- Email: [email protected]
Health disparities research with the national institute on aging (NIA)
Podium Presentations: Monday, July 20, 2015 Marie Sarazin12, Bruno Dubois13, Eloi Magnin14, Daniela Galimberti15, Elio Scarpini15, Stefano F. Cappa16, John R. Hodges17, Glenda M. Halliday18, Lauren Bartley19, Jose T. Bras20, John Hardy4, Martin N. Rossor4, John Collinge4, Nick C. Fox4, Simon Mead1, 1University College London, London, United Kingdom; 2Mayo Clinic, Jacksonville, FL, USA; 3MRC Prion Unit, UCL, London, United Kingdom; 4UCL Institute of Neurology, London, United Kingdom; 5Mayo Clinic, Rochester, MN, USA; 6 Mayo Clinic, Jacksonvile, FL, USA; 7University of California San Francisco, San Francisco, CA, USA; 8University Hospital Virgen del Rocıo, Seville, Spain; 9Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom; 10VU University Medical Center, Amsterdam, Netherlands; 11UC San Diego / VA San Diego Healthcare System, San Diego, CA, USA; 12INSERM U610, H^opital de la Salp^etriere, Paris, France; 13INSERM- Universite Pierre et Marie Curie, IHU-ICM, Paris, France; 14Regional Memory Centre (CMRR), Depart of Neurology, CHU Besanc¸on, Besanc¸on, France; 15University of Milan, Fondazione C a Granda, IRCCS Ospedale Policlinico, Milan, Italy; 16 Vita-Salute San Raffaele University, Milan, Italy; 17University of New South Wales, Sydney, Australia; 18Neuroscience Research Australia and University of New South Wales, Sydney, Australia; 19Neuroscience Research Australia, Sydney, Australia; 20UCL Institue of Neurology, London, United Kingdom. Contact e-mail: [email protected] Background: Posterior cortical atrophy (PCA) is a rare, early-onset
neurodegenerative syndrome, typically an Alzheimer’s disease (AD) variant, associated with abnormalities of visual processing and other posterior cortical functions. Risk factors for PCA are poorly characterized, mainly because of the rarity of the syndrome. We formed an international consortium to assess association with known genetic risk factors in AD and DLB, and to perform an exploratory genome-wide study. Methods: Members of the atypical Alzheimer’s disease PIA identified patients fulfilling consensus (Tang-Wai) criteria for PCA with DNA available. DNA was genotyped at UCL on Illumina OmniExpress arrays. Following standard QC, results were compared with 10,547 controls to calculate risk at 23 loci derived from studies of AD and DLB; results were also compared with published data in typical AD. We then performed an exploratory genome-wide association study (GWAS) comparing PCA and unselected controls using methodologies accounting for population structure and imputing SNPs not present on genotyping arrays. Results: 302 patients from eleven international centers were included. Average age at symptom-onset was 58.966.9yrs. Of those with CSF, amyloid PET or autopsy data available (n¼82, 27%) all had evidence for Alzheimer pathology. We found an association at the APOE locus (p¼6x10-14), but the effect size was smaller than reported for typical AD (rs2075650 odds Ratio (OR) (PCA) 2.03 vs OR (typical AD) 2.53, p¼0.03). We found evidence for risk at implicated SNPs in/ near CR1 (p¼7x10-4), ABCA7 (p¼0.02) and BIN1 (p¼0.04) with OR CIs overlapping those in typical AD. ORs at implicated SNPs in/near INPP5D and NME8 did not overlap with those in typical AD. Noting that the study is under-powered and lacking a replication cohort, exploratory GWAS confirmed APOE as a risk for PCA but also revealed three novel loci achieving genome-wide significance: rs2525776 near SEMA3C (p¼1x10-8, OR¼3.3[2.1-5.1]), rs76854344 near CNTNAP5 (p¼8x10-10 OR¼1.9[1.5-2.3]) and rs72907046 near FAM46A (p¼1x10-9 OR¼3.2[2.1-4.9]). None of these loci was associated with typical AD based on IGAP GWAS data. Conclusions: These results reveal evidence for differences in the genetic profile between typical AD and PCA which if replicated may provide important insights into factors driving selective vulnerability and phenotypic diversity in Alzheimer’s disease.
P169
MONDAY, JULY 20, 2015 FOCUSED TOPIC SESSIONS FTS-02 ALZHEIMER’S DISEASE RESEARCH: EMERGING DIRECTIONS FOR ADDRESSING HEALTH DISPARITIES FTS-02-01
HEALTH DISPARITIES RESEARCH WITH THE NATIONAL INSTITUTE ON AGING (NIA)
Carl V. Hill1,2, Cerise Elliott2, 1National Institutes of Health, Bethesda, MD, USA; 2National Institute on Aging, Bethesda, MD, USA. Contact e-mail: [email protected] Background: The National Institute on Aging (NIA) leads a broad
scientific effort to understand the nature of aging and to extend healthy, active years of life. The NIA seeks to (1) support and conduct genetic, biological, clinical, behavioral, social, and economic research on aging, (2) foster the development of research and clinician scientists in aging, (3) provide research resources and (4) disseminate information about aging and advances in research to the public, health care professionals, and the scientific community, among a variety of audiences. Methods: A current strategic direction of the NIA is to improve the scientific community’s ability to reduce health disparities among older adults. Results: In collaboration with each of NIA’s extramural divisions, the NIA Office of Special Populations seeks to stimulate health disparities research that considers cognitive, biological, social and clinical factors and various levels of analyses for considering health disparities. Conclusions: The learning objectives for this presentation include an overview and introduction to the NIA, discussion of the NIA Office of Special Populations and its functions and description of health disparities research opportunities with the NIA and its extramural divisions. FTS-02-02
DECONSTRUCTING RACE AND EDUCATION FOR RESEARCH ON DISPARITIES IN ALZHEIMER’S DISEASE AND COGNITIVE AGING
Jennifer J. Manly, Columbia University Medical Center, New York, NY, USA. Contact e-mail: [email protected] Background: Several studies show that African Americans and His-
panics are more likely to suffer from Alzheimer’s Disease (AD) and cognitive impairment. Most of the data supporting these disparities are cross-sectional. Although fewer in number and sample size, longitudinal studies have also supported the conclusion that ethnic minorities are more likely to develop incident dementia and experience more rapid cognitive decline. Despite this evidence, there are significant research gaps in understanding the underlying mechanisms for racial/ethnic disparities in cognitive aging and Alzheimer’s disease. Methods: In this talk, I will present data from multiple studies related to gaps in knowledge about disparities in AD. Results: Research has shown that racial disparities in AD and cognitive decline can be accounted for by social, psychosocial and educational factors. Critically, many of these potential mediators suggest that there are early life influences on cognitive trajectory in late life, and that these factors are potentially modifiable. I will also present discuss research that tests for modification of risk factors, biomarkers, and effectiveness of interventions on cognitive decline and AD by race or education. Conclusions: Research has shown that racial disparities in AD and cognitive decline can be accounted for by social, psychosocial and educational factors, but many studies are unable to explore these factors because they
neurodegenerative syndrome, typically an Alzheimer’s disease (AD) variant, associated with abnormalities of visual processing and other posterior cortical functions. Risk factors for PCA are poorly characterized, mainly because of the rarity of the syndrome. We formed an international consortium to assess association with known genetic risk factors in AD and DLB, and to perform an exploratory genome-wide study. Methods: Members of the atypical Alzheimer’s disease PIA identified patients fulfilling consensus (Tang-Wai) criteria for PCA with DNA available. DNA was genotyped at UCL on Illumina OmniExpress arrays. Following standard QC, results were compared with 10,547 controls to calculate risk at 23 loci derived from studies of AD and DLB; results were also compared with published data in typical AD. We then performed an exploratory genome-wide association study (GWAS) comparing PCA and unselected controls using methodologies accounting for population structure and imputing SNPs not present on genotyping arrays. Results: 302 patients from eleven international centers were included. Average age at symptom-onset was 58.966.9yrs. Of those with CSF, amyloid PET or autopsy data available (n¼82, 27%) all had evidence for Alzheimer pathology. We found an association at the APOE locus (p¼6x10-14), but the effect size was smaller than reported for typical AD (rs2075650 odds Ratio (OR) (PCA) 2.03 vs OR (typical AD) 2.53, p¼0.03). We found evidence for risk at implicated SNPs in/ near CR1 (p¼7x10-4), ABCA7 (p¼0.02) and BIN1 (p¼0.04) with OR CIs overlapping those in typical AD. ORs at implicated SNPs in/near INPP5D and NME8 did not overlap with those in typical AD. Noting that the study is under-powered and lacking a replication cohort, exploratory GWAS confirmed APOE as a risk for PCA but also revealed three novel loci achieving genome-wide significance: rs2525776 near SEMA3C (p¼1x10-8, OR¼3.3[2.1-5.1]), rs76854344 near CNTNAP5 (p¼8x10-10 OR¼1.9[1.5-2.3]) and rs72907046 near FAM46A (p¼1x10-9 OR¼3.2[2.1-4.9]). None of these loci was associated with typical AD based on IGAP GWAS data. Conclusions: These results reveal evidence for differences in the genetic profile between typical AD and PCA which if replicated may provide important insights into factors driving selective vulnerability and phenotypic diversity in Alzheimer’s disease.
P169
MONDAY, JULY 20, 2015 FOCUSED TOPIC SESSIONS FTS-02 ALZHEIMER’S DISEASE RESEARCH: EMERGING DIRECTIONS FOR ADDRESSING HEALTH DISPARITIES FTS-02-01
HEALTH DISPARITIES RESEARCH WITH THE NATIONAL INSTITUTE ON AGING (NIA)
Carl V. Hill1,2, Cerise Elliott2, 1National Institutes of Health, Bethesda, MD, USA; 2National Institute on Aging, Bethesda, MD, USA. Contact e-mail: [email protected] Background: The National Institute on Aging (NIA) leads a broad
scientific effort to understand the nature of aging and to extend healthy, active years of life. The NIA seeks to (1) support and conduct genetic, biological, clinical, behavioral, social, and economic research on aging, (2) foster the development of research and clinician scientists in aging, (3) provide research resources and (4) disseminate information about aging and advances in research to the public, health care professionals, and the scientific community, among a variety of audiences. Methods: A current strategic direction of the NIA is to improve the scientific community’s ability to reduce health disparities among older adults. Results: In collaboration with each of NIA’s extramural divisions, the NIA Office of Special Populations seeks to stimulate health disparities research that considers cognitive, biological, social and clinical factors and various levels of analyses for considering health disparities. Conclusions: The learning objectives for this presentation include an overview and introduction to the NIA, discussion of the NIA Office of Special Populations and its functions and description of health disparities research opportunities with the NIA and its extramural divisions. FTS-02-02
DECONSTRUCTING RACE AND EDUCATION FOR RESEARCH ON DISPARITIES IN ALZHEIMER’S DISEASE AND COGNITIVE AGING
Jennifer J. Manly, Columbia University Medical Center, New York, NY, USA. Contact e-mail: [email protected] Background: Several studies show that African Americans and His-
panics are more likely to suffer from Alzheimer’s Disease (AD) and cognitive impairment. Most of the data supporting these disparities are cross-sectional. Although fewer in number and sample size, longitudinal studies have also supported the conclusion that ethnic minorities are more likely to develop incident dementia and experience more rapid cognitive decline. Despite this evidence, there are significant research gaps in understanding the underlying mechanisms for racial/ethnic disparities in cognitive aging and Alzheimer’s disease. Methods: In this talk, I will present data from multiple studies related to gaps in knowledge about disparities in AD. Results: Research has shown that racial disparities in AD and cognitive decline can be accounted for by social, psychosocial and educational factors. Critically, many of these potential mediators suggest that there are early life influences on cognitive trajectory in late life, and that these factors are potentially modifiable. I will also present discuss research that tests for modification of risk factors, biomarkers, and effectiveness of interventions on cognitive decline and AD by race or education. Conclusions: Research has shown that racial disparities in AD and cognitive decline can be accounted for by social, psychosocial and educational factors, but many studies are unable to explore these factors because they