Understanding the relationships between health and aging is essential for delaying morbidity and maximizing independence in aging populations as life expectancies increase. Loss of cognitive function is a feared age-associated condition and growing public health concern. Alzheimer’s disease (AD), the most common cause of dementia, has no curative therapies. Characterizing the relationships between risk factors, biomarkers, and AD progression is critical for the development of effective disease prediction, clinical intervention, and ultimately, disease prevention. The Emory Healthy Aging Study (EHAS) and the Emory Healthy Brain Study (EHBS), which is nested within EHAS, aim to further the understanding of healthy aging and the pathogenesis of age-related illnesses in well-characterized, community-based prospective cohorts and to identify biomarkers for the earliest manifestations of AD for the facilitation of preventative interventions. The EHAS is an innovative, longitudinal, web-based study enrolling English-speaking adults in the U.S. who agree to be contacted for future studies. Using validated instruments, the annual questionnaire enquires about demographics, socioeconomics, self-reported cognitive function, personal and family medical history, lifestyle, and psychosocial factors. Cognitive assessments are also obtained using an ambulatory device. Nested within EHAS, the EHBS is enrolling up to 2,500 EHAS participants, 50–75 years old, who do not have a diagnosis of AD, mild cognitive impairment, or any other memory disorder. EHBS in-person, biennial study visits, include neuropsychological testing, cardiovascular measures, retinal and brain imaging, biospecimen collection (blood, cerebrospinal fluid, gut microbiome), and other assessments. Since spring 2016, EHAS and EHBS have enrolled 12,500 and 863 participants with completed baseline assessments, respectively. Data and biospecimens from EHBS participants will support a broad range of AD biomarker discovery efforts, and follow-up of EHAS participants will enable assessment of self-reported cognitive trajectories and accumulation of incident cases of a variety of health conditions. The EHAS design supports the interval deployment of new study instruments and targeted sampling for ancillary studies. This project will increase our knowledge about healthy aging, improve our understanding of risk factors for cognitive impairment and dementias, support development of biomarkers, and facilitate studies of age-associated disorders including AD.

United Nations Department of Economic and Social Affairs. Population Division: World Population Prospects: The 2017 Revision, Key Findings and Advance Tables. Working Paper No. ESA/WP/248 2017.
Cosco TD, Prina AM, Perales J, Stephan BC, Brayne C. Operational definitions of successful aging: a systematic review.
Int Psychogeriatr
. 2014 Mar;26(3):373–81.
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis.
Alzheimers Dement
. 2013 Jan;9(1):63–75.e2.
Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence.
Lancet Neurol
. 2011 Sep;10(9):819–28.
Xu W, Tan L, Wang HF, Jiang T, Tan MS, Tan L, et al. Meta-analysis of modifiable risk factors for Alzheimer’s disease.
J Neurol Neurosurg Psychiatry
. 2015 Dec;86(12):1299–306.
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers.
Lancet Neurol
. 2013 Feb;12(2):207–16.
Mehta D, Jackson R, Paul G, Shi J, Sabbagh M. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010–2015.
Expert Opin Investig Drugs
. 2017 Jun;26(6):735–9.
Steenland K, Zhao L, Goldstein F, Cellar J, Lah J. Biomarkers for predicting cognitive decline in those with normal cognition.
J Alzheimers Dis
. 2014;40(3):587–94.
Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, et al.; Alzheimer’s Disease Neuroimaging Initiative. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects.
Ann Neurol
. 2009 Apr;65(4):403–13.
Fagan AM, Xiong C, Jasielec MS, Bateman RJ, Goate AM, Benzinger TL, et al.; Dominantly Inherited Alzheimer Network. Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer’s disease.
Sci Transl Med
. 2014 Mar;6(226):226ra30.
Jack CR Jr, Holtzman DM. Biomarker modeling of Alzheimer’s disease.
. 2013 Dec;80(6):1347–58.
Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA. Inequalities in dementia incidence between six racial and ethnic groups over 14 years.
Alzheimers Dement
. 2016 Mar;12(3):216–24.
Howard VJ, Kleindorfer DO, Judd SE, McClure LA, Safford MM, Rhodes JD, et al. Disparities in stroke incidence contributing to disparities in stroke mortality.
Ann Neurol
. 2011 Apr;69(4):619–27.
Safford MM, Brown TM, Muntner PM, Durant RW, Glasser S, Halanych JH, et al.; REGARDS Investigators. Association of race and sex with risk of incident acute coronary heart disease events.
. 2012 Nov;308(17):1768–74.
Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, et al. Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity.
Am J Epidemiol
. 2003 Jun;157(11):1015–22.
Centers for Disease Control and Prevention.
National Diabetes Statistics Report, 2017
. Atlanta (GA): Centers for Disease Control and Prevention, US Department of Health and Human Services; 2017.
Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, et al.; Amyloid Biomarker Study Group. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
. 2015 May;313(19):1924–38.
Lampert EJ, Roy Choudhury K, Hostage CA, Petrella JR, Doraiswamy PM; Alzheimer’s Disease Neuroimaging Initiative. Prevalence of Alzheimer’s pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
PLoS One
. 2013 Apr;8(4):e60747.
Amariglio RE, Donohue MC, Marshall GA, Rentz DM, Salmon DP, Ferris SH, et al.; Alzheimer’s Disease Cooperative Study. Tracking early decline in cognitive function in older individuals at risk for Alzheimer disease dementia: the Alzheimer’s Disease Cooperative Study Cognitive Function Instrument.
JAMA Neurol
. 2015 Apr;72(4):446–54.
Walsh SP, Raman R, Jones KB, Aisen PS; Alzheimer’s Disease Cooperative Study Group. ADCS Prevention Instrument Project: the Mail-In Cognitive Function Screening Instrument (MCFSI).
Alzheimer Dis Assoc Disord
. 2006 Oct-Dec;20(4 suppl 3):S170–8.
Kroenke K, Spitzer RL, Williams JB, Löwe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review.
Gen Hosp Psychiatry
. 2010 Jul-Aug;32(4):345–59.
Wilson R, Barnes L, Bennett D. Assessment of lifetime participation in cognitively stimulating activities.
J Clin Exp Neuropsychol
. 2003 Aug;25(5):634–42.
Langer RD, White E, Lewis CE, Kotchen JM, Hendrix SL, Trevisan M. The Women’s Health Initiative Observational Study: baseline characteristics of participants and reliability of baseline measures.
Ann Epidemiol
. 2003 Oct;13(9 suppl):S107–21.
Qureshi AI, Giles WH, Croft JB, Bliwise DL. Habitual sleep patterns and risk for stroke and coronary heart disease: a 10-year follow-up from NHANES I.
. 1997 Apr;48(4):904–11.
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al.; Writing Group Members; American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association.
. 2016 Jan;133(4):e38–360.
Cherbuin N, Sachdev P, Anstey KJ. Neuropsychological predictors of transition from healthy cognitive aging to mild cognitive impairment: the PATH through life study.
Am J Geriatr Psychiatry
. 2010 Aug;18(8):723–33.
Luks TL, Oliveira M, Possin KL, Bird A, Miller BL, Weiner MW, et al. Atrophy in two attention networks is associated with performance on a Flanker task in neurodegenerative disease.
. 2010 Jan;48(1):165–70.
Hampstead BM, Stringer AY, Stilla RF, Amaraneni A, Sathian K. Where did I put that? Patients with amnestic mild cognitive impairment demonstrate widespread reductions in activity during the encoding of ecologically relevant object-location associations.
. 2011 Jul;49(9):2349–61.
Buschke H, Fuld PA. Evaluating storage, retention, and retrieval in disordered memory and learning.
. 1974 Nov;24(11):1019–25.
Kelleher RJ, Soiza RL. Evidence of endothelial dysfunction in the development of Alzheimer’s disease: is Alzheimer’s a vascular disorder?
Am J Cardiovasc Dis
. 2013 Nov;3(4):197–226.
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al.; European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications.
Eur Heart J
. 2006 Nov;27(21):2588–605.
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al.; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force.
J Am Coll Cardiol
. 2002 Jan;39(2):257–65.
Hamburg NM, Keyes MJ, Larson MG, Vasan RS, Schnabel R, Pryde MM, et al. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study.
. 2008 May;117(19):2467–74.
Burke GL, Evans GW, Riley WA, Sharrett AR, Howard G, Barnes RW, et al. Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study.
. 1995 Mar;26(3):386–91.
Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study.
. 1997 Sep;96(5):1432–7.
Beauchet O, Annweiler C, Callisaya ML, De Cock AM, Helbostad JL, Kressig RW, et al. Poor Gait Performance and Prediction of Dementia: Results From a Meta-Analysis.
J Am Med Dir Assoc
. 2016 Jun;17(6):482–90.
Scherder E, Eggermont L, Swaab D, van Heuvelen M, Kamsma Y, de Greef M, et al. Gait in ageing and associated dementias; its relationship with cognition.
Neurosci Biobehav Rev
. 2007;31(4):485–97.
Egerton T, Thingstad P, Helbostad JL. Comparison of programs for determining temporal-spatial gait variables from instrumented walkway data: PKmas versus GAITRite.
BMC Res Notes
. 2014 Aug;7(1):542.
Bahureksa L, Najafi B, Saleh A, Sabbagh M, Coon D, Mohler MJ, et al. The Impact of Mild Cognitive Impairment on Gait and Balance: A Systematic Review and Meta-Analysis of Studies Using Instrumented Assessment.
. 2017;63(1):67–83.
Subar AF, Kirkpatrick SI, Mittl B, Zimmerman TP, Thompson FE, Bingley C, et al. The Automated Self-Administered 24-hour dietary recall (ASA24): a resource for researchers, clinicians, and educators from the National Cancer Institute.
J Acad Nutr Diet
. 2012 Aug;112(8):1134–7.
Benton A, Hannay HJ, Varney NR. Visual perception of line direction in patients with unilateral brain disease.
. 1975 Oct;25(10):907–10.
Benton AL. Neuropsychological assessment.
Annu Rev Psychol
. 1994;45(1):1–23.
Carson N, Leach L, Murphy KJ. A re-examination of Montreal Cognitive Assessment (MoCA) cutoff scores.
Int J Geriatr Psychiatry
. 2018 Feb;33(2):379–88.
Clark LJ, Gatz M, Zheng L, Chen YL, McCleary C, Mack WJ. Longitudinal verbal fluency in normal aging, preclinical, and prevalent Alzheimer’s disease.
Am J Alzheimers Dis Other Demen
. 2009 Dec;24(6):461–8.
Derby CA, Burns LC, Wang C, Katz MJ, Zimmerman ME, L’italien G, et al. Screening for predementia AD: time-dependent operating characteristics of episodic memory tests.
. 2013 Apr;80(14):1307–14.
Fama R, Sullivan EV, Shear PK, Cahn-Weiner DA, Yesavage JA, Tinklenberg JR, et al. Fluency Performance Patterns in Alzheimer’s Disease and Parkinson’s Disease.
Clin Neuropsychol
. 1998;12(4):487–99.
Grober E, Lipton RB, Hall C, Crystal H. Memory impairment on free and cued selective reminding predicts dementia.
. 2000 Feb;54(4):827–32.
Grober E, Wakefield D, Ehrlich AR, Mabie P, Lipton RB. Identifying memory impairment and early dementia in primary care.
Alzheimers Dement (Amst)
. 2017 Feb;6:188–95.
Holtzer R, Goldin Y, Zimmerman M, Katz M, Buschke H, Lipton RB. Robust norms for selected neuropsychological tests in older adults.
Arch Clin Neuropsychol
. 2008 Sep;23(5):531–41.
Ivanova I, Salmon DP, Gollan TH. The multilingual naming test in Alzheimer’s disease: clues to the origin of naming impairments.
J Int Neuropsychol Soc
. 2013 Mar;19(3):272–83.
Loring DW, Martin RC, Meador KJ, Lee GP. Psychometric construction of the Rey-Osterrieth Complex Figure: methodological considerations and interrater reliability.
Arch Clin Neuropsychol
. 1990;5(1):1–14.
Mitrushina M, Uchiyama C, Satz P. Heterogeneity of cognitive profiles in normal aging: implications for early manifestations of Alzheimer’s disease.
J Clin Exp Neuropsychol
. 1995 May;17(3):374–82.
Monsell SE, Dodge HH, Zhou XH, Bu Y, Besser LM, Mock C, et al.; Neuropsychology Work Group Advisory to the Clinical Task Force. Results From the NACC Uniform Data Set Neuropsychological Battery Crosswalk Study.
Alzheimer Dis Assoc Disord
. 2016 Apr-Jun;30(2):134–9.
Mungas D. Differential clinical sensitivity of specific parameters of the Rey Auditory-Verbal Learning Test.
J Consult Clin Psychol
. 1983 Dec;51(6):848–55.
Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.
J Am Geriatr Soc
. 2005 Apr;53(4):695–9.
Reitan RM. Validity of the Trail Making Test as an Indicator of Organic Brain Damage.
Percept Mot Skills
. 1958;8(3):271–6.
Rey A.
L’examen Clinique en psychologie
. Paris: Presses Universitaires; 1958.
Rey A, Osterrieth PA. Translations of excerpts from Andre Rey’s Psychological examination of traumatic encephalopathy and P. A. Osterrieth’s The Complex Figure Copy Test.
Clin Neuropsychol
. 1993;7:4–21.
Weintraub S, Besser L, Dodge HH, Teylan M, Ferris S, Goldstein FC, et al. Version 3 of the Alzheimer Disease Centers’ Neuropsychological Test Battery in the Uniform Data Set (UDS).
Alzheimer Dis Assoc Disord
. 2018 Jan-Mar;32(1):10–7.
Koronyo Y, Biggs D, Barron E, Boyer DS, Pearlman JA, Au WJ, et al. Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease.
JCI Insight
. 2017 Aug;2(16):2.
Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, Miller CA, Ko MK, Black KL, et al. Identification of amyloid plaques in retinas from Alzheimer’s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model.
. 2011 Jan;54(suppl 1):S204–17.
He X, Koo BB, Killiany RJ.
Edited Magnetic Resonance Spectroscopy Detects an Age-Related Decline in Nonhuman Primate Brain GABA Levels
. Biomed Res Int. 2016;2016:6523909.
Thomas BP, Sheng M, Tseng BY, Tarumi T, Martin-Cook K, Womack KB, et al. Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment.
J Cereb Blood Flow Metab
. 2017 Apr;37(4):1508–16.
Langley J, Huddleston DE, Liu CJ, Hu X. Reproducibility of locus coeruleus and substantia nigra imaging with neuromelanin sensitive MRI.
. 2017 Apr;30(2):121–5.
Molinuevo JL, Cami J, Carné X, Carrillo MC, Georges J, Isaac MB, et al. Ethical challenges in preclinical Alzheimer’s disease observational studies and trials: results of the Barcelona summit.
Alzheimers Dement
. 2016 May;12(5):614–22.
Ekman A, Dickman PW, Klint A, Weiderpass E, Litton JE. Feasibility of using web-based questionnaires in large population-based epidemiological studies.
Eur J Epidemiol
. 2006;21(2):103–11.
Russell CW, Boggs DA, Palmer JR, Rosenberg L. Use of a web-based questionnaire in the Black Women’s Health Study.
Am J Epidemiol
. 2010 Dec;172(11):1286–91.
Ebert JF, Huibers L, Christensen B, Christensen MB. Paper- or Web-Based Questionnaire Invitations as a Method for Data Collection: Cross-Sectional Comparative Study of Differences in Response Rate, Completeness of Data, and Financial Cost.
J Med Internet Res
. 2018 Jan;20(1):e24.
Smith B, Smith TC, Gray GC, Ryan MA; Millennium Cohort Study Team. When epidemiology meets the Internet: Web-based surveys in the Millennium Cohort Study.
Am J Epidemiol
. 2007 Dec;166(11):1345–54.
Scarabino D, Gambina G, Broggio E, Pelliccia F, Corbo RM. Influence of family history of dementia in the development and progression of late-onset Alzheimer’s disease.
Am J Med Genet B Neuropsychiatr Genet
. 2016 Mar;171B(2):250–6.
Amariglio RE, Donohue MC, Marshall GA, Rentz DM, Salmon DP, Ferris SH, et al.; Alzheimer’s Disease Cooperative Study. Tracking early decline in cognitive function in older individuals at risk for Alzheimer disease dementia: the Alzheimer’s Disease Cooperative Study Cognitive Function Instrument.
JAMA Neurol
. 2015 Apr;72(4):446–54.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.