Sarah FleischmanCME Program Manager, Medscape, LLCDisclosure: Sarah Fleischman has disclosed no relevant financial relationships.From Medscape Education Clinical BriefsFour Questions May Assist Clinicians in Detecting aMCI CMENews Author: Deborah BrauserCME Author: Penny Murata, MDCME Released: 03/01/2012; Valid for credit through 03/01/2013Clinical ContextAmnestic mild cognitive impairment (aMCI) refers to a syndrome of memory performance of at least 1.5 SDs below the age- and education-adjusted normative values on a verbal memory test plus subjective memory complaints, preserved global cognition, and preserved activities of daily living, as reported by Petersen and colleagues in the March 1999 issue of the Archives of Neurology. However, persons who are cognitively normal can also report memory and cognitive problems, as noted by Levey and colleagues in the July 2006 issue of Clinical Therapeutics. A pilot study by Sabbagh and colleagues in the 2010 issue of the Journal of Alzheimer's Disease found that the Alzheimer's Questionnaire (AQ) has a sensitivity of 87% and a specificity of 94% for aMCI.This case-control study by Malek-Ahmadi and colleagues assesses which AQ items are predictive of aMCI.Study Synopsis and PerspectiveJust 4 simple questions may help clinicians distinguish between patients with normal age-related memory loss and those with aMCI, an early risk factor for Alzheimer's disease (AD), new research suggests.In a case-control study of almost 100 elderly participants, difficulty with 4 questions from the AQ dementia assessment test significantly indicated aMCI. These questions dealt with statement repetitions, dates and times, finances, and sense of direction."As the population is aging, more and more people are having subjective memory complaints," lead author Michael Malek-Ahmadi, MSPH, from the Banner Sun Health Research Institute in Sun City, Arizona, told Medscape Medical News. Banner Sun created the free-to-download AQ."So it is important to find accurate ways to quickly identify those who might be in the early stages of Alzheimer's and needing further evaluation," he said.The investigators note that this early identification could potentially help in cost containment, resource management, and improved disease outcome."While the AQ cannot be used as a definitive guide to diagnosing AD or aMCI, it is a simple-to-use tool for primary care doctors to use as an indicator as to whether an individual needs to be assessed further or if the patient is within normal limits for their age in regard to cognitive symptoms," added Malek-Ahmadi.The study was published online February 3 in BMC Geriatrics.The Ayes Have It In a study published last year in the Journal of Alzheimer's Disease, Malek-Ahmadi and colleagues found that overall, the AQ had both high sensitivity (odds ratio [OR], 86.96) and high specificity (OR, 94.00) for indicating aMCI."The intent of this study [was] to determine which AQ items are predictive of aMCI," write the investigators.They evaluated data from the ongoing AQ validation study on 47 patients considered to have aMCI (57% men; mean age, 74.36 years) and 51 individuals considered "cognitively normal" (43% men; mean age, 78.59 years)."Individuals whose performance was 1.5 standard deviations...below age- and education-corrected means on a delayed recall measure of verbal memory were classified as aMCI," report the researchers.The 21-item AQ (which is divided into 5 domains: memory, orientation, functional ability, visuospatial ability, and language) was completed by caregivers or family members of each participant.In addition, the participants underwent several neuropsychological tests, including the Rey Auditory Verbal Learning Test, the Wechsler Memory ScaleRevised logical memory test, the Trails A and B tests, the Controlled Oral Word Association Test, and the Stroop Color/Word test.Results showed that "yes" answers to the following AQ questions were significant indicators of aMCI: DOES THE PATIENT REPEAT QUESTIONS/STATEMENTS IN THE SAME DAY? (OR, 13.12; 95% CONFIDENCE INTERVAL [CI], 3.02 - 57.66; P = .001) DOES THE PATIENT HAVE TROUBLE REMEMBERING THE DATE, YEAR, AND TIME? (OR, 17.97; 95% CI, 2.63 - 122.77; P = .003) DOES THE PATIENT HAVE DIFFICULTY MANAGING FINANCES? (OR, 11.60; 95% CI, 2.10 - 63.99; P = .005) DOES THE PATIENT HAVE A DECREASED SENSE OF DIRECTION? (OR, 5.84; 95% CI, 1.09 - 32.30; P = .04)Items pertaining to repetition of statements, orientation, ability to manage finances, and visuospatial disorientation had high discriminatory power."Overall...items pertaining to repetition of statements, orientation, ability to manage finances, and visuospatial disorientation had high discriminatory power," write the investigators.Self-Report Version in the WorksAdditional analysis examining only these 4 AQ questions showed a sensitivity to aMCI of 80.30% and a specificity of 81.80%."Although those 4 questions were strongly predictive, it was in a relatively small sample. So I would recommend that clinicians use the entire AQ," said Malek-Ahmadi."The symptoms of Alzheimer's can vary quite a bit, which is why the questionnaire includes 21 questions. In addition, if a loved one or spouse is reporting other symptoms, those should obviously be taken into account as well."He added that it is also important to educate the general public about what symptoms are and are not indicative of AD.If we can provide better education about symptoms, that helps us to be more accurate in identifying people who need treatment."I think that's one of the biggest issues we face in the field. If we can provide better education about symptoms, that helps us to be more accurate in identifying people who need treatment."The investigators are now developing a self-reported version of the AQ for patients to fill out if they do not have anyone who can accompany them on an office visit.For now, the current informant-reported AQ is freely available to clinicians upon request to the study authors.Timely Research"This is a really strong group of researchers and a well-thought-out, timely study to be looking at cognitive impairment very early in the disease process," Maria C. Carrillo, PhD, senior director of medical and scientific relations at the Alzheimer's Association, told Medscape Medical News.Dr. Carrillo reported that the Alzheimer's Association, along with the National Institute on Aging, recently revised its recommended criteria and guidelines for diagnosing AD."That revision now includes mild cognitive impairment and even preclinical Alzheimer's disease, which means you have very little symptoms of disease and maybe just some brain changes," she said.She also noted that the Alzheimer's Association currently has an educational Web site for clinicians and the public called "Know the 10 Signs" of AD."We're all looking for a better way to detect memory changes that could be due to dementia or Alzheimer's disease, such as the test explained in this paper," said Dr. Carrillo."The investigators found that 4 questions were really key to determining whether a person had Alzheimer's-type memory problems. And our Web site comprises aspects of those questions amongst its 10 warning signs. So we really encourage caregivers to check out the site and think about these points when they have concerns about their loved ones' cognition."Dr. Carrillo added that having a simple test available to help a physician in the diagnosis process is especially important now that Medicare and Medicaid have agreed to cover cognitive examinations within annual wellness visits for elderly beneficiaries.Tests need to be short, easy to administer, and easy for clinicians to understand."We're really excited about that. And the Alzheimer's Association and the National Institute on Aging are working with those organizations to determine which cognitive tests should be included. And some of our recommendations are used in this paper: tests need to be short, easy to administer, and easy for clinicians to understand," she explained."This is going to be important for the next 10 to 15 years, so we need to make sure we incorporate a better way to detect cognitive changes in a general practitioner's office. These things are actually happening. So this is a really important study that could possibly contribute to future practice."Dr. Carrillo also noted that the Alzheimer's Association "is very excited" about the recent announcement, as reported by Medscape Medical News, by the Obama Administration of a significant investment in AD research."This infusion of funds is important, and the Alzheimers Association appreciates this step by the Administration," said Harry Johns, president and chief executive officer of the Alzheimers Association, in a release at the time."In order to meet the expectations of all Americans affected by this epidemic, the plan must address the critical need for care and support as well as accelerate research toward prevention, treatment and ultimately a cure," said Johns."Although we need to point out that this current study is still early and included less than 100 people, again, it's very timely and an important type of research that needs to be done," added Dr. Carrillo.The study was funded by the Arizona Alzheimer's Research Consortium and the Banner Sun Health Research Institute and Alzheimer's Institute, and by grants from the National Institute on Aging and the Arizona Department of Health Services. The study authors and Dr. Carrillohave disclosed no relevant financial relationships.BMC Geriatrics. Published online February 3, 2012.Full articleStudy Highlights Data from 98 persons were used from a validation study of the AQ. 47 patients with aMCI came from the practice of a neurologist. 51 patients with normal cognition came from annual assessment of a brain and body donation program. Exclusion criteria were mental retardation, epilepsy, cerebral infarction or hemorrhage, multiple sclerosis, brain tumor, major depressive disorder, schizophrenia, traumatic brain injury, and substance abuse. The gold standard for a diagnosis of aMCI was a clinician's diagnosis based on cognitive and medical history, informant interview, and neuropsychological testing with use of Petersen criteria. aMCI was determined by performance at least 1.5 SDs below age- and education-corrected means on delayed recall measure of verbal memory. The gold standard for cognitively normal status was based on consensus by a neurologist, a geriatric psychiatrist, and a neuropsychologist. Cognitively normal patients had no cognitively based limitations of activities of daily living identified by clinician interview, scored above 1.5 SDs on age- and education-corrected means on neuropsychological tests, and received a global Clinical Dementia Rating score of 0. The mean age of participants was 76.56 years. Participants in the cognitively normal group vs those in the aMCI group were older (78.59 vs 74.36 years) and slightly more educated. However, they were similar in sex (43% vs 57% men) and had similar scores on the Mini-Mental State Examination (28.47 vs 26.89). Neuropsychological tests included the Rey Auditory Verbal Learning Test, WMS-R Logical Memory, Trails A, Trails B, Controlled Oral Word Association Test, Animal Fluency, Stroop Color/Word, and Judgment of Line Orientation. The AQ has 21 items covering 5 domains: memory, orientation, functional ability, visuospatial ability, and language. The AQ score ranges from 0 to 27, with 6 items known to be predictive of clinical AD worth 2 points each and 15 items worth 1 point each. Age- and education-adjusted multiple forward stepwise logistic regression analysis determined the predictive ability of individual AQ items for the outcome of aMCI. 4 AQ items were strong predictors of aMCI: Does the patient repeat questions or statements or stories in the same day? (OR, 13.12; 95% CI, 3.02 - 57.66; P = .001) Does the patient frequently have trouble knowing the day, date, month, year, and time, or does the patient reference a newspaper or calendar for the date more than once a day? (OR, 17.97; 95% CI, 2.63 - 122.77; P = .003) Excluding physical limitations, does the patient have trouble paying bills or doing finances, or are family members taking over because of concerns about the patient's ability to manage finances? (OR, 11.60; 95% CI, 2.10 - 63.99; P = .005) Does the patient have a decreased sense of direction? (OR, 5.84; 95% CI, 1.09 - 32.30; P = .04) A logistic regression analysis using the 4 significant AQ items corrected for age and education showed a sensitivity of 80.30%, a specificity of 81.80%, and an area under the curve of 0.94. Nagelkerke's R2 of 0.71 indicated that the 4 significant AQ items account for a large proportion of the variance between participants with aMCI and those with normal cognition. Study limitations were wide CIs for the ORs of the significant AQ items, the need for the informant to complete the AQ, and homogeneous ethnicity of the study sample.Clinical Implications The following 4 items in the AQ are strong indicators of aMCI: repetition of statements, questions, or both; trouble knowing the day, date, month, year, and time; difficulty managing finances; and a decreased sense of direction. Additional analysis examining only the 4 AQ questions showed a sensitivity to aMCI of 80.30% and a specificity of 81.80%.Disclaimer

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