Browsing by Author "Unverzagt, Frederick W."
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Item [(11)C]PiB PET in Gerstmann-Sträussler-Scheinker disease(e-Century Publishing Corporation, 2016) Deters, Kacie D.; Risacher, Shannon L.; Yoder, Karmen K.; Oblak, Adrian L.; Unverzagt, Frederick W.; Murrell, Jill R.; Epperson, Francine; Tallman, Eileen F.; Quaid, Kimberly A.; Farlow, Martin R.; Saykin, Andrew J.; Ghetti, Bernardino; Department of Pathology & Laboratory Medicine, IU School of MedicineGerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [(11)C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [(11)C]PiB PET scans using standard methods. Approximately one year after the initial scan, each of the three asymptomatic carriers (two with PRNP P102L mutation, one with PRNP F198S mutation) underwent a second [(11)C]PiB PET scan. Three P102L carriers, one F198S carrier, and one non-carrier of the F198S mutation were cognitively normal, while one F198S carrier was cognitively impaired during the course of this study. No [(11)C]PiB uptake was observed in any subject at baseline or at follow-up. Neuropathologic study of the symptomatic individual revealed PrP-immunopositive plaques and tau-immunopositive neurofibrillary tangles in cerebral cortex, subcortical nuclei, and brainstem. PrP deposits were also numerous in the cerebellar cortex. This is the first study to investigate the ability of [(11)C]PiB PET to bind to PrP-amyloid in GSS F198S subjects. This finding suggests that [(11)C]PiB PET is not suitable for in vivo assessment of PrP-amyloid plaques in patients with GSS.Item The ACTIVE cognitive training trial and predicted medical expenditures(BioMed Central, 2009-06-29) Wolinsky, Fredric D.; Mahncke, Henry W.; Kosinski, Mark; Unverzagt, Frederick W.; Smith, David M.; Jones, Richard N.; Stoddard, Anne; Tennstedt, Sharon L.; Medicine, School of MedicineBackground Health care expenditures for older adults are disproportionately high and increasing at both the individual and population levels. We evaluated the effects of the three cognitive training interventions (memory, reasoning, or speed of processing) in the ACTIVE study on changes in predicted medical care expenditures. Methods ACTIVE was a multisite randomized controlled trial of older adults (≥ 65). Five-year follow-up data were available for 1,804 of the 2,802 participants. Propensity score weighting was used to adjust for potential attrition bias. Changes in predicted annualmedical expenditures were calculated at the first and fifth annual follow-up assessments using a new method for translating functional status scores. Multiple linear regression methods were used in this cost-offset analysis. Results At one and five years post-training, annual predicted expenditures declinedby $223 (p = .024) and $128 (p = .309), respectively, in the speed of processing treatment group, but there were no statistically significant changes in the memory or reasoning treatment groups compared to the no-contact control group at either period. Statistical adjustment for age, race, education, MMSE scores, ADL and IADL performance scores, EPT scores, chronic condition counts, and the SF-36 PCS and MCS scores at baseline did not alter the one-year ($244; p = .012) or five-year ($143; p = .250) expenditure declines in the speed of processing treatment group. Conclusion The speed of processing intervention significantly reduced subsequent annual predicted medical care expenditures at the one-year post-baseline comparison, but annual savings were no longer statistically significant at the five-year post-baseline comparison.Item Age Differences in the Association of Obstructive Sleep Apnea Risk with Cognition and Quality of Life(Wiley, 2014-02) Addison-Brown, Kristin J.; Letter, Abraham J.; Yaggi, Klar; McClure, Leslie A.; Unverzagt, Frederick W.; Howard, Virginia J.; Lichtman, Judith H.; Wadley, Virginia G.; Department of Psychiatry, IU School of MedicineUsing a sample of 2925 stroke-free participants drawn from a national population-based study, we examined cross-sectional associations of obstructive sleep apnea risk (OSA) with cognition and quality of life and whether these vary with age, while controlling for demographics and co-morbidities. Included participants from the REasons for Geographic And Racial Differences in Stroke Study were aged 47-93. OSA risk was categorized as high or low based on responses to the Berlin Sleep Questionnaire. Cognitive function was assessed with standardized fluency and recall measures. Depressive symptoms were assessed with the four-item Center for Epidemiologic Studies Depression Scale. Health-related Quality of Life (HRQoL) was assessed with the Medical Outcomes Study Short Form-12 (SF-12). MANCOVA statistics were applied separately to the cognitive and quality of life dependent variables while accounting for potential confounders (demographics, co-morbidities). In fully adjusted models, those at high risk for OSA had significantly lower cognitive scores (Wilks’ Lambda = 0.996, F(3, 2786) = 3.31, p < .05) and lower quality of life (depressive symptoms and HRQoL) (Wilks’ Lambda = 0.989, F(3, 2786) = 10.02, p < .0001). However, some of the associations were age-dependent. Differences in cognition and quality of life between those at high and low obstructive sleep apnea risk were most pronounced during middle age, with attenuated effects after age 70.Item The American Heart Association Life's Simple 7 and incident cognitive impairment: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study(Ovid Technologies Wolters Kluwer -American Heart Association, 2014-06) Thacker, Evan L.; Gillett, Sarah R.; Wadley, Virginia G.; Unverzagt, Frederick W.; Judd, Suzanne E.; McClure, Leslie A.; Howard, Virginia J.; Cushman, Mary; Department of Psychiatry, IU School of MedicineBACKGROUND: Life's Simple 7 is a new metric based on modifiable health behaviors and factors that the American Heart Association uses to promote improvements to cardiovascular health (CVH). We hypothesized that better Life's Simple 7 scores are associated with lower incidence of cognitive impairment. METHODS AND RESULTS: For this prospective cohort study, we included REasons for Geographic And Racial Differences in Stroke (REGARDS) participants aged 45+ who had normal global cognitive status at baseline and no history of stroke (N=17 761). We calculated baseline Life's Simple 7 score (range, 0 to 14) based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. We identified incident cognitive impairment using a 3-test measure of verbal learning, memory, and fluency obtained a mean of 4 years after baseline. Relative to the lowest tertile of Life's Simple 7 score (0 to 6 points), odds ratios of incident cognitive impairment were 0.65 (0.52, 0.81) in the middle tertile (7 to 8 points) and 0.63 (0.51, 0.79) in the highest tertile (9 to 14 points). The association was similar in blacks and whites, as well as outside and within the Southeastern stroke belt region of the United States. CONCLUSIONS: Compared with low CVH, intermediate and high CVH were both associated with substantially lower incidence of cognitive impairment. We did not observe a dose-response pattern; people with intermediate and high levels of CVH had similar incidence of cognitive impairment. This suggests that even when high CVH is not achieved, intermediate levels of CVH are preferable to low CVH.Item Antihypertensive Medication and Dementia Risk in Older Adult African Americans with Hypertension: A Prospective Cohort Study(Springer, 2018-04) Murray, Michael D.; Hendrie, Hugh C.; Lane, Kathleen A.; Zheng, Mengjie; Ambuehl, Roberta; Li, Shanshan; Unverzagt, Frederick W.; Callahan, Christopher M.; Gao, Sujuan; Psychiatry, School of MedicineBACKGROUND: African Americans are especially at risk of hypertension and dementia. Antihypertensive medications reduce the risk of cardiovascular events, but may also reduce the risk of dementia. OBJECTIVE: To assess the longitudinal effects of antihypertensive medications and blood pressure on the onset of incident dementia in a cohort of African Americans. DESIGN: Prospective cohort. PARTICIPANTS: 1236 community-dwelling patients from an inner-city public health care system, aged 65 years and older, with a history of hypertension but no history of dementia, and who had at least three primary care visits and a prescription filled for any medication. MAIN MEASURES: Blood pressure was the average of three seated measurements. Dementia was diagnosed using a two-stage design, with a screening evaluation every 2 to 3 years followed by a comprehensive in-home clinical evaluation for those with a positive screen. Laboratory, inpatient and outpatient encounter data, coded diagnoses and procedures, and medication records were derived from a health information exchange. KEY RESULTS: Of the 1236 hypertensive participants without dementia at baseline, 114 (9%) developed incident dementia during follow-up. Individuals prescribed any antihypertensive medication (n = 816) were found to have a significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114) compared to untreated hypertensive participants (n = 420). When this analysis was repeated including a variable indicating suboptimally treated blood pressure (> 140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30, p = 0.2217). CONCLUSIONS: Control of blood pressure in older adult African American patients with hypertension is a key intervention for preventing dementia, with similar benefits from most of the commonly available antihypertensive medications.Item APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba(Cambridge University Press, 2014-06) Hendrie, Hugh C.; Murrell, Jill; Baiyewu, Olusegun; Lane, Kathleen A.; Purnell, Christianna; Ogunniyi, Adesola; Unverzagt, Frederick W.; Hall, Kathleen; Callahan, Christopher M.; Saykin, Andrew J.; Gureje, Oye; Hake, Ann; Foroud, Tatiana; Gao, Sujuan; Department of Psychiatry, IU School of MedicineBackground There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer’s disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline. Methods In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox’s proportional hazards regression and mixed effects models. Results After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425). Conclusions In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.Item Application of Neuropsychological Criteria to Classify Mild Cognitive Impairment in the ACTIVE Study(American Psychological Association, 2020-11) Thomas, Kelsey R.; Cook, Sarah E.; Bondi, Mark W.; Unverzagt, Frederick W.; Gross, Alden L.; Willis, Sherry L.; Marsiske, Michael; Psychiatry, School of MedicineObjective: Comprehensive neuropsychological criteria (NP criteria) for mild cognitive impairment (MCI) has reduced diagnostic errors and better predicted progression to dementia than conventional MCI criteria that rely on a single impaired score and/or subjective report. This study aimed to implement an actuarial approach to classifying MCI in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. Method: ACTIVE study participants (N = 2,755) were classified as cognitively normal (CN) or as having MCI using NP criteria. Estimated proportion of MCI participants and reversion rates were examined as well as baseline characteristics by MCI subtype. Mixed effect models examined associations of MCI subtype with 10-year trajectories of self-reported independence and difficulty performing instrumental activities of daily living (IADLs). Results: The proportion of MCI participants was estimated to be 18.8%. Of those with MCI at baseline, 19.2% reverted to CN status for all subsequent visits. At baseline, the multidomain-amnestic MCI group generally had the greatest breadth and depth of cognitive impairment and reported the most IADL difficulty. Longitudinally, MCI participants showed faster IADL decline than CN participants (multidomain-amnestic MCI > single domain-amnestic MCI > nonamnestic MCI). Conclusion: NP criteria identified a proportion of MCI and reversion rate within ACTIVE that is consistent with prior studies involving community-dwelling samples. The pattern of everyday functioning change suggests that being classified as MCI, particularly amnestic MCI, is predictive of future loss of independence. Future work will apply these classifications in ACTIVE to better understand the relationships between MCI and health, social, and cognitive intervention-related factors.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 Association of cognitive impairment and breast cancer survivorship on quality of life in younger breast cancer survivors(Springer, 2021) Von Ah, Diane; Crouch, Adele D.; Monahan, Patrick O.; Stump, Timothy E; Unverzagt, Frederick W.; Storey, Susan; Cohee, Andrea A.; Cella, David; Champion, Victoria L.Purpose Younger breast cancer survivors (BCS) often report cognitive impairment and poor quality of life (QoL), which could be interrelated. The purpose of this study was to examine the association of cognitive impairment and breast cancer status (BCS versus healthy control (HC)), with QoL, which included psychological (depressive symptoms, well-being, perceived stress, and personal growth) and physical well-being (physical functioning and fatigue). Methods Four hundred ninety-eight BCS (≤45 years at diagnosis) who were 3 to 8 years post-chemotherapy treatment and 394 HC completed subjective questionnaires and a one-time neuropsychological assessment, including tests of attention, memory, processing speed, and verbal fluency. For each test, cognitive impairment was defined as scoring 1.5 and 2.0 standard deviations below the mean of the HC group. Separate linear regression models for each outcome were ran controlling for known covariates. Results BCS reported significantly more memory problems than HC (p < 0.0001), with up to 23% having significant impairment. Cognitive performance did not differ significantly between BCS and HCs. BCS vs. HCs had greater depression and fatigue, yet more personal growth. Objective and subjective cognitive impairment were significantly related to greater depressive symptoms and perceived stress and lower well-being and physical functioning; whereas, objective impairment was related to less personal growth and subjective impairment was related to greater fatigue. Conclusions Younger BCS report significant cognitive impairment years after treatment which may relate to greater decrements in QoL.Item Blood Pressure and Cognitive Decline Over 8 Years in Middle-Aged and Older Black and White Americans(American Heart Association, 2019-02) Levine, Deborah A.; Galecki, Andrzej T.; Langa, Kenneth M.; Unverzagt, Frederick W.; Kabeto, Mohammed U.; Giordani, Bruno; Cushman, Mary; McClure, Leslie A.; Safford, Monika M.; Wadley, Virginia G.; Psychiatry, School of MedicineAlthough the association between high blood pressure (BP), particularly in midlife, and late-life dementia is known, less is known about variations by race and sex. In a prospective national study of 22 164 blacks and whites ≥45 years without baseline cognitive impairment or stroke from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), enrolled 2003 to 2007 and followed through September 2015, we measured changes in cognition associated with baseline systolic and diastolic BP (SBP and DBP), as well as pulse pressure (PP) and mean arterial pressure, and we tested whether age, race, and sex modified the effects. Outcomes were global cognition (Six-Item Screener; primary outcome), new learning (Word List Learning), verbal memory (Word List Delayed Recall), and executive function (Animal Fluency Test). Median follow-up was 8.1 years. Significantly faster declines in global cognition were associated with higher SBP, lower DBP, and higher PP with increasing age ( P<0.001 for age×SBP×follow-up-time, age×DBP×follow-up-time, and age×PP×follow-up-time interaction). Declines in global cognition were not associated with mean arterial pressure after adjusting for PP. Blacks, compared with whites, had faster declines in global cognition associated with SBP ( P=0.02) and mean arterial pressure ( P=0.04). Men, compared with women, had faster declines in new learning associated with SBP ( P=0.04). BP was not associated with decline of verbal memory and executive function, after controlling for the effect of age on cognitive trajectories. Significantly faster declines in global cognition over 8 years were associated with higher SBP, lower DBP, and higher PP with increasing age. SBP-related cognitive declines were greater in blacks and men.