- Email: [email protected]
ASSOCIATION BETWEEN ANTIDEPRESSANT USE AND INCIDENT MCI IN OLDER ADULTS WITH DEPRESSION
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Poster Presentations: Wednesday, July 19, 2017 P4-485
VASCULAR RISK FACTORS AGGRAVATE THE RISK OF DEPRESSION AFTER YOUNG ISCHEMIC STROKE
Dongwei Lu, Dong Sun, Junjian Zhang, Zhongnan Hospital, Wuhan University, Wuhan, China. Contact e-mail: 961790390@ qq.com Figure 1. Power value of waves, p-value - *:p<0.05, **:p<0.01.
Beta(13w30Hz), Gamma(30w50Hz). Absolute power is the sum of each EEG power wave. Relative power was calculated as the absolute power of each wave divided by the sum of absolute power of all waves. Relative power without delta was calculated as the absolute power of each wave divided by the sum of absolute power of the rest waves excepting for delta. Results: Alpha wave showed the striking results among all waves. Alpha absolute power in AD decreased compared to control group. (Figure 1.A) The relative power and the relative power without delta waves in AD decreased compared to the control group (Figure 1.B, C), which has shown similiar to other studies. The alpha power’s gap between AD patients and controls showed the clear distinction in the relative power without delta. The most effective result was obtained from relative power without delta. Conclusions: Variance of delta had most influence on the result. Even though obtaining EEG was difficult due to delta signal, we showed the possibility that dementia could be diagnosed by measuring EEG signals, especially using relative power of brain waves without delta. This study was supported by 2016 Fund of Chungnam National University.
P4-484
BLOOD-BRAIN BARRIER DYSFUNCTION MAY MEDIATE COGNITIVE IMPAIRMENT DUE TO VASCULAR RISK FACTORS BURDENS
Dongwei Lu, Dong Sun, Junjian Zhang, Zhongnan Hospital, Wuhan University, Wuhan, China. Contact e-mail: [email protected] Background: Vascular risk factors (VRF) can lead to cognitive
impairment, independently of obvious detectable brain lesions. Blood-brain barrier(BBB) is the critical component for the neurovascular unit and micro-environment homeostasis. However, the impact of BBB integrity on the cognitive impairment in strokefree VRFs burdened patients is still elusive.This study was investigate the relationship between them. Methods: VRFs were quantified by the Framingham Stroke Risk Profile(FSRP). 20 low-risk(<10%) and 24 high-risk(>10%) patients were enrolled in this study. A battery of cognitive assessments and DCE-MRI were executed in these patients. Vascularity volume index and BBB permeability were evaluated as the BBB function indicators in the areas of left hippocampus and left frontal white matter. Pearson and partial correlation were used to explore the relationship between FSRP, cognitive function and BBB function. Results: Compared with the less burdened VRF group, high-risk group suffered more cognitive impairment in the domains of global cognitive function, working memory and delayed memory. The high-risk group also showed more BBB dysfunction in the left hippocampus(both vascularity volume index and BBB permeability). After correction of age and sex, FSRP score had a correlation between these three cognitive domains and the BBB permeability (r¼0.368, P¼0.02) in left hippocampus. Conclusions: BBB dysfunction may mediate the pathophysiological mechanism of VRFs related cognitive impairment. Effective management of VRFs is necessary to reduce the cognitive impairment.
Background: With the change of the lifestyle, the young ischemic stroke
has an increasing prevalence. New evidence shows that vascular risk factors (VRFs), such as hypertension and dyslipidemia, have an association with the functional prognosis after young ischemic stroke. The post-stroke mental status can influence the cognitive function and quality of life. But there are limited researches for the young post-stroke patients. In this study, we studied the impact of VRFs on post-stroke mental status to provide more evidence for the second prevention of post-stroke depression or anxiety. Methods: This study is a crosssectional study which enrolled 84 first-ever young ischemic stroke patients. These vascular risk factors were recorded: hypertension, diabetes mellitus, dyslipidemia, hyperhomocysteinemia, history of coronary heart disease, fibrillation, obesity, smoking and alcohol abuse. The participants were divided into three groups according to the number of VRFs: low-risk group (0-1 VRF), medium-risk group (2-3 VRFs) and high-risk group (4VRFs). Hamilton anxiety scale (HAMA) and Hamilton depression scale（HAMD） were used to assess the mental status after 2 weeks after the ischemic stroke. Bayes discrimination was used to explore the predominant risk factors. ANAVO analysis was used to compare the differences between groups. Age, sex, the NIHSS score on admission and stroke volumes were controlled. The multiple stepwise linear analysis was used to explore the relation between VRFs and the scores of HAMA or HAMD. Results: The Bayes discrimination showed that hypertension, dyslipidemia, smoking and hyperhomocysteinemia were the predominant VRFs in this study. As for the score of HAMA and HAMD, there was no difference between groups, before controlling the covariants. After controlling the age, sex, the NIHSS on admission and the stroke volumes, the multiple linear analysis showed that the number of VRFs had an association with HAMD score(B¼0.90，P¼0.047),but not HAMA score. Conclusions: Vascular risk factors aggravate the risk of post-stroke depression after young ischemic stroke. Earlier and effective intervention of vascular risk factors may be effective for the post-stroke depression.
P4-486
ASSOCIATION BETWEEN ANTIDEPRESSANT USE AND INCIDENT MCI IN OLDER ADULTS WITH DEPRESSION
Fang Han1, Tyler Bonnett2, Willa D. Brenowitz3, Merilee Teylan3, Lilah M. Besser3, Kegang Cao1, Ying Gao1, X. H. Zhou2, Walter A. Kukull3, 1 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; 2University of Washington, Seattle, WA, USA; 3National Alzheimer’s Coordinating Center, University of Washington, Seattle, WA, USA. Contact e-mail: [email protected] Background: The relationship between antidepressant use and
cognitive function is uncertain. Since individuals’ antidepressant use may change throughout follow-up, we used a time-dependent analysis to examine the association between antidepressant use and risk of MCI among older adults with depression. Methods: We used data from the National Alzheimer’s Coordinating Center (NACC). NACC maintains data from participants evaluated prospectively by over 30 past and present Alzheimer’s Disease Centers located throughout the United States. Participants were evaluated
Poster Presentations: Wednesday, July 19, 2017
annually according to a standardized protocol, the Uniform Data Set. Eligible subjects were aged 60 years or older, cognitively normal but depressed at baseline, and had at least 3 in-person visits from 2005 through 2016. Depression was defined as any two of the five aspects: self-reported depression history which was active in the last 2 years, depression in the last month assessed by Neuropsychiatric Inventory Questionnaire, depressed mood judged by the clinician, active depression diagnosis based on the clinician’s best judgement, or baseline Geriatric Depression Scale score at least 6. MCI was diagnosed if one didn’t have dementia but had cognitive complaint not normal for his or her age, and had cognitive decline but essentially normal functional activities. Those who progressed from normal to dementia were assumed to have passed through MCI. Time-dependent Cox proportional hazard models examined the association between self-reported antidepressant use and risk of MCI. Results: Out of 669 eligible participants, 488 reported antidepressant use at least once. Of the antidepressant users, 126 (25.82%) eventually developed MCI. A larger number of participants who never used antidepressant eventually developed MCI (61 out of 181, 33.70%). A log rank test indicated that unadjusted MCI-free survival rate was better for antidepressant users (P ¼ 0.051). However, after adjusting for covariates and accounting for time-dependent antidepressant use, the relationship no longer attained statistical significance (HR: 0.89; 95% CI: 0.70-1.14; P ¼ 0.36). Conclusions: We did not find a significant association between antidepressant use and incident MCI in adjusted models. This result may be partly due to modeling that can account for a participant’s variation in antidepressant use prior to onset of MCI.
P4-487
PATIENT ENGAGEMENT IN ALZHEIMER’S AND MILD COGNITIVE IMPAIRMENT CLINICAL TRIALS
Marieke I. Cajal, Craig Curtis, Ira J. Goodman, Compass Research, Bioclinica, Orlando, FL, USA. Contact e-mail: [email protected] Background: With such a large number of individuals affected by Alzheimer’s disease (AD) or Mild Cognitive Impairment (MCI), we could expect fast enrollment into clinical trials. In reality, we are facing several obstacles: 1) Patients are underdiagnosed. 2) Patients have a limited knowledge of clinical trials and some misconceptions. 3) AD/MCI clinical trials are complex, prohibiting participation. Methods: The easiest and fastest way to sensibilise and educate a large number of people is online. However, many of the individuals affected by AD/MCI do not have sophisticated digital media and computer experience. In situations where the subject has been diagnosed with AD, their children often navigate online for answers. Our biggest challenge is in recruiting participants for MCI trials, when younger family members might not be aware their parent has memory problems. Although an online presence is necessary and desired to improve overall awareness and dialogue inside families, it is insufficient alone. We diversified and adapted our engagement strategies to reach those individuals. We developed a large community outreach effort, offering services such as educational seminars, free memory testing, and genetic testing through Spartan Bioscience. Our events were advertised in the newspapers, on the radio, or through local AD community actors. The objective was to raise awareness of MCI symptoms and clinical trials as well as to give participants an opportunity to ask questions to a doctor.
P1521
Different formats, focus, and services offered at those events were tested. Results: Community events dedicated to providing education on memory loss had the most success. Patient’s engagement increased when those were coupled with the opportunity to undergo a memory test or genetic testing. Out of 75 AD/MCI patients screened in clinical trials within one month, 21% originated from community events, 38% from referrals, 21% from our database, and 11% from digital media and online efforts. Conclusions: Community outreach should not be overlooked to engage potential MCI participants and diversification of outreach methods should be favored. Participants were especially responsive to opportunities to learn more about their specific risk, whether through a memory test, genetic testing, or clinical trials offering a work-up including brain scans.
P4-488
THE INTEGRATED ALZHEIMER’S DISEASE RATING SCALE (IADRS): FINDINGS FROM THE EXPEDITION3 TRIAL
Alette M. Wessels, Brandy R. Matthews, Sherie A. Dowsett, Scott W. Andersen, Eric R. Siemers, Eli Lilly and Company, Indianapolis, IN, USA. Contact e-mail: [email protected] Background: The Integrated Alzheimer’s Disease Rating Scale (iADRS) is a composite tool that combines scores from 2 widely accepted measures, the Alzheimer’s Disease Assessment ScaleCognitive subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) (Wessels A., et al JPAD, 2015). The iADRS measures both cognition and function; it has demonstrated acceptable psychometric properties and been shown effective in capturing both disease progression from mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) through moderate AD dementia, and significant separation of placebo versus active drug effect across the early disease spectrum. Here, we report iADRS findings from the EXPEDITION3 study. Since the EXPEDITION 3 dataset
Figure 1. Repeated measures analysis of iADRS in the mild AD populations from solanezumab EXPEDITION 3 study.
Poster Presentations: Wednesday, July 19, 2017 P4-485
VASCULAR RISK FACTORS AGGRAVATE THE RISK OF DEPRESSION AFTER YOUNG ISCHEMIC STROKE
Dongwei Lu, Dong Sun, Junjian Zhang, Zhongnan Hospital, Wuhan University, Wuhan, China. Contact e-mail: 961790390@ qq.com Figure 1. Power value of waves, p-value - *:p<0.05, **:p<0.01.
Beta(13w30Hz), Gamma(30w50Hz). Absolute power is the sum of each EEG power wave. Relative power was calculated as the absolute power of each wave divided by the sum of absolute power of all waves. Relative power without delta was calculated as the absolute power of each wave divided by the sum of absolute power of the rest waves excepting for delta. Results: Alpha wave showed the striking results among all waves. Alpha absolute power in AD decreased compared to control group. (Figure 1.A) The relative power and the relative power without delta waves in AD decreased compared to the control group (Figure 1.B, C), which has shown similiar to other studies. The alpha power’s gap between AD patients and controls showed the clear distinction in the relative power without delta. The most effective result was obtained from relative power without delta. Conclusions: Variance of delta had most influence on the result. Even though obtaining EEG was difficult due to delta signal, we showed the possibility that dementia could be diagnosed by measuring EEG signals, especially using relative power of brain waves without delta. This study was supported by 2016 Fund of Chungnam National University.
P4-484
BLOOD-BRAIN BARRIER DYSFUNCTION MAY MEDIATE COGNITIVE IMPAIRMENT DUE TO VASCULAR RISK FACTORS BURDENS
Dongwei Lu, Dong Sun, Junjian Zhang, Zhongnan Hospital, Wuhan University, Wuhan, China. Contact e-mail: [email protected] Background: Vascular risk factors (VRF) can lead to cognitive
impairment, independently of obvious detectable brain lesions. Blood-brain barrier(BBB) is the critical component for the neurovascular unit and micro-environment homeostasis. However, the impact of BBB integrity on the cognitive impairment in strokefree VRFs burdened patients is still elusive.This study was investigate the relationship between them. Methods: VRFs were quantified by the Framingham Stroke Risk Profile(FSRP). 20 low-risk(<10%) and 24 high-risk(>10%) patients were enrolled in this study. A battery of cognitive assessments and DCE-MRI were executed in these patients. Vascularity volume index and BBB permeability were evaluated as the BBB function indicators in the areas of left hippocampus and left frontal white matter. Pearson and partial correlation were used to explore the relationship between FSRP, cognitive function and BBB function. Results: Compared with the less burdened VRF group, high-risk group suffered more cognitive impairment in the domains of global cognitive function, working memory and delayed memory. The high-risk group also showed more BBB dysfunction in the left hippocampus(both vascularity volume index and BBB permeability). After correction of age and sex, FSRP score had a correlation between these three cognitive domains and the BBB permeability (r¼0.368, P¼0.02) in left hippocampus. Conclusions: BBB dysfunction may mediate the pathophysiological mechanism of VRFs related cognitive impairment. Effective management of VRFs is necessary to reduce the cognitive impairment.
Background: With the change of the lifestyle, the young ischemic stroke
has an increasing prevalence. New evidence shows that vascular risk factors (VRFs), such as hypertension and dyslipidemia, have an association with the functional prognosis after young ischemic stroke. The post-stroke mental status can influence the cognitive function and quality of life. But there are limited researches for the young post-stroke patients. In this study, we studied the impact of VRFs on post-stroke mental status to provide more evidence for the second prevention of post-stroke depression or anxiety. Methods: This study is a crosssectional study which enrolled 84 first-ever young ischemic stroke patients. These vascular risk factors were recorded: hypertension, diabetes mellitus, dyslipidemia, hyperhomocysteinemia, history of coronary heart disease, fibrillation, obesity, smoking and alcohol abuse. The participants were divided into three groups according to the number of VRFs: low-risk group (0-1 VRF), medium-risk group (2-3 VRFs) and high-risk group (4VRFs). Hamilton anxiety scale (HAMA) and Hamilton depression scale（HAMD） were used to assess the mental status after 2 weeks after the ischemic stroke. Bayes discrimination was used to explore the predominant risk factors. ANAVO analysis was used to compare the differences between groups. Age, sex, the NIHSS score on admission and stroke volumes were controlled. The multiple stepwise linear analysis was used to explore the relation between VRFs and the scores of HAMA or HAMD. Results: The Bayes discrimination showed that hypertension, dyslipidemia, smoking and hyperhomocysteinemia were the predominant VRFs in this study. As for the score of HAMA and HAMD, there was no difference between groups, before controlling the covariants. After controlling the age, sex, the NIHSS on admission and the stroke volumes, the multiple linear analysis showed that the number of VRFs had an association with HAMD score(B¼0.90，P¼0.047),but not HAMA score. Conclusions: Vascular risk factors aggravate the risk of post-stroke depression after young ischemic stroke. Earlier and effective intervention of vascular risk factors may be effective for the post-stroke depression.
P4-486
ASSOCIATION BETWEEN ANTIDEPRESSANT USE AND INCIDENT MCI IN OLDER ADULTS WITH DEPRESSION
Fang Han1, Tyler Bonnett2, Willa D. Brenowitz3, Merilee Teylan3, Lilah M. Besser3, Kegang Cao1, Ying Gao1, X. H. Zhou2, Walter A. Kukull3, 1 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; 2University of Washington, Seattle, WA, USA; 3National Alzheimer’s Coordinating Center, University of Washington, Seattle, WA, USA. Contact e-mail: [email protected] Background: The relationship between antidepressant use and
cognitive function is uncertain. Since individuals’ antidepressant use may change throughout follow-up, we used a time-dependent analysis to examine the association between antidepressant use and risk of MCI among older adults with depression. Methods: We used data from the National Alzheimer’s Coordinating Center (NACC). NACC maintains data from participants evaluated prospectively by over 30 past and present Alzheimer’s Disease Centers located throughout the United States. Participants were evaluated
Poster Presentations: Wednesday, July 19, 2017
annually according to a standardized protocol, the Uniform Data Set. Eligible subjects were aged 60 years or older, cognitively normal but depressed at baseline, and had at least 3 in-person visits from 2005 through 2016. Depression was defined as any two of the five aspects: self-reported depression history which was active in the last 2 years, depression in the last month assessed by Neuropsychiatric Inventory Questionnaire, depressed mood judged by the clinician, active depression diagnosis based on the clinician’s best judgement, or baseline Geriatric Depression Scale score at least 6. MCI was diagnosed if one didn’t have dementia but had cognitive complaint not normal for his or her age, and had cognitive decline but essentially normal functional activities. Those who progressed from normal to dementia were assumed to have passed through MCI. Time-dependent Cox proportional hazard models examined the association between self-reported antidepressant use and risk of MCI. Results: Out of 669 eligible participants, 488 reported antidepressant use at least once. Of the antidepressant users, 126 (25.82%) eventually developed MCI. A larger number of participants who never used antidepressant eventually developed MCI (61 out of 181, 33.70%). A log rank test indicated that unadjusted MCI-free survival rate was better for antidepressant users (P ¼ 0.051). However, after adjusting for covariates and accounting for time-dependent antidepressant use, the relationship no longer attained statistical significance (HR: 0.89; 95% CI: 0.70-1.14; P ¼ 0.36). Conclusions: We did not find a significant association between antidepressant use and incident MCI in adjusted models. This result may be partly due to modeling that can account for a participant’s variation in antidepressant use prior to onset of MCI.
P4-487
PATIENT ENGAGEMENT IN ALZHEIMER’S AND MILD COGNITIVE IMPAIRMENT CLINICAL TRIALS
Marieke I. Cajal, Craig Curtis, Ira J. Goodman, Compass Research, Bioclinica, Orlando, FL, USA. Contact e-mail: [email protected] Background: With such a large number of individuals affected by Alzheimer’s disease (AD) or Mild Cognitive Impairment (MCI), we could expect fast enrollment into clinical trials. In reality, we are facing several obstacles: 1) Patients are underdiagnosed. 2) Patients have a limited knowledge of clinical trials and some misconceptions. 3) AD/MCI clinical trials are complex, prohibiting participation. Methods: The easiest and fastest way to sensibilise and educate a large number of people is online. However, many of the individuals affected by AD/MCI do not have sophisticated digital media and computer experience. In situations where the subject has been diagnosed with AD, their children often navigate online for answers. Our biggest challenge is in recruiting participants for MCI trials, when younger family members might not be aware their parent has memory problems. Although an online presence is necessary and desired to improve overall awareness and dialogue inside families, it is insufficient alone. We diversified and adapted our engagement strategies to reach those individuals. We developed a large community outreach effort, offering services such as educational seminars, free memory testing, and genetic testing through Spartan Bioscience. Our events were advertised in the newspapers, on the radio, or through local AD community actors. The objective was to raise awareness of MCI symptoms and clinical trials as well as to give participants an opportunity to ask questions to a doctor.
P1521
Different formats, focus, and services offered at those events were tested. Results: Community events dedicated to providing education on memory loss had the most success. Patient’s engagement increased when those were coupled with the opportunity to undergo a memory test or genetic testing. Out of 75 AD/MCI patients screened in clinical trials within one month, 21% originated from community events, 38% from referrals, 21% from our database, and 11% from digital media and online efforts. Conclusions: Community outreach should not be overlooked to engage potential MCI participants and diversification of outreach methods should be favored. Participants were especially responsive to opportunities to learn more about their specific risk, whether through a memory test, genetic testing, or clinical trials offering a work-up including brain scans.
P4-488
THE INTEGRATED ALZHEIMER’S DISEASE RATING SCALE (IADRS): FINDINGS FROM THE EXPEDITION3 TRIAL
Alette M. Wessels, Brandy R. Matthews, Sherie A. Dowsett, Scott W. Andersen, Eric R. Siemers, Eli Lilly and Company, Indianapolis, IN, USA. Contact e-mail: [email protected] Background: The Integrated Alzheimer’s Disease Rating Scale (iADRS) is a composite tool that combines scores from 2 widely accepted measures, the Alzheimer’s Disease Assessment ScaleCognitive subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) (Wessels A., et al JPAD, 2015). The iADRS measures both cognition and function; it has demonstrated acceptable psychometric properties and been shown effective in capturing both disease progression from mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) through moderate AD dementia, and significant separation of placebo versus active drug effect across the early disease spectrum. Here, we report iADRS findings from the EXPEDITION3 study. Since the EXPEDITION 3 dataset
Figure 1. Repeated measures analysis of iADRS in the mild AD populations from solanezumab EXPEDITION 3 study.