bleeding—particularly for those on anticoagulants—but also in general because of the widespread use of NSAIDs [nonsteroidal anti-inflammatory drugs] in older adults.

What is on the horizon in terms of pharmacological management of AD?

The hope and goal is for disease-modifying treatments. We need to identify agents that can ideally stop, or at least slow down, the underlying biological changes, the development of beta-amyloid plaques and tau “tangles” that lead to neuronal death and destruction. We have been successful in developing better diagnostic tools with CSF biomarkers and PET scans that can demonstrate the amyloid protein, but we do not yet have the treatment options to go with these tools. Most of the pharmacologic treatments currently in clinical trials use infusion delivery as the administration method, as it is thought to be the most effective for delivery across the blood-brain barrier. However, this is a costly delivery system, and I am concerned that the cost will be prohibitive even if an agent can be identified as a viable treatment.

Almost all pharmacologic management to date is focused on cognitive decline and utilizes cognitive outcome measures. Little has been done to address the behavioral symptoms, which in my experience are often the most disturbing and difficult to manage. The pharmacologic treatments we have for behavioral disorders associated with AD and other dementias are far from ideal, were developed for younger populations with other psychological conditions, and have many limitations when applied to this population.

What barriers remain in AD research?

The two major barriers to Alzheimer’s research are money and participation. AD may be among the most underfunded medical conditions. As a country when we put our money and best minds into solving a problem, we are usually successful. If we did this for AD, I am optimistic we would have treatments, and maybe even a cure. AD is a slow, progressive disease, and thus research involves participation over rather extended periods of time (6-18 months) to have outcome measures that are meaningful. We would be able to see results much sooner, even preliminary results, if we could get people to participate in research. There are other unique barriers to research participation for people with AD, or even MCI, that need to be addressed: time (eg, infusions take 1 hour or longer and are done frequently), transportation (eg, cognitive impairment can lead to driving cessation), need for a study partner, need to remain in one location for an extended period time, and so forth.