Browsing by Author "Unverzagt, Frederick"
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Item A comparison of techniques for deriving clustering and switching scores from verbal fluency word lists(Frontiers Media, 2022-09-14) Bushnell, Justin; Svaldi, Diana; Ayers, Matthew R.; Gao, Sujuan; Unverzagt, Frederick; Del Gaizo, John; Wadley, Virginia G.; Kennedy, Richard; Goñi, Joaquín; Clark, David Glenn; Neurology, School of MedicineObjective: To compare techniques for computing clustering and switching scores in terms of agreement, correlation, and empirical value as predictors of incident cognitive impairment (ICI). Methods: We transcribed animal and letter F fluency recordings on 640 cases of ICI and matched controls from a national epidemiological study, amending each transcription with word timings. We then calculated clustering and switching scores, as well as scores indexing speed of responses, using techniques described in the literature. We evaluated agreement among the techniques with Cohen's κ and calculated correlations among the scores. After fitting a base model with raw scores, repetitions, and intrusions, we fit a series of Bayesian logistic regression models adding either clustering and switching scores or speed scores, comparing the models in terms of several metrics. We partitioned the ICI cases into acute and progressive cases and repeated the regression analysis for each group. Results: For animal fluency, we found that models with speed scores derived using the slope difference algorithm achieved the best values of the Watanabe-Akaike Information Criterion (WAIC), but with good net reclassification improvement (NRI) only for the progressive group (8.2%). For letter fluency, different models excelled for prediction of acute and progressive cases. For acute cases, NRI was best for speed scores derived from a network model (3.4%), while for progressive cases, the best model used clustering and switching scores derived from the same network model (5.1%). Combining variables from the best animal and letter F models led to marginal improvements in model fit and NRI only for the all-cases and acute-cases analyses. Conclusion: Speed scores improve a base model for predicting progressive cognitive impairment from animal fluency. Letter fluency scores may provide complementary information.Item Association Between MIND Diet Score and Cortical Thickness in an Aging Population(Wiley, 2025-01-09) Dempsey, Desarae A.; Apostolova, Liana G.; Brosch, Jared R.; Clark, David G.; Farlow, Martin R.; Mathew, Sunu; Unverzagt, Frederick; Wang, Sophia; Gao, Sujuan; Clark, Daniel; Saykin, Andrew J.; Risacher, Shannon L.; Neurology, School of MedicineBackground The Mediterranean diet has been associated with decreased brain atrophy (Staubo et al. 2016,Alz&Dem), but the MIND (Mediterranean‐Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay) diet, designed for dementia prevention (Morris et al. 2015, Alz&Dem), remains underexplored for its impact on brain atrophy. We investigated the MIND diet’s association with cortical thickness (CT) in the Indiana Alzheimer’s Disease Research Center (IADRC) sample. Methods 134 participants (49 CN, 45 SCD, 30 MCI, 10 AD/other) completed a self‐report MIND diet questionnaire at the IADRC, which was coded into high, medium, or low intake groups for each food (5 ‘unhealthy’ food groups were reverse scored) and completed an MRI scan on a 3T scanner. The cortical surface was parcellated using FreeSurfer v6. We selected two regions of interest (ROIs) reflecting AD‐associated neurodegeneration: temporal and global CT. We examined the association of MIND diet scores (0‐15) and food groups with CT using regression models adjusted for age, sex, race, education, and diagnosis. Results Higher MIND diet scores were associated with greater mean temporal CT (r = 0.269, p = 0.002) and greater mean global CT (r = 0.230, p = 0.008). In multivariable‐adjusted models, the association persisted for temporal but not global CT. Among the 15 food components, greater olive oil (r = 0.034, p<0.001), fish (r = 0.181, p = 0.040), beans (r = 0.237, p = 0.008), and nuts (r = 0.214, p = 0.014), and reduced fast food intake (r = 0.188, p = 0.035) were significantly associated with temporal CT. These associations, except for nuts, remained significant in multivariable‐adjusted models, with an additional relationship found for chicken (r = 0.189, p = 0.038). Among the 15 food components, greater olive oil (r = 0.243, p = 0.008), and beans (0.180, p = 0.044), and reduced fast food (r = 0.212, p = 0.017) were significantly associated with global CT. Only reduced fast food retained significance in the multivariable‐adjusted models. Conclusions Greater adherence to the MIND diet was associated with greater CT in both global and temporal regions. Specific components, including increased olive oil, beans, nuts, fish, and reduced fast food, showed significant associations with CT, suggesting elements within the diet driving this association. These findings highlight the potential neuroprotective effects of the MIND diet, emphasizing the importance of dietary patterns in preserving brain health during aging.Item Cognitive Dysfunction in Older Breast Cancer Survivors(2020-09) Crouch, Adele Deborah Lenae; Von Ah, Diane; Champion, Victoria; Pressler, Susan J.; Unverzagt, Frederick; Huber, LesaUp to 75% of the more than 3.5 million breast cancer survivors (BCS) living in the United States report cognitive dysfunction. However, little is known about cognitive dysfunction among older BCS, who may be at greater risk. Therefore, the purpose of this dissertation was to characterize cognitive dysfunction in older BCS. Specific aims included: (1) synthesize the literature regarding cognitive dysfunction in older BCS; and (2) examine the relationships between a) objective cognitive function (immediate memory, delayed memory, attention, executive function-working memory, verbal fluency) and subjective cognitive function (attention); b) demographic factors, medical factors, treatment factors, and cancer-related symptoms (depressive symptoms, anxiety, fatigue, sleep disturbance) and cognitive function; and c) comorbidity and cognitive function and physical functioning, and quality of life (QoL) in older BCS. In an integrative review, to address aim 1, 12 studies were identified. Up to 41% of older BCS showed objective cognitive dysfunction on neuropsychological assessment, up to 64% reported subjective cognitive dysfunction concerns pre-treatment, and 50% incurred cognitive decline from pre- to post-treatment. Cognitive dysfunction was associated with older age, multiple comorbidities, chemotherapy, sleep disturbance, neuropsychological symptom cluster, frailty, and poorer QoL. To address aim 2, data were leveraged from a large, nationwide, QoL in younger versus older BCS study (PI: Champion), which included 335 older BCS who were ≥60 years of age, had breast cancer (stage I-IIIa), received chemotherapy, and were 3-8 years post-diagnosis without recurrence. Findings included up to 19% of older BCS had mild-moderate objective cognitive dysfunction on at least one neuropsychological assessment, with 26% reporting poor-moderate subjective attention function. BCS, who were older, had less education and more depressive symptoms had greater cognitive dysfunction. Objective attention and executive function-working memory significantly and positively correlated with subjective attention. In turn, subjective cognitive dysfunction and increased number of comorbidities were related to poorer physical functioning. Subjective cognitive dysfunction was also related to poorer QoL. The findings from this study highlights the prevalence and complexity of cognitive dysfunction in older BCS. Further research is needed to better understand the intersection of aging, cancer, comorbidities and cognitive dysfunction and the negative implications in older BCS.Item Delirium and neuropsychological recovery among emergency general surgery survivors (DANE): study protocol for a randomized controlled trial and collaborative care intervention(BMC, 2023-10-03) Mohanty, Sanjay; Holler, Emma; Ortiz, Damaris; Meagher, Ashley; Perkins, Anthony; Bylund, Peggy; Khan, Babar; Unverzagt, Frederick; Xu, Hupuing; Ingraham, Angela; Boustani, Malaz; Zarzaur, Ben; Surgery, School of MedicineBackground: Delirium is a complex neuropsychiatric syndrome which consists of acute and varying changes in cognition and consciousness. Patients who develop delirium are at increased risk for a constellation of physical, cognitive, and psychological disabilities long after the delirium has ended. Collaborative care models integrating primary and specialty care in order to address patients with complex biopsychosocial needs have been demonstrated to improve outcomes in patients with chronic diseases. The purpose of this study is to evaluate the ability of a collaborative care model on the neuropsychologic recovery of delirium survivors following emergency surgery. Methods: This protocol describes a multicenter (eight hospitals in three states) randomized controlled trial in which 528 patients who develop delirium following emergency surgery will be randomized to either a collaborative care model or usual care. The efficacy of the collaborative care model on cognitive, physical, and psychological recovery in these delirium survivors will then be evaluated over 18 months. Discussion: This will be among the first randomized clinical trials in postoperative delirium survivors evaluating an intervention designed to mitigate the downstream effects of delirium and improve the neuropsychologic recovery after surgery. We hope that the results of this study will add to and inform strategies to improve postoperative recovery in this patient group.Item Depressive Symptoms and Risk of Stroke in a National Cohort of Black and White Participants From REGARDS(Wolters Kluwer, 2021) Ford, Cassandra D.; Gray, Marquita S.; Crowther, Martha R.; Wadley, Virginia G.; Austin, Audrey L.; Crowe, Michael G.; Pulley, LeaVonne; Unverzagt, Frederick; Kleindorfer, Dawn O.; Kissela, Brett M.; Howard, Virginia J.; Psychiatry, School of MedicineObjective: The purpose of this study was to examine depressive symptoms as a risk factor for incident stroke and determine whether depressive symptomatology was differentially predictive of stroke among Black and White participants. Methods: The study comprised 9,529 Black and 14,516 White stroke-free participants, aged 45 and older, enrolled in the REasons for Geographic and Racial Differences in Stroke (2003-2007). Incident stroke was the first occurrence of stroke. Association between baseline depressive symptoms (assessed via the 4-item Center for Epidemiologic Studies Depression Scale [CES-D-4]: 0, 1-3, or ≥4) and incident stroke was analyzed with Cox proportional hazards models adjusted for demographics, stroke risk factors, and social factors. Results: There were 1,262 strokes over an average follow-up of 9.21 (SD 4.0) years. Compared to participants with no depressive symptoms, after demographic adjustment, participants with CES-D-4 scores of 1-3 had 39% increased stroke risk (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.23-1.57), with slight attenuation after full adjustment (HR = 1.27, 95% CI = 1.11-1.43). Participants with CES-D-4 scores of ≥4 experienced 54% higher risk of stroke after demographic adjustment (HR = 1.54, 95% CI = 1.27-1.85), with risk attenuated in the full model similar to risk with 1-3 symptoms (HR = 1.25, 95% CI = 1.03-1.51). There was no evidence of a differential effect by race (p = 0.53). Conclusions: The association of depressive symptoms with increased stroke risk was similar among a national sample of Black and White participants. These findings suggest that assessment of depressive symptoms should be considered in primary stroke prevention for both Black and White participants.Item Epilepsy Self-Management in Older Adults: A Qualitative Study(2012-03-19) Miller, Wendy Renee; Buelow, Janice; Bakas, Tamilyn; Habermann, Barbara; Unverzagt, FrederickEpilepsy is the most common chronic neurological condition in the United States, and it is incurable. Those who suffer from it must engage in both collaborative and independent management of their condition for the remainder of their lives. The treatment and care of those with epilepsy must therefore include not only medical interventions, which alone cannot cure the disorder or prevent the disability associated with it, but must also prepare persons for and facilitate their independent management—self-management—of the disorder. Self-management is a process that affects important outcomes including resource utilization, mortality, and quality of life. In the United States, those age 60 years and older have the highest incidence of new-onset epilepsy. Despite the high incidence of epilepsy in this population, coupled with the knowledge that self-management affects important outcomes, a thorough search of the literature suggests that self-management experiences of older adults diagnosed with epilepsy late in life have not been investigated. The purpose of the study was to examine, using a qualitative descriptive design, the self-management experiences of older adults diagnosed with epilepsy at or after age 60. Semi-structured interviews were used to generate data. A total of 20 older adults participated. Major findings indicate that older adults in the sample, and particularly the women, experienced a delay in receiving an epilepsy diagnosis. These older adults experienced multiple problems and life changes since diagnosis—some of which are unique to this population and many of which are amenable to intervention. These older adults devise and execute a variety of management strategies, within a system, that are classified as disease/treatment-focused and problem/life changes-focused. These strategies further are categorized as proactive or reactive, with proactive strategies being pre-planned and effective, and reactive strategies being unplanned and less effective. Knowledge generated from this study reveals the problems experienced by older adults with epilepsy, as well as their management needs. These findings will inform future studies, the aim of which will be to investigate more thoroughly these problems and needs and, ultimately, to inform interventions aimed at resolving this population’s problems and concerns while also improving outcomes.Item Genetic variants for Alzheimer’s disease and comorbid conditions(Sage, 2024) Pan, Minmin; Lai, Dongbing; Unverzagt, Frederick; Apostolova, Liana; Hendrie, Hugh C.; Saykin, Andrew; Foroud, Tatiana; Gao, Sujuan; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Alzheimer's disease and related dementias (ADRD) frequently co-occur with comorbidities such as diabetes and cardiovascular diseases in elderly populations. Objective: Utilize a life-course approach to identify genetic variants that are associated with the co-occurrence of ADRD and another comorbid condition. Methods: Research data from African American participants of the Indianapolis-Ibadan Dementia Project (IIDP) linked with electronic medical record (EMR) data and genome-wide association study (GWAS) data were utilized. The age of onset for ADRD was obtained from longitudinal follow-up of the IIDP study. Age of onset for comorbid conditions was obtained from EMR. The analysis included 1177 African Americans, among whom 174 were diagnosed with ADRD. A semi-parametric marginal bivariate survival model was used to examine the influence of single nucleotide polymorphisms (SNPs) on dual time-to-event outcomes while adjusting for sex, years of education, and the first principal component of GWAS data. Results: Targeted analysis of 20 SNPs that were reported to be associated with ADRD revealed that six were significantly associated with dual-disease outcomes, specifically congestive heart failure and cancer. In addition, eight novel SNPs were identified for associations with both ADRD and a comorbid condition. Conclusions: Using a bivariate survival model approach, we identified genetic variants associated not only with ADRD, but also with comorbid conditions. Our utilization of dual-disease models represents a novel analytic strategy for uncovering shared genetic variants for multiple disease phenotypes.Item Lipoprotein(a) and risk of cognitive impairment in Black and White Americans: the Reasons for Geographic and Racial Differences in Stroke cohort(Elsevier, 2023-08-08) Rentería, Miguel Arce; McClure, Leslie A.; Callas, Peter W.; LaBode-Richman, Vanessa M.; Kroll, Danielle S.; Manly, Jennifer J.; Kroll, Danielle S.; Manly, Jennifer J.; Zakai, Neil A.; Unverzagt, Frederick; Cushman, Mary; Psychiatry, School of MedicineBackground: Cognitive impairment has a substantial vascular etiology. Higher lipoprotein(a) [Lp(a)] is associated with cardiovascular disease risk, but its association with cognitive function is uncertain. We hypothesized that Lp(a) is a risk factor for cognitive impairment, a relationship that would be modified by race and sex. Objectives: To study the association of Lp(a) with cognitive impairment in a biracial cohort. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 Black and White Americans aged >45 years from 2003 to 2007. After 3.4 years, among participants with normal baseline cognition, baseline Lp(a) was measured in 434 cases of incident cognitive impairment and 557 controls. Cognitive impairment was defined as scores below the sixth percentile based on age, sex, race, and education norms on 2 or 3 components of a 3-test battery administered every 2 years. Results: Median Lp(a) was higher in Black than in White individuals. Among Black participants, the adjusted odds ratio (OR) of cognitive impairment per SD higher increment Lp(a) was 1.39 (95% CI: 1.05, 1.84). The OR in White participants was 1.03 (95% CI: 0.87, 1.21; P for race difference = .03). The relationship of Lp(a) with cognitive trajectory differed by sex and race. Elevated Lp(a) was associated with worse baseline memory in Black men and a steeper trajectory of verbal fluency decline in Black men than in White men and women. Conclusion: Higher Lp(a) was associated with increased risk of cognitive impairment in Black but not White individuals. Future studies should evaluate the biological and social mechanisms through which race and Lp(a) interact to increase risk of cognitive impairment.Item Post-Processing Automatic Transcriptions with Machine Learning for Verbal Fluency Scoring(Elsevier, 2023) Bushnell, Justin; Unverzagt, Frederick; Wadley, Virginia G.; Kennedy, Richard; Del Gaizo, John; Clark, David Glenn; Neurology, School of MedicineObjective: To compare verbal fluency scores derived from manual transcriptions to those obtained using automatic speech recognition enhanced with machine learning classifiers. Methods: Using Amazon Web Services, we automatically transcribed verbal fluency recordings from 1400 individuals who performed both animal and letter F verbal fluency tasks. We manually adjusted timings and contents of the automatic transcriptions to obtain "gold standard" transcriptions. To make automatic scoring possible, we trained machine learning classifiers to discern between valid and invalid utterances. We then calculated and compared verbal fluency scores from the manual and automatic transcriptions. Results: For both animal and letter fluency tasks, we achieved good separation of valid versus invalid utterances. Verbal fluency scores calculated based on automatic transcriptions showed high correlation with those calculated after manual correction. Conclusion: Many techniques for scoring verbal fluency word lists require accurate transcriptions with word timings. We show that machine learning methods can be applied to improve off-the-shelf ASR for this purpose. These automatically derived scores may be satisfactory for some applications. Low correlations among some of the scores indicate the need for improvement in automatic speech recognition before a fully automatic approach can be reliably implemented.Item Serum magnesium concentration and incident cognitive impairment: the reasons for geographic and racial differences in stroke study(Springer, 2021) Chen, Cheng; Xun, Pengcheng; Unverzagt, Frederick; McClure, Leslie A.; Ryan Irvin, Marguerite; Judd, Suzanne; Cushman, Mary; He, Ka; Psychiatry, School of MedicinePurpose: To examine the prospective association between serum Mg level and the incidence of cognitive impairment. Methods: A random sub-cohort (n = 2063) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was included in this study. Baseline serum Mg concentration was measured using inductively coupled plasma mass spectrometry. According to the current reference interval of serum magnesium (0.75-0.95 mmol/L), we classified participants below the interval as Level 1 and used it as the referent. The rest of the study population were equally divided into three groups, named Level 2 to 4. Incident cognitive impairment was identified using the Six-Item Screener. Multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. Results: After adjustment for potential confounders, an inverse threshold association between serum Mg level and incident cognitive impairment was observed. Compared to those with hypomagnesemia (Level 1: < 0.75 mmol/L), the relative odds of incident cognitive impairment was reduced by 41% in the second level [OR (95% CI) = 0.59 (0.37, 0.94)]; higher serum Mg level did not provide further benefits [Level 3 and 4 versus Level 1: OR (95% CI) = 0.54 (0.34, 0.88) and 0.59 (0.36, 0.96), P for linear trend = 0.08]. Conclusions: Findings from this prospective study suggest that sufficient Mg status within the normal range may be beneficial to cognitive health in the US general population.