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Evaluation of Cognitive Impairment in Older Adults Combining Brief Informant and Performance Measures

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Evaluation of Cognitive Impairment in Older Adults Combining Brief Informant and Performance Measures ORIGINAL CONTRIBUTION Evaluation of Cognitive Impairment in Older Adults Combining Brief Informant and Performance Measures James E. Galvin, MD, MPH; Catherine M. Roe, PhD; John C. Morris, MD Objective: To combine the AD8, a brief informant in- Results: A model combining the AD8 interview (odds terview, with performance measures to develop a brief ratio, 1.91; 95% confidence interval, 1.6-2.3) and the Con- screening tool to improve detection of cognitive impair- sortium to Establish a Registry for Alzheimer Disease 10- ment and dementia in general practice. item Word List Recall (odds ratio, 1.43; 95% confidence in- terval, 1.2-1.7) predicted dementia with 91.5% correct Design: The AD8 was administered to informants. classification (AUC=0.968; 95% confidence interval, 0.93- Clinicians conducted independent patient evaluations 0.99). A cutoff of 2 or greater on the AD8 and less than and administered the Clinical Dementia Rating Scale 5 items remembered on the Word List Recall was sensitive and a 30-minute neuropsychological battery. Logistic (94%) and specific (82%). For cognitive impairments not regression was used to determine the best combination meeting dementia criteria, combining AD8 (odds ratio, 2.31; of brief tests to correctly classify patients as having no 95%confidenceinterval,1.3-4.0)andWordListRecall(odds dementia, uncertain dementia, or dementia. The area ratio, 1.42; 95% confidence interval, 1.1-1.8) was most pre- under the receiver operator characteristic curve (AUC) dictive(AUC=0.91;95%confidenceinterval,0.8-1.0).Using evaluated the discriminative ability of the combined the same cutoffs as those used for dementia gave the best tests. combination of sensitivity (85%) and specificity (84%). Patients/Setting: Patients (n=255) were consecu- Conclusion: Combining the AD8 interview with the Word tive referrals to a dementia clinic. Patients had a mean±SD List Recall improves the ability to detect the presence of age of 73.3±11.3 years, with 13.7±3.0 (mean±SD) years dementia. The AD8 can be administered to an informant of education. The sample was 56% women; 77% of pa- and, when combined with Word List Recall, is a powerful tients were white. yet brief method of detecting cognitive impairment. Main Outcome Measure: Dementia classification. Arch Neurol. 2007;64:718-724 HE DIAGNOSIS OF ALZHEI- is 1 example of a brief test that reflects skills mer disease (AD) and re- that are preserved in old age but are im- lated dementias remains a paired very early in AD8 and in mild cog- clinical one, founded on in- nitive impairment (MCI).3 traindividual decline in Brief cognitive tests help differentiate cognition with interference in accus- cognitively healthy older adults from those T 9 tomed daily activities. Efforts to develop with dementia and are easily applicable methods that detect early dementia are im- in clinical practice.4 However, the most portant, as early diagnosis may increase the commonly used brief screening tool, the benefit from new therapies.1,2 Memory im- Mini-Mental State Examination (MMSE),10 pairments are the earliest signs of AD3-5; while reasonably accurate in detecting however, formal neuropsychological as- moderate dementia, lacks the sensitivity sessments are time consuming, costly, and and specificity to detect very mild impair- not readily available to all patients.3 Ef- ment11,12 and may not be culturally sensi- Author Affiliations: forts to develop sensitive and specific cog- tive.13 Brief cognitive tests may also be lim- Departments of Neurology nitive screening tools that are valid, easy ited in their ability to detect change, (Drs Galvin and Morris), to administer, and minimally time con- because baseline testing is often unavail- Anatomy and Neurobiology suming are needed.3 Given the time con- able.14 It is also unclear how helpful many (Dr Galvin), Pathology and straints in most clinical settings, short of these brief measures would be in de- Immunology (Dr Morris), and 15 Division of Biostatistics and the batteries would be useful in detecting de- tecting MCI or nonamnestic forms of 6 16-18 Alzheimer’s Disease Research mentia. The delayed Word List Recall of dementia. Center (Dr Roe), Washington the Consortium to Establish a Registry Informant-based assessments of intra- University, St Louis, Mo. for Alzheimer Disease (CERAD)7 battery individual change, such as the Clinical De- (REPRINTED) ARCH NEUROL / VOL 64, MAY 2007 WWW.ARCHNEUROL.COM 718 ©2007 American Medical Association. All rights reserved. mentia Rating Scale (CDR),19 may be more sensitive than set of participants with a CDR score of 0.5 had cognitive im- brief performance measures that rely on interindividual pairments that did not meet criteria for dementia. We opera- norms to detect cognitive change. We used this premise tionalized these individuals as having uncertain dementia 15 to develop a brief interview, the AD8,14,20 which distin- comparable with MCI. guishes individuals with very mild dementia from those without dementia, regardless of etiology. The AD8,14 NEUROPSYCHOLOGICAL EVALUATION which is based on intraindividual decline, has been dem- onstrated to be a valid and reliable screening tool for de- Each patient was administered a 30-minute test battery at the 20 time of his or her office visit. Episodic memory was assessed mentia. We explored the potential added value of neu- 27 ropsychological testing combined with the AD8 in by the logical memory subtest of the Wechsler Memory Scale, developing a brief screening battery for use in general prac- and the CERAD 10-item Word List Recall, immediate and de- layed.7,8 The Animal Fluency Test28 assessed semantic memory, tice to improve clinicians’ ability to detect cognitive dis- and the 15-item Boston Naming Test29 assessed confronta- orders at the earliest possible stage. tional naming. Three measures addressed psychomotor, visuo- spatial, and executive abilities: the digit symbol subtest of the METHODS Wechsler Adult Intelligence Scale,30 the Trail-Making A Test,31 and the Trail-Making B Test.31 Brief global measures included the MMSE10 and the Short Blessed Test (SBT).32 STUDY PARTICIPANTS Participants were drawn from a consecutive series of referrals STATISTICAL ANALYSIS to the Memory Diagnostic Center, a dementia specialty prac- tice at Washington University School of Medicine, for evalua- All analyses were performed using SPSS, version 13.0 (SPSS tion of cognitive, behavioral, and mood disorders. Diagnoses Inc, Chicago, Ill). Descriptive statistics were used to report ranged from no dementia through all levels of dementia sever- the demographic characteristics of the patients and infor- ity. When calling for an appointment, the patient identified an mants, neuropsychological tests, and dementia stages. Group informant to provide additional information on cognitive and means were compared using analysis of variance; post hoc functional change. A total of 255 patient-informant dyads agreed comparisons were made using Tukey’s Honestly Significant to participate. No patient-informant dyad contributed more than Difference test. 1 visit to the data set. The Washington University Human Stud- Logistic regression models were developed to determine ies Committee approved all procedures. the best combination of brief tests (defined here as taking Ͻ7 minutes to complete) to correctly classify patients as having no dementia (CDR score 0=0) or dementia (CDR score 0.5 or ADMINISTRATION OF THE AD8 greater=1). Continuous test scores were used to initially iden- tify the tests and combinations of tests that significantly pre- The AD8 contains 8 questions (yes or no) that ask the infor- 14,20 dicted dementia. Once the predictive tests were identified, we mant to rate change in cognition and function. After in- determined the best cutoff scores for use in clinical practice. formed consent, the informant rated the patient, and the num- Psychometric tests included in the logistic regression analyses ber of yes answers was totaled to obtain the AD8 score. The were the MMSE, SBT, Word List Recall (immediate and Memory Diagnostic Center physicians were blinded to the re- delayed), and the Animal Fluency, Boston Naming, and Trail- sults of AD8 administration. (A copy of the AD8 table with scor- Making A tests. The Trail-Making B Test, and the Wechsler ing rules may be found at http://alzheimer.wustl.edu/About Memory Scale logical memory and Wechsler Adult Intelli- _Us/PDFs/AD8form2005.pdf.) gence Scale digit symbol subtests were excluded from the analyses because of the length of time needed to administer CLINICAL ASSESSMENT them and the complexity of scoring and interpretation. We used 3 approaches to test the validity of the models. First, all The Memory Diagnostic Center physicians conducted inde- variables (AD8 and psychometrics) were entered simulta- pendent, semistructured interviews with the patient and a knowl- neously to determine which variables independently predicted edgeable collateral source (usually the spouse or a close fam- a CDR score greater than 0 when adjusting for scores on the ily member).21-23 Each patient-caregiver dyad was interviewed remaining tests. We also used 2 stepwise approaches (forward to generate a diagnosis and CDR score. The diagnostic criteria and backward) with the AD8 forced into the model and the for AD were consistent with the definition from the Diagnostic psychometric tests as candidates for stepwise entry. The prob- and Statistical Manual of Mental Disorders, Fourth Edition24 and ability was 0.05 for stepwise entry and 0.10 for removal. of “probable AD” with the National Institute of Neurological Because similar models were elicited using forward and back- and Communication Disorders and Stroke–Alzheimer’s Dis- ward stepwise methods, only results from the forward step- ease and Related Disorders Association criteria.25 Published cri- wise regressions are reported. The odds ratios (ORs) and con- teria were used for other dementing disorders.16-18 fidence intervals (CIs) were reported for each measure; the The CDR was used to determine the presence or absence of percentage correctly classified as demented is reported.
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