ABSTRACT

This literature review broadly examines disability in Alzheimer's disease (AD). The paper addresses the various types of disability in AD, as well as the presumed causes and the economic and social costs of such disability. The influence of various types of treatment of disability,

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Alzheimer's disease (AD), the most common type of dementia, is a progressive neurological disorder that increasingly robs individuals of cognitive, behavioral, and functional skills. Psychological and psychiatric disorders, such as depression, agitation, or paranoia, are also common. Risk factors for AD include advanced age, genetics (the presence of the one or two apolipoprotein E-4 alleles), as well as female gender and possibly previous head trauma. In terms of current prevalence rates, about 10% of the US population has AD at age 70, but this number increases to roughly 40% by age 90 (Green et al. 2002). Current estimates indicate that there are now about 4.5 million Americans living with AD (Herbert, Scherr, Bienias, Bennett, & Evans, 2003). Given that the symptoms of AD are so pervasive and that they impact every aspect of life, it is not surprising that significantly disability is associated with the disease, particularly in its latter stages, and that the care of afflicted individuals requires a major investment of societal resources. Moreover, given the increasing lifespan of the US and the likely increased prevalence of AD, further comprehension of the disability associated with AD is particularly relevant. The purpose of this article is thus to (a) describe disability associated with AD, (b) address the causes of such disability, (c) describe the economic effects of such disability and finally to (d) detail the effect of current treatments for AD. Disability, for our purposes, can be conceptualized as a reduction or loss of functional capacity resulting from an impairment, which for dementia is primarily secondary to cognitive deficits (Barberger-Gateau, Fabrigoule, Amieva, Helmer, & Dartigues, 2002).

Disability in AD

A voluminous literature documents the various types of disabilities common in AD. For clinical and research purposes, these are typically divided into difficulties with basic and instrumental activities of daily living. Instrumental activities include, among others, managing money, and making and keeping appointments, whereas basic activities include, among others, bathing, toileting, and eating. Such activities are critical for the ability to live independently, as well as to be self-sufficient in decision-making about personal, medical, and financial issues. Assessment of these activities of daily living is necessary for diagnosis as for instance, the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) requires that the cognitive deficits of AD "cause significant impairment in social or occupational functioning". These are assessed either via patient self-report (which becomes increasingly difficulty as the disease progresses), collateral report about the patient, or actual functional measures. The latter measures consist of tasks in which the examinee must, for instance, count money, dial a telephone, and put on a shirt. There are a variety of advantages and disadvantages of each approach, discussion of which is beyond the scope of this paper (for review see Demers, Oremus, Perrault, Champoux, & Wolfson, 2000).

What does the research literature say about such disability? First, there is no question that individuals with AD are disabled when compared to age-matched non-neurologically involved control participants. For instance, Lomax, Brown, and Howard (2004) found that individuals with AD scored approximately one standard deviation worse (a relatively large difference) than controls when patients and collaterals reported about a variety of tasks in the previous 24-hour period, such as self-care. When disability was conceptualized in terms of the International Classification of Functioning, Disability, and Health (ICF), Muo, Schindler, Vernero, Schindler, Ferrario, and Frisoni (2005) found individuals with AD to have the most impairment in cognitive areas, not surprisingly, but also in mobility, self-care, domestic life, as well as communication and interaction. These deficits were determined by a trained rater based on patient observation, collateral interview, and review of medical records. When individuals with mild AD were assessed on performance based measures, they performed significantly below published norms on the Direct Assessment of Functional Status (Farias, Harrell, Neumann, & Houtz, 2003). This task requires, for instance, telling time, writing a check, and preparing a letter. Second, and not surprisingly, individuals with more advanced AD have increased difficulties with both basic and instrumental activities of daily living versus those with mild or moderate AD (Suh, Ju, Yeon, & Shah, 2004). Su et al. (2004) also documented a decline in activities of daily living across all AD severities across a one-year time frame. More clinically, an individual with mild AD may still be able to live alone, manage basic activities of living, but need assistance with instrumental activities of living, whereas an individual with severe AD may be bed-ridden, unable to communicate meaningfully, and require 24-hour care.

In many studies, a significant amount of the variance in tasks of daily living is accounted for by cognitive functioning. For instance, Farias et al. (2003) found that cognitive or neuropsychological measures accounted for 50% of the variance on the performance-based measure noted above and 25% of the variance on an informant based measure of activities of daily living. These findings were from the total score on the activities of daily living measure and a variety of neuropsychological measures including those measuring memory and visuospatial construction. In another AD sample, Loewenstein, Rubert, Arguelles, and Duara (1995) found that a different set of neuropsychological measures accounted for roughly 20% of the variance in the same functional measure used by Farias et al. (2003), though data was not reported on an overall measure so a direct comparison can not be made. Moreover, Loewenstein et al. (1995) found that different tests predicted activities of living differentially based on the ethnicity of their sample (English or Spanish speaking). Baum, Edwards, Yonan, and Storandt (1995) took a broader approach and administered neuropsychological measures, as well as three functional tasks of activities of daily living. The Manual Apraxia Battery assesses a variety of skilled movements (e.g., Show me what you do with a cup), the Simulated Activities of Daily Living requires a range of everyday tasks (e.g., rise from a large chair, manage buttons), and the Kitchen Assessment Task has the examinee perform everyday kitchen activities (e.g., hand washing and making cooked pudding). Neuropsychological measures were strongly correlated with many of the tasks, except for the more routine motor tasks, such as rising from a chair and buttoning buttons. Broadly consistent with the above findings, Marshall, Fairbanks, Tekin, Vinters, and Cummings (2006) found significant positive correlations between AD pathology in several brain regions and scores on an activity of daily living scale as completed by collaterals of individuals with AD. The neuropathological measures, including neuritic plaque and neurofibrillary tangle counts, were done at autopsy and the activities of daily living scale was measured in the last year of life.

Cognitive deficits are not the only contributor to functional disability in individuals with AD--psychiatric disturbance, which is common in dementia (for review see Lyketsos, Lopez, Jones, Fitzpatrick, Breitner, & DeKosky, 2002), can also have a pernicious affect on disability status. Espiritu, Rashid, Mast, Fitzgerald, Steinberg, and Lichtenberg (2001) found self-reported depression in a mixed dementia sample (about 75% suffered from AD) to predict independently a measure of instrumental activities of daily living. In a study conducted in France with an unspecified dementia sample, Dorenlot, Harboun, Bige, Henrard, and Ankri (2005) found that depression was an independent risk factor for early institutionalization. For instance, almost 40% of dementia sufferers institutionalized in the first year after diagnosis also had major depression, whereas only 7% of those institutionalized more than two years after diagnosis had major depression. Other psychiatric issues may also be relevant, as Mok, Chu, Chung, Chan, and Hui (2004) found that hallucinations were negatively correlated to and significant predictors of two different measures of activities of daily living in individuals with probable AD. Additionally, McDaniel, Edland, & Heyman (1995) found that diminished insight in individuals with AD was associated with poorer activities of daily living. In addition to psychological issues, other factors such as health co-morbidities, social support availability and quality, treatment and rehabilitation availability and quality, and even familial attitudes toward depression can impact functional abilities in AD (Barberger-Gateau et al., 2002).

Costs Associated with AD

Given the significant disability in many individuals with AD, it is not surprising that the attendant costs, both economically and socially, are enormous. In estimating the economics of AD, two main types of costs are estimated--direct and indirect costs. Direct costs include medical care, treatment and care services, direct personal costs (e.g., home modifications), whereas indirect costs for both patient and caregiver include productivity losses, as well as the opportunity costs associated with travel and waiting for providers. Such an economic analysis does not address psychological burden, stress, and decreased quality of life in both patient and caregiver. These latter issues, particularly caregiver stress and burden, have been amply demonstrated and they have even independently predicted nursing home placement for the individual with dementia (Yaffe et al., 2002). Nonetheless, when direct and indirect costs are totaled, the estimated economic burden of AD is huge; a variety of studies using different economic approaches have estimated that the annual cost of caring for a patient with AD in the US to be roughly $40,000 to $50,000 per year in 2000 dollars (see Leung, Yeung, Chi, & Chu, 2003). For instance, Rice et al. (1993) estimated that mean care for institutionalized AD individuals in Northern California was $42,049 (in 1990 dollars) per year, whereas community based care was $12,572 per year. Importantly, the type of care needed and the cost is likely to vary significantly across dementia severity, as a mildly demented person with AD may remain at home, with some supervision, but a more severely demented person may require institutional placement and 24-hour care. Souetre et al. (1995), in fact, found that almost twice as much was spent in France for severely demented individuals versus those with mild to moderate dementia. In the above study by Rice et al. (1993), the total annual cost for caring for severely demented individuals in California institutions was estimated to be $52,667 and $39,558 for mildly to moderately impaired individuals. When the above figures have been applied across the number of individuals suffering from AD, the costs are staggering. Using 1997 dollars, the total cost was estimated to be $88 billion in the US (Meek, McKeithan, & Schumock, 1998).

Treatment of Disability in AD

The huge financial and societal cost of AD has served as one impetus for the development of a new class of medications in the past twenty years or so to treat and/or manage this disease. The largest number of these medications are the cholinesterase inhibitors (e.g., donepezil), which are designed to enhance cholinergic function, and thus cognitive functioning. In fact, research has demonstrated that, relative to a placebo group, AD participants who were prescribed donepezil, showed modest cognitive improvement or, at the very least, did not decline, over the short (24 weeks) treatment phase in one well-executed study (Rogers et al., 1998). Presumably, such improved cognitive functioning enhances activities of daily living; a variety of studies have demonstrated that these medications are in fact broadly effective in slowing the progression of AD. Mohs et al. (2001), in a one-year placebo controlled study of donepezil, found that AD participants taking this medication demonstrated stability in activities of daily living and their overall functional decline was delayed by about five month compared to controls. In a similar design with moderate to severe AD participants, Feldman et al. (2003) found donepezil to also persevere activities of daily living and to slow the rate of decline over a six month period. As a result, caregivers of these AD participants spent significantly less time assisting these patients as compared to the control participants and reported less concomitant stress. Research on psychosocial interventions such as music, validation, and cognitive stimulation therapies, have not been as well-executed as the above studies (i.e., such research typically lacks randomized controlled trials) nor have they been found to particularly efficacious (see Sink, Holden, & Yaffe, 2005 for comprehensive review). Overall, while these results of medication trials are promising, their effect on cognitive and functional abilities should be viewed as relatively modest as they serve to, for the most part, prolong the inevitable progression of AD. These medications do not, however, prolong life expectancy.

Economic Issues

Even if modest clinically, cognitive and functional improvements in individuals with AD can realize significant costs savings if they, for instance, reduce the intensity of care necessary or prolong a nursing home stay by several months. Ward et al. (2003) predicted economic saving and costs associated with cholinesterase inhibitor (galantamine) treatment from randomized clinical trials in the United Kingdom. They estimated that, compared to AD individuals not receiving this medication, those taking the medication had a 2.5 month delay to full time care and thus required 12% less full-time care. So, despite the increase in cost associated with this medication, these costs are partially offset by the delay in the need for full-time care. Other research has found similar results or, the very least, that these medications tend to be cost neutral (see Shah & Jenkins, 2003 for review). However, in a US sample, Neumann et al. (1999) estimates were more conservative, as they concluded that donepezil would be cost-effective for mild but not moderate AD and only after two years of treatment. At present, the research on economic savings should be viewed as tentative as it based on multiple assumptions, estimates, and projections. For instance, because there is no long-term data on the effect of anti-dementia medications (none of the existing randomized controlled studies are for more than one year), economic analyses are projected across the expected life expectancy of individuals with AD, likely disease course, and known effect of the medications early in the disease. Because there is substantial variability across these factors, the above projections may not be reliable. Longer-term longitudinal studies in which the economic progression and cost of AD is tracked is needed in the future. Such studies should also evaluate the informal costs associated with delay in nursing home placement for individuals with AD such as caregiver stress; because such costs are typically more difficult to measure and conceptualize, they are not as widely understood as the economic measures described above.

The above individual treatments have been supplemented with broader community-based interventions, funded by Congress in 1990, known as the Alzheimer's Disease Demonstration Grants to the States. A variety of states have implemented new and innovative ways of diagnosing, managing, and treating AD, as well as educating family members and providers. For instance, in Georgia, trained staff provides mobile day care for individuals with AD in rural areas, whereas in Maine in-home evaluation teams travel throughout the state to provide diagnostic services and educate families and providers about AD (Starns, Karner, & Montgomery, 2002). More broadly, these programs and others have sought to develop partnerships across local, state, and federal organizations. While caregivers of AD individuals tend to be satisfied with services such as these, particularly when caregivers have access to services without significant bureaucracy (Townsend & Kosloski, 2002), this research has not been as rigorous as the randomized controlled trials of medications. At this point, the extent to which such interventions actually improve management of AD or perhaps prolong nursing home placement is simply not known. Moreover, it is not known how such community based programs work in concert with the cholinesterase medication in the management and treatment of AD.

Given the aging of the US population, the prevalence of AD will increase in the future, as will the burden of caring for millions of individuals with significant cognitive and behavioral limitations. While diagnostic efforts have improved, particularly neuroimaging and neuropsychological assessment, treatment and management issues remain less well understood and studied. This is partly due to the fact that for the first time our society has huge numbers of elderly individuals living with dementia (previous societies with shorter life expectancies simply did not have such a problem), as well as the challenge of working with a chronic, degenerative neurological disorder. Yet with the increasing numbers of individuals with AD, long-term management and treatment issues have become increasingly important and should remain the focus of continued research. In particular, further information on long term outcomes of cholinesterase inhibitors is welcome, as is additional outcome data on community-based and psychosocial interventions.

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GEORGE J. DEMAKIS

University of North Carolina at Charlotte