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2. Obesity, diabetes and their metabolic correlates in middle‐aged adults with Down syndrome.

Author

Luchsinger, J. A., Pang, D., Krinsky‐McHale, S. J., Schupf, N., Lee, J. H., Silverman, W., and Zigman, W. B.

Subjects
METABOLIC syndrome risk factors, CROSS-sectional method, DOWN syndrome, LEPTIN, RESEARCH funding, BODY mass index, GLYCOSYLATED hemoglobin, LIPIDS, INSULIN, DESCRIPTIVE statistics, ADIPONECTIN, DIABETES, OBESITY, C-reactive protein, MIDDLE age
Abstract

Background: Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre‐diabetes and diabetes, high levels of insulin, non‐high‐density lipoprotein (HDL) cholesterol, leptin and high‐sensitivity C‐reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle‐aged adults with Down syndrome is also related to an adverse metabolic profile. Methods: This cross‐sectional study included 143 adults with Down syndrome, with a mean age of 55.7 ± 5.7 years and 52.5% women. Body mass index (BMI) was classified as underweight (BMI < 18.5 kg/m2), normal (BMI 18.5–24.9 kg/m2), overweight (BMI 25–29.9 kg/m2) and obese (BMI ≥ 30 kg/m2). Diabetes was ascertained by history or by haemoglobin A1c (HbA1c) as normal glucose tolerance (HbA1c < 5.7%), pre‐diabetes (HbA1c 5.7–6.4%) and diabetes (HbA1c ≥ 6.5%). We measured non‐fasting lipids, hsCRP, insulin, adiponectin and leptin. Results: The majority of the sample had an overweight (46.9%) or obesity (27.3%) status. However, there was a relatively low prevalence of pre‐diabetes (9.8%) and diabetes (6.9%). Overweight and obesity status were not associated with lower HDL and adiponectin and higher insulin, non‐HDL cholesterol and hsCRP as expected in adults without Down syndrome. However, overweight and obesity were strongly associated with higher leptin (P < 0.001). Conclusions: The only metabolic correlate of obesity in middle‐aged adults with Down syndrome was high leptin levels. Our findings are limited by non‐fasting laboratory tests but suggest that middle‐aged adults with Down syndrome do not have the adverse metabolic profile related to obesity found in adults without Down syndrome. [ABSTRACT FROM AUTHOR]

Published
2024
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4. A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

Author

Chouraki, V, De Bruijn, R F A G, Chapuis, J, Bis, J C, Reitz, C, Schraen, S, Ibrahim-Verbaas, C A, Grenier-Boley, B, Delay, C, Rogers, R, Demiautte, F, Mounier, A, Fitzpatrick, A L, Berr, C, Dartigues, J-F, Uitterlinden, A G, Hofman, A, Breteler, M, Becker, J T, Lathrop, M, Schupf, N, Alpérovitch, A, Mayeux, R, van Duijn, C M, Buée, L, Amouyel, P, Lopez, O L, Ikram, M A, Tzourio, C, and Lambert, J-C

Published
2014
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6. 3rd IANA (International Academy on Nutrition and Aging) Meeting Nutrition, Exercise & Alzheimer and Clinical Trials on Sarcopenia August 1–2, 2008 Hyatt Regency Tamaya Resort 1300 Tuyuna Trail Santa Ana Pueblo, NM USA

Author

Andrieu, S., Barberger-Gateau, P., Raffaitin, C., Berr, C., Tzourio, C., Dartigues, J. -F., Gin, H., Fitten, L. J., Ortiz, F., Fairbanks, L., Bartzokis, G., Lu, P., Ringman, J., Heyn, P. C., Locher, J. L., Salvà, A., Andrieu, S., Fernández, E., Vellas, B., van de Rest, O., Geleijnse, J. M., Kok, F. J., van Staveren, W. A., Beekman, A. T. F., Hoefnagels, W. H. L., de Groot, C. P. G. M., Angevaren, M., Aufdemkampe, G., Verhaar, H. J. J., Aleman, A., Vannees, L., Arkin, S., Florez, H., Gerstein, H., Sheridan, P., Bosch, J., Goldberg, R., Kaspar, K. M., Drawert, S. M., Marcus, R. L., Kidde, J., Dibble, L., Addison, O., LaStayo, P. C., Scarmeas, N., Stern, Y., Schupf, N., Luchsinger, J. A., Sharkey, J. R., Laditka, J. N., Laditka, S. B., Liu, R., Hochhalter, A., Robare, J. F., Türner, N., Judge, M., Foster, T. C., Erdos, B., Cudykier, I., Scarpace, P. J., Weiss, L. A., Bergstrom, J., Kritz-Silverstein, D., Barrett-Connor, Elizabeth, Yurko-Mauro, K., Nelson, E., Quinn, J., Sattler, F. R., Castaneda-Sceppa, C., Binder, E. F., Schroeder, E. T., Wang, Y., Bhasin, S., Kawakubo, M., Stewart, Y., Hahn, C., Colletti, P., Roubenoff, R., Yarasheski, K. E., Azen, S. P., Aoki, Y., Yamamoto, T., Otuka, T., Blanc-Bisson, C., Bourdel-Marchasson, I., Bocock, M. A., Keller, H. H., Bowman, G., Baxter, J., Oken, B., Frei, B., Traber, M., Leonard, S., Kaye, J., Shannon, J., Quinn, J., Carlsson, M., Gustafson, Y., Eriksson, S., Littbrand, H., Håglin, L., Danthiir, V., Wilson, C., Nettelbeck, T., Burns, N., Wittert, G., Noakes, M., Clifton, P., DiMaria-Ghalili, R. A., Grieger, J. A., Nowson, C. A., Wattanapenpaiboon, N. T., Holstein, J., Robinson, C., Hartmann, C., Rueb, S., Heffel, L., Dintaman, S., Reynolds, J., Fleming, L., Crull, M., Goldey, J., Serper, L. L., Hubbard, R., Westengard, J., Horning, M., Ishige, Y., Aoki, Y., Keller, H. H., Keller, H. H., LaStayo, P. C., Marcus, R. L., Smith, S., Kidde, J., Dibble, L., Butler, C., Hill, M., LaStayo, P. C., Marcus, R. L., Dibble, L., Kidde, J., Peters, C., Meier, W., Laughlin, G. A., Kritz-Silverstein, D., von Muhlen, D., Barrett-Connor, E., Olariu, L., Petcu, M., Tulcan, C., Pup, M., Otilingam, P., Gate, M., Pasinetti, G. M., Ray, B., Chauhan, N. B., Bailey, J. A., Lahiri, D. K., Shatenstein, B., Kergoat, M. -J., Reid, I., Chicoine, M. -E., Vaz, L., Stewart, R., Sabbah, W., Tsakos, G., D’Aiuto, F., Watt, R. G., Sturman, M., Kelly, J., Fleischman, D., Leurgans, S., Bennett, D., Morris, M. C., Suominen, M. H., Muurinen, S., Soini, H., Pitkälä, K. H., Yamamoto, T., Fujinoki, C., and Aoki, Y.

Published
2008
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10. Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study

Author

Bae, J.B. Lipnicki, D.M. Han, J.W. Sachdev, P.S. Kim, T.H. Kwak, K.P. Kim, B.J. Kim, S.G. Kim, J.L. Moon, S.W. Park, J.H. Ryu, S.-H. Youn, J.C. Lee, D.Y. Lee, D.W. Lee, S.B. Lee, J.J. Jhoo, J.H. Llibre-Rodriguez, J.J. Llibre-Guerra, J.J. Valhuerdi-Cepero, A.J. Ritchie, K. Ancelin, M.-L. Carriere, I. Skoog, I. Najar, J. Sterner, T.R. Scarmeas, N. Yannakoulia, M. Dardiotis, E. Meguro, K. Kasai, M. Nakamura, K. Riedel-Heller, S. Roehr, S. Pabst, A. Van Boxtel, M. Köhler, S. Ding, D. Zhao, Q. Liang, X. Scazufca, M. Lobo, A. De-La-Cámara, C. Lobo, E. Kim, K.W. Makkar, S.R. Crawford, J.D. Thalamuthu, A. Kochan, N.A. Leung, Y. Lo, J.W. Turana, Y. Castro-Costa, E. Larijani, B. Nabipour, I. Rockwood, K. Shifu, X. Lipton, R.B. Katz, M.J. Preux, P.-M. Guerchet, M. Lam, L. Ninimiya, T. Walker, R. Hendrie, H. Guaita, A. Chen, L.-K. Shahar, S. Dominguez, J. Krishna, M. Ganguli, M. Anstey, K.J. Crowe, M. Haan, M.N. Kumagai, S. Ng, T.P. Brodaty, H. Mayeux, R. Schupf, N. Petersen, R. Lipton, R. Lowe, E.S. Jorm, L.

Subjects
mental disorders
Abstract

Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. Conclusion: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes. © 2020 The Author(s).

Published
2020

14. Sleep and subjective cognitive decline in cognitively healthy elderly: Results from two cohorts

Author

Tsapanou, A. Vlachos, G.S. Cosentino, S. Gu, Y. Manly, J.J. Brickman, A.M. Schupf, N. Zimmerman, M.E. Yannakoulia, M. Kosmidis, M.H. Dardiotis, E. Hadjigeorgiou, G. Sakka, P. Stern, Y. Scarmeas, N. Mayeux, R.

Abstract

Subjective cognitive decline may reflect a dementia prodrome or modifiable risk factor such as sleep disturbance. What is the association between sleep and subjective cognitive decline? Cross-sectional design, from two studies of older adults: the WHICAP in the USA and the HELIAD in Greece. A total of 1,576 WHICAP and 1,456 HELIAD participants, without mild cognitive impairment, dementia or severe depression/anxiety, were included. Participants were mostly women, with 12 (WHICAP) and 8 (HELIAD) mean years of education. Sleep problems were estimated using the Sleep Scale from the Medical Outcomes Study. Subjective cognitive decline was assessed using a structured complaint questionnaire that queries for subjective memory and other cognitive symptoms. Multinomial or logistic regression models were used to examine whether sleep problems were associated with complaints about general cognition, memory, naming, orientation and calculations. Age, sex, education, sleep medication, use of medications affecting cognition, co-morbidities, depression and anxiety were used as co-variates. Objective cognition was also estimated by summarizing neuropsychological performance into composite z-scores. Sleep problems were associated with two or more complaints: WHICAP: β = 1.93 (95% confidence interval: 1.59–2.34), p ≤.0001; HELIAD: β = 1.48 (95% confidence interval: 1.20–1.83), p ≤.0001. Sleep problems were associated with complaints in all the cognitive subcategories, except orientation for the WHICAP. The associations were noted regardless of objective cognition. At any given level of objective cognition, sleep disturbance is accompanied by subjective cognitive impairment. The replicability in two ethnically, genetically and culturally different cohorts adds validity to our results. The results have implications for the correlates, and potential aetiology of subjective cognitive decline, which should be considered in the assessment and treatment of older adults with cognitive complaints. © 2018 European Sleep Research Society

Published
2019

15. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need

Author

Babulal, G.M. Quiroz, Y.T. Albensi, B.C. Arenaza-Urquijo, E. Astell, A.J. Babiloni, C. Bahar-Fuchs, A. Bell, J. Bowman, G.L. Brickman, A.M. Chételat, G. Ciro, C. Cohen, A.D. Dilworth-Anderson, P. Dodge, H.H. Dreux, S. Edland, S. Esbensen, A. Evered, L. Ewers, M. Fargo, K.N. Fortea, J. Gonzalez, H. Gustafson, D.R. Head, E. Hendrix, J.A. Hofer, S.M. Johnson, L.A. Jutten, R. Kilborn, K. Lanctôt, K.L. Manly, J.J. Martins, R.N. Mielke, M.M. Morris, M.C. Murray, M.E. Oh, E.S. Parra, M.A. Rissman, R.A. Roe, C.M. Santos, O.A. Scarmeas, N. Schneider, L.S. Schupf, N. Sikkes, S. Snyder, H.M. Sohrabi, H.R. Stern, Y. Strydom, A. Tang, Y. Terrera, G.M. Teunissen, C. Melo van Lent, D. Weinborn, M. Wesselman, L. Wilcock, D.M. Zetterberg, H. O'Bryant, S.E. International Society to Advance Alzheimer's Research Treatment, Alzheimer's Association

Abstract

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise “state-of-the-science” report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations. © 2018 The Authors

Published
2019

16. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need

Author

Babulal, GM, Quiroz, YT, Albensi, BC, Arenaza-Urquijo, E, Astell, AJ, Babiloni, C, Bahar-Fuchs, A, Bell, J, Bowman, GL, Brickman, AM, Chetelat, G, Ciro, C, Cohen, AD, Dilworth-Anderson, P, Dodge, HH, Dreux, S, Edland, S, Esbensen, A, Evered, L, Ewers, M, Fargo, KN, Fortea, J, Gonzalez, H, Gustafson, DR, Head, E, Hendrix, JA, Hofer, SM, Johnson, LA, Jutten, R, Kilborn, K, Lanctot, KL, Manly, JJ, Martins, RN, Mielke, MM, Morris, MC, Murray, ME, Oh, ES, Parra, MA, Rissman, RA, Roe, CM, Santos, OA, Scarmeas, N, Schneider, LS, Schupf, N, Sikkes, S, Snyder, HM, Sohrabi, HR, Stern, Y, Strydom, A, Tang, Y, Terrera, GM, Teunissen, C, van Lent, DM, Weinborn, M, Wesselman, L, Wilcock, DM, Zetterberg, H, O'Bryant, SE, Int Soc Adv Alzheimers Res Treatme, and Alzheimers Assoc

Subjects
Ethnoracial, Diversity, Alzheimer's related dementias, Translational, Ethnicity, Underserved, Alzheimer's disease
Abstract

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

Published
2019

17. Prevalent and Incident Physical and Cognitive Independence Among the Oldest Old: The Long Life Family Study:The Long Life Family Study

Author

Santanasto, A J, Marron, M M, Wojczynski, M, Schupf, N, Sebastiani, P, Cosentino, S, Christensen, K, and Newman, A B

Abstract

We examined 7-year change in prevalence of physical (no difficultly performing ADLs), cognitive (Mini Mental State Examination score ≥23) and overall independence (physically and cognitively independent) in LLFS subjects aged 90 ± 6 years. At baseline (n=1442), 84\ 85\% and 71\% were physically, cognitively and overall independent, respectively. After 7-years, 951 (66\ died and 108 (8\ were lost to follow-up. Importantly, 92\% of those lost to follow-up compared to 60.0\% of those who died had baseline independence. Among 7-year survivors, the prevalence of physical, cognitive and overall independence was 74\ 82\% and 61\ respectively. Of those physically, cognitively and overall independent at baseline, 78\ 86\ and 69\% remained independent. Prevalence increased by just 10\% despite the 31\% incidence among 7-year survivors, mainly attributable to high mortality risk among those dependent at baseline. A large proportion of this cohort remained independent, which supports further investigation of factors underlying preserved function at extreme ages.

Published
2018
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18. Long-term Exposure to Ambient Air Pollution, APOE-ε4 status, and Trajectories of Cognitive Decline in an Urban Cohort of Older Adults

Author

Schupf N, Bohme A, Wellenius G, Manly J, Kulick E, Joyce N, Mayeux R, Elkind M, and Kaufman J

Subjects
Global and Planetary Change, Ambient air pollution, Epidemiology, business.industry, Health, Toxicology and Mutagenesis, Environmental health, Cohort, Public Health, Environmental and Occupational Health, Medicine, Cognitive decline, business, Pollution, Term (time)
Published
2019
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19. Does Literacy Moderate the Relationship between Age of Migration and Cognitive Change: Results from the Washington Heights-Inwood Community Aging Project (WHICAP)

Author

Carrión, C I, primary, Arias, F, additional, Diaz-Santos, M, additional, Levy, S-A, additional, Hill-Jarrett, T G, additional, Avila, J, additional, Jones, R, additional, Rivera Mindt, M, additional, Arce, M, additional, Schupf, N, additional, Mayeux, R, additional, and Manly, J, additional

Published
2019
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22. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias : Update and areas of immediate need

Author

Babulal, G.M., Quiroz, Y.T., Albensi, B.C., Arenaza-Urquijo, E., Astell, A.J., Babiloni, Claudio, Bahar-Fuchs, A., Bell, J., Bowman, G.L., Brickman, A.M., Chételat, G., Ciro, C., Cohen, A.D., Dilworth-Anderson, P., Dodge, H.H., Dreux, S., Edland, S., Esbensen, A., Evered, L., Ewers, M., Fargo, K.N., Fortea, Juan, Gonzalez, H., Gustafson, D.R., Head, Elizabeth, Hendrix, J.A., Hofer, S.M., Johnson, L.A., Jutten, R., Kilborn, K., Lanctôt, K.L., Manly, J.J., Martins, R.N., Mielke, M.M., Morris, M.C., Murray, M.E., Oh, E.S., Parra, M.A., Rissman, R.A., Roe, C.M., Santos, O.A., Scarmeas, N., Schneider, L.S., Schupf, N., Sikkes, S., Snyder, H.M., Sohrabi, H.R., Stern, Y., Strydom, A., Tang, Y., Terrera, Graciela Muniz, Teunissen, Charlotte E, Melo van Lent, D., Weinborn, M., Wesselman, L., Wilcock, D.M., Zetterberg, Henrik, O'Bryant, S.E., Universitat Autònoma de Barcelona, Babulal, G.M., Quiroz, Y.T., Albensi, B.C., Arenaza-Urquijo, E., Astell, A.J., Babiloni, Claudio, Bahar-Fuchs, A., Bell, J., Bowman, G.L., Brickman, A.M., Chételat, G., Ciro, C., Cohen, A.D., Dilworth-Anderson, P., Dodge, H.H., Dreux, S., Edland, S., Esbensen, A., Evered, L., Ewers, M., Fargo, K.N., Fortea, Juan, Gonzalez, H., Gustafson, D.R., Head, Elizabeth, Hendrix, J.A., Hofer, S.M., Johnson, L.A., Jutten, R., Kilborn, K., Lanctôt, K.L., Manly, J.J., Martins, R.N., Mielke, M.M., Morris, M.C., Murray, M.E., Oh, E.S., Parra, M.A., Rissman, R.A., Roe, C.M., Santos, O.A., Scarmeas, N., Schneider, L.S., Schupf, N., Sikkes, S., Snyder, H.M., Sohrabi, H.R., Stern, Y., Strydom, A., Tang, Y., Terrera, Graciela Muniz, Teunissen, Charlotte E, Melo van Lent, D., Weinborn, M., Wesselman, L., Wilcock, D.M., Zetterberg, Henrik, O'Bryant, S.E., and Universitat Autònoma de Barcelona

Abstract

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa", La "Marató TV3" grant (20141210 to J.F.), Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

Published
2019

27. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need

Author

Babulal, G.M., Quiroz, Y.T., Albensi, B.C., Arenaza-Urquijo, E., Astell, A.J., Babiloni, C., Bahar-Fuchs, A., Bell, J., Bowman, G.L., Brickman, A.M., Chételat, G., Ciro, C., Cohen, A.D., Dilworth-Anderson, P., Dodge, H.H., Dreux, S., Edland, S., Esbensen, A., Evered, L., Ewers, M., Fargo, K.N., Fortea, J., Gonzalez, H., Gustafson, D.R., Head, E., Hendrix, J.A., Hofer, S.M., Johnson, L.A., Jutten, R., Kilborn, K., Lanctôt, K.L., Manly, J.J., Martins, R.N., Mielke, M.M., Morris, M.C., Murray, M.E., Oh, E.S., Parra, M.A., Rissman, R.A., Roe, C.M., Santos, O.A., Scarmeas, N., Schneider, L.S., Schupf, N., Sikkes, S., Snyder, H.M., Sohrabi, H.R., Stern, Y., Strydom, A., Tang, Y., Terrera, G.M., Teunissen, C., Melo van Lent, D., Weinborn, M., Wesselman, L., Wilcock, D.M., Zetterberg, H., O'Bryant, S.E., Babulal, G.M., Quiroz, Y.T., Albensi, B.C., Arenaza-Urquijo, E., Astell, A.J., Babiloni, C., Bahar-Fuchs, A., Bell, J., Bowman, G.L., Brickman, A.M., Chételat, G., Ciro, C., Cohen, A.D., Dilworth-Anderson, P., Dodge, H.H., Dreux, S., Edland, S., Esbensen, A., Evered, L., Ewers, M., Fargo, K.N., Fortea, J., Gonzalez, H., Gustafson, D.R., Head, E., Hendrix, J.A., Hofer, S.M., Johnson, L.A., Jutten, R., Kilborn, K., Lanctôt, K.L., Manly, J.J., Martins, R.N., Mielke, M.M., Morris, M.C., Murray, M.E., Oh, E.S., Parra, M.A., Rissman, R.A., Roe, C.M., Santos, O.A., Scarmeas, N., Schneider, L.S., Schupf, N., Sikkes, S., Snyder, H.M., Sohrabi, H.R., Stern, Y., Strydom, A., Tang, Y., Terrera, G.M., Teunissen, C., Melo van Lent, D., Weinborn, M., Wesselman, L., Wilcock, D.M., Zetterberg, H., and O'Bryant, S.E.

Abstract

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross‐PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

Published
2018

28. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K i

Author

Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), Levy, D. (Daniel), Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), and Levy, D. (Daniel)

Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Published
2018
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29. Whole-exome sequencing in 20,197 persons for rare variants in Alzheimer's disease

Author

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, Raghavan, NS, Brickman, AM, Andrews, H, Manly, JJ, Schupf, N, Lantigua, R, Wolock, CJ, Kamalakaran, S, Petrovski, S, Tosto, G, Vardarajan, BN, Goldstein, DB, and Mayeux, R

Abstract

OBJECTIVE: The genetic bases of Alzheimer's disease remain uncertain. An international effort to fully articulate genetic risks and protective factors is underway with the hope of identifying potential therapeutic targets and preventive strategies. The goal here was to identify and characterize the frequency and impact of rare and ultra-rare variants in Alzheimer's disease, using whole-exome sequencing in 20,197 individuals. METHODS: We used a gene-based collapsing analysis of loss-of-function ultra-rare variants in a case-control study design with data from the Washington Heights-Inwood Columbia Aging Project, the Alzheimer's Disease Sequencing Project and unrelated individuals from the Institute of Genomic Medicine at Columbia University. RESULTS: We identified 19 cases carrying extremely rare SORL1 loss-of-function variants among a collection of 6,965 cases and a single loss-of-function variant among 13,252 controls (P = 2.17 × 10-8; OR: 36.2 [95% CI: 5.8-1493.0]). Age-at-onset was 7 years earlier for patients with SORL1 qualifying variant compared with noncarriers. No other gene attained a study-wide level of statistical significance, but multiple top-ranked genes, including GRID2IP,WDR76 and GRN, were among candidates for follow-up studies. INTERPRETATION: This study implicates ultra-rare, loss-of-function variants in SORL1 as a significant genetic risk factor for Alzheimer's disease and provides a comprehensive dataset comparing the burden of rare variation in nearly all human genes in Alzheimer's disease cases and controls. This is the first investigation to establish a genome-wide statistically significant association between multiple extremely rare loss-of-function variants in SORL1 and Alzheimer's disease in a large whole-exome study of unrelated cases and controls.

Published
2018

30. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author

Feitosa, MF, Kraja, AT, Chasman, DI, Sung, YJ, Winkler, TW, Ntalla, I, Guo, XQ, Franceschini, N, Cheng, CY (Ching-Yu), Sim, XL, Vojinovic, Dina, Marten, J, Musani, SK, Li, CW, Bentley, AR, Brown, MR, Schwander, K, Richard, MA, Noordam, R, Aschard, H, Bartz, TM, Bielak, LF, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Lohman, KK, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, S M, Wojczynski, MK, Alver, M, Boissel, M, Cai, QY, Campbell, A (Archie), Chai, JF, Chen, X, Divers, J, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, He, MI, Hsu, FC, Jackson, AU, Kahonen, M, Kasturiratne, A, Komulainen, P, Kuhnel, B, Laguzzi, F, Luan, J, Matoba, N, Nolte, IM, Padmanabhan, S, Riaz, M, Rueedi, R, Robino, A, Said, MA, Scott, RA, Sofer, T, Stancakova, A, Takeuchi, F, Tayo, BO, van der Most, PJ, Varga, TV, Vitart, V, Wang, YJ, Ware, EB, Warren, HR, Weiss, S, Wen, WQ, Yanek, LR, Zhang, WH, Zhao, JH, Afaq, S, Amin, Najaf, Amini, M, Arking, DE, Aung, T, Boerwinkle, E, Borecki, I, Broeckel, U, Brown, M, Brumat, M, Burke, GL, Canouil, M, Chakravarti, A, Charumathi, S, Chen, YDI, Connell, JM, Correa, A, Fuentes, LDL, de Mutsert, R, de Silva, HJ, Deng, X, Ding, J, Duan, Q, Eaton, CB, Ehret, G, Eppinga, RN, Evangelou, E, Fau, JD, Felix, SB, Forouhi, NG, Forrester, T, Franco Duran, OH, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, Mohsen, Gigante, B, Gu, CC, Gu, DF, Hagenaars, SP, Hallmans, G, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hirata, M, Howard, BV, Ikram, Arfan, John, U, Katsuya, T, Khor, CC, Kilpelainen, TO, Koh, WP, Krieger, JE, Kritchevsky, SB, Kubo, M, Kuusisto, J, Lakka, TA, Langefeld, CD, Langenberg, C, Launer, LJ, Lehne, B, Lewis, CE, Li, YZ, Lin, S, Liu, JJ, Liu, JM, Loh, M, Louie, T, Magi, R, McKenzie, CA, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, KL, Momozawa, Y, Nalls, MA, Nelson, CP, Sotoodehnia, N, Norris, JM, O'Connell, JR, Palmer, ND, Perls, T, Pedersen, NL, Peters, A, Peyser, PA, Poulter, N, Raffel, LJ, Raitakari, OT, Roll, K, Rose, LM, Rosendaal, FR, Rotter, JI, Schmidt, CO, Schreiner, PJ, Schupf, N, Scott, WR, Sever, PS, Shi, Y, Sidney, S, Sims, M, Sitlani, CM, Smith, JA, Snieder, H, Starr, JM, Strauch, K, Stringham, HM, Tan, NYQ, Tang, H, Taylor, KD, Teo, YY, Tham, YC, Turner, ST, Uitterlinden, André, Vollenweider, P, Waldenberger, M, Wang, LH, Wang, YX, Wei, W, Williams, C, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, Chambers, JC, Deary, IJ, Esko, T, Farrall, M, Franks, PW, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Jonas, JB, Kamatani, Y, Kato, N, Kooner, JS, Kutalik, Z, Laakso, M, Laurie, CC, Leander, K, Lehtimaki, T, Study, LC, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Poiasek, O, Porteous, DJ, Rauramaa, R, Samani, NJ, Scott, J, Shu, XO, van der Harst, P, Wagenknecht, LE, Wareham, NJ, Watkins, H, Weir, DR, Wickremasinghe, AR, Wu, TC, Zheng, W, Bouchard, C, Christensen, K, Evans, MK, Gudnason, V, Horta, BL, Kardia, SLR, Liu, YM, Pereira, AC, Psaty, BM, Ridker, PM, van Dam, RM, Gauderman, WJ, Zhu, XF, Mook, Dennis, Fornage, M, Rotimi, CN, Cupples, LA, Kelly, TN, Fox, ER, Hayward, C, Duijn, Cornelia, Tai, ES, Wong, TY, Kooperberg, C, Palmas, W, Rice, K, Morrison, AC, Elliott, P, Caulfield, MJ, Munroe, PB, Rao, DC, Province, MA, Levy, D, Feitosa, MF, Kraja, AT, Chasman, DI, Sung, YJ, Winkler, TW, Ntalla, I, Guo, XQ, Franceschini, N, Cheng, CY (Ching-Yu), Sim, XL, Vojinovic, Dina, Marten, J, Musani, SK, Li, CW, Bentley, AR, Brown, MR, Schwander, K, Richard, MA, Noordam, R, Aschard, H, Bartz, TM, Bielak, LF, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Lohman, KK, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, S M, Wojczynski, MK, Alver, M, Boissel, M, Cai, QY, Campbell, A (Archie), Chai, JF, Chen, X, Divers, J, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, He, MI, Hsu, FC, Jackson, AU, Kahonen, M, Kasturiratne, A, Komulainen, P, Kuhnel, B, Laguzzi, F, Luan, J, Matoba, N, Nolte, IM, Padmanabhan, S, Riaz, M, Rueedi, R, Robino, A, Said, MA, Scott, RA, Sofer, T, Stancakova, A, Takeuchi, F, Tayo, BO, van der Most, PJ, Varga, TV, Vitart, V, Wang, YJ, Ware, EB, Warren, HR, Weiss, S, Wen, WQ, Yanek, LR, Zhang, WH, Zhao, JH, Afaq, S, Amin, Najaf, Amini, M, Arking, DE, Aung, T, Boerwinkle, E, Borecki, I, Broeckel, U, Brown, M, Brumat, M, Burke, GL, Canouil, M, Chakravarti, A, Charumathi, S, Chen, YDI, Connell, JM, Correa, A, Fuentes, LDL, de Mutsert, R, de Silva, HJ, Deng, X, Ding, J, Duan, Q, Eaton, CB, Ehret, G, Eppinga, RN, Evangelou, E, Fau, JD, Felix, SB, Forouhi, NG, Forrester, T, Franco Duran, OH, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, Mohsen, Gigante, B, Gu, CC, Gu, DF, Hagenaars, SP, Hallmans, G, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hirata, M, Howard, BV, Ikram, Arfan, John, U, Katsuya, T, Khor, CC, Kilpelainen, TO, Koh, WP, Krieger, JE, Kritchevsky, SB, Kubo, M, Kuusisto, J, Lakka, TA, Langefeld, CD, Langenberg, C, Launer, LJ, Lehne, B, Lewis, CE, Li, YZ, Lin, S, Liu, JJ, Liu, JM, Loh, M, Louie, T, Magi, R, McKenzie, CA, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, KL, Momozawa, Y, Nalls, MA, Nelson, CP, Sotoodehnia, N, Norris, JM, O'Connell, JR, Palmer, ND, Perls, T, Pedersen, NL, Peters, A, Peyser, PA, Poulter, N, Raffel, LJ, Raitakari, OT, Roll, K, Rose, LM, Rosendaal, FR, Rotter, JI, Schmidt, CO, Schreiner, PJ, Schupf, N, Scott, WR, Sever, PS, Shi, Y, Sidney, S, Sims, M, Sitlani, CM, Smith, JA, Snieder, H, Starr, JM, Strauch, K, Stringham, HM, Tan, NYQ, Tang, H, Taylor, KD, Teo, YY, Tham, YC, Turner, ST, Uitterlinden, André, Vollenweider, P, Waldenberger, M, Wang, LH, Wang, YX, Wei, W, Williams, C, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, Chambers, JC, Deary, IJ, Esko, T, Farrall, M, Franks, PW, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Jonas, JB, Kamatani, Y, Kato, N, Kooner, JS, Kutalik, Z, Laakso, M, Laurie, CC, Leander, K, Lehtimaki, T, Study, LC, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Poiasek, O, Porteous, DJ, Rauramaa, R, Samani, NJ, Scott, J, Shu, XO, van der Harst, P, Wagenknecht, LE, Wareham, NJ, Watkins, H, Weir, DR, Wickremasinghe, AR, Wu, TC, Zheng, W, Bouchard, C, Christensen, K, Evans, MK, Gudnason, V, Horta, BL, Kardia, SLR, Liu, YM, Pereira, AC, Psaty, BM, Ridker, PM, van Dam, RM, Gauderman, WJ, Zhu, XF, Mook, Dennis, Fornage, M, Rotimi, CN, Cupples, LA, Kelly, TN, Fox, ER, Hayward, C, Duijn, Cornelia, Tai, ES, Wong, TY, Kooperberg, C, Palmas, W, Rice, K, Morrison, AC, Elliott, P, Caulfield, MJ, Munroe, PB, Rao, DC, Province, MA, and Levy, D

Published
2018

31. Circulating inflammatory biomarkers in relation to brain structural measurements in a non-demented elderly population

Author

Gu, Y. Vorburger, R. Scarmeas, N. Luchsinger, J.A. Manly, J.J. Schupf, N. Mayeux, R. Brickman, A.M.

Abstract

The aim of this investigation was to determine whether circulating inflammatory biomarkers c-reactive protein (CRP), interleukin-6 (IL6), and alpha 1-antichymotrypsin (ACT) were related to structural brain measures assessed by magnetic resonance imaging (MRI). High-resolution structural MRI was collected on 680 non-demented elderly (mean age 80.1 years) participants of a community-based, multiethnic cohort. Approximately three quarters of these participants also had peripheral inflammatory biomarkers (CRP, IL6, and ACT) measured using ELISA. Structural measures including brain volumes and cortical thickness (with both global and regional measures) were derived from MRI scans, and repeated MRI measures were obtained after 4.5 years. Mean fractional anisotropy was used as the indicator of white matter integrity assessed with diffusion tensor imaging. We examined the association of inflammatory biomarkers with brain volume, cortical thickness, and white matter integrity using regression models adjusted for age, gender, ethnicity, education, APOE genotype, and intracranial volume. A doubling in CRP (b = −2.48, p = 0.002) was associated with a smaller total gray matter volume, equivalent to approximately 1.5 years of aging. A doubling in IL6 was associated with smaller total brain volume (b = −14.96, p

Published
2017

32. Self-reported sleep disordered breathing as risk factor for mortality in the elderly

Author

Tsapanou, A. Gu, Y. O'Shea, D. Manly, J. Schupf, N. Scarmeas, N. Stern, Y.

Abstract

Background This study aimed to examine the association between self-reported sleep disordered breathing (SDB) ("awaken short of breath or with a headache") and mortality in a large and ethnically diverse group of community-dwelling elderly people. Methods A total of 1288 participants, 65 years and older, were examined longitudinally. Sleep problems were estimated using the Medical Outcomes Study Sleep Scale examining sleep disturbance, snoring, awaken short of breath or with a headache, sleep adequacy, and sleep somnolence. Cox regression analysis was used to examine the association between sleep problems and mortality. Age, gender, education, ethnicity, and body mass index were included as covariates. In further analyses we included hypertension, diabetes, heart disease, and stroke as additional covariates. Results The participants were followed for up to 6 years (mean = 2.9, standard deviation = 1.1), and 239 (18.6%) participants died during the follow-up. In unadjusted models, SDB at the initial visit was associated with mortality (hazard ratio [HR] = 1.37; 95% confidence interval [CI] 1.21-1.55; P

Published
2016

33. Daytime somnolence as an early sign of cognitive decline in a community-based study of older people

Author

Tsapanou, A. Gu, Y. O'Shea, D. Eich, T. Tang, M.-X. Schupf, N. Manly, J. Zimmerman, M. Scarmeas, N. Stern, Y.

Abstract

Objective This study aimed to examine the association between self-reported sleep problems and cognitive decline in community-dwelling older people. We hypothesized that daytime somnolence predicts subsequent cognitive decline. Methods This is a longitudinal study in a 3.2-year follow-up, with 18-month intervals. The setting is the Washington Heights-Inwood Community Aging Project. There were 1098 participants, who were over 65 years old and recruited from the community. Sleep problems were estimated using five sleep categories derived from the RAND Medical Outcome Study Sleep Scale: sleep disturbance, snoring, awaken short of breath/with a headache, sleep adequacy, and daytime somnolence. Four distinct cognitive composite scores were calculated: memory, language, speed of processing, and executive functioning. We used generalized estimating equations analyses with cognitive scores as the outcome, and time, sleep categories and their interactions as the main predictors. Models were initially unadjusted and then adjusted for age, gender, education, ethnicity, depression, and apolipoprotein E-ε4 genotype. Results Increased daytime somnolence (including feeling drowsy/sleepy, having trouble staying awake, and taking naps during the day) was linked to slower speed of processing both cross-sectionally (B = -0.143, p = 0.047) and longitudinally (B = -0.003, p = 0.027). After excluding the demented participants at baseline, the results remained significant (B = -0.003, p = 0.021). Conclusions Our findings suggest that daytime somnolence may be an early sign of cognitive decline in the older population. Copyright © 2015 John Wiley & Sons, Ltd.

Published
2016

35. The Prevalence of Mild Cognitive Impairment in Diverse Geographical and Ethnocultural Regions: The COSMIC Collaboration

Author

Sachdev, P.S., Lipnicki, D.M., Kochan, N.A., Crawford, J.D., Thalamuthu, A., Andrews, G., Brayne, C., Matthews, F.E., Stephan, B.C.M., Lipton, R.B., Katz, M.J., Ritchie, K., Carrière, I., Ancelin, M.L, Lam, L.C.W., Wong, C.H.Y., Fung, A.W.T., Guaita, A., Vaccaro, R., Davin, A., Ganguli, M., Dodge, H., Hughes, T., Anstey, K.J., Cherbuin, N., Butterworth, P., Ng, T.P., Gao, Q., Reppermund, S., Brodaty, H., Schupf, N., Manly, J., Stern, Y., Lobo, A., Lopez-Anton, R., Santabárbara, J., Zimmerman, M., Derby, C., Leung, G.T.Y., Chan, W.C., Polito, L., Abbondanza, S., Valle, E., Colombo, M., Vitali, S.F., Fossi, S., Zaccaria, D., Forloni, G., Villani, S., Christensen, H., MacKinnon, A., Easteal, S., Jacomb, T., Maxwell, K., Bowman, A., Burns, K., Broe, A., Dekker, J., Dooley, L., De Permentier, M., Fairjones, S., Fletcher, J., French, T., Foster, C., Nugent-Cleary-Fox, E., Gooi, C., Harvey, E., Helyer, R., Hsieh, S., Hughes, L., Jacek, S., Johnston, M., McCade, D., Meeth, S., Milne, E., Moir, A., O'Grady, R., Pfaeffli, K., Pose, C., Reuser, L., Rose, A., Schofield, P., Shahnawaz, Z., Sharpley, A., Thompson, C., Queisser, W., Wong, S., Mayeux, R., Brickman, A., Luchsinger, J., Sanchez, D., Tang, M.X., Andrews, H., Marcos, G., De-La-Cámara, C., Saz, P., Ventura, T., Quintanilla, M.A., Lobo, E., University of South Wales (USW), University of Cambridge [UK] (CAM), Newcastle University [Newcastle], Albert Einstein College of Medicine [New York], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Imperial College London, The Chinese University of Hong Kong [Hong Kong], Tai Po Hospital, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Neurology, Oregon Health and Science University [Portland] (OHSU), University of Michigan [Ann Arbor], University of Michigan System, Australian National University (ANU), National University of Singapore (NUS), University of New South Wales [Sydney] (UNSW), Columbia University [New York], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Zaragoza - Universidad de Zaragoza [Zaragoza], and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Gerontology, Male, medicine.medical_specialty, Asia, Epidemiology, Cross-sectional study, Clinical Dementia Rating, lcsh:Medicine, Neuropsychological Tests, Prevalence, Medicine, Dementia, Humans, Cognitive Dysfunction, Longitudinal Studies, Cooperative Behavior, lcsh:Science, Cognitive impairment, Aged, Aged, 80 and over, Multidisciplinary, business.industry, FOS: Clinical medicine, lcsh:R, Neurosciences, Australia, Mild cognitive impairment, Cognition, Middle Aged, medicine.disease, Europe, Cross-Sectional Studies, Disease Progression, lcsh:Q, Mental health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Cooperative behavior, Alzheimer's disease, business, Demography
Abstract

International audience; BACKGROUND : Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI).METHODS : Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment.RESULTS : The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01).CONCLUSION : Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

Published
2015
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36. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Author

Mace, A. (Aurelien), Tuke, M.A. (Marcus A.), Deelen, P. (Patrick), Kristiansson, K. (Kati), Mattsson, H. (Hannele), Nõukas, M. (Margit), Sapkota, Y. (Yadav), Schick, U.M. (Ursula), Porcu, E. (Eleonora), Rüeger, S. (Sina), McDaid, A.F. (Aaron F.), Porteous, D.J. (David J.), Winkler, T.W. (Thomas W.), Salvi, E. (Erika), Shrine, N.R.G. (Nick), Liu, X. (Xueping), Ang, W.Q. (Wei), Zhang, W. (Weihua), Feitosa, M.F., Venturini, C. (Cristina), Most, P.J. (Peter) van der, Rosengren, A. (Anders), Wood, A.R. (Andrew), Beaumont, R.N. (Robin N.), Jones, S.E. (Samuel E.), Ruth, K.S. (Katherine S.), Yaghootkar, H. (Hanieh), Tyrrell, A.W.R., Havulinna, A.S. (Aki), Boers, H. (Harmen), Mägi, R. (Reedik), Kriebel, J. (Jennifer), Müller-Nurasyid, M. (Martina), Perola, M. (Markus), Nieminen, M.S. (Markku), Lokki, M.L., Kähönen, M. (Mika), Viikari, J. (Jorma), Geller, F. (Frank), Lahti, J., Palotie, A. (Aarno), Koponen, P. (Päivikki), Lundqvist, A. (Annamari), Rissanen, H. (Harri), Bottinger, E.P. (Erwin), Afaq, S. (Saima), Wojczynski, M.K. (Mary ), Lenzini, P. (Petra), Nolte, I.M. (Ilja), Sparsø, T. (Thomas), Schupf, N. (Nicole), Christensen, K. (Kaare), Perls, T.T. (Thomas T.), Newman, A.B. (Anne B.), Werge, T.M. (Thomas), Snieder, H. (Harold), Spector, T.D. (Timothy), Chambers, J.C. (John C.), Koskinen, S. (Seppo), Melbye, M. (Mads), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Tobin, M.D. (Martin), Wain, L.V. (Louise V.), Sinisalo, J. (Juha), Peters, A. (Annette), Meitinger, T. (Thomas), Martin, N.G. (Nicholas), Wray, N.R. (Naomi), Montgomery, G.W. (Grant W.), Medland, S.E. (Sarah), Swertz, M.A. (Morris A.), Vartiainen, E. (Erkki), Borodulin, K. (Katja), Männistö, S. (Satu), Murray, A. (Anna), Bochud, M. (Murielle), Jacquemont, S. (Sébastien), Rivadeneira, F. (Fernando), Hansen, T. (Thomas), Oldehinkel, A.J. (Albertine), Mangino, M. (Massimo), Province, M.A. (Mike), Deloukas, P. (Panos), Kooner, J.S. (Jaspal S.), Freathy, R.M. (Rachel), Pennell, C.E. (Craig), Feenstra, B. (Bjarke), Strachan, D.P. (David), Lettre, G. (Guillaume), Hirschhorn, J.N. (Joel), Cusi, D. (Daniele), Heid, I.M. (Iris), Hayward, C. (Caroline), Männik, K. (Katrin), Beckmann, J.S. (Jacques), Loos, R.J.F. (Ruth), Nyholt, D.R. (Dale), Metspalu, A. (Andres), Hagen, K. (Knut), Weedon, M.N. (Michael), Salomaa, V. (Veikko), Franke, L. (Lude), Reymond, A. (Alexandre), Frayling, T.M. (Timothy M.), Kutalik, Z. (Zoltán), Mace, A. (Aurelien), Tuke, M.A. (Marcus A.), Deelen, P. (Patrick), Kristiansson, K. (Kati), Mattsson, H. (Hannele), Nõukas, M. (Margit), Sapkota, Y. (Yadav), Schick, U.M. (Ursula), Porcu, E. (Eleonora), Rüeger, S. (Sina), McDaid, A.F. (Aaron F.), Porteous, D.J. (David J.), Winkler, T.W. (Thomas W.), Salvi, E. (Erika), Shrine, N.R.G. (Nick), Liu, X. (Xueping), Ang, W.Q. (Wei), Zhang, W. (Weihua), Feitosa, M.F., Venturini, C. (Cristina), Most, P.J. (Peter) van der, Rosengren, A. (Anders), Wood, A.R. (Andrew), Beaumont, R.N. (Robin N.), Jones, S.E. (Samuel E.), Ruth, K.S. (Katherine S.), Yaghootkar, H. (Hanieh), Tyrrell, A.W.R., Havulinna, A.S. (Aki), Boers, H. (Harmen), Mägi, R. (Reedik), Kriebel, J. (Jennifer), Müller-Nurasyid, M. (Martina), Perola, M. (Markus), Nieminen, M.S. (Markku), Lokki, M.L., Kähönen, M. (Mika), Viikari, J. (Jorma), Geller, F. (Frank), Lahti, J., Palotie, A. (Aarno), Koponen, P. (Päivikki), Lundqvist, A. (Annamari), Rissanen, H. (Harri), Bottinger, E.P. (Erwin), Afaq, S. (Saima), Wojczynski, M.K. (Mary ), Lenzini, P. (Petra), Nolte, I.M. (Ilja), Sparsø, T. (Thomas), Schupf, N. (Nicole), Christensen, K. (Kaare), Perls, T.T. (Thomas T.), Newman, A.B. (Anne B.), Werge, T.M. (Thomas), Snieder, H. (Harold), Spector, T.D. (Timothy), Chambers, J.C. (John C.), Koskinen, S. (Seppo), Melbye, M. (Mads), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Tobin, M.D. (Martin), Wain, L.V. (Louise V.), Sinisalo, J. (Juha), Peters, A. (Annette), Meitinger, T. (Thomas), Martin, N.G. (Nicholas), Wray, N.R. (Naomi), Montgomery, G.W. (Grant W.), Medland, S.E. (Sarah), Swertz, M.A. (Morris A.), Vartiainen, E. (Erkki), Borodulin, K. (Katja), Männistö, S. (Satu), Murray, A. (Anna), Bochud, M. (Murielle), Jacquemont, S. (Sébastien), Rivadeneira, F. (Fernando), Hansen, T. (Thomas), Oldehinkel, A.J. (Albertine), Mangino, M. (Massimo), Province, M.A. (Mike), Deloukas, P. (Panos), Kooner, J.S. (Jaspal S.), Freathy, R.M. (Rachel), Pennell, C.E. (Craig), Feenstra, B. (Bjarke), Strachan, D.P. (David), Lettre, G. (Guillaume), Hirschhorn, J.N. (Joel), Cusi, D. (Daniele), Heid, I.M. (Iris), Hayward, C. (Caroline), Männik, K. (Katrin), Beckmann, J.S. (Jacques), Loos, R.J.F. (Ruth), Nyholt, D.R. (Dale), Metspalu, A. (Andres), Hagen, K. (Knut), Weedon, M.N. (Michael), Salomaa, V. (Veikko), Franke, L. (Lude), Reymond, A. (Alexandre), Frayling, T.M. (Timothy M.), and Kutalik, Z. (Zoltán)

Abstract

There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increa

Published
2017
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38. Data from a cross-sectional study on Apolipoprotein E (APOE-ε4) and snoring/sleep apnea in non-demented older adults

Author

Tsapanou, A. Scarmeas, N. Gu, Y. Manly, J. Schupf, N. Stern, Y. Barral, S.

Abstract

In the present data, we provide the details of the cross-sectional study, from the Washington Heights-Inwood Community Aging Project (WHICAP) that examined the association between Apolipoprotein E (APOE-ε4) and snoring/sleep apnea. A total of 1944 non-demented older adults constituted our sample. Sleep dysfunction was measured using sleep categories derived from the Medical Outcomes Study Sleep Scale. Stratified analyses were conducted in order to examine the association between APOE-ε4 and sleep variables by ethnic group. For further analyses and enhanced discussion, see ". Examining the association between Apolipoprotein E (APOE) and self-reported sleep disturbances in non-demented older adults" by Tsapanou et al. (2015) [1]. © 2015 The Authors.

Published
2015

39. Mediterranean diet and brain structure in a multiethnic elderly cohort

Author

Gu, Y. Brickman, A.M. Stern, Y. Habeck, C.G. Razlighi, Q.R. Luchsinger, J.A. Manly, J.J. Schupf, N. Mayeux, R. Scarmeas, N.

Abstract

Objective: To determine whether higher adherence to a Mediterranean-type diet (MeDi) is related with larger MRI-measured brain volume or cortical thickness. Methods: In this cross-sectional study, high-resolution structural MRI was collected on 674 elderly (mean age 80.1 years) adults without dementia who participated in a community-based, multiethnic cohort. Dietary information was collected via a food frequency questionnaire. Total brain volume (TBV), total gray matter volume (TGMV), total white matter volume (TWMV), mean cortical thickness (mCT), and regional volume or CT were derived from MRI scans using FreeSurfer program. We examined the association of MeDi (scored as 0-9) and individual food groups with brain volume and thickness using regression models adjusted for age, sex, ethnicity, education, body mass index, diabetes, and cognition. Results: Compared to lower MeDi adherence (0-4), higher adherence (5-9) was associated with 13.11 (p 5 0.007), 5.00 (p 5 0.05), and 6.41 (p 5 0.05) milliliter larger TBV, TGMV, and TWMV, respectively. Higher fish (b57.06, p 50.006) and lower meat (b 58.42, p50.002) intakes were associated with larger TGMV. Lower meat intake was also associated with larger TBV (b 5 12.20, p 5 0.02). Higher fish intake was associated with 0.019 mm (p 5 0.03) larger mCT. Volumes of cingulate cortex, parietal lobe, temporal lobe, and hippocampus and CT of the superior-frontal region were associated with the dietary factors. Conclusions: Among older adults,MeDi adherence was associated with less brain atrophy, with an effect similar to 5 years of aging. Higher fish and lower meat intake might be the 2 key food elements that contribute to the benefits of MeDi on brain structure. © 2015 American Academy of Neurology.

Published
2015

40. Examining the association between Apolipoprotein E (APOE) and self-reported sleep disturbances in non-demented older adults

Author

Tsapanou, A. Scarmeas, N. Gu, Y. Manly, J. Schupf, N. Stern, Y. Barral, S.

Abstract

We aimed to examine the association between Apolipoprotein E (APOE) and sleep disturbances. This is a cross-sectional study, from the Washington Heights-Inwood Community Aging Project (WHICAP). A total of 1944 non-demented older adults took part in the study. Sleep dysfunction was measured using sleep categories derived from the Medical Outcomes Study Sleep Scale. Genetic association between APOE-ε4 genotype and sleep disturbances was assessed using unadjusted linear regression models. Secondary analyses were conducted adjusting for age, sex, education, ethnicity and body mass index (BMI). In the unadjusted model, individuals carrying the APOE-ε4 allele showed lower levels of snoring (β = -0.02, SE = 0.01, p = 0.010) and sleep apnea (β = -0.01, SE = 0.01, p = 0.037) when compared to non-ε4 carriers. After covariates' adjustment, ε4 carriers demonstrated stronger association with lower levels of both snoring (β = -0.02, SE = 0.01, p = 0.006), and sleep apnea (β = -0.01, SE = 0.01, p = 0.018). Our results suggest that APOE-ε4 is associated with decreased problems in snoring and sleep apnea, in non-demented older adults. © 2015 Elsevier Ireland Ltd.

Published
2015

41. Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population

Author

Gu, Y. Honig, L.S. Schupf, N. Lee, J.H. Luchsinger, J.A. Stern, Y. Scarmeas, N.

Abstract

Leukocyte telomere length (LTL) is considered as the marker of biological aging and may be related to environmental factors. The current study aimed to examine the relation between Mediterranean-type diet and LTL. We used a cross-sectional study of 1743 multi-ethnic community residents of New York aged 65 years or older. Mediterranean-type diet (MeDi) was calculated from dietary information collected using a food frequency questionnaire. LTL was measured from leukocyte DNA using a real-time PCR method to measure T/S ratio, the ratio of telomere (T) to single-copy gene (S) sequence. Regression analysis showed that the MeDi score was not associated with LTL in the overall study population (β = 12.5; p = 0.32) after adjusting for age, sex, education, ethnicity, caloric intake, smoking, and physical and leisure activities. However, we found a significant association between MeDi and LTL among non-Hispanic whites (β = 48.3; p = 0.05), and the results held after excluding dementia subjects (β = 49.6; p = 0.05). We further found that, in the whole population, vegetable and cereal consumption above the sex-specific population median was associated with longer LTL (β = 89.1, p = 0.04) and shorter LTL (β = −93.5; p = 0.03), respectively. Among non-Hispanic whites, intake of meat or dairy below sex-specific population medians was associated with longer LTL (β = 154.7, p = 0.05; β = 240.5, p < 0.001, respectively). We found that higher adherence to a MeDi was associated with longer LTL among whites but not among African Americans and Hispanics. Additionally, a diet high in vegetables but low in cereal, meat, and dairy might be associated with longer LTL among healthy elderly. © 2015, American Aging Association.

Published
2015

43. Alcohol intake and brain structure in a multiethnic elderly cohort

Author

Gu, Y. Scarmeas, N. Short, E.E. Luchsinger, J.A. DeCarli, C. Stern, Y. Manly, J.J. Schupf, N. Mayeux, R. Brickman, A.M.

Abstract

Background & aims: Evidence suggests that consuming light-to-moderate amounts of alcohol reduces the risk of dementia and is associated better cognitive function and less cardiovascular disease, relative to those consuming no or heavy alcohol. There are only minimal data on the association between alcohol and brain magnetic resonance imaging (MRI) markers. This study aimed to examine the association between alcohol and brain structure measured with MRI. Methods: In this cross-sectional study, high-resolution structural MRI was collected on 589 multi-ethnic community residents of New York aged ≥65 with available alcohol intake assessments via a food frequency questionnaire. Total brain volume (TBV), white matter hyperintensity volume (WMHV), and presence of infarcts were derived from MRI scans with established methods. We examined the association of alcohol intake with these imaging markers using regression models adjusted for demographic, clinical, and vascular risk factors. Results: Compared to non-drinking, light-to-moderate total alcohol (b=0.007, p=0.04) or wine (b=0.008, p=0.05) intake, but not beer or liquor intake, was associated with larger TBV. Further analysis showed a dose-response association between alcohol (p-trend=0.03) or wine (p-trend=0.006)and TBV. Overall, alcohol intake was not associated with WMHV or brain infarcts. Conclusions: Our study suggests that among older adults in the community, light-to-moderate alcohol intake, in particular wine, is associated with larger TBV. These findings suggest that light to moderate alcohol consumption is potentially beneficial for brain aging, but replication is needed. © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Published
2014

44. Serum IgG antibody levels to periodontal microbiota are associated with incident alzheimer disease

Author

Noble, J.M. Scarmeas, N. Celenti, R.S. Elkind, M.S.V. Wright, C.B. Schupf, N. Papapanou, P.N.

Abstract

Background: Periodontitis and Alzheimer disease (AD) are associated with systemic inflammation. This research studied serum IgG to periodontal microbiota as possible predictors of incident AD. Methods: Using a case-cohort study design, 219 subjects (110 incident AD cases and 109 controls without incident cognitive impairment at last follow-up), matched on race-ethnicity, were drawn from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a cohort of longitudinally followed northern Manhattan residents aged >65 years. Mean follow-up was five years (SD 2.6). In baseline sera, serum IgG levels were determined for bacteria known to be positively or negatively associated with periodontitis (Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans Y4, Treponema denticola, Campylobacter rectus, Eubacterium nodatum, and Actinomyces naeslundii genospecies-2). In all analyses, we used antibody threshold levels shown to correlate with presence of moderate-severe periodontitis. Results: Mean age was 72 years (SD 6.9) for controls, and 79 years (SD 4.6) for cases (p640 ng/ml, present in 10% of subjects) was associated with increased risk of AD (HR=2.0, 95%CI: 1.1-3.8). This association was stronger after adjusting for other significant titers (HR=3.1, 95%CI: 1.5-6.4). In this model, high anti-E. nodatum IgG (>1755 ng/ml; 19% of subjects) was associated with lower risk of AD (HR=0.5, 95%CI: 0.2-0.9). Conclusions: Serum IgG levels to common periodontal microbiota are associated with risk for developing incident AD. © 2014 Noble et al.

Published
2014

46. The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: The COSMIC Collaboration

Author

Sachdev, PS, Lipnicki, DM, Kochan, NA, Crawford, JD, Thalamuthu, A, Andrews, G, Brayne, C, Matthews, FE, Stephan, BCM, Lipton, RB, Katz, MJ, Ritchie, K, Carrière, I, Ancelin, ML, Lam, LCW, Wong, CHY, Fung, AWT, Guaita, A, Vaccaro, R, Davin, A, Ganguli, M, Dodge, H, Hughes, T, Anstey, KJ, Cherbuin, N, Butterworth, P, Ng, TP, Gao, Q, Reppermund, S, Brodaty, H, Schupf, N, Manly, J, Stern, Y, Lobo, A, Lopez-Anton, R, Santabárbara, J, Zimmerman, M, Derby, C, Leung, GTY, Chan, WC, Polito, L, Abbondanza, S, Valle, E, Colombo, M, Vitali, SF, Fossi, S, Zaccaria, D, Forloni, G, Villani, S, Christensen, H, MacKinnon, A, Easteal, S, Jacomb, T, Maxwell, K, Bowman, A, Burns, K, Broe, A, Dekker, J, Dooley, L, De Permentier, M, Fairjones, S, Fletcher, J, French, T, Foster, C, Nugent-Cleary-Fox, E, Gooi, C, Harvey, E, Helyer, R, Hsieh, S, Hughes, L, Jacek, S, Johnston, M, McCade, D, Meeth, S, Milne, E, Moir, A, O'Grady, R, Pfaeffli, K, Pose, C, Reuser, L, Rose, A, Schofield, P, Shahnawaz, Z, Sharpley, A, Thompson, C, Queisser, W, Wong, S, Mayeux, R, Brickman, A, Luchsinger, J, Sanchez, D, Tang, MX, Andrews, H, Marcos, G, De-La-Cámara, C, Saz, P, Ventura, T, Quintanilla, MA, Lobo, E, Sachdev, PS, Lipnicki, DM, Kochan, NA, Crawford, JD, Thalamuthu, A, Andrews, G, Brayne, C, Matthews, FE, Stephan, BCM, Lipton, RB, Katz, MJ, Ritchie, K, Carrière, I, Ancelin, ML, Lam, LCW, Wong, CHY, Fung, AWT, Guaita, A, Vaccaro, R, Davin, A, Ganguli, M, Dodge, H, Hughes, T, Anstey, KJ, Cherbuin, N, Butterworth, P, Ng, TP, Gao, Q, Reppermund, S, Brodaty, H, Schupf, N, Manly, J, Stern, Y, Lobo, A, Lopez-Anton, R, Santabárbara, J, Zimmerman, M, Derby, C, Leung, GTY, Chan, WC, Polito, L, Abbondanza, S, Valle, E, Colombo, M, Vitali, SF, Fossi, S, Zaccaria, D, Forloni, G, Villani, S, Christensen, H, MacKinnon, A, Easteal, S, Jacomb, T, Maxwell, K, Bowman, A, Burns, K, Broe, A, Dekker, J, Dooley, L, De Permentier, M, Fairjones, S, Fletcher, J, French, T, Foster, C, Nugent-Cleary-Fox, E, Gooi, C, Harvey, E, Helyer, R, Hsieh, S, Hughes, L, Jacek, S, Johnston, M, McCade, D, Meeth, S, Milne, E, Moir, A, O'Grady, R, Pfaeffli, K, Pose, C, Reuser, L, Rose, A, Schofield, P, Shahnawaz, Z, Sharpley, A, Thompson, C, Queisser, W, Wong, S, Mayeux, R, Brickman, A, Luchsinger, J, Sanchez, D, Tang, MX, Andrews, H, Marcos, G, De-La-Cámara, C, Saz, P, Ventura, T, Quintanilla, MA, and Lobo, E

Abstract

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

Published
2015

47. Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research

Author

O'Bryant, SE, Gupta, V, Henriksen, K, Edwards, M, Jeromin, A, Lista, S, Bazenet, C, Soares, H, Lovestone, S, Hampel, H, Montine, T, Blennow, K, Foroud, T, Carrillo, M, Graff-Radford, N, Laske, C, Breteler, M, Shaw, L, Trojanowski, JQ, Schupf, N, Rissman, RA, Fagan, AM, Oberoi, P, Umek, R, Weiner, MW, Grammas, P, Posner, H, Martins, R, O'Bryant, SE, Gupta, V, Henriksen, K, Edwards, M, Jeromin, A, Lista, S, Bazenet, C, Soares, H, Lovestone, S, Hampel, H, Montine, T, Blennow, K, Foroud, T, Carrillo, M, Graff-Radford, N, Laske, C, Breteler, M, Shaw, L, Trojanowski, JQ, Schupf, N, Rissman, RA, Fagan, AM, Oberoi, P, Umek, R, Weiner, MW, Grammas, P, Posner, H, and Martins, R

Published
2015

48. The Prevalence of Mild Cognitive Impairment in Diverse Geographical and Ethnocultural Regions: The COSMIC Collaboration

Author

Arendt, T, Sachdev, PS, Lipnicki, DM, Kochan, NA, Crawford, JD, Thalamuthu, A, Andrews, G, Brayne, C, Matthews, FE, Stephan, BCM, Lipton, RB, Katz, MJ, Ritchie, K, Carriere, I, Ancelin, M-L, Lam, LCW, Wong, CHY, Fung, AWT, Guaita, A, Vaccaro, R, Davin, A, Ganguli, M, Dodge, H, Hughes, T, Anstey, KJ, Cherbuin, N, Butterworth, P, Ng, TP, Gao, Q, Reppermund, S, Brodaty, H, Schupf, N, Manly, J, Stern, Y, Lobo, A, Lopez-Anton, R, Santabarbara, J, Arendt, T, Sachdev, PS, Lipnicki, DM, Kochan, NA, Crawford, JD, Thalamuthu, A, Andrews, G, Brayne, C, Matthews, FE, Stephan, BCM, Lipton, RB, Katz, MJ, Ritchie, K, Carriere, I, Ancelin, M-L, Lam, LCW, Wong, CHY, Fung, AWT, Guaita, A, Vaccaro, R, Davin, A, Ganguli, M, Dodge, H, Hughes, T, Anstey, KJ, Cherbuin, N, Butterworth, P, Ng, TP, Gao, Q, Reppermund, S, Brodaty, H, Schupf, N, Manly, J, Stern, Y, Lobo, A, Lopez-Anton, R, and Santabarbara, J

Abstract

BACKGROUND: Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). METHODS: Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. RESULTS: The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). CONCLUSION: Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

Published
2015

50. Plasma Amyloid β predicts cognitive decline

Author

Cosentino, S., Stern, Y., Sokolov, E., Scarmeas, N., Manly, J., Tang, M.X., Schupf, N., and Mayeux, R.

Subjects
Aged, 80 and over, Male, Amyloid beta-Peptides, Genotype, Enzyme-Linked Immunosorbent Assay, Article, Community Health Planning, Peptide Fragments, Apolipoproteins E, Humans, Female, Longitudinal Studies, Cognition Disorders, Aged
Abstract

To determine if plasma β-amyloid (Aβ) levels (1) can be linked to specific cognitive changes that constitute conversion to Alzheimer disease (AD) and (2) correspond to cognitive change independent of dementia.Longitudinal study including 3 visits during approximately 4¹/₂ years (2000-2006).Northern Manhattan community.Eight hundred eighty individuals from a population-based and ethnically diverse sample who had 2 plasma Aβ measurements and were dementia free at the time of the first Aβ sample; 481 remained cognitively healthy, 329 were cognitively or functionally impaired but not demented at any point, and 70 developed AD.General estimating equations tested the association between plasma Aβ (baseline and change in values) and cognitive change (composite score and memory, language, and visuospatial indices).High baseline plasma Aβ42 (P = .01) and Aβ40 (P = .01) and decreasing/relatively stable Aβ42 (P = .01) values were associated with faster decline in multiple cognitive domains. In those who remained cognitively healthy, high baseline plasma Aβ42 (P = .01) and decreasing/relatively stable plasma Aβ42 (P = .01) was associated with faster cognitive decline, primarily in memory.The association between plasma Aβ and multiple aspects of cognition more clearly specifies the previously documented downward trajectory of plasma Aβ with AD onset. The predominant association with memory seen only in healthy elderly individuals also suggests that plasma Aβ is linked with even earlier neurologic changes that may or may not culminate in dementia.

Published
2010

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