Words are, of course, the most powerful drug used by mankind. Not only do words infect, egotize, narcotize, and paralyze, but they enter into and colour the minutest cells of the brain.1
This feature issue of Topics in Geriatric Rehabilitation (TGR) focuses on plasticity and cognitive-communication interventions for individuals living with Alzheimer disease (AD). Alzheimer disease is one of the most common forms of dementia. Dementia is an acquired, persistent loss of intellectual abilities that includes significant impairments in memory and in at least 1 other sphere of mental ability. The initial presentation of AD involves difficulty with memory involving recent events and problems learning new material, problems with language, mathematical ability, and difficulty with judgment. As the condition progresses, individuals may experience difficulty with remote memory, language (aphasia), purposeful movement (apraxia); the ability to carry out instrumental and activities of daily living, walking, feeding, recognizing close relatives; and incontinence.2
Alzheimer disease is the most frequent neurodegenerative condition among older adults worldwide, and its prevalence rises exponentially with age, with rates doubling every 5 years. According to the World Health Organization, there are 18 million people living with a diagnosis of AD, and globally, the disease is expected to nearly double to 34 million by 2025. The full effect of population ageing and AD is yet to come to fruition, as the “global ageing crisis” will peak in the United States by 2023 and by the middle of the 21st century in most developed countries. In 2000, the direct and total national cost associated with AD in the United States was US $536 billion and US $1.75 trillion, respectively. The National Institute on Aging estimates that up to 50% of Americans older than 85 years may have AD. Currently, more than 5 million older Americans are living with a diagnosis of AD, not counting the roughly 200 000 individuals younger than 65 years with early-onset AD.
Much research is underway to investigate risk factors for developing AD or dementia. Among the most provocative theories linking behaviors with triggers of AD is the linguistic ability in early life (ie, the well-known Nun study). Others include occurrence of head injury, “brain reserve,” cardiovascular risk factors, exposure to neurotoxins or electromagnetic fields, smoking, and alcohol. Possible protective factors (for a review, see Graves, 2007) may be administration of anti-inflammatory agents; hormone replacement therapy; antioxidants; and cognitive, social, or motor enrichment (ie, aerobic exercise). The cause of AD remains a mystery and, as of yet, there is no cure.
While research is pointing the way to better rehabilitative treatments, it will possibly take many years before we know with certainty which modalities are best and which are ineffective. Since time is one resource people with neurodegenerative conditions, such as AD, have preciously little of, there is an urgent need for rehabilitation health care professionals to intervene in the process of AD. We believe that interventions that focus on tailored cognitive, linguistic, and social activity should be the standard of rehabilitative care for all people with cognitive impairment or AD. For this reason, this special edition is an important tool for the intervention and prevention of the common symptoms of this devastating disease. The information presented here can be readily applied in the practice for nonpharmacological approaches for AD.
Mapping the mind
Learning seems to trigger endogenous neurogenesis, synaptogenesis, and angiogenesis. While volumes have been written about the molecular mechanisms of learning-induced brain changes in healthy brain tissue, few reports have detailed the potential of the “injured” brain to change its structure and function in response to self-produced activity, a process known as plasticity. Recent meta-analyses by Schroeter and colleagues4 conducted with 1351 patients have attempted to uncover patterns of brain changes across disease severity. Results suggest plasticity patterns in early AD that affect architecturally specific brain areas: the transentorhinal and hippocampal regions, functionally the inferior parietal lobes and precuneous. Results further suggest that atrophy in transentorhinal area/hippocampus and hypermetabolism/hypoperfusion in the inferior parietal lobes predicts transition from amnesic mild cognitive impairment (MCI) to AD whereas changes in the posterior cingulated cortex and precuneous do not.4
The contribution by Nikki L. Hill, Ann M. Kolanowski, and David J. Gill extends these observations and gives an overview of the plasticity potential of the human brain in the early stages of AD (prodromal-stage amnestic MCI). Hill and colleagues' research summarizes studies by using biomedical brain imaging devices, such as functional magnet resonance imaging (fMRI), and positron emission tomography (PET), which characterize changes in brain activity in early AD. These imaging devices are in widespread clinical use in most major trauma centers where they produce 3-dimensional images of functional metabolic processes in the brain. In PET, which was introduced in the late 1950s by researchers at Massachusetts General Hospital, a radioactive tracer isotope is injected into the bloodstream, and as the tracer decays, its concentration in brain tissue is recorded by a PET scanner. Currently, differential diagnosis of MCI and AD is a challenge. This complicates the recruitment of homogenous samples of patients into intervention studies, tailoring treatments to patients at specific stages of the disease or interpreting results of prospective trials. Technologies such as PET and fMRI can reduce this uncertainty and be used as outcome measures of rehabilitative care.
Of interest to the readers of TGR, recently an advisory committee to the Food and Drug Administration approved the use of a new radioactive tracer isotope to assess the characteristics of amyloid proteins—or plaques—in the living human AD brain (for more information, see citation 5). As the readers of TGR know, amyloid plaques are a hallmark of AD. Once this tracer proves useful in research studies, it may eventually fill a major void in AD clinical care. How to harness the power of neuronal plasticity still remains a mystery, and many important clinical questions remain. Which factors are baseline predictors of rates of hippocampal atrophy in MCI? Are these factors different for individuals at different stages of AD? Which clinical paper-and-pencil tests correlate with changes in PET or fMRI in early AD? Are volumetric MRI more telling than clinical predictors of AD or early cognitive impairment? We are sure that we will be hearing great things from Hill's team in future reports.
Linguistic analysis of walking and talking
One purpose of rehabilitation is to restore quality of life. For many clinicians, the day-to-day challenge lies in keeping clients from disengaging physically, mentally, and socially. It is important to keep patients clinically engaged, because loneliness and living in isolation may be prodegenerative and may be associated with early symptoms of AD and motor decline. Social neuroscience is a branch of rehabilitation research that examines human physical, mental, and social engagements.5 Rehabilitative environments that promote social engagement and communication and minimize stress can improve rehabilitative outcome as well as decrease the psychosocial burden for the person with the diagnosis; yet, few studies have examined this in AD.
In their article titled “Watching What You Say: Walking and Conversing in Dementia,” Boyd Davis and her international research team (Margaret Maclagan, Tasos Karakostas, Simon Hsiang, and Dena Shenk) reported preliminary results of 3 therapeutic communication studies aimed to delineate the relationship between language interaction and questioning strategies among individuals with cognitive impairment and caregivers. Echoing Rudyard Kipling, the words we use shape our brain and our behavior—but what if the very communication that is used to shape this interaction instead triggers situations that lead to slips, trips, and injurious falls? Davis and colleagues introduced the concept of linguistic-communicative paradigms to study walking and talking among individuals with cognitive impairment. We think that this is a highly innovative and clinically relevant approach and will surely lead to deeper insights about the disease process and better treatments.
In their pilot studies, Davis focuses on the dyadic interaction, the relationship between question types and performance on standardized tests of gait (walking). The technology employed to study gait is fairly inexpensive and highly portable. The GAITRite (CIR Systems Inc, Havertown, Pennsylvania) portable mat, on which the subject walks (the “poor man's” 3-dimensional motion-analysis system), is an electronic gait-analysis system with embedded sensors, which measure temporal and spatial gait variables (ie, gait speed, cadence, stride time, stride length, single support, and double support time). Instead of bringing patients to the hospital or university setting, their research brings the infrastructure to the patients' home environment. What is so translational about this research is that Davis's research takes the science of gait and cognitive-linguistic dual-task analysis and brings it into a community-based neighborhood setting. Federal entities such as the Institute of Medicine and the National Institutes of Health support the use of translational research that brings infrastructure to community settings.
The authors' provocative results are that pause length is associated with the risk of dementia and specific gait markers that identify individuals at risk of AD. This opens up a new way of examining dementia onset and severity. While their report gives preliminary insights into the methodology and potential of their approach, we will be excited to learn more after forthcoming studies examining the risk of falls, accidents, and injuries in relation to question type, and how these indices relate to PET or fMRI data.
Nidhi Mahendra, Amanda Scullion, and Cassandra Hammerschlag's article titled “Cognitive-Linguistic Interventions for People With Dementia: A Practitioner's Guide to Three Evidence-Based Techniques” identifies the features of successful cognitive-linguistic interventions for people with dementia and provides descriptions of 3 such interventions: spaced retrieval training, memory books and memory wallets, and Montessori-based interventions. Mahendra and colleagues' well-written, thoughtful review article outlines impaired and spared cognitive-communicative abilities, details the impact of AD on human memory systems, and then goes on to identify and discuss salient components of cognitive and linguistic teaching and learning environments. Usually rehabilitation studies lack descriptions of their interventions, which makes it difficult to compare interventions from one study to another. Mahendra and colleagues' article is a welcome addition to the field.
Mahendra and colleagues review should help clinicians identify specific exercises and the stages of dementia for which they may be appropriate. Their article also is well suited for teaching memory systems and neurobiological substrates and can be especially valuable in the classroom when used together with Hill's article on plasticity mechanisms and Davis's pilot studies on communicative-linguistic markers. While much clinical research remains to be done in this important area, clinician-academicians such as Mahendra and Davis are already leading the way.
Cognitive training in mild cognitive impairment
The contribution by the international team of Fotini Kounti, Evaggelia Bakoglidou, Christina Agogiatou, and Magda Tsolaki with their colleagues Nancy B. Emerson Lombardo and Lynn Lazarus Serper reports on pilot work on the effect of cognitive training on standardized neuropsychological measures among 58 individuals with MCI. The study's intervention, RHEA, is a training program designed to enhance cognitive function and activities of daily living through the execution of motion instructions. This is a strong prospective trial. The control and intervention groups were well balanced at baseline. It is especially encouraging that parameters in the control group resisted change during the course of the intervention, while several of the parameters in the intervention group did improve. Future work should use randomized controlled designs, blinded assessors and statisticians, and more focused cognitive-linguistic interventions, perhaps of the paradigm suggested by Davis or Mahendra.
Nonpharmacological clinical trials on cognitive interventions in individuals with MCI are important because interventions at early stages of impairment may have an effect on the rate of progression of cognitive decline, may help to predict cognitive decline from premorbid status, etc. As in any rigorous clinical rehabilitation study, the intervention protocol, dosing, and treatment should be meticulously documented for future studies' development and translation to practical settings. In addition, the effect sizes and power should be reported. The effect size is expressed in standardized units and is available on most statistical software packages. Using the effect size, it is possible to compare the size of the treatment effect from one study to the next, and this also helps the field by making it easier to conduct meta-analyses. Meta-analyses may lead to treatment guidelines. Currently, there are few agreed-upon treatment guidelines in rehabilitation.
Although Kounti's study is not a randomized controlled trial (RCT), the study does raise many interesting questions, specifically, what was the mechanism of change and were the changes in standardized test scores clinically significant to the patient? What constitutes a clinically important change score? What constitutes a clinically important outcome for the patient? Further, what were the PET/fMRI profiles of patient responders versus nonresponders? In time, we are sure that these questions will be answered by this group's exciting research collaboration and others that will be motivated by their research.
Intergenerational behavioral treatments
We agree with scholars who argue that quality of health care will be affected by workforce shortages of physicians and geriatric health care providers. Of particular relevance is that as AD progresses, greater resources are required to maintain quality of life. Shortages in the workforce seriously threaten the quality and quantity of health care delivery. Solutions to this situation are desperately needed. While RCTs are the gold standard for efficacy studies, an RCT is not appropriate for many clinically important questions that transcend the Bio-Psych-Social model, such as “what is the experience like to be a student working with people with dementia from the perspective of students and mentors of students who work with people with dementia?”
Sharon Arkin's interesting article provides first answers to this question. Her article is titled “Service Learning Students as Alzheimer Treatment Providers: Long-term Follow-up Study Shows Continued Involvement in Education, Health Care and Service.” Arkins' research finally takes us to the level of the community by presenting results of her large ethnographic study describing the experiences (thoughts/feelings) of students who had worked with individuals with dementia as part of their “Elder Rehab” coursework with Arkin at the University of Arizona and whom Arkin had followed up 10 years later to investigate how the “Elder Rehab” experience had affected their career choices.
As anyone who has ever supervised students during internship experiences will know, mentoring students transitioning from academic to community-based settings is a very rewarding experience but one that has rarely been investigated systematically. It goes without saying that hands-on experiences during internships, volunteering, and service learning are the key to developing a deeper understanding of the issues of what it is like to provide care and supports for individuals with AD. Arkins' study suggests that these academic/clinical ties prepare students for life-long careers in the AD field. While there are excellent AD service-learning models to chose from, Arkins' is one of the few to describe the process in detail from her own perspective and from the perspective of the participant.
We hope the readers of TGR will be as delighted as we are with this collection of studies and that they will provide a blueprint for clinicians eager to develop academic-community interventions to improve the rehabilitative care of all individuals with dementia and MCI.
—Mark A. Hirsch, PhD
Department of Physical Medicine and Rehabilitation,
Carolinas Rehabilitation, Charlotte, North Carolina
—Patricia C. Heyn, PhD
Physical Medicine and Rehabilitation Department,
School of Medicine,
University of Colorado, Denver
1. Kipling R. The Times, , 1923.
2. Graves AB. Alzheimer's disease and vascular dementia. In: Neuroepidemiology: From Principles to Practice. Nelson LM, Tanner CM, Van Den Eeden SK, McGuire VM, eds. New York, NY: Oxford University Press; 2004:102–130.
3. Alzheimer's Association. Alzheimer's Disease Facts and Figures, 2007.
4. Schroeter ML, Stein T, Maslowski N, Neumann J. Neural correlates of Alzheimer's disease and mild cognitive impairment: a systematic and quantitative meta-analysis involving 1351 patients. Neuroimage. 2009;47(4):1196–1206.
5. Kolata G. FDA sees promise in Alzheimer's imaging drug. In: The Dana Foundation's: Brain in the news. Dana Press; 2011:1–2.