Overview of Alzheimer's disease

Nurs Clin N Am 39 (2004) 545–559

Overview of Alzheimer’s disease

Elaine Souder, PhD, RNa,b,*,Cornelia Beck, PhD, RNc,d

aCollege of Nursing, Department of Nursing Science, University of Arkansas for Medical

Sciences, 4301 West Markham, Slot 529, Little Rock, AR 72205, USAbEducation Core, University of Arkansas for Medical Sciences Alzheimer’s Disease Center,

4301 West Markham, Little Rock, AR 72205, USAcCollege of Medicine, Departments of Geriatrics and Psychiatry and Behavioral Sciences,

University of Arkansas for Medical Sciences, 4301 West Markham,

Little Rock, AR 72205, USAdUniversity of Arkansas for Medical Sciences Alzheimer’s Disease Center,

4301 West Markham, Slot 808, Little Rock, AR 72205, USA

Alzheimer’s disease (AD) is a growing concern in society because ofdemographic shifts. In fact, most Americans can relate to this disease,because they know a family member, friend, or neighbor who has beendiagnosed with this common form of dementia. This article provides currentinformation on the definition, demographics, assessment, settings for care,nonpharmacological and pharmacological management, and prevention ofAD. Where possible, research evidence has been referenced to provide themost current information available.

Definition of Alzheimer’s disease

The Diagnostic and Statistical Manual of Mental Disorders, FourthEdition, Text Revision [1] specifies the criteria for dementia of theAlzheimer’s type as a gradual and progressive loss of memory plus anadditional cognitive deficit severe enough to cause significant social oroccupational dysfunction. The cognitive deficit can include languagedisturbance, impaired ability to perform motor activities, inability torecognize familiar objects, or difficulty with abstract organization andplanning. The diagnosis requires ruling out other medical or mentalconditions that might cause similar symptoms. If the person with thediagnosis of dementia of the Alzheimer’s type is 65 years of age or younger,

* Corresponding author.

E-mail address: [email protected] (E. Souder).

0029-6465/04/$ - see front matter � 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.cnur.2004.02.010

mailto:[email protected]

546 E. Souder, C. Beck / Nurs Clin N Am 39 (2004) 545–559

a notation is added to indicate an early onset. There is a growing emphasison the importance of early recognition and diagnosis of AD, because this isthe stage at which current medications are most useful. It allows researchersand clinicians to study dementia over a longer period of time, and itprovides opportunities for affected individuals and their families to attend tolegal and care planning decisions.

Demographics

Alzheimer’s disease is rapidly becoming an epidemic in society. It isestimated that approximately 4.5 million Americans have AD, and anestimated 13.2 million people will be diagnosed with AD by the year 2050, ifno prevention or cure is found [2]. After the age of 65, the risk that anindividual will have AD increases twofold every 5 years. Seven percent of theestimated 4.5 million people who have Alzheimer’s disease are between theages of 65 and 74, 53% between 75 and 84 years old, and 40% age 85 or older[2]. Although only a few people in their mid 30s or 40s are diagnosed withAD, one in every 10 persons over the age of 65 has the disease, and almosthalf the population age 85 or older has AD [3]. The 85-year-old-and-overcohort group is not only most at risk for developing Alzheimer’s disease, butthey are also the fastest growing age group in the United States [4].

Although age is the greatest risk factor for AD, it is not the only one.There is considerable debate on whether gender is a risk factor fordeveloping Alzheimer’s disease. Because most people living with Alzheimer’sdisease are women, the disease sometimes is described as a women’s healthissue. In studies which included a significant number of older men (age 85and older), however, no significant difference between men and women inthe occurrence of AD was found [5]. Nevertheless, after the age of 90,women have been shown to be at greater risk for the development ofAlzheimer’s disease, while men are at greater risk for the development ofvascular dementia [6]. Whatever the importance of the gender factor, it isclear that more women will develop the disease and will live longer with thedisease, with a greater burden for women [5].

Educational status also seems to be linked to the development of AD. Ithas been suggested that education makes a difference, because persons withhigher education perform more cognitive functions and are able to preserveadaptive functioning even though neuropathology is present [7]. In EastBoston, low educational status, low occupation prestige, and low income allwere found to be related to increased risk for the development of AD [8]. Inaddition to low education and occupation levels, low levels of recreationalactivities have been connected to higher risks of AD [9]. Hall et al [10]suggest that educational status alone cannot explain the difference in risk,because too many covariables, such as poverty level, are present. Theyfound that rural residents with low education had significantly increased

547E. Souder, C. Beck / Nurs Clin N Am 39 (2004) 545–559

chances of developing AD, but this was not true for urban residents whohad low education levels. This suggests that environmental factors in ruralareas, in addition to a low level of education, may increase the risk of AD inthat population.

Gender and educational status may be questionable risk factors, butresearchers are finding that race is definitely a factor. In 2002, theAlzheimer’s Association released a publication summarizing recent researchthat described the silent epidemic of AD in African-Americans [11], who areestimated to have a 14% to 100% greater risk for AD than Caucasians.Additionally, if a first-degree relative has AD, African-Americans arealmost 44% more likely than Caucasians to develop the disease [12]. Geneticand environmental factors also seem to be more significant in African-Americans. For example, diabetes, high blood pressure, and high cholesterolare linked to AD. Sixty-five percent of African-American Medicarebeneficiaries have hypertension, while only 51% of Caucasian beneficiarieshave hypertension [13]. African-Americans are at a 60% greater risk fordeveloping type 2 diabetes and have a greater risk of stroke and vasculardementia than Caucasians [14]. In addition to higher prevalence rates,African-Americans may have a more severe disease than Caucasians whenage, educational status, and activities of daily living are controlled [15].

Alzheimer’s disease places a substantial financial burden on allAmericans. Businesses suffer $36.5 billion per year in lost productivityfrom absenteeism of employees who care for a family member with AD.They lose another $24.5 billion paying for medical care for individualsdiagnosed with AD. The average annual cost to Medicare for a persondiagnosed with Alzheimer’s disease was approximately $6000 in 1994, 2.6times greater than the cost for those not diagnosed with Alzheimer’s disease[16]. In 1999, those with AD had three times the number of hospital staysper year, 2.8 times higher hospital costs, and 3.1 times higher Medicarehome health care costs than Medicare beneficiaries without a diagnosis ofAD or other dementia [17]. Additionally, 95% of Medicare beneficiarieswith AD or other dementia also had at least one chronic illness, whichincreased the number of hospital stays and the costs of skilled nursingfacility, home health, and hospital services over those of AD or the chronicdisease alone [17]. Families currently spend an average of $12,500 per yearon out-of-pocket medical care expenses for family members with AD. Overhalf of all nursing home residents have AD or a related disease. The averagelifetime cost per patient is $174,000 [18].

Assessment

Diagnosis of AD used to be based on the exclusion of other possibledisorders. Now, however, it generally is agreed that a diagnosis of probableAD can be made based on typical findings during life and confirmed by


studying brain tissue at death. Nurses have opportunities in all clinicalencounters with older adults to consider the possibility of early dementia.Signs and symptoms that may raise suspicion include difficulty understand-ing questions or instructions during a clinical encounter, withdrawal,paranoia, depression, personality changes, agitation, and family report offorgetfulness or difficulties performing daily activities. Brief screeninginstruments are readily available and can provide a quick assessment todetermine if further evaluation is indicated. Examples of commonly usedcognitive screens include the Mini-Mental State Examination (MMSE) [19]and the Blessed Information-Memory-Concentration Test (IMC) [20].

Several guidelines for diagnosing AD have been formulated by specialtygroups [21]. The most essential component is documentation of the onsetand progression of symptoms through a careful family and medical historyin addition to functional assessment. Physical and neurological examina-tions are usually normal in early AD. Laboratory tests can be performed toidentify comorbidities that may be playing a role. Although low vitaminB-12 and thyroid levels are found frequently, in most cases they do notappear to be responsible for the cognitive decline. Neuropsychologicalevaluation can identify cognitive deficits and provide a baseline againstwhich to measure future change. The role of neuroimaging with magneticresonance imaging (MRI), positron emission tomography (PET), or singlephoton emission computed tomography (SPECT) in the diagnostic processis controversial. Although many experts recommend brain MRI to rule outpathological lesions, the utility of PET and SPECT remain in question.

Settings for care

The preferred living arrangement for patients with dementia is in thecommunity. When dementia worsens, activities of daily living becomeimpaired, and behavioral symptoms emerge, then assisted living or nursinghomes may become necessary.

Of the four million Americans with AD, an estimated 70% receive care athome from family and friends [22]. The annual cost of care for a person withdementia living at home is $47,083, 73% of which is unpaid, while the cost ina nursing home is $47,591, only 12% of which is unpaid [23]. Significantlymore dementia caregivers than nondementia caregivers use home andcommunity-based care such as temporary care services, adult day care/seniorcenters, personal or nursing care services, meal services, assistive devices, andhome modifications [24]. Other sources of payment for home care are theDepartment of Veterans’ Affairs and state and local governments [23].

Ninety percent of dementia caregivers want to postpone institutionallong-term care [25]. One possible approach to delaying institutionalization isthe development of more targeted in-home services [26], such as helpingpatients rise in the morning and retire at night. Another approach istechnology. The Center for Aging Services Technologies [27] is bringing


together representatives from many sectors to discuss making aging servicesmore efficient, effective, wellness-oriented, and consumer-friendly throughtechnology. The Medical Automation Research Center at the University ofVirginia, for example, has developed a smart house that uses a system ofsensors and computers to monitor virtually every movement of a personliving there and alert doctors or family members when the system detectspotential safety or other problems [28]. A smart house in the UnitedKingdom includes a locator, which consists of a wall-mounted panelshowing items (eg, keys or purse) as both pictures and words beside a button.If someone loses an item, the user can press the appropriate button, and thelost item emits a warbling sound [29].

According to Zimmerman et al [30], the annual growth rate of assistedliving is between 15% and 20% [31]; predictions indicate that in the nextdecade it will serve more elders than nursing homes do [32,33]. The NationalCenter for Assisted Living defines assisted living as a congregate residen-tial setting that provides or coordinates personal care services, 24-hoursupervision, assistance activities, and health-related services. Assisted livingservices can be provided in freestanding facilities, near or integrated withskilled nursing facilities, as components of continuing care retirementcommunities, or at independent housing complexes [34]. Because states, andnot the federal government, regulate assisted living facilities, they functionunder various quality and safety standards and have different names such asresidential care, board and care, and adult care facilities, or homes withservices. Only 17 states require a licensed nurse in assisted living, but eight donot specify registered nurse or licensed practical nurse. Some states requirethat registerednurses be available 24 hours a day. Theymaynotmandate themto be on-site, however, or may mandate that they be present only duringmedication administration or other (often unspecified) nursing services [35].

Including rent and most additional fees, assisted living averages $1873amonth.More than 65%of assisted living residents paywith their own funds;14%paywithSupplemental Security Income (a federal assistance program forolder adults and persons with disabilities), and 9% pay with Medicaid [34].

Residents of assisted living need help with 2.3 activities of daily living(ADL) on average [34], while the average home and community-basedprogram recipient needs assistance with only 1.6 ADL [36]. Forty percent to60% of all assisted living residents have dementia [37]. Thirteen percent to18% display behavioral symptoms [30]. Several states have introduced modelprograms for dementia care in assisted living [38–41], and 37% of assistedliving facilities offered special care units for dementia; however, 24 states andthe District of Columbia do not specify Alzheimer’s unit requirements.Further, a General Accounting Office report in 1999 [10] found provision ofincorrect, incomplete, and misleading information; inadequate care; in-sufficient staffing; and medication errors in assisted living facilities.

Nursing homes provide significantly more health services and thussignificantly more stringent admission policies than assisted living facilities


[42]. At least 50% of nursing home residents suffer from dementia [43]. In1996, just over 19% of all nursing homes had one or more special-needsnursing units, and over half of these units were reserved for residents withdementia [44]. Several collaborative studies have found improved behaviorand social interaction but not better functioning or cognition in residents ofspecial care units [45].

Attention now is being focused on the need for specialized hospice carefor patients with dementia, and nursing homes are trying to find the bestway to provide these services. It remains unclear whether these patientsare served best by hospice units that also house persons without dementia,or whether they need special units that provide dementia-specific hospicecare.

Interventions for management of behavioral symptoms

About 54% percent of nursing home residents [46] and 24% ofcommunity dwellers with dementia [47] have behavioral symptoms thatnegatively affect these patients and everyone else in their environment. Themost widely tested interventions to reduce or eliminate behavioralsymptoms in patients with dementia have involved auditory and tactilestimulation or exercise/movement or multi-level interventions.

Several interventions have been implemented in research studies tomanagebehavioral symptoms in dementia. Music therapy significantly decreasedagitation [48] in adult day care and increased melatonin concentrations inserum of inpatient veterans [49]. Research has shown, however, that nursinghome residents respond better when they listen to music that they prefer[50,51]. Residents were significantly more likely to have a happy facialexpression when listening to the tape of a family member (simulated presencetherapy) than with placebo or usual care [52].

Studies on the efficacy of visual stimulation in nursing home residentshave yielded contradictory results. Daily light therapy reduced behavioralsymptoms in two studies [53,54], but a randomized controlled trial of brightlight therapy showed no significant effects on behavioral symptoms [55].

Interventions involving touch significantly reduced behavioral symptomsin nursing home residents who liked touch [56]. One study found thattrained and certified therapy dogs had positive effects on nursing homeresidents who did not fear dogs [57], and another study found thatparticipants exhibited fewer behavioral symptoms with a resident dog [58].Studies of aromatherapy have yielded both positive and negative results innursing home residents. Those who received aromatherapy with MelissaOfficinalis (lemon balm) showed a 35% reduction in agitation [59], andaromatherapy with massage was more effective in reducing behavioralsymptoms than either conversation with aromatherapy or massage only [60].A study in which three different aromas were administered, however,


showed no decrease in behavioral symptoms during the administration [61].An intervention using 23 activities, such as sewing cards, fishing boxes andtetherball, proved effective in reducing agitation in one nursing home butnot in another [62]. Among community dwellers, progressive musclerelaxation led to a decrease in behavioral symptoms [63]. Also, communitydwellers who received Snoezelen, which involves visual, auditory, tactile,and olfactory stimulation, showed a significant improvement in behaviorand affect or mood [64]. A study testing the efficacy of therapeutic touchfound a decrease in agitated behavior in nursing home residents [65].

Nursing home residents who participated in exercise and movementprograms also showed a decrease in agitated behavior [66,67]. A lawn gliderintervention reduced pulse and respiratory rates, but not aggressivebehavior in nursing home residents [68]. A pilot study, however, foundthat nursing home residents had significantly reduced agitation while ina Merry Walker, a steel-constructed device with four wheels, which allowsa 360-degree turning radius [69].

Studies testing multiple interventions have shown both positive andnegative results. Remington [70] found that calmingmusic, handmassage, andsimultaneous calming music and hand massage reduced physically non-aggressive behaviors in nursing home residents more than no intervention.Another study of individually tailored psychosocial, nursing, and medicalinterventions found decreases in behavioral symptoms among nursing homeresidents [71]. In a clinical trial of at-home recreational therapy with 23different interventions, including therapeutic cooking, art/craft therapy, andwheelchair biking, significant decreases in agitation occurred [72]. Alessi et al[73] found an intervention that combined increased daytime physical activityplus a nighttime program to decrease noise and sleep-disruptive nursing carepractices produced a 22% decrease in observed agitation in nursing homeresidents. Beck et al [74] conducted a clinical trial of environmental andbehavioral strategies to promote functional independence, a psychosocialactivities intervention that involved 25 standardized modules, and anintervention that combined the two approaches in nursing homes. Therewere no significant treatment effects for any of the interventions, but residentsdisplayed more positive affect. A study of a multi-sensory exercise programthat included several sensory stimulations and integrated storytelling andimaging strategies showed improvements in overall mood, engagement, andresting heart rate in nursing home residents [75,76].

Few studies have investigated the role of pain in triggering behavioralsymptoms in patients with dementia. Pain assessment relies on the patient’sability to describe it, making it difficult to assess in patients who have severecognitive impairment and cannot respond to pain assessment instruments.A recent study found that aggressive behaviors occurred significantly moreoften in subjects with two or more pain-related diagnoses. Subjects witharthritis had significantly higher aggression scores than those withoutarthritis, but almost 60% of residents with arthritis had received no pain


medication in the previous month [77]. For a more detailed discussion ofpain, see the Horgas article in this issue.

Pharmacologic management

Drug interventions in AD are of two major types: cholinesteraseinhibitors and various drugs used to manage secondary and problematicbehaviors.

A major neurotransmitter, acetylcholine, is deficient in the brains ofindividuals with AD. Use of cholinesterase inhibitors is based on thecholinergic hypothesis, according to which ‘‘cognitive, functional, andbehavioral dysfunction associated with Alzheimer’s disease may be causedby an inability to transmit neurologic impulses across cholinergic synapses’’[78]. The inhibitors are thought to prevent the breakdown of acetylcholine,a brain chemical believed to be important for memory and thinking.

The four cholinesterase inhibitors approved by the US Food and DrugAdministration to treat symptoms of mild-to-moderate AD are tacrine,donepezil, rivastigmine, and galantamine. Tacrine, the first drug to be used,is prescribed rarely now because of its significant hepatic toxicity and theneed for four doses daily. Except for tacrine, the drugs have been shown tobe relatively safe; they have similar actions and costs and are selectedprimarily based on their adverse effect profile. These medications can helpdelay symptoms or prevent symptoms from becoming worse for a limitedtime, and they may help control some behavioral symptoms.

In October 2003, the FDA recommended approval of the drug memantineas a treatment for moderate to severe AD. The drug, marketed in the UnitedStates as Nemenda, was developed and used in Germany for a decade, and itshows promise for usewithmoderate-to-later stageAD.Unlike currently useddrugs, which boost acetylcholine levels, memantine helps to regulate theactivity of glutamate, which plays an essential role in learning and memory.There have been several trials in theUnited States. In apivotal study publishedin 2003, 252 patients (67% women; mean age 76 years) with moderate-to-severeAD from32US centers randomlywere assigned in a double-blind studyto receive placeboor 20mgofmemantine daily for 28weeks. Patients receivingmemantine had better outcomes on cognition, behavior, and ADL. Further,their caregivers reported significantly fewer number of hours of careassistance, compared with the control group. The withdrawal rate was 23%in the memantine group and 33% in the placebo group [79].

A variety of drugs may be used to manage secondary symptoms of ADranging from depression to severe agitation. Depression is a commoncomorbidity with dementia that responds to treatment with antidepressantssuch as sertraline, citalopram, and fluoxetine. Agitation, paranoid delusions,and hallucinations alsomay present at various points in the illness course, andthey may respond to atypical antipsychotic agents such as risperidone andolanzapine. Also, use of a sedating antidepressant such as paroxetine may


treat underlying agitation and promote sleep. These drugs can help tomanagedifficult behaviors and improve the life of the individual with dementia and thecaregiver. A recent comprehensive discussion of treatment considerationsexamined the complex nature of drug interactions, and the wide variety ofdrugs available to manage problematic behaviors [80].

Prevention

Interactions between identified risk factors, such as gene-environmentinteractions, are important in the development of dementia [81]. Studieshave found that the ApoE genotype interacts with ethnicity [82], diabetes[83], and dietary factors [84,85].

Like other chronic diseases, AD may result to some degree from thepatient’s own behaviors: the choices made as individuals and a society mayaffect its development [86]. Although some dementia risk factors, such asadvanced age, family history of AD, or genetic predisposition, cannot bechanged, patients can try to avoid head injury, keep their minds active, andevade vascular disease, diabetes, high cholesterol, high homocysteine levels,and metal exposure [86].

Aspects of a healthy lifestyle such as a proper diet, regular physicalactivity, and reduced stress also may protect against AD. A healthy dietincludes low intake of saturated fat and cholesterol; high intake ofantioxidant-rich foods, fruits, vegetables, and whole grains; and adequatewater consumption [86]. Improving dietary intake may affect AD prevalencedirectly through intake of antioxidant-rich and low-cholesterol foods, andindirectly, through prevention of other AD risk factors, such as high bloodpressure, high cholesterol, and diabetes [86].

Several cross-sectional studies have reported that patients with AD hadlower serum levels of antioxidants, including alpha tocopherol (vitamin E)and ascorbic acid (vitamin C) compared with control subjects [87]. Inaddition, the Rotterdam study reported that adults with higher intake atbaseline of foods rich in vitamins E and C had lower incidence of dementia[88]. Likewise, the Chicago Health and Aging Project found that increasedvitamin E intake from foods (not supplements) was associated with decreasedrisk of developing dementia among persons who lacked an ApoE 4 allele [85].Research has found that diets high in saturated and monosaturated fats areassociated with worsening cognitive decline [89]; diets high in unsaturated fatand low in saturated fat are associated with better cognitive function [90].Longitudinal cohort studies have shown that high intake of fish, whichcontain high levels of omega-3 long-chain polyunsaturated fatty acid, isassociated with reduced risk of dementia [91,92]. Consuming more vitaminsB6 and B12 and folic acid also may protect against dementia by reducinghomocysteine levels [93].

Case-control studies suggest that low physical activity is a risk factor fordementia [9,94]; participation in sports, exercising, andwalking duringmidlife


have been associated with reduced risk for dementia [9]. A recent study foundthat older women who had higher levels of physical activity were less likely todevelop cognitive impairment [95]. Also, a Canadian longitudinal studysupported the protective effect of physical activity in reducing risk of dementia[96]. The effect of stressmanagement in preventing dementia has received littleattention, although stress has consistent negative effects on hypertension andheart disease [97].

Like physical exercise, mental activity may deter dementia. A longitu-dinal study of religious orders found that persons in the upper 10% ofcognitive activity were 47% less likely to develop dementia than those in thelowest 10% of cognitive activity [98].

Recent longitudinal studies that collected risk factor data decades beforedisease onset support the view that risk factors such as hypertension, highcholesterol, low cognitive activities, and diabetes in midlife and earlier areassociated with developing dementia [98–100]. Some studies even suggestthat exposure to risk factors in the prenatal period and early childhood mayaffect dementia development [101]. Because the neurodegenerative processesin dementia appear to start long before cognition deteriorates, preventiveefforts such as good dietary habits and physical and cognitive activityprobably need to begin early in life [86].

Summary

In conclusion, many researchers from multiple disciplines are addressingAD at many levels, ranging from prevention, to cellular alterations, totreatment modalities, and coping and care giving with the consequences ofthe ravages left by the disease. Although much has been learned in the lastseveral decades of active research, much remains to be learned. In its currentstatus, AD is a chronic disease without a cure, which provides ampleopportunities for nursing management throughout the course progression.

Acknowledgment

The authors wish to acknowledge the able assistance of Tanya L. Terry,M.S. and Val Shue, B.A. in the preparation of this manuscript.

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Overview of Alzheimer's disease