Browsing by Author "Selzler, Katherine J."
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Item Clinician Attitudes and Confidence on the Detection and Management of Cognitive Impairment: Results from the Davos Alzheimer’s Collaborative Early Detection Program(Wiley, 2025-01-09) Barkman Ferrell, Phyllis; Murray, James F.; Ball, Daniel E.; dos Santos Filho, Otelo Corrêa; de Sá Paiva Lima, Marcilea Dias; Govia, Ishtar; Robinson, Janelle; Kowa, Hisatomo; López-Ortega, Mariana; McKean, Alison; Chambers, Wendy; Baksh, Magda R.; Baldivieso, Valeria; Willis, Deanna R.; Fowler, Nicole R.; Selzler, Katherine J.; Medicine, School of MedicineBackground: Early symptoms of cognitive impairment are frequently undetected. The Davos Alzheimer’s Collaborative System Preparedness (DAC‐SP) Early Detection program implemented a digital cognitive assessment (DCA) in primary care and other non‐specialty settings to increase the rate of detection of cognitive impairment. Methods: The DAC‐SP Early Detection program was initiated in 2021 in seven healthcare systems across six countries. Clinicians were trained on a DCA, including positive tests for cognitive impairment and diagnostic assessment. Prior to training or naïve to implementing a DCA in clinical practice, clinicians’ attitudes and confidence in diagnosis and managing dementia were assessed using the validated General Practitioners Attitude and Confidence Scale for Dementia (GPACS‐D), which is comprised of 15 items in three subscales: Confidence in Clinical Abilities, Attitude towards Care, and Engagement. Each item is measured on a 5‐point Likert scale (1 = strongly disagree; 5 = strongly agree), and subscale scores are standardized. A total of 265 pre‐training surveys were completed across the 7 sites. The GPACS‐D results were calculated by averaging individual physician results per the validated scoring algorithm. The cross‐site results were calculated by taking an equally weighted average across the seven sites. Results: The GPACS‐D results across the seven sites are presented in Table 1. Across all sites, baseline attitude towards care was the highest of the three subscales. For most sites, confidence in clinical abilities received the lowest scores, with engagement scores only modestly higher. The total and subscale scores were consistent across sites, supported by the relatively low standard deviation. Conclusion: The findings from the GPACS‐D total and subscale scores suggest that prior to receiving training on using a digital cognitive assessment for their patient populations, clinicians’ attitudes towards the diagnosis and management of cognitive impairment were similar across the seven sites, and independent of the country in which they practice. Despite positive attitudes toward care, the results suggest that education or training focused more on engagement and confidence may improve early detection and care of patients with cognitive impairment, particularly as new diagnostic and therapeutic options emerge.Item Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer’s Disease(IOS, 2015-07) Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J.; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard; Department of Neurological Surgery, IU School of MedicineAbstract Background: The temporal relationship of cognitive deficit and functional impairment in Alzheimer’s disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. Objective: To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Methods: Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. Results: In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Conclusions: Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.Item Implementing Digital Cognitive Assessments to Detect Cognitive Impairment: Results from the Davos Alzheimer’s Collaborative Early Detection Program(Wiley, 2025-01-09) MacLeod, Tim; Murray, James F.; dos Santos Filho, Otelo Corrêa; de Sá Paiva Lima, Marcilea Dias; Govia, Ishtar; Robinson, Janelle; Kowa, Hisatomo; Morimoto, Kohei; López-Ortega, Mariana; McKean, Alison; Ritchie, Craig; Baksh, Magda R.; Smith, Steven R.; Willis, Deanna R.; Brosch, Jared R.; Small, Seamus; Martin, Tammy; Selzler, Katherine J.; Medicine, School of MedicineBackground: Cognitive impairment is frequently undetected or undiagnosed in the early stages. To increase the rates of detecting cognitive impairment, the Early Detection program of the Davos Alzheimer’s Collaborative System Preparedness (DAC‐SP) implemented digital cognitive assessments (DCA) in primary care and other non‐specialty settings. Methods: The DAC‐SP Early Detection program was initiated in 2021 in seven healthcare systems across six countries. Sites were able to choose from several DCAs, and clinicians were provided training, including recognizing signs and symptoms of cognitive decline, and provided with post‐diagnostic support. Patients were eligible for a DCA if they were over 60 years of age, able to hear and see well enough to complete the assessments, and had no prior diagnosis of dementia. The DCA tools included Linus Health’s Core Cognitive Evaluation, Cogstate Cognigram, and Cogstate Brief Battery. Results: The DCA results across the seven sites are presented in Table 1. There was notable variability in the number of patients screened across sites, which could be attributed to multiple factors (i.e., number of clinics onboarded/trained, additional testing for language and culture appropriateness of DCA tool prior to deployment, reduction in the number of elderly people visiting clinics during the COVID‐19 pandemic, available time of clinicians, etc.). The rate of cognitive impairment (abnormal and borderline) was also numerically higher at sites outside the US, independent of the DCA tool used. However, this study was not designed to evaluate operating characteristics of DCA tools, so further research is needed. Approximately 60% of the patients in the DAC‐SP Early Detection program tested abnormal or borderline for cognitive issues, suggesting the need for additional clinical assessment and follow‐up. Conclusion: Findings from the DAC‐SP Early Detection program demonstrated a DCA can be implemented in existing patient care workflows, including primary care settings, and across healthcare systems globally with different resource settings. Adoption of DCAs in clinical practice can help improve the ability to detect symptoms of cognitive impairment and provide much needed earlier screening and care for patients and their families.Item Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease(2018-01) Honig, Lawrence S.; Vellas, Bruno; Woodward, Michael; Boada, Mercè; Bullock, Roger; Borrie, Michael; Hager, Klaus; Andreasen, Niels; Scarpini, Elio; Liu‑Seifert, Hong; Case, Michael; Dean, Robert A.; Hake, Ann; Sundell, Karen; Hoffmann, Vicki Poole; Carlson, Christopher; Khanna, Rashna; Mintun, Mark; DeMattos, Ronald; Selzler, Katherine J.; Siemers, Eric; Pathology and Laboratory Medicine, School of MedicineBACKGROUND Alzheimer’s disease is characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The humanized monoclonal antibody solanezumab was designed to increase the clearance from the brain of soluble Aβ, peptides that may lead to toxic effects in the synapses and precede the deposition of fibrillary amyloid. METHODS We conducted a double-blind, placebo-controlled, phase 3 trial involving patients with mild dementia due to Alzheimer’s disease, defined as a Mini–Mental State Examination (MMSE) score of 20 to 26 (on a scale from 0 to 30, with higher scores indicating better cognition) and with amyloid deposition shown by means of florbetapir positron-emission tomography or Aβ1-42 measurements in cerebrospinal fluid. Patients were randomly assigned to receive solanezumab at a dose of 400 mg or placebo intravenously every 4 weeks for 76 weeks. The primary outcome was the change from baseline to week 80 in the score on the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14; scores range from 0 to 90, with higher scores indicating greater cognitive impairment). RESULTS A total of 2129 patients were enrolled, of whom 1057 were assigned to receive solanezumab and 1072 to receive placebo. The mean change from baseline in the ADAS-cog14 score was 6.65 in the solanezumab group and 7.44 in the placebo group, with no significant between-group difference at week 80 (difference, −0.80; 95% confidence interval, −1.73 to 0.14; P=0.10). As a result of the failure to reach significance with regard to the primary outcome in the prespecified hierarchical analysis, the secondary outcomes were considered to be descriptive and are reported without significance testing. The change from baseline in the MMSE score was −3.17 in the solanezumab group and −3.66 in the placebo group. Adverse cerebral edema or effusion lesions that were observed on magnetic resonance imaging after randomization occurred in 1 patient in the solanezumab group and in 2 in the placebo group. CONCLUSIONS Solanezumab at a dose of 400 mg administered every 4 weeks in patients with mild Alzheimer’s disease did not significantly affect cognitive decline.