Alzheimer`s Disease and Dementia Spotlight

Interview: 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. Annals of Long-Term Care^® (ALTC) 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.

ALTC: 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 course. 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.

Clinical Trial Seeks to Pinpoint Reasons for High Rate of Medication Discontinuation Among Users of Acetylcholinesterase Inhibitors

Acetylcholinesterase inhibitors (AChEIs), including donepezil, rivastigmine, and galantamine, are the main-stay drugs for symptomatically treating patients with mild to moderate Alzheimer’s disease. Although these agents have similar efficacy profiles, few studies have compared them in terms of adherence, as these agents have been associated with such side effects as nausea, vomiting, and diarrhea. The approximate rate of discontinuation of all AChEIs is reportedly in the range of 30% by 12 weeks. A group of Indiana-based researchers is currently conducting the first randomized controlled trial to evaluate adherence to AChEIs among older adults with Alzheimer’s disease. Led by Noll L. Campbell, PharmD, Department of Pharmacy Practice, Purdue University School of Pharmacy, West Lafayette, IN, investigators have already enrolled 140 patients with Alzheimer’s disease during the past 2 years from a memory care practice of the four healthcare systems located in central Indiana. Per the enrollment criteria, the patients have agreed to initiate therapy with an AChEI, excluding those who are already receiving treatment with an AChEI. Patients will be randomly assigned to receive either donepezil, rivastigmine, or galantamine. The two primary outcome measures will be tolerability and discontinuation rate among the three medication groups.

The data will be collected via telephone-based surveys at baseline, 6, 12, and 18 weeks; and rates of medication discontinuation and adherence will be assessed through electronic dispensing and claims records retrieved from participating pharmacies and payer sources within the Indiana Network for Patient Care. The survey will be administered by a research assistant, who is blind to the randomization allocation and will ask the patients’ caregivers about adverse events and adherence. The approximate date and reason for discontinuation will be noted. In the study protocol report, which was published in July in Trials, the researchers noted, “This study also has the potential to advance theories of tolerability among participants using novel covariates that may predict clinical outcomes and translate to future scientific work within this vulnerable population.” Read more about this ongoing trial.

White Paper Defines Best Practices of Palliative Care in Dementia Patients

Patients with dementia at the end of life benefit from palliative care. Many healthcare providers, along with the input of patients and their family caregivers, choose a palliative approach, thereby prioritizing relief from suffering over potentially invasive life-prolonging treatments for comorbid medical conditions. There are evidence-based guidelines to aid decision-making in some clinical situations, such as palliative care of pressure ulcers and use of feeding tubes; however, there is no consensus-based definition of palliative care in dementia—until now. In July, a team of experts from the European Association for Palliative Care (EAPC) published a white paper defining optimal palliative care in older adults with dementia. The paper can be found online ahead of print in Palliative Medicine.

The EAPC team performed a Delphi study to build systematic consensus of the core domains of palliative care in dementia patients. Based on reviews of the literature, position papers, legal documents, and clinical experience, the team developed a set of 11 domains and 57 recommendations, which were then evaluated by 89 experts representing 27 countries. Full consensus was reached on the following eight domains: person-centered care, communication, and shared decision-making; optimal treatment of symptoms and providing comfort; setting care goals and advance planning; continuity of care; psychosocial and spiritual support; family care and involvement; education of the healthcare team; and societal and ethical issues. After revision, the team reached full consensus on the prognostication and recognition of dying, and moderate consensus on the different stages of dementia as they relate to care goals, and recommendations regarding nutrition and hydration.

The authors made several observations about the results of their Delphi study. The available evidence is stronger in long-term care settings than in community settings, they noted, likely because more patients with dementia die in this care setting. “When palliative care is initiated early, professional caregivers with only limited experience of people with dementia may require guidance. Therefore, palliative care research for dementia patients at home and in hospitals deserves more attention,” the authors wrote. Another high priority for future research is refining the goals of care across dementia stages, especially given the increasing possibility of early diagnosis. The authors advise that healthcare administrators refer to this white paper as a framework to help identify gaps in curricula or in information provided to families; to develop quality indicators; and to develop and enforce policies.