Sophia Wang

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A Pilot Study of the BE SMART (Brain Health Education to Promote Cognitive Screening in Minority Communities and to Increase Diverse Participation in Alzheimer’s Disease Research and Clinical Trials) Intervention

Black and Hispanic older adults are at higher risk for Alzheimer’s disease (AD). However, they are often unaware of the importance of early detection of AD and often lack access to cognitive screening. The BE SMART intervention will address these gaps by educating minority communities about the value of early detection of AD and offering free cognitive screening. 

The overall goal of Dr. Wang's research project is to design and test the BE SMART intervention. The culturally tailored intervention includes a bilingual education program for minority communities about the value of early detection of AD and cognitive screening, optional free cognitive screening, and feedback about the screening results. Dr. Wang and her research partners use the sites of community partners to overcome access concerns about receiving cognitive screening. Bilingual educational materials in English and Spanish, e.g. brochures, videos, in person scripts are available to the community. The community outcomes of the research project include increased awareness of the value of early detection of AD and increased participation in cognitive screening. The intervention addresses health disparities in AD which disproportionately affects minority communities. Dr. Wang's translation of research into better health outcomes for Black and Hispanic older adults is another excellent example of how IUPUI's faculty members are TRANSLATING their RESEARCH INTO PRACTICE.

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    Risk factors for dementia in older intensive care unit (ICU) survivors
    (Wiley, 2023) Wang, Sophia; Perkins, Anthony J.; Chi, Rosalyn; Yates, Brandon A.; Khan, Sikandar H.; Gao, Sujuan; Boustani, Malaz; Khan, Babar A.; Psychiatry, School of Medicine
    Introduction: As the number of older intensive care unit (ICU) survivors grows, there is an urgent need to identify modifiable risk factors for post-ICU dementia. Methods: We performed a secondary data analysis of 3144 ICU patients ≥ 50 years of age without a history of dementia or severe mental illness who were screened as part of the Pharmacological Management of Delirium (PMD) study. Delirium was assessed using the Confusion Assessment Method for the ICU. Dementia was identified using International Classification of Diseases Ninth and Tenth revision codes for dementia or prescription of anti-dementia medication. Results: Average age (standard deviation) was 65.2 ± 9.5 years; 50.4% were female; and 37.3% were Black. Analyses identified stroke (adjusted hazard ratio [HR] 2.49; 95% confidence interval [CI: 1.52, 4.07], P < 0.001), and depression (adjusted HR 3.03; 95% CI [1.80, 5.10], P < 0.001) as post-ICU risk factors for dementia. Discussion: Future studies will need to examine whether interventions targeting post-ICU stroke and depression can lower dementia incidence in ICU survivors. Highlights: Risk factors for post-intensive care unit (ICU) dementia were distinct from those of Alzheimer's disease. Cardiovascular risk factors were not associated with dementia in older ICU survivors. Post-ICU stroke was associated with a higher risk of dementia in older ICU survivors. Post-ICU depression was associated with a higher risk of dementia in older ICU survivors.
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    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 Medicine
    Introduction: 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.
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    Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study
    (Public Library of Science, 2023-09-01) Khan, Sikandar H.; Perkins, Anthony J.; Eltarras, Ahmed M.; Chi, Rosalyn; Athar, Ammar A.; Wang, Sophia; Campbell, Noll L.; Gao, Sujuan; Boustani, Malaz A.; Khan, Babar A.; Medicine, School of Medicine
    Objective: In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. Design: Prospective observational study. Setting: Intensive care unit (ICU). Patients: 178 ICU patients with delirium, alive and remaining in ICU at one week. Interventions: None. Measurements and main results: Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. Conclusion: In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.
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    Healthy Aging Brain Care Monitor Caregiver Version (HABC-M CG): An Informant-Based Screening Tool for Post-Intensive Care Syndrome (PICS)
    (American Association of Critical-Care Nurses, 2022) Wang, Sophia; Jawed, Yameena; Perkins, Anthony; Gao, Sujuan; Seyffert, Sarah; Khan, Sikandar; Boustani, Malaz; Khan, Babar; Psychiatry, School of Medicine
    Background: Cognitive impairment is common in intensive care unit survivors, pointing to the potential utility of a caregiver-based tool to screen for post-intensive care syndrome. Objective: To validate the Healthy Aging Brain Care Monitor, Caregiver Version (HABC-M CG), as a caregiver-based tool to screen for post-intensive care syndrome. Methods: A total of 116 patients who survived a stay in the intensive care unit completed standardized assessments of cognition, psychological symptoms, and physical functioning, and their caregivers completed the HABC-M CG. The Cronbach α was used to measure the internal consistency of the scale items. Validity of the HABC-M CG versus comparison tests was measured using the Spearman rank correlation. Generalized linear models were used to adjust for age, sex, and education level. Results: The total scale and all subscales of the HABC-M CG showed excellent internal consistency (Cronbach α = 0.88-0.93). Scores on the psychological subscale correlated with standardized measures of depressive symptoms (Spearman ρ = 0.58). Scores on the cognitive subscale correlated with the Mini-Mental State Examination score (Spearman ρ = -0.33). Scores on the functional subscale correlated with scores on the Physical Self-Maintenance Scale (Spearman ρ = -0.36). Conclusion: The HABC-M CG is a valid informant-based clinical tool for the assessment of symptoms of post- intensive care syndrome.
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    Improving Recovery and Outcomes Every Day after the ICU (IMPROVE): study protocol for a randomized controlled trial
    (BMC, 2018-03-27) Wang, Sophia; Hammes, Jessica; Khan, Sikandar; Gao, Sujuan; Harrawood, Amanda; Martinez, Stephanie; Moser, Lyndsi; Perkins, Anthony; Unverzagt, Frederick W.; Clark, Daniel O.; Boustani, Malaz; Khan, Babar; Psychiatry, School of Medicine
    Background: Delirium affects nearly 70% of older adults hospitalized in the intensive care unit (ICU), and many of those will be left with persistent cognitive impairment or dementia. There are no effective and scalable recovery models to remediate ICU-acquired cognitive impairment and its attendant elevated risk for dementia or Alzheimer disease (AD). The Improving Recovery and Outcomes Every Day after the ICU (IMPROVE) trial is an ongoing clinical trial which evaluates the efficacy of a combined physical exercise and cognitive training on cognitive function among ICU survivors 50 years and older who experienced delirium during an ICU stay. This article describes the study protocol for IMPROVE. Methods: IMPROVE is a four-arm, randomized controlled trial. Subjects will be randomized to one of four arms: cognitive training and physical exercise; cognitive control and physical exercise; cognitive training and physical exercise control; and cognitive control and physical exercise control. Facilitators administer the physical exercise and exercise control interventions in individual and small group formats by using Internet-enabled videoconference. Cognitive training and control interventions are also facilitator led using Posit Science, Inc. online modules delivered in individual and small group format directly into the participants' homes. Subjects complete cognitive assessment, mood questionnaires, physical performance batteries, and quality of life scales at baseline, 3, and 6 months. Blood samples will also be taken at baseline and 3 months to measure pro-inflammatory cytokines and acute-phase reactants; neurotrophic factors; and markers of glial dysfunction and astrocyte activation. Discussion: This study is the first clinical trial to examine the efficacy of combined physical and cognitive exercise on cognitive function in older ICU survivors with delirium. The results will provide information about potential synergistic effects of a combined intervention on a range of outcomes and mechanisms of action.
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    Barriers and facilitators to participating in Alzheimer’s disease biomarker research in Black and White older adults
    (Wiley, 2023-06-05) Eliacin, Johanne; Polsinelli, Angelina J.; Epperson, Francine; Gao, Sujuan; Van Heiden, Sarah; Westmoreland, Glenda; Richards, Ralph; Richards, Mollie; Campbell, Christopher; Hendrie, Hugh; Risacher, Shannon L.; Saykin, Andrew J.; Wang, Sophia; Medicine, School of Medicine
    Introduction: The study examined Black and White prospective participants' views of barriers to and facilitators of participation in Alzheimer's disease (AD) biomarker research. Methods: In a mixed-methods study, 399 community-dwelling Black and White older adults (age ≥55) who had never participated in AD research completed a survey about their perceptions of AD biomarker research. Individuals from lower socioeconomic and education backgrounds and Black men were over-sampled to address perspectives of traditionally under-represented groups. A subset of participants (n = 29) completed qualitative interviews. Results: Most participants expressed interest in biomarker research (overall 69%). However, Black participants were comparatively more hesitant than White participants (28.9% vs 15.1%), were more concerned about study risks (28.9% vs 15.1%), and perceived multiple barriers to participating in brain scans. These results persisted even after adjusting for trust and perceived knowledge of AD. Information was a primary barrier (when absent) and incentive (when provided) for AD biomarker research participation. Black older adults desired more information about AD (eg, risk, prevention), general research processes, and specific biomarker procedures. They also desired return of results to make informed decisions about their health, research-sponsored community awareness events, and for researchers to mitigate the burden placed on participants in research (eg, transportation, basic needs). Conclusion: Our findings increase representativeness in the literature by focusing on individuals with no history of AD research experience and those from traditionally underrepresented groups in research. Results suggest that the research community needs to improve information sharing and raising awareness, increase their presence in the communities of underrepresented groups, reduce incidental costs, and provide valuable personal health information to participants to increase interest. Specific recommendations for improving recruitment are addressed. Future studies will assess the implementation of evidence-based, socioculturally sensitive recruitment strategies to increase enrollment of Black older adults into AD biomarker studies. HIGHLIGHTS: Individuals from under-represented groups are interested in Alzheimer's disease (AD) biomarker research. After adjusting for trust and AD knowledge, Black participants were still more hesitant .Information is a barrier (when absent) to and incentive (when given) for biomarker studies. Reducing burden (e.g., transportation) is essential for recruiting Black older adults.
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    Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19
    (Wolters Kluwer, 2023-01-18) Khan, Sikandar H.; Perkins, Anthony J.; Chi, Rosalyn; Seyffert, Sarah; Conrad, Peter; Lindroth, Heidi; Wang, Sophia; Mulkey, Malissa; Gao, Sujuan; Khan, Babar; Medicine, School of Medicine
    Critically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity. Design: Retrospective, observational cohort study. Setting: ICUs at two large, urban, academic referral hospitals. Patients: All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed. Interventions: None. Measurements and main results: Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57; 95% CI, 1.17-2.12; p < 0.01) and ferritin quartiles (OR, 1.36; 95% CI, 1.02-1.81; p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49; 95% CI, 1.14-1.94; p < 0.01) and coma independently (OR, 1.52; 95% CI, 1.08-2.14; p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33; 95% CI, 1.04-1.70; p = 0.026) and coma independently (OR, 1.59; 95% CI, 1.14-2.23; p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36; 95% CI, 1.03-1.79; p = 0.030) and delirium severity the next day (β = 0.30; se, 0.07; p ≤ 0.01). Conclusions: Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.
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    Accelerating diversity in Alzheimer's disease research by partnering with a community advisory board
    (Wiley, 2023-05-28) Pena-Garcia, Alex; Richards, Ralph; Richards, Mollie; Campbell, Christopher; Mosley, Hank; Asper, Joseph; Eliacin, Johanne; Polsinelli, Angelina; Apostolova, Liana; Hendrie, Hugh; Tackett, Andrew; Elliott, Caprice; Van Heiden, Sarah; Gao, Sujuan; Saykin, Andrew; Wang, Sophia; Medicine, School of Medicine
    Introduction: Community advisory boards (CABs) and researcher partnerships present a promising opportunity to accelerate enrollment of underrepresented groups (URGs). We outline the framework for how the CAB and researchers at the Indiana Alzheimer's Disease Research Center (IADRC) partnered to accelerate URG participation in AD neuroimaging research. Methods: CAB and the IADRC researchers partnered to increase the CAB's impact on URG study enrollment through community and research interactions. Community interactions included the CAB collaboratively building a network of URG focused community organizations and collaborating with those URG-focused organizations to host IADRC outreach and recruitment events. Research interactions included direct impact (CAB members referring themselves or close contacts as participants) and strategic impact, mainly by the CAB working with researchers to develop and refine URG focused outreach and recruitment strategies for IADRC and affiliated studies to increase URG representation. We created a database infrastructure to measure how these interactions impacted URG study enrollment. Results: Out of the 354 URG research referrals made to the IADRC between October 2019 and December 2022, 267 referrals were directly referred by the CAB (N = 36) or from community events in which CAB members organized and/or volunteered at (N = 231). Out of these 267 referrals, 34 were enrolled in IADRC and 2 were enrolled in Indiana University Longitudinal Early Onset AD Study (IU LEADS). Of note, both studies require the prospective participants to be willing to do MRI and PET scans. As of December 2022, 30 out of the 34 enrolled participants have received a consensus diagnosis; the majority were cognitively normal (64.7%), with the remainder having mild cognitive impairment (17.6%) or early-stage AD (2.9%). Discussion: The IADRC CAB-researcher partnership had a measurable impact on the enrollment of African American/Black adults in AD neuroimaging studies. Future studies will need to test whether this conceptual model works for other sites and for other URGs.
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    Feasibility of a virtual reality intervention in the intensive care unit
    (Elsevier, 2021) Jawed, Yameena T.; Golovyan, Dmitriy; Lopez, David; Khan, Sikandar H.; Wang, Sophia; Freund, Chauncey; Imran, Sundus; Bin Hameed, Usman; Smith, Joseph P.; Kok, Lotte; Khan, Babar A.; Medicine, School of Medicine
    Background: Delirium prevention requires optimal management of pain and anxiety. Given the limitations of current pharmacologic interventions, evaluation of novel non-pharmacological interventions is required. Virtual reality (VR) stimulation may be a promising intervention because of its capability to reduce psychophysiological stress, pain, and anxiety and to restore cognitive and attentional capacities. Objective: To ascertain patients' and providers' perceptions of acceptability and safety of VR intervention in the intensive care unit (ICU). Methods: We enrolled a cohort of 15 ICU patients and 21 health care providers to administer a 15-minute session showing a relaxing beach scene with VR headsets and nature sound effects. Participants were then asked to rate their experiences on a Likert scale survey. Results: The majority of patients (86%, 12 of 14) rated the headsets as moderately to very comfortable. All had moderate or greater sense of presence in the virtual environment, and 79% (11 of 14) rated their overall experience at 3 or greater (5 indicating that they enjoyed it very much). Seventy-one percent (10 of 14) of the patients felt that their anxiety was better with VR, and 57% (8 of 14) did not notice a change in their pain or discomfort. All health care providers found the headset to be at least moderately comfortable and felt a moderate or greater sense of presence. All providers concluded that VR therapy should be available for their patients. Both groups experienced minimal side effects. Conclusion: In this prospective study of perceptions of VR therapy for ICU patients and health care providers, there was a high level of acceptance, with minimal side effects, for both groups despite their low levels of prior experience with virtual reality and video gaming.
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    Post-Operative Delirium and Its Relationship with Biomarkers for Dementia: A Meta-Analysis
    (Cambridge University Press, 2022) Wang, Sophia; Greene, Ryan; Song, Yiqing; Chan, Carol; Lindroth, Heidi; Khan, Sikandar; Rios, Gabriel; Sanders, Robert D.; Khan, Babar; Psychiatry, School of Medicine
    Objectives: This study seeks to identify Alzheimer's and related dementias (ADRD) biomarkers associated with postoperative delirium (POD) via meta-analysis. Design: A comprehensive search was conducted. Studies met the following inclusion criteria: >18 years of age, identified POD with standardized assessment, and biomarker measured in the AT(N)-X (A = amyloid, T = tau, (N)=neurodegeneration, X-Other) framework. Exclusion criteria: focus on prediction of delirium, delirium superimposed on dementia, other neurologic or psychiatric disorders, or terminal delirium. Reviewers extracted and synthesized data for the meta-analysis. Setting: Meta-analysis. Participants: Patients with POD. Measurements: Primary outcome: association between POD and ATN-X biomarkers. Secondary outcomes involved sample heterogeneity. Results: 28 studies were included in this meta-analysis. Studies focused on inflammatory and neuronal injury biomarkers; there were an insufficient number of studies for amyloid and tau biomarker analysis. Two inflammatory biomarkers (IL-6, and CRP) showed a significant relationship with POD (IL-6 n = 10, standardized mean difference (SMD): 0.53, 95% CI: 0.36-0.70; CRP n = 14, SMD: 0.53, 95% CI: 0.33-0.74). Two neuronal injury biomarkers (blood-based S100B and NfL) were positively associated with POD (S100B n = 5, SMD: 0.40, 95% CI: 0.11-0.69; NFL n = 2, SMD: 0.93, 95% CI: 0.28-1.57). Of note, many analyses were impacted by significant study heterogeneity. Conclusions: This meta-analysis identified an association between certain inflammatory and neuronal injury biomarkers and POD. Future studies will need to corroborate these relationships and include amyloid and tau biomarkers in order to better understand the relationship between POD and ADRD.