Browsing by Author "Hammers, Dustin B."
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Item Application of Different Standard Error Estimates in Reliable Change Methods(Oxford University Press, 2021) Hammers, Dustin B.; Duff, Kevin; Neurology, School of MedicineObjective: This study attempted to clarify the applicability of standard error (SE) terms in clinical research when examining the impact of short-term practice effects on cognitive performance via reliable change methodology. Method: This study compared McSweeney's SE of the estimate (SEest) to Crawford and Howell's SE for prediction of the regression (SEpred) using a developmental sample of 167 participants with either normal cognition or mild cognitive impairment (MCI) assessed twice over 1 week. One-week practice effects in older adults: Tools for assessing cognitive change. Using these SEs, previously published standardized regression-based (SRB) reliable change prediction equations were then applied to an independent sample of 143 participants with MCI. Results: This clinical developmental sample yielded nearly identical SE values (e.g., 3.697 vs. 3.719 for HVLT-R Total Recall SEest and SEpred, respectively), and the resultant SRB-based discrepancy z scores were comparable and strongly correlated (r = 1.0, p < .001). Consequently, observed follow-up scores for our sample with MCI were consistently below expectation compared to predictions based on Duff's SRB algorithms. Conclusions: These results appear to replicate and extend previous work showing that the calculation of the SEest and SEpred from a clinical sample of cognitively intact and MCI participants yields similar values and can be incorporated into SRB reliable change statistics with comparable results. As a result, neuropsychologists utilizing reliable change methods in research investigation (or clinical practice) should carefully balance mathematical accuracy and ease of use, among other factors, when determining which SE metric to use.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 Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea(Springer Nature, 2024-04-25) Chun, Min Young; Chae, Wonjeong; Seo, Sang Won; Jang, Hyemin; Yun, Jihwan; Na, Duk L.; Kang, Dongwoo; Lee, Jungkuk; Hammers, Dustin B.; Apostolova, Liana G.; Jang, Sung-In; Kim, Hee Jin; Neurology, School of MedicineBackground: Early-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear. We aimed to investigate how hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and osteoporosis influence the development and mortality of EOD and LOD, respectively. Methods: Using the Korean National Health Insurance Service (NHIS) database, we collected 546,709 dementia-free individuals and followed up for 11 years. In the two study groups, the Younger group (< 65 years old) and the Older group (≥ 65 years old), we applied Cox proportional hazard models to assess risk factors for development of EOD and LOD, respectively. Then, we assessed risk factors for mortality among EOD and LOD. Results: Diabetes mellitus and osteoporosis increased the risk of EOD and LOD development. Hypertension increased the risk of EOD, while atrial fibrillation increased the risk of LOD. Conversely, hyperlipidemia exhibited a protective effect against LOD development. Additionally, diabetes mellitus increased mortality in EOD and LOD. Hypertension and atrial fibrillation increased mortality in LOD, while hyperlipidemia decreased mortality in EOD and LOD. Conclusions: Risk factors influencing dementia development and mortality differed in EOD and LOD. Targeted public health interventions addressing age-related risk factors may reduce dementia incidence and mortality.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 Neuropsychiatric symptom burden in early‐onset and late‐onset Alzheimer's disease as a function of age(Wiley, 2024) Polsinelli, Angelina J.; Johnson, Sierah; Crouch, Adele; Lane, Kathleen A.; Pena-Garcia, Alex; Hammers, Dustin B.; Wang, Sophia; Gao, Sujuan; Apostolova, Liana G.; Neurology, School of MedicineIntroduction: We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. Methods: Cross-sectional data from 2940 EOAD, 8665 LOAD, and 8775 age-stratified CU individuals (early-CU, n = 2433; late-CU, n = 6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. Results: Presence (ps < 0.0001) and severity (ps < 0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps < 0.05) and nighttime behaviors more frequent and severe in LOAD (ps < 0.05). Discussion: Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. Highlights: Adjusting for age effect, elation and eating problems are more frequent in EOAD. Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD. Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD.Item Prevalence of Suspected Dementia in a Sample of Adults Living in Kinshasa-Democratic Republic of the Congo(Wiley, 2023) Ikanga, Jean; Reyes, Anny; Kaba, Didine; Akilimali, Pierre; Mampunza, Samuel; Epenge, Emmanuel; Gikelekele, Guy; Kavugho, Immaculee; Tshengele, Nathan; Hammers, Dustin B.; Alonso, Alvaro; Neurology, School of MedicineBackground: The prevalence of dementia in Sub-Saharan Africa, particularly in French-speaking countries, has received limited attention. This study investigates the prevalence and risk factors of suspected dementia in elderly adults in Kinshasa, Democratic Republic of the Congo (DRC). Methods: A community-based sample of 355 individuals over 65 years old was selected using multistage probability sampling in Kinshasa. Participants were screened using the Community Screening Instrument for Dementia, Alzheimer's Questionnaire, Geriatric Depression Scale, Beck Anxiety Inventory, and Individual Fragility Questionnaire, followed by clinical interview and neurological examination. Suspected dementia diagnoses were made based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria including significant cognitive and functional impairments. Prevalence and odds ratios (ORs) with 95% confidence interval (CI) were calculated using, respectively, regression and logistic regression. Results: Among 355 participants (mean age 74, SD = 7; 51% male), the crude prevalence of suspected dementia was 6.2% (9.0% in women and 3.8% in men). Female sex was a significant factor associated with suspected dementia [OR = 2.81, 95% CI (1.08-7.41)]. The prevalence of dementia increased with age (14.0% after 75 years and 23.1% after 85 years), with age being significantly associated with suspected dementia [OR = 5.42, 95% CI (2.86-10.28)]. Greater education was associated with a lower prevalence of suspected dementia [OR = 2.36, 95% CI (2.14-2.94), comparing those with ≥7.3 years of education to those with <7.3 years of education]. Other factors associated with the prevalence of suspected dementia included being widowed (OR = 1.66, 95% CI (1.05-2.61), being retired or semi-retired (OR = 3.25, 95% CI (1.50-7.03)], a diagnosis of anxiety [OR = 2.56, 95% CI (1.05-6.13)], and death of a spouse or a relative after age 65 [OR = 1.73, 95% CI (1.58-1.92)]. In contrast, depression [OR = 1.92, 95% CI (0.81-4.57)], hypertension [OR = 1.16, 95% CI (0.79-1.71)], body mass index (BMI) [OR = 1.06, 95% CI (0.40-2.79)], and alcohol consumption [OR = 0.83, 95% CI (0.19-3.58)] were not significantly associated with suspected dementia. Conclusions: This study found a prevalence of suspected dementia in Kinshasa/DRC similar to other developing countries and Central African countries. Reported risk factors provide information to identify high-risk individuals and develop preventive strategies in this setting.Item 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 MedicineThe 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.