Browsing by Author "King, Jace B."

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    How do short‐term practice effects compare to biomarkers of Alzheimer’s disease?
    (Wiley, 2025-01-03) Duff, Kevin; Hammers, Dustin B.; Koppelmans, Vincent; King, Jace B.; Hoffman, John M.; Neurology, School of Medicine
    Background: Practice effects on cognitive testing in Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) remain understudied, especially with how they compare to biomarkers of AD. The current study sought to add to this growing literature. Method: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) repeated a brief battery of cognitive tests twice across one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE e4 status. Result: The intact participants showed significantly larger practice effects than the other two groups on an overall composite measure, and those with MCI showed significantly larger practice effects than those with AD. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact>MCI>AD). For APOE e4, the intact had significantly fewer copies of e4 than MCI and AD. Overall, the effect sizes of practice effects were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons (see Table). Conclusion: Short‐term practice effects on cognitive tests appear to be a sensitive marker in late life cognitive disorders, as they separated groups better than commonly‐used biomarkers in AD. Further refinement of short‐term practice effects as a tool for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.
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    Relationship between a novel learning slope metric and Alzheimer’s disease biomarkers
    (Taylor & Francis, 2022) Hammers, Dustin B.; Suhrie, Kayla; Dixon, Ava; Gradwohl, Brian D.; Archibald, Zane G.; King, Jace B.; Spencer, Robert J.; Duff, Kevin; Hoffman, John M.; Neurology, School of Medicine
    The Learning Ratio (LR) is a novel learning score examining the proportion of information learned over successive learning trials relative to information available to be learned. Validation is warranted to understand LR's sensitivity to Alzheimer's disease (AD) pathology. One-hundred twenty-three participants across the AD continuum underwent memory assessment, quantitative brain imaging, and genetic analysis. LR scores were calculated from the HVLT-R, BVMT-R, RBANS List Learning, and RBANS Story Memory, and compared to total hippocampal volumes,18F-Flutemetamol composite SUVR uptake, and APOE ε4 status. Lower LR scores were consistently associated with smaller total hippocampal volumes, greater cerebral β-amyloid deposition, and APOE ε4 positivity. This LR score outperformed a traditional learning slope calculation in all analyses. LR is sensitive to AD pathology along the AD continuum - more so than a traditional raw learning score - and reducing the competition between the first trial and subsequent trials can better depict learning capacity.
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    Repeatable Battery for the Assessment of Neuropsychological Status and its relationship to biomarkers of Alzheimer’s disease
    (Taylor & Francis, 2023) Duff, Kevin; Suhrie, Kayla R.; Hammers, Dustin B.; Dixon, Ava M.; King, Jace B.; Koppelmans, Vincent; Hoffman, John M.; Neurology, School of Medicine
    Background: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated with commonly used biomarkers of Alzheimer’s disease (AD). However, prior studies have typically utilized small and poorly characterized samples, and they have not analyzed the subtests of the RBANS. The current study sought to expand on prior work by examining the relationship between the Indexes and subtest scores of the RBANS and three AD biomarkers: amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and APOE ε4 status. Method: One-hundred twenty-one older adults across the AD continuum (intact, amnestic Mild Cognitive Impairment, mild AD), who were mostly Caucasian and well-educated,underwent assessment with the RBANSand collection of the three biomarkers. Results: Greater amyloid deposition was significantly related to lower scores on all five Indexes and the Total Scale score of the RBANS, as well as 11 of 12 subtests. For bilateral hippocampal volume, significant correlations were observed for 4 of the 5 Indexes, Total Scale score, and 9 of 12 subtests, with smaller hippocampi being related to lower RBANS scores. Participants with at least one APOE ε4 allele had significantly lower scores on 3 of the 5 Indexes, Total Scale score, and 8 of the 12 subtests. Conclusions: In this sample of participants across the dementia spectrum, most RBANSIndexes and subtests showed relationships with the amyloid deposition, hippocampal volumes, and APOE status, with poorer performance on the RBANS being associated with biomarker positivity. Although memory scores on the RBANS have traditionally been linked to biomarkers in AD, other Index and subtest scores also hold promise as indicators of AD. Replication in a more diverse sample is needed.
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    Short-Term Practice Effects on Cognitive Tests Across the Late Life Cognitive Spectrum and How They Compare to Biomarkers of Alzheimer’s Disease
    (Sage, 2024) Duff, Kevin; Hammers, Dustin B.; Koppelmans, Vincent; King, Jace B.; Hoffman, John M.; Neurology, School of Medicine
    Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.
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    The Quick Dementia Rating System and Its Relationship to Biomarkers of Alzheimer's Disease and Neuropsychological Performance
    (Karger, 2022) Duff, Kevin; Wan, Laura; Levine, Deborah A.; Giordani, Bruno; Fowler, Nicole R.; Fagerlin, Angela; King, Jace B.; Hoffman, John M.; Medicine, School of Medicine
    Introduction: The Quick Dementia Rating System (QDRS) is a brief, patient-reported dementia staging tool that has approximated scores on the Clinical Dementia Rating Scale in patients with Alzheimer's disease (AD). However, no studies have examined its relationship with AD-related biomarkers. Methods: One-hundred twenty-one older adults (intact, amnestic mild cognitive impairment, mild AD) completed the QDRS, and three biomarkers (amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and apolipoprotein [APOE] ε4 status). Results: The Total score on the QDRS was statistically significantly related to all three biomarkers (after controlling for age, education, sex, and race), with greater levels of dementia severity being associated with greater amyloid deposition, smaller hippocampi, and having copies of APOE ε4 allele. Discussion: In participants across the cognitive spectrum, the QDRS showed modest relationships with amyloid deposition, hippocampal volumes, and APOE status. Therefore, the QDRS may offer a cost-effective screening method for clinical trials in AD.