Interrater agreement for diagnosis of Alzheimer's disease

Farrer, Lindsay A.; Cupples, L. Adrienne; Blackburn, Sharon; Kiely, Dan K.; Auerbaeh, S.; Growdon, John H.; Connor-Lacke, L; Karlinsky, Harry; Thibert, A.; Burke, James R.; Utley, C.; Chui, Helena C.; Ireland, AJ; Duara, Ranjan; Lopez-Alberola, Roberto; Larson, Eric B.; O'Connell, S.; Kukull, Walter A.

doi:10.1212/wnl.44.4.652

Cited by 40 publications

(24 citation statements)

References 12 publications

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“…4,6,[13][14][15] Specifically, we used two sources of information to develop these risk curves: (1) gender-and age-specific incidence curves for first-degree relatives of persons with AD (comparable to those previously published in Green et al, 4 Cupples et al, 14 and Lautenschlager et al 15 ). and (2) APOE genotype-specific odds ratio estimates for each gender and age reported in a meta analysis of data from over 50 studies worldwide.…”

Section: Methodsmentioning

confidence: 99%

Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: The REVEAL study

Cupples

Farrer

Sadovnick

et al. 2004

Genetics in Medicine

150

123

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Purpose: The REVEAL study is a randomized, controlled study of the psychological and behavioral impact of APOE disclosure in a risk assessment protocol provided to first degree relatives of patients with Alzheimer's disease. The protocol presents risk information as cumulative incidence curves. This article describes how these curves were estimated. Methods: Curves were calculated using Bayes' rule to compute the posterior survival curves incorporating APOE information. Results: A combination of survival data from the MIRAGE study and gender-and age-specific APOE odds ratios were used to create risk curves for males and females within each of the 6 APOE genotypes. Conclusion: Utilizing comparative genotype relative risk information and survival data from family studies, estimates of gender-, age-, and genotype-specific risk can be generated for use in a risk assessment research study that features genotype disclosure. Alzheimer's disease (AD) is the leading cause of cognitive impairment among older persons, 1 and in the U.S., the prevalence of AD will continue to increase with the aging population. 2 Although the etiology of AD is not fully understood, there is clear evidence that genetic factors are important determinants of AD. 3,4 The gene for apolipoprotein E (APOE) has been identified as a common susceptibility polymorphism 5 with allele ⑀4 conferring 5 to 15 times greater risk, depending upon whether an individual has one or two copies. 6 The ⑀4 allele is common in the U.S. population with a frequency of about 14%. Although individuals with one or two ⑀4 alleles can attain late age without developing AD, the burden of risk attributable to APOE is substantial. 7 Relatives of individuals affected with AD are increasingly aware that they may be at increased risk for developing AD themselves. Surveys and data from this study have demonstrated that substantial portions of such relatives, often over half of respondents, are interested in more fully understanding their risk. 7-11 The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) study was established to evaluate the feasibility, safety, and behavioral responses of providing general information on risk and specific risk assessment, including APOE genotype disclosure, to adult children of patients with AD (the "subjects" of our study). 12 These subjects were recruited either through systematic ascertainment from AD research registries at Boston University, Case Western, and Cornell or through self-referral at each site. After a general information session and administration of baseline questionnaires, subjects were randomly assigned to either the "Control" group that would receive risk information based on age, gender, and family history only or the "Intervention" group that would receive the same risk information as the controls plus risk information based on the subject's APOE genotype. After disclosure of the risk information by a genetic counselor, the Control and Intervention groups were followed for one year through telephone and in-person st...

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Section: Methodsmentioning

confidence: 99%

Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: The REVEAL study

Cupples

Farrer

Sadovnick

et al. 2004

Genetics in Medicine

150

123

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“…The reliability of the diagnosis of AD is moderate (generalized kappa's in the 0.51 to 0.73 range) in Class II studies. [8][9][10] When standardized clinical diagnostic criteria are used, interrater reliability 6 and consistency of diagnosis between the initial visit and 1-year follow-up is high (95% in Forette 11 ). There are 13 studies, 3 Class I 12-14 and 10 Class II, 9,[15][16][17][18][19][20][21][22] that have addressed the diagnostic accuracy of the clinical diagnosis of AD using neuropathologic confirmation as the "gold standard."…”

Section: Are Current Diagnostic Criteria Able To Establish a Diagnosimentioning

confidence: 99%

Practice parameter: Diagnosis of dementia (an evidence-based review)

et al. 2001

Self Cite

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Article abstract-Objective: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. Background: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. Methods: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? Recommendations: Based on evidence in the literature, the following recommendations are made.

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“…The MIRAGE study is the largest genetic epidemiological study of its kind to date, focusing on both African American and white families. 13,14,65 As a result, it provided a potential basis for clarifying risk profiles for African Americans and risk estimates to FDRs of persons with AD. The study found significantly higher risk for dementia among FDRs of African Americans compared with whites (RR 1.6; 95% CI 1.4 -1.9).…”

Section: The Mirage Studymentioning

confidence: 99%

“…The MIRAGE study recruited patients with AD from 17 specialty clinics between May 1991 and March 2001, using methods published elsewhere. 14,65,79 The dementia risk models stratified by ethnicity as presented by Green et al 13 provided a basis for creating AD models for the REVEAL study.…”

Section: Feasibility and Creation Of Customized Risk Curvesmentioning

confidence: 99%

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

Christensen

Roberts

Royal

et al. 2008

Genetics in Medicine

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Purpose: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. Methods: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicityspecific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. Results: Review of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Researchers are identifying a growing number of genetic markers that are associated with increased or decreased risk for common, complex diseases. Consequently, the development of genetic risk assessment and risk communication strategies are areas of critical importance, especially given that laypersons often have a difficult time in understanding probabilistic information. 1,2 Protocols for disclosing genetic information have been developed and refined for various forms of cancer, 3-6 but similar efforts have been made only recently for other diseases. 7,8 One area of recent focus is Alzheimer disease (AD).AD is the most common form of dementia among the elderly, affecting an estimated five million individuals in the United States. Well over 10 million Americans are expected to have the condition by 2050 as the population continues to age. 9 Many risk factors are well-characterized, including age and family history, 10 -14 whereas many others are under investigation, including education level, 15,16 head trauma, 17,18 high blood pressure, 19 caloric intake, and high cholesterol. 20,21 Regarding genetic factors, rare mutations on genes coding for amyloid precursor protein, presenilin 1, and presenilin 2 have been identified that are deterministic for early-onset AD. 22 Apolipoprotein E (APOE), in contrast, affects susceptibility to AD and has three major forms. APOE ⑀3, the most common allele, is found in over half the US population. The ⑀4 allele is associated with increased risk for AD whereas the ⑀2 allele has a protective effect. 23,24 The ⑀4 allele is neither necessary nor sufficient for AD though, and individuals with the ⑀2 allele still have risk for AD. APOE variants are also associated with other conditions such as hyperlipoproteinemia and atherosclerosis 25 and may play a role in the development of ma...

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Interrater agreement for diagnosis of Alzheimer's disease

Cited by 40 publications

References 12 publications

Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: The REVEAL study

Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: The REVEAL study

Practice parameter: Diagnosis of dementia (an evidence-based review)

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

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