title: Neuropathologic correlates of trial-related instruments for Alzheimer's disease.
abstract: To advance disease-modifying therapies, it is critical to understand the relationship between the neuropathological changes of Alzheimer's Disease (AD) and the clinical measures used in therapeutic trials. We reviewed neuropathologically proven cases of AD from the National Alzheimer's Coordinating Center (NACC) and examined correlations between neuropathological changes and clinical-trial related instruments collected as part of the Uniform Dataset (UDS). We explored the relationships between neurofibrillary tangles, neuritic plaques, and total pathology burden with immediate and delayed recall, Clinical Dementia Rating-Sum of Boxes, Functional Activity Questionnaire, Neuropsychiatric Inventory Questionnaire, and Mini-Mental State Examination scores. 169 patients in NACC database had appropriate neuropathological and clinical data. All instruments correlated highly with neuritic plaques, Braak staging, and total pathology. Correlation coefficients for the relationships were relatively modest, suggesting that the pathologic burden examined accounts for between 13 and 40% of the variance of each of the instruments assessed. We conclude that there is a strong correlation between clinical trial-related measures and neuropathology identified at autopsy in AD. The amount of variance explained by the pathology is limited and other factors, both disease- and measurement-related, contribute to the variability observed in clinical measurements.
authors.affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas, Nevada.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Cummings
authors.affiliation: Department of Neurology, The Mary S Easton Center for Alzheimer's Disease Research at The David Geffen School of Medicine at UCLA Los Angeles, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Ringman
authors.affiliation: Department of Pathology & Laboratory Medicine (Neuropathology), The Mary S Easton Center for Alzheimer's Disease Research at The David Geffen School of Medicine at UCLA Los Angeles, CA, USA.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
keywords: Alzheimer’s disease (AD); Clinical therapeutic trials; clinical-trial related instruments; correlation; neuropathological changes
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