The WHICAP WES study consists of a multi-ethnic cohort of 4,100 individuals followed over several years. Participants were community-living Medicare recipients 65 years and older recruited from northern Manhattan to participate in the Washington Heights-Inwood Columbia Aging Project. Potential participants were identified based on residence in US Census tracts within the study catchment area. Recruitment occurred in three waves: 1992 (N = 2126), 1999 (N = 2174), and 2009 (N = 2128). Participants completed a baseline assessment and were followed up at 18- to 24-month intervals for up to 25 years. During each session, participants were administered a neuropsychological battery and asked about their general health, functional ability, and medical history and were re‐consented for sharing of genetic information and autopsy. Evaluations were conducted in English or Spanish, based on language preference. The cohort participants were non-demented initially, 65 years of age or older, and comprised of non‐Hispanic whites, African Americans, and Caribbean Hispanics from the Dominican Republic. A consensus diagnosis was derived for each participant by experienced clinicians based on NINCDS‐ADRDA criteria for possible, probable, or definite AD, or moderate or high likelihood of neuropathological criteria of AD.

Every individual with whole‐exome sequencing has at least a baseline and one follow‐up assessment and examination, and for those who have died, the presence or absence of dementia was determined using a brief, validated telephone interview with participant informants: the Dementia Questionnaire (DQ) and the Telephone Interview of Cognitive Status (TICS). 4,100 exome sequenced WHICAP individuals were designated with case or control status. Whole‐exome sequencing of the WHICAP cohort was performed at Columbia University.

Richard P. Mayeux, MD, MSc

Nicole Schupf, Ph.D.

PO1AG07232, R01AG037212, RF1AG054023, UL1TR001873

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

For investigators using WHICAP data:

Data collection and sharing for this project was supported by the Washington Heights-Inwood Columbia Aging Project (WHICAP, PO1AG07232, R01AG037212, RF1AG054023) funded by the National Institute on Aging (NIA) and by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1TR001873. This manuscript has been reviewed by WHICAP investigators for scientific content and consistency of data interpretation with previous WHICAP Study publications. We acknowledge the WHICAP study participants and the WHICAP research and support staff for their contributions to this study.

Gu Y, Gutierrez J, Meier IB, Guzman VA, Manly JJ, Schupf N, Brickman AM, Mayeux R. Circulating inflammatory biomarkers are related to cerebrovascular disease in older adults. Neurol Neuroimmunol Neuroinflamm. 2018 Nov 14;6(1):e521. doi: 10.1212/NXI.0000000000000521. eCollection 2019 Jan. PubMed PMID: 30568999; PubMed Central PMCID: PMC6278856.

Gurland BJ, Wilder DE, Lantigua R, Stern Y, Chen J, Killeffer EH, Mayeux R. Rates of dementia in three ethnoracial groups. Int J Geriatr Psychiatry. 1999 Jun;14(6):481-93. PubMed PMID: 10398359.

Gutierrez J, Guzman V, Khasiyev F, Manly J, Schupf N, Andrews H, Mayeux R, Brickman AM. Brain arterial dilatation and the risk of Alzheimer’s disease. Alzheimers Dement. 2019 May;15(5):666-674. doi: 10.1016/j.jalz.2018.12.018. Epub  2019 Mar 1. PubMed PMID: 30827874; PubMed Central PMCID: PMC6511479.

Lee JH, Cheng R, Schupf N, Manly J, Lantigua R, Stern Y, Tycko B, Rogaeva E, Wakutani Y, Farrer L, St George-Hyslop P, Mayeux R. The Association Between Genetic Variants in SORL1 and Alzheimer’s Disease in an Urban, Multiethnic, Community-Based Cohort. Arch Neurol. 2007 Apr; 64(4): 501–506. doi: 10.1001/archneur.64.4.501 PMCID: PMC2639214.

Lee S, Zhou X, Gao Y, Vardarajan B, Reyes-Dumeyer D, Rajan KB, Wilson RS, Evans DA, Besser LM, Kukull WA, Bennett DA, Brickman AM, Schupf N, Mayeux R, Barral S. Episodic memory performance in a multi-ethnic longitudinal study of 13,037 elderly. PLoS One. 2018 Nov 21;13(11):e0206803. doi: 10.1371/journal.pone.0206803. eCollection 2018. PubMed PMID: 30462667; PubMed Central PMCID: PMC6248922.

Mayeux R, Schupf N. Blood-based biomarkers for Alzheimer’s disease: plasmaAβ40 and Aβ42, and genetic variants. Neurobiol Aging. 2011 Dec;32 Suppl 1:S10-9. Doi10.1016/j.neurobiolaging.2011.09.004. Review. PubMed PMID: 22078169; PubMed Central PMCID: PMC3233700.

Raghavan NS, Brickman AM, Andrews H, Manly JJ, Schupf N, Lantigua R, Wolock CJ, Kamalakaran S, Petrovski S, Tosto G, Vardarajan BN, Goldstein DB, Mayeux R; Alzheimer’s Disease Sequencing Project. Whole-exome sequencing in 20,197 persons for rare variants in Alzheimer’s disease. Ann Clin Transl Neurol. 2018 May 24;5(7):832-842. doi: 10.1002/acn3.582. eCollection 2018 Jul. Erratum in: Ann Clin Transl Neurol. 2019 Feb 25;6(2):416. PubMed PMID: 30009200; PubMed Central PMCID: PMC6043775.

Sariya S, Lee JH, Mayeux R, Vardarajan BN, Reyes-Dumeyer D, Manly JJ, Brickman AM, Lantigua R, Medrano M, Jimenez-Velazquez IZ, Tosto G. Rare Variants Imputation in Admixed Populations: Comparison Across Reference Panels and Bioinformatics Tools. Front Genet. 2019 Apr 3;10:239. doi: 10.3389/fgene.2019.00239. eCollection 2019. PubMed PMID: 31001313; PubMed Central PMCID: PMC6456789.

Tang MX, Cross P, Andrews H, Jacobs DM, Small S, Bell K, Merchant C, Lantigua R, Costa R, Stern Y, Mayeux R. Incidence of AD in African Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Neurology, 2001; 56(1): 49-56.

Tosto G, Vardarajan B, Sariya S, Brickman AM, Andrews H, Manly JJ, Schupf N, Reyes-Dumeyer D, Lantigua R, Bennett DA, De Jager PL, Mayeux R. Association of Variants in PINX1 and TREM2 With Late-Onset Alzheimer Disease. JAMA Neurol. 2019 May 6. doi: 10.1001/jamaneurol.2019.1066. [Epub ahead of print] PubMed PMID:31058951; PubMed Central PMCID: PMC6503572.