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Boustani M, Peterson B, Harris R, et al. Screening for Dementia [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2003 Jun. (Systematic Evidence Reviews, No. 20.)

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Screening for Dementia [Internet].

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1Introduction

Background

Dementia is an acquired syndrome of decline in memory and at least one other cognitive domain such as language, visuo-spatial, or executive function sufficient to interfere with social or occupational functioning in an alert person.1 Multiple diseases can cause the syndrome of dementia. The large majority of people with dementia have neurodegenerative disease or cerebrovascular ischemia as the underlying cause. Between 60% and 70% of people with the dementia syndrome have Alzheimer's disease; about 20% to 30% have vascular or mixed vascular and Alzheimer's disease causes. A smaller number have other causes such as Lewy body dementia, frontal dementia, Parkinson's disease, hypothyroidism, and vitamin B12 deficiency.2, 3

To date, research has produced no effective approach for primary prevention of dementia. Chemoprevention has been advocated, but data on effectiveness are lacking. Although control of hypertension reduces the risk of cerebrovascular accidents, its role in reducing small vessel vascular dementia is less clear. The wealth of literature has been on screening for dementia with the hope of reducing its burden of suffering by earlier intervention.

Routine history and physical examinations do not readily diagnose dementia during clinic or physician visits. Multiple studies in the United States and abroad indicate low identification of dementia by primary care physicians.4–11 More than 50% of patients with dementia have never been diagnosed by a physician.12–14 This raises the possibility that effective screening tests might be able to identify people with dementia at an early stage, thus allowing the possibility of earlier intervention.

No national organization recommends routine screening for dementia syndrome. The 1996 Guide to Clinical Preventive Services from the US Preventive Services Task Force (USPSTF) found insufficient evidence to make a recommendation either for or against screening.15 Since that USPSTF review, however, several studies have been published concerning both pharmacologic and caregiver interventions. Given the new evidence and the large and growing importance of this condition, the RTI International-University of North Carolina Evidence-based Practice Center (RTI-UNC EPC) undertook this review for the use of the USPSTF in reconsidering its previous conclusions.

Burden of Suffering

The aging of the US population has been accompanied by a dramatic rise in the prevalence of the dementia syndrome. Several population-based studies indicate that 3% to 11% of persons over age 65 years and 25% to 47% of those over 85 have dementia.16–21 In 1997, the number of people with Alzheimer's disease in the United States was estimated to be 2.32 million, more than 90% of whom were age 60 years and older.22

Alzheimer's disease is considered the 8th leading cause of death in persons over the age of 65 and is 11th overall in the United States.23 Median survival estimates of people with dementia have been 5.0 to 9.3 years after diagnosis; a recent study found the median survival time, adjusting for date of onset, to be 3.3 years.24 The annual societal cost of dementia is approximately $100 billion, from both health care and related costs and lost wages for patients and family caregivers.9

Dementia causes a high burden of suffering for patients and their families. For patients, it leads to cognitive and functional deterioration, behavioral complications, increased use of health and social services, complicated clinical management of other comorbid conditions, and increased risk for medical complications such as delirium, falls, motor vehicle crashes, incontinence, fractures, and infections.25, 26

For family caregivers, dementia can lead to financial and emotional stress. Family members, usually elderly spouses, care for 66% to 75% of demented people at home.27 The progressive nature of the dementia syndrome has especially negative effects on the caregiver; most studies have found higher levels of anxiety, depression, and use of psychotropic medications in caregivers compared with population controls.28–33 One study reported that 80% of caregivers of dementia patients have chronic fatigue, depression, or anger.34 Recent data have suggested that caregiver burden can be an important determinant of the severity and frequency of demented patients' behavioral problems and of the need to place patients in an institutional setting.27, 29, 35–38

Epidemiology

Associated Conditions

Experts disagree about definitions for cognitive impairment without dementia and the relationship of these conditions to the development of dementia. Observers have defined more benign conditions with terms such as “age-associated memory impairment” (AAMI), “age-related cognitive decline,” and “mild cognitive disorder.”39 A study of patients diagnosed with memory impairment found that, after 3 years, 9.1% met Diagnostic and Statistical Manual III, Revised (DSM-IIIR) criteria for dementia, 7.4% had worse cognitive functioning but did not have criteria for dementia, and 59.1% still met criteria for AAMI.40 Almost 15% of these patients had improved functioning that no longer met AAMI criteria. “Mild cognitive impairment” (MCI) is a more severe condition that has a stronger association with the development of dementia. An estimated 10% to 15% of patients with MCI progress to dementia annually.41

Risk Factors

Age is the best studied and strongest risk factor for the dementia syndrome. The incidence rate among people ages 65 to 69 years is about 2.4 cases per 1,000 person-years, and incidence approximately doubles in each subsequent 5-year period.42 A significant rise in the prevalence of dementia begins around age 75; rates of 1% to 3.5% in persons' ages 65 to 74 years jump to 6% to 15% in those ages 75 to 84 years.

The risk of Alzheimer's disease is related to family history. Individuals whose parents both had Alzheimer's disease have a 54% cumulative risk of developing this condition by age 80. This risk is about 1.5 times greater than the risk faced by those with 1 parent with Alzheimer's disease and nearly 5 times greater than for those with neither parent affected. First-degree relatives of patients with Alzheimer's disease have a cumulative lifetime risk of 39%, approximately twice the risk of Alzheimer's disease in the general population.43

Some genetic mutations have been associated with Alzheimer's disease. For example, about 20% to 30% of the general population and 45% to 60% of people with late-onset Alzheimer's disease have the apolipoprotein E-4 gene.44 In a study of people with Down syndrome, 55% of individuals between 50 and 59 years and 75% of those 60 years of age and older had Alzheimer's disease.45

Cardiovascular risk factors are associated with vascular dementia. The presence of lacunar infarctions leading to symptomatic change is independently related to diastolic blood pressure, serum creatinine, tobacco smoking, carotid stenosis, male sex, and a history of diabetes.46 A cross-sectional study found all indicators of atherosclerosis (vessel wall thickness, plaques of the carotid arteries, and the ratio of ankle-to-brachial systolic blood pressure) to be associated with all dementias, with odds ratios ranging from 1.3 to 1.9.47

Head trauma is also associated with Alzheimer's disease. A case-control study of Alzheimer's disease found the odds ratio of Alzheimer's disease to be 3.5 when comparing patients with previous head trauma to controls.48

Screening Tools

Most screening tests for dementia can be divided into cognitive tests of patients and functional assessments using both patients and other informants.25 Newer strategies include testing for genetic mutations.

Cognitive tests, the primary screening approach that researchers have investigated, include the Mini-Mental Status Examination (MMSE), a widely used and studied test.49 Several other cognitive tests that have been proposed are not relevant to the primary care setting, an environment that demands tests that are relatively brief, require minimal administration resources or training, and are reasonably accurate.25 Among other available cognitive testing strategies, the Clock-Drawing Test (CDT), which can take less than 1 minute to administer, has the best potential for meeting these criteria.50 The small number of methodologically sound studies regarding other clinically relevant cognitive tests limits our ability to evaluate them adequately.

Some informant-based functional tests, such as the Functional Activities Questionnaire (FAQ),51 the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE),52 and the Instrumental Activities of Daily Living (IADL) Questionnaire,53 have also been tested. These instruments offer “everyday relevance,” acceptability by subjects, adaptability to various types of patients, administrative ease, longitudinal perspective, and cross-cultural portability. The primary limitations of these tests are that not all patients have caregivers and that some functions (e.g., cognition) are not tested.54 Most importantly, few methodologically sound studies regarding the accuracy of these questionnaires have been completed.

Testing for genetic mutations may be a potential advance in screening for people at risk of Alzheimer's disease. Investigations regarding genetic profiles associated with Alzheimer's disease have, however, provided limited population-based data regarding absolute dementia prevalence or risk among genotypic individuals. These tests also present weighty ethical issues with respect to their application to individual patients.55

Using cognitive tests, functional questionnaires, and genetic testing in the primary care setting poses substantial feasibility problems. This review will focus on the 2 tests of greatest potential near-term usefulness, the MMSE and the CDT.

Treatment Modalities

Early diagnosis and treatment are clearly relevant to the potentially reversible dementias (e.g., hypothyroidism, vitamin B12 deficiency); theoretically, treatment should begin early to be most helpful. The literature shows, however, that the probability of discovering a truly reversible cause is less than 1.5%; thus, the magnitude of the possible benefits of screening depends heavily on the treatment of irreversible dementias.56–62

Treatment of irreversible dementia falls into 2 categories. Primary treatment attempts to halt or slow disease progression; secondary treatment deals with controlling the symptoms of the disease.

Primary treatment targets basic pathophysiologic mechanisms and seeks to affect the level of cognitive function (or its rate of decline) over time. For example, early detection of vascular dementia could lead to benefit through more aggressive control of such risk factors as atrial fibrillation, blood pressure, thrombotic tendencies, and dyslipidemia. For Alzheimer's disease, treatment with cholinesterase inhibitors and vitamin E do not reverse the disease process but may slow its progression.

Secondary or symptomatic treatment targets patients' psychiatric and behavioral symptoms and caregivers' stress and burden. Both types of treatment can affect health-related quality of life. Early detection of dementia may also induce some negative outcomes such as possible discrimination, inability to obtain life or health insurance, and, in extreme cases, suicide.63, 64

In summary, the current management of dementia is not limited to improving patients' cognition. Rather, it also targets multiple outcomes, such as improving functional autonomy, decreasing institutionalization, decreasing behavioral problems related to dementia, limiting automobile crashes and accidental falls, and lowering caregiver stress.

Organization of this Systematic Evidence Review

Chapter 2 provides an overview of our methods for producing this systematic evidence review. Chapter 3 presents the results of our literature search and synthesis organized by key questions. The results and limitations of the literature are discussed in Chapter 4 with attention to ramifications for future research. Tables accompanying the text can be found at the end of each chapter; references are at the end of the entire report. Appendix A contains acknowledgments; Appendix B contains the evidence tables developed from the literature synthesis; and Appendix C gives an overview of the scales used in dementia intervention trials, followed by a detailed description of a selected few.

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