Howard A. Fink
A series of review articles found limited or inconsistent data supporting the accuracy of biomarkers and cognitive tests for diagnosing and differentiating Alzheimer’s disease, as well as drug treatments that minimally impacted functional decline.
The reviews, published in Annals of Internal Medicine, will inform new American Academy of Family Physicians guidelines.
Accuracy of biomarkers
The authors wrote that diagnosing the different types of dementia can be difficult.
“We believed that the most relevant clinical question was whether adding biomarker testing to clinical evaluation improved accuracy vs. clinical evaluation alone,” Howard A. Fink, MD, MPH, director of the Minneapolis Veterans’ Affairs Geriatric Research Education and Clinical Center, told Healio Primary Care.
Biomarker tests for Alzheimer’s disease have shown at least moderate sensitivity and specificity 0.50 and higher). These tests include brain imaging, amyloid positron emission tomography, fluorodeoxyglucose positron emission tomography, MRI, single-photon emission CT and cerebrospinal fluid test. Data on the direct harms of biomarker testing were “scant” and no data existed on the possible negative downstream consequences.
“Small single studies in research settings of uncertain applicability to clinical practice suggested amyloid PET, fluorodeoxyglucose PET and a combination of cerebrospinal fluid tests might increase accuracy when added to clinical evaluation,” Fink said.
Time and availability prevent many primary care physicians from using neuropsychological tests to diagnose dementia and its different subtypes, the authors wrote. Therefore, they focused on short cognitive tests that could be administered in primary care settings.
The authors wrote that the median sensitivity and median specificity scores of certain tests were all high or near high 0.79 or higher). These tests included the Brief Alzheimer Screen, Mini-Mental State Examination, Montreal Cognitive Assessment, the clock-drawing test, the delayed recall test and language fluency test.
The authors also noted that these tests were “less accurate” in differentiating mild clinical Alzheimer-type dementia from normal cognition or clinical Alzheimer-type dementia from mild cognitive impairment. However, Fink said cognitive tests may help determine which older adults need further evaluation or provide “sufficient objective evidence of cognitive impairment to support an Alzheimer’s dementia diagnosis.”
Previous reports indicated that compared with placebo, the magnitude of the effect cholinesterase inhibitors and memantine had on improving cognition and function was limited. To update this evidence base, the authors compared 16 treatments to placebo in their review.
They found that across clinical Alzheimer-type dementia severity, there was an abundance of low-strength evidence to suggest that cholinesterase inhibitors offered only average improvements in cognition at most. The treatments did not increase the likelihood of moderate improvement in global clinical impressions, and adverse events associated with their use led to nonadherence among patients. The impact of prescription drugs on behavioral and psychological symptoms was limited by mostly insufficient data, as was the impact of supplements on all clinical Alzheimer-type dementia outcomes.
“Most drugs had few trials without high risk of bias, especially for supplements, active drug comparisons, behavioral and psychological symptoms and longer trials,” Fink and colleagues wrote. – by Janel Miller
Fink H, et al. Ann Intern Med. 2020;doi:10.7326/M19-3888.
Fink H, et al. Ann Intern Med. 2020;doi:10.7326/M19-3887.
Hemmy LS, et al. Ann Intern Med. 2020;doi:10.7326/M19-3889.
Disclosures: Fink reports that the evidence synthesis on which the biomarker and treatment manuscripts were based was funded by an Agency for Healthcare Research and Quality contract. Please see the reviews for all other authors’ relevant financial disclosures.