Browsing by Author "Hake, Ann"

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    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 Medicine
    Background 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.
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    Improvement in Function after Lasmiditan Treatment: Post Hoc Analysis of Data from Phase 3 Studies
    (Springer, 2020-12) Smith, Timothy; Krege, John H.; Rathmann, Suchitrita S.; Dowsett, Sherie A.; Hake, Ann; Nery, Emel S. M.; Matthews, Brandy R.; Doty, Erin G.; Neurology, School of Medicine
    Introduction: Migraine is associated with substantial functional impairment and affects many aspects of daily life. Methods: Using data from SAMURAI and SPARTAN (double-blind, placebo-controlled, phase 3 studies) and GLADIATOR (an open-label, phase 3 study enrolling patients who had completed SAMURAI or SPARTAN), we assessed the effects of lasmiditan on migraine-related functional disability at multiple time points from 0.5 to 48 h post dose by asking patients to rate how much the migraine was interfering with normal activities. Pooled data from SAMURAI and SPARTAN (SAMURAI + SPARTAN) and data from GLADIATOR were analyzed using the intention-to-treat populations. Results: For SPARTAN + SAMURAI, significantly more patients who received lasmiditan at any dose versus placebo reported freedom from migraine-related functional disability at every timepoint from 2 h post dose, and this difference persisted to 48 h (p < 0.05). Significant differences from placebo in freedom from migraine-related functional disability commenced at 1 h post dose for lasmiditan 200 mg, 1.5 h for lasmiditan 100 mg, and 2 h for lasmiditan 50 mg. Findings from GLADIATOR supported those from SAMURAI + SPARTAN. Conclusion: All doses of lasmiditan resulted in an improvement in migraine-related functional disability that persisted to 48 h. In SAMURAI + SPARTAN, a significant difference from placebo was observed as early as 1 h post dose. TRIAL REGISTRATION AT CLINICALTRIALS.GOV: SAMURAI (NCT02439320), SPARTAN (NCT02605174), and GLADIATOR (NCT02565186).
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    Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans
    (International Society on Hypertension in Blacks, 2015) Hendrie, Hugh C.; Hake, Ann; Lane, Kathleen; Purnell, Christianna; Unverzagt, Frederick; Smith-Gamble, Valerie; Murrell, Jill; Ogunniyi, Adesola; Baiyewu, Olusegun; Callahan, Chris; Saykin, Andrew J.; Taylor, Stanley; Hall, Kathleen; Gao, Su; Department of Neurology, IU School of Medicine
    OBJECTIVE: To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. DESIGN: Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. SETTING: Indianapolis, Indiana. PARTICIPANTS: From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. MAIN OUTCOME MEASURES: Incident dementia and incident AD. RESULTS: After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. CONCLUSIONS: Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.
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    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 Medicine
    BACKGROUND 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.