Residual vectors for Alzheimer disease diagnosis and prognostication


  • David Glenn Clark

    for the Alzheimer Disease Neuroimaging Initiative
    1. Birmingham VA Medical Center, Birmingham, Alabama
    2. Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama
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  • Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (\ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators is available at

  • Funded by a Career Development Award from the Department of Veterans Affairs (E6553W), the ADNI (National Institutes of Health Grant U01 AG024904), and also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation.

David G. Clark, M.D., 1720 7th Avenue South, SC 620C, Birmingham, AL 35294. Tel: +1-205-996-6050; Fax: +1-205-975-7365; E-mail:


Alzheimer disease (AD) is an increasingly prevalent neurodegenerative condition and a looming socioeconomic threat. A biomarker for the disease could make the process of diagnosis easier and more accurate, and accelerate drug discovery. The current work describes a method for scoring brain images that is inspired by fundamental principles from information retrieval (IR), a branch of computer science that includes the development of Internet search engines. For this research, a dataset of 254 baseline 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) scans was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). For a given contrast, a subset of scans (nine of every 10) was used to compute a residual vector that typified the difference, at each voxel, between the two groups being contrasted. Scans that were not used for computing the residual vector (the remaining one of 10 scans) were then compared to the residual vector using a cosine similarity metric. This process was repeated sequentially, each time generating cosine similarity scores on 10% of the FDG-PET scans for each contrast. Statistical analysis revealed that the scores were significant predictors of functional decline as measured by the Functional Activities Questionnaire (FAQ). When logistic regression models that incorporated these scores were evaluated with leave-one-out cross-validation, cognitively normal controls were discerned from AD with sensitivity and specificity of 94.4% and 84.8%, respectively. Patients who converted from mild cognitive impairment (MCI) to AD were discerned from MCI nonconverters with sensitivity and specificity of 89.7% and 62.9%, respectively, when FAQ scores were brought into the model. Residual vectors are easy to compute and provide a simple method for scoring the similarity between an FDG-PET scan and sets of examples from a given diagnostic group. The method is readily generalizable to any imaging modality. Further interdisciplinary work between IR and clinical neuroscience is warranted.