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Browsing by Author "Hammers, Dustin B."
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Item Assessing and validating reliable change across ADNI protocols(Taylor & Francis, 2022) Hammers, Dustin B.; Kostadinova, Ralitsa; Unverzagt, Frederick W.; Apostolova, Liana G.; Alzheimer’s Disease Neuroimaging Initiative; Neurology, School of MedicineObjective: Reliable change methods can aid in determining whether changes in cognitive performance over time are meaningful. The current study sought to develop and cross-validate 12-month standardized regression-based (SRB) equations for the neuropsychological measures commonly administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI) longitudinal study. Method: Prediction algorithms were developed using baseline score, retest interval, the presence/absence of a 6-month evaluation, age, education, sex, and ethnicity in two different samples (n = 192 each) of robustly cognitively intact community-dwelling older adults from ADNI - matched for demographic and testing factors. The developed formulae for each sample were then applied to one of the samples to determine goodness-of-fit and appropriateness of combining samples for a single set of SRB equations. Results: Minimal differences were seen between Observed 12-month and Predicted 12-month scores on most neuropsychological tests from ADNI, and when compared across samples the resultant Predicted 12-month scores were highly correlated. As a result, samples were combined and SRB prediction equations were successfully developed for each of the measures. Conclusions: Establishing cross-validation for these SRB prediction equations provides initial support of their use to detect meaningful change in the ADNI sample, and provides the basis for future research with clinical samples to evaluate potential clinical utility. While some caution should be considered for measuring true cognitive change over time - particularly in clinical samples - when using these prediction equations given the relatively lower coefficients of stability observed, use of these SRBs reflects an improvement over current practice in ADNI.Item Baseline neuropsychiatric symptoms and psychotropic medication use midway through data collection of the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort(Wiley, 2023) Polsinelli, Angelina J.; Wonderlin, Ryan J.; Hammers, Dustin B.; Pena Garcia, Alex; Eloyan, Anii; Taurone, Alexander; Thangarajah, Maryanne; Beckett, Laurel; Gao, Sujuan; Wang, Sophia; Kirby, Kala; Logan, Paige E.; Aisen, Paul; Dage, Jeffrey L.; Foroud, Tatiana; Griffin, Percy; Iaccarino, Leonardo; Kramer, Joel H.; Koeppe, Robert; Kukull, Walter A.; La Joie, Renaud; Mundada, Nidhi S.; Murray, Melissa E.; Nudelman, Kelly; Soleimani-Meigooni, David N.; Rumbaugh, Malia; Toga, Arthur W.; Touroutoglou, Alexandra; Vemuri, Prashanthi; Atri, Alireza; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph; Mendez, Mario F.; Womack, Kyle; Musiek, Erik; Onyike, Chiadi U.; Riddle, Meghan; Rogalski, Emily; Salloway, Steven; Sha, Sharon J.; Turner, Raymond S.; Wingo, Thomas S.; Wolk, David A.; Carrillo, Maria C.; Dickerson, Bradford C.; Rabinovici, Gil D.; Apostolova, Liana G.; LEADS Consortium; Neurology, School of MedicineIntroduction: We examined neuropsychiatric symptoms (NPS) and psychotropic medication use in a large sample of individuals with early-onset Alzheimer's disease (EOAD; onset 40-64 years) at the midway point of data collection for the Longitudinal Early-onset Alzheimer's Disease Study (LEADS). Methods: Baseline NPS (Neuropsychiatric Inventory - Questionnaire; Geriatric Depression Scale) and psychotropic medication use from 282 participants enrolled in LEADS were compared across diagnostic groups - amyloid-positive EOAD (n = 212) and amyloid negative early-onset non-Alzheimer's disease (EOnonAD; n = 70). Results: Affective behaviors were the most common NPS in EOAD at similar frequencies to EOnonAD. Tension and impulse control behaviors were more common in EOnonAD. A minority of participants were using psychotropic medications, and use was higher in EOnonAD. Discussion: Overall NPS burden and psychotropic medication use were higher in EOnonAD than EOAD participants. Future research will investigate moderators and etiological drivers of NPS, and NPS differences in EOAD versus late-onset AD. Keywords: early-onset Alzheimer's disease; early-onset dementia; mild cognitive impairment; neuropharmacology; neuropsychiatric symptoms; psychotropic medications.Item Criterion Validation of Tau PET Staging Schemes in Relation to Cognitive Outcomes(IOS Press, 2023) Hammers, Dustin B.; Lin, Joshua H.; Polsinelli, Angelina J.; Logan, Paige E.; Risacher, Shannon L.; Schwarz, Adam J.; Apostolova, Liana G.; Alzheimer’s Disease Neuroimaging Initiative; Neurology, School of MedicineBackground: Utilization of NIA-AA Research Framework requires dichotomization of tau pathology. However, due to the novelty of tau-PET imaging, there is no consensus on methods to categorize scans into "positive" or "negative" (T+ or T-). In response, some tau topographical pathologic staging schemes have been developed. Objective: The aim of the current study is to establish criterion validity to support these recently-developed staging schemes. Methods: Tau-PET data from 465 participants from the Alzheimer's Disease Neuroimaging Initiative (aged 55 to 90) were classified as T+ or T- using decision rules for the Temporal-Occipital Classification (TOC), Simplified TOC (STOC), and Lobar Classification (LC) tau pathologic schemes of Schwarz, and Chen staging scheme. Subsequent dichotomization was analyzed in comparison to memory and learning slope performances, and diagnostic accuracy using actuarial diagnostic methods. Results: Tau positivity was associated with worse cognitive performance across all staging schemes. Cognitive measures were nearly all categorized as having "fair" sensitivity at classifying tau status using TOC, STOC, and LC schemes. Results were comparable between Schwarz schemes, though ease of use and better data fit preferred the STOC and LC schemes. While some evidence was supportive for Chen's scheme, validity lagged behind others-likely due to elevated false positive rates. Conclusions: Tau-PET staging schemes appear to be valuable for Alzheimer's disease diagnosis, tracking, and screening for clinical trials. Their validation provides support as options for tau pathologic dichotomization, as necessary for use of NIA-AA Research Framework. Future research should consider other staging schemes and validation with other outcome benchmarks.Item Demographically-corrected normative data for the RBANS Learning Ratio in a sample of older adults(Taylor & Francis, 2022) Hammers, Dustin B.; Duff, Kevin; Spencer, Robert J.; Neurology, School of MedicineBackground: A novel learning slope score - the Learning Ratio (LR) - has recently been developed that appears to be sensitive to memory performance and AD pathology more optimally than traditional learning slope calculations. While promising, this research to date has been both experimental and based on group differences, and therefore does not aid in the interpretation of individual LR performance for either clinical or research settings. The objective of the current study was to develop demographically-corrected normative data on these LR learning slopes on verbal learning measures from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Method: The current study examined the influence of age and education on LR metrics for the List Learning, Story Memory, and an Aggregated RBANS score in 200 cognitively intact adults aged 65 or older using linear regression. Results: Age and education correlated with most LR metrics, but no sex differences were observed. Linear regression permitted the prediction of LR values from age and education, which are then compared to observed LR values. The result is demographically-corrected T scores for these LR metrics. Conclusions: By comparing observed and predicted LR scores calculated from regression-based prediction equations, this represents the first step towards interpretation of individual performances on this metric for clinical decision making and treatment planning purposes. With future replication in diverse and heterogenous samples, we hope to offer a new clinical tool for the examination of learning slopes in older adults.Item Examining the role of repeated test exposure over 12 months across ADNI protocols(Wiley, 2022) Hammers, Dustin B.; Duff, Kevin; Apostolova, Liana G.; Alzheimer's Disease Neuroimaging Initiative; Neurology, School of MedicineObjective: Changes to study protocols during longitudinal research may alter cognitive testing schedules over time. Unlike in prior Alzheimer's Disease Neuroimaging Initiative (ADNI) protocols, where testing occurred twice annually, participants enrolled in the ADNI-3 are no longer exposed to cognitive materials at 6 months. This may affect their 12-month performance relative to earlier ADNI cohorts, and potentially confounds data harmonization attempts between earlier and later ADNI protocols. Method: Using data from participants enrolled across multiple ADNI protocols, this study investigated whether test exposure during 6-month cognitive evaluation influenced scores on subsequent 12-month evaluation. Results: No interaction effects were observed between test exposure group and time at 12 months on cognitive performance. No improvements, and limited declines, were seen between baseline and 12-month follow-up scores on most measures. Conclusions: The 6-month testing session had minimal impact on 12-month performance in ADNI. Collapsing longitudinal data across ADNI protocols in future research appears appropriate.Item Validation of and Demographically Adjusted Normative Data for the Learning Ratio Derived from the RAVLT in Robustly Intact Older Adults(Oxford University Press, 2022) Hammers, Dustin B.; Spencer, Robert J.; Apostolova, Liana G.; Alzheimer’s Disease Neuroimaging Initiative; Neurology, School of MedicineBackground: The learning ratio (LR) is a novel learning slope score that was developed to identify learning more accurately by considering the proportion of information learned after the first trial of a multi-trial learning task. Specifically, LR is the number of items learned after trial one divided by the number of items yet to be learned. Although research on LR has been promising, convergent validation, clinical characterization, and demographic norming of this LR metric are warranted to understand its clinical utility when derived from the Rey Auditory Verbal Learning Test (RAVLT). Method: Data from 674 robustly cognitively intact older participants from the Alzheimer's Disease Neuroimaging Initiative (aged 54- 89) were used to calculate the LR metric. Comparison of LR's relationship with standard memory measures was undertaken relative to other traditional learning slope metrics. In addition, retest reliability at 6, 12, and 24 months was examined, and demographically adjusted normative comparisons were developed. Results: Lower LR scores were associated with poorer performances on memory measures, and LR scores outperformed traditional learning slope calculations across all analyses. Retest reliability exceeded acceptability thresholds across time, and demographically adjusted normative equations suggested better performance for cognitively intact participants than those with mild cognitive impairment. Conclusions: These results suggest that this LR score possesses sound retest reliability and can better reflect learning capacity than traditional learning slope calculations. With the added development and validation of regression-based normative comparisons, these findings support the use of the RAVLT LR as a clinical tool to inform clinical decision-making and treatment.