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1. Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Author

Boen, R, Kaufmann, T, van der Meer, D, Frei, O, Agartz, I, Ames, D, Andersson, M, Armstrong, NJ, Artiges, E, Atkins, JR, Bauer, J, Benedetti, F, Boomsma, DI, Brodaty, H, Brosch, K, Buckner, RL, Cairns, MJ, Calhoun, V, Caspers, S, Cichon, S, Corvin, AP, Crespo-Facorro, B, Dannlowski, U, David, FS, de Geus, EJC, de Zubicaray, GI, Desrivieres, S, Doherty, JL, Donohoe, G, Ehrlich, S, Eising, E, Espeseth, T, Fisher, SE, Forstner, AJ, Fortaner-Uya, L, Frouin, V, Fukunaga, M, Ge, T, Glahn, DC, Goltermann, J, Grabe, HJ, Green, MJ, Groenewold, NA, Grotegerd, D, Grontvedt, GR, Hahn, T, Hashimoto, R, Hehir-Kwa, JY, Henskens, FA, Holmes, AJ, Haberg, AK, Haavik, J, Jacquemont, S, Jansen, A, Jockwitz, C, Joensson, EG, Kikuchi, M, Kircher, T, Kumar, K, Le Hellard, S, Leu, C, Linden, DE, Liu, J, Loughnan, R, Mather, KA, Mcmahon, KL, Mcrae, AF, Medland, SE, Meinert, S, Moreau, CA, Morris, DW, Mowry, BJ, Muehleisen, TW, Nenadic, I, Noethen, MM, Nyberg, L, Ophoff, RA, Owen, MJ, Pantelis, C, Paolini, M, Paus, T, Pausova, Z, Persson, K, Quide, Y, Marques, TR, Sachdev, PS, Sando, SB, Schall, U, Scott, RJ, Selbaek, G, Shumskaya, E, Silva, AI, Sisodiya, SM, Stein, F, Stein, DJ, Straube, B, Streit, F, Strike, LT, Teumer, A, Teutenberg, L, Thalamuthu, A, Tooney, PA, Tordesillas-Gutierrez, D, Trollor, JN, Van't Ent, D, van den Bree, MBM, van Haren, NEM, Vazquez-Bourgon, J, Voelzke, H, Wen, W, Wittfeld, K, Ching, CRK, Westlye, LT, Thompson, PM, Bearden, CE, Selmer, KK, Alnaes, D, Andreassen, OA, Sonderby, IE, Boen, R, Kaufmann, T, van der Meer, D, Frei, O, Agartz, I, Ames, D, Andersson, M, Armstrong, NJ, Artiges, E, Atkins, JR, Bauer, J, Benedetti, F, Boomsma, DI, Brodaty, H, Brosch, K, Buckner, RL, Cairns, MJ, Calhoun, V, Caspers, S, Cichon, S, Corvin, AP, Crespo-Facorro, B, Dannlowski, U, David, FS, de Geus, EJC, de Zubicaray, GI, Desrivieres, S, Doherty, JL, Donohoe, G, Ehrlich, S, Eising, E, Espeseth, T, Fisher, SE, Forstner, AJ, Fortaner-Uya, L, Frouin, V, Fukunaga, M, Ge, T, Glahn, DC, Goltermann, J, Grabe, HJ, Green, MJ, Groenewold, NA, Grotegerd, D, Grontvedt, GR, Hahn, T, Hashimoto, R, Hehir-Kwa, JY, Henskens, FA, Holmes, AJ, Haberg, AK, Haavik, J, Jacquemont, S, Jansen, A, Jockwitz, C, Joensson, EG, Kikuchi, M, Kircher, T, Kumar, K, Le Hellard, S, Leu, C, Linden, DE, Liu, J, Loughnan, R, Mather, KA, Mcmahon, KL, Mcrae, AF, Medland, SE, Meinert, S, Moreau, CA, Morris, DW, Mowry, BJ, Muehleisen, TW, Nenadic, I, Noethen, MM, Nyberg, L, Ophoff, RA, Owen, MJ, Pantelis, C, Paolini, M, Paus, T, Pausova, Z, Persson, K, Quide, Y, Marques, TR, Sachdev, PS, Sando, SB, Schall, U, Scott, RJ, Selbaek, G, Shumskaya, E, Silva, AI, Sisodiya, SM, Stein, F, Stein, DJ, Straube, B, Streit, F, Strike, LT, Teumer, A, Teutenberg, L, Thalamuthu, A, Tooney, PA, Tordesillas-Gutierrez, D, Trollor, JN, Van't Ent, D, van den Bree, MBM, van Haren, NEM, Vazquez-Bourgon, J, Voelzke, H, Wen, W, Wittfeld, K, Ching, CRK, Westlye, LT, Thompson, PM, Bearden, CE, Selmer, KK, Alnaes, D, Andreassen, OA, and Sonderby, IE

Abstract

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference. RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.

Published
2024

2. Author Correction: Multi-cohort and longitudinal Bayesian clustering study of stage and subtype in Alzheimer's disease.

Author

Poulakis, K, Pereira, JB, Muehlboeck, J-S, Wahlund, L-O, Smedby, Ö, Volpe, G, Masters, CL, Ames, D, Niimi, Y, Iwatsubo, T, Ferreira, D, Westman, E, Japanese Alzheimer’s Disease Neuroimaging Initiative, Australian Imaging, Biomarkers and Lifestyle study, Poulakis, K, Pereira, JB, Muehlboeck, J-S, Wahlund, L-O, Smedby, Ö, Volpe, G, Masters, CL, Ames, D, Niimi, Y, Iwatsubo, T, Ferreira, D, Westman, E, Japanese Alzheimer’s Disease Neuroimaging Initiative, and Australian Imaging, Biomarkers and Lifestyle study

Published
2024

4. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).

Author

Davies, G, Armstrong, N, Bis, JC, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, CA, Kirin, M, Lahti, J, van der Lee, SJ, Le Hellard, S, Liu, T, Marioni, RE, Oldmeadow, C, Postmus, I, Smith, AV, Smith, JA, Thalamuthu, A, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, SE, Hill, WD, Liewald, DC, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, AA, Au, R, Becker, JT, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, BM, Campbell, H, Corley, J, De Jager, PL, Dufouil, C, Eriksson, JG, Espeseth, T, Faul, JD, Ford, I, Generation Scotland, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Heiss, G, Hofman, A, Holliday, EG, Huffman, J, Kardia, SLR, Kochan, N, Knopman, DS, Kwok, JB, Lambert, J-C, Lee, T, Li, G, Li, S-C, Loitfelder, M, Lopez, OL, Lundervold, AJ, Lundqvist, A, Mather, KA, Mirza, SS, Nyberg, L, Oostra, BA, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, BM, Redmond, P, Reppermund, S, Rotter, JI, Schmidt, H, Schuur, M, Schofield, PW, Scott, RJ, Steen, VM, Stott, DJ, van Swieten, JC, Taylor, KD, Trollor, J, Trompet, S, Uitterlinden, AG, Weinstein, G, Widen, E, Windham, BG, Jukema, JW, and Wright, AF

Subjects
Generation Scotland, Humans, Genetic Predisposition to Disease, HMGN1 Protein, Cohort Studies, Cognition, Cognition Disorders, Neuropsychological Tests, Phenotype, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Scotland, Female, Male, Atherosclerosis, Genome-Wide Association Study, and over, Polymorphism, Single Nucleotide, Psychiatry, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Published
2015

8. The ChatGPT Artificial Intelligence Chatbot: How Well Does It Answer Accounting Assessment Questions?

Author

Wood, DA, Achhpilia, MP, Adams, MT, Aghazadeh, S, Akinyele, K, Akpan, M, Allee, KD, Allen, AM, Almer, ED, Ames, D, Arity, V, Barr-Pulliam, D, Basoglu, KA, Belnap, A, Bentley, JW, Berg, T, Berglund, NR, Berry, E, Bhandari, A, Bhuyan, MNH, Black, PW, Blondeel, E, Bond, D, Bonrath, A, Borthick, AF, Boyle, ES, Bradford, M, Brandon, DM, Brazel, JF, Brockbank, BG, Burger, M, Byzalov, D, Cannon, JN, Caro, C, Carr, AH, Cathey, J, Cating, R, Charron, K, Chavez, S, Chen, J, Chen, JC, Chen, JW, Cheng, C, Cheng, X, Christensen, BE, Church, KS, Cicone, NJ, Constance, P, Cooper, LA, Correia, CL, Coyne, J, Cram, WA, Curtis, A, Daigle, RJ, Dannemiller, S, Davenport, SA, Dawson, GS, De Meyst, KJL, Dell, S, Demirkan, S, Denison, CA, Desai, H, DeSimone, S, Diehl, LM, Dimes, R, Dong, B, Donnelly, A, du Pon, A, Duan, HK, Duffey, A, Dunn, RT, Durkin, MP, Dzuranin, AC, Eberle, RM, Ege, MS, El Mahdy, D, Esplin, A, Eulerich, M, Everaert, P, Farah, N, Farish, L, Favere-Marchesi, M, Fayard, D, Filosa, JR, Ford, M, Franz, DR, Fulmer, BP, Fulmer, S, Furner, ZZ, Gantman, S, Garner, S, Garrett, J, Geng, X, Golden, J, Goldman, W, Gomez, J, Gooley, M, Granitto, SP, Green, KY, Greenman, CL, Gupta, G, Guymon, RN, Hale, K, Harper, CJ, Hartt, SA, Hawk, H, Hawkins, SR, Hawkins, EM, Hay, DC, Heinzelmann, R, Henderson, CD, Hendricks, BE, Heninger, WG, Hill, MS, Holden, N, Holderness, DK, Holt, TP, Hoopes, JL, Hsieh, S-F, Huang, F, Huang, H-W, Huang, T-C, Huels, BW, Hunter, K, Hurley, PJ, Inger, K, Islam, S, Ison, I, Issa, H, Jackson, AB, Jackson, SC, Janvrin, DJ, Jimenez, PD, Johanson, D, Judd, JS, Kawada, BS, Kelton, AS, Kern, S, Kerr, JN, Keune, MB, Kim, M, Knox, BD, Kogan, G, Kotb, A, Krane, R, Kremin, J, Krieg, KS, Kugel, J, Kulset, EM, Kuruppu, C, LaDuca, G, Lamberton, BA, Lamboy-Ruiz, MA, Lang, B, Larocque, SA, Larson, MP, Lawson, BP, Lawson, JG, Lee, L, Lenk, MM, Li-Kuehne, M, Liljegren, J, Lin, Y-H, Liu, W-P, Liu, Z, Lock, B, Long, JH, Loraas, T, Lowensohn, S, Loy, TR, Lyngstadaas, H, Maas, W, MacGregor, JE, Madsen, DØ, Malone, CL, Margolin, M, Marshall, ME, Martin, RM, Mpofu, CM, McCoy, C, McGuigan, NC, McSwain, DN, Meckfessel, MD, Mellon, MJ, Melton, OS, Mercado, JM, Mitsuda, S, Modugu, K, Moehrle, S, Chaghervand, AM, Moffitt, K, Moon, JS, Muehlmann, B, Murray, J, Mwaungulu, ES, Myers, N, Naegle, JC, Ndicu, MJ, Nelson, AS, Nguyen, AL, Niederkofler, T, Nikbakht, E, O'Brien, AD, Ogunade, KM, O'Leary, D, Oler, MJ, Oler, DK, Olsen, KJ, Otalor, JI, Outlaw, KW, Ozlanski, ME, Parlier, J, Paterson, JS, Pearson, CA, Petersen, MJ, Petra, ST, Pickard, MD, Pickerd, J, Pinsker, R, Plante, C, Plečnik, JM, Price, RA, Quick, LA, Raedy, J, Raschke, R, Ravenscraft, J, Richardson, V, Rixom, BA, Robertson, JF, Rock, I, Romney, MA, Rozario, A, Ruff, MF, Rupley, K, Saeedi, A, Saiewitz, A, Salzsieder, LW, Sarkar, S, Saulls, M, Scanlan, TA, Schaefer, TJ, Schaupp, D, Schneider, GP, Seebeck, A, Sellers, RD, Seto, SC, Sevel, R-L, Shan, Y, Sherwood, MG, Singorahardjo, M, Skaftadottir, HK, Skomra, J, Smith, JL, Smith, DO, Smith, J, Snow, MC, Sommerfeldt, RD, Sorensen, KB, Sorensen, TL, Spieler, AC, Stallings, MA, Stallings, L, Stancill, A, Stanley, JD, Stefaniak, CM, Stephens, NM, Stewart, BW, Stratopoulos, TC, Street, DA, Subedi, M, Summers, SL, Sundkvist, CH, Synn, C, Tadesse, A, Tapis, GP, Tassin, K, Taylor, S, Teal, M, Teeter, R, Tharapos, M, Theis, JC, Thomas, J, Thompson, KS, Thornock, TA, Tietz, W, Travalent, AM, Trinkle, BS, Truelson, JM, Turner, MC, Vagner, B, Vakilzadeh, H, van der Geest, J, van Pelt, V, Vandervelde, SD, Vega, J, Vera-Muñoz, S, Villanueva, B, Vincent, NE, Wagener, M, Walton, S, Warne, RC, Watanabe, OV, Watson, D, Watson, MW, Weber, J, Weirich, T, West, AN, Wilford, AL, Wilson, AB, Winrow, B, Winrow, T, Winrow, TS, Wiseman, D, Witte, AL, Wood, BD, Wood, J, Woolley, D, Wright, NS, Wu, J, Xiong, X, Yatsenko, D, Yazzie, CE, Young, GM, Zhang, C, Zimmerman, AB, Zoet, E, Wood, DA, Achhpilia, MP, Adams, MT, Aghazadeh, S, Akinyele, K, Akpan, M, Allee, KD, Allen, AM, Almer, ED, Ames, D, Arity, V, Barr-Pulliam, D, Basoglu, KA, Belnap, A, Bentley, JW, Berg, T, Berglund, NR, Berry, E, Bhandari, A, Bhuyan, MNH, Black, PW, Blondeel, E, Bond, D, Bonrath, A, Borthick, AF, Boyle, ES, Bradford, M, Brandon, DM, Brazel, JF, Brockbank, BG, Burger, M, Byzalov, D, Cannon, JN, Caro, C, Carr, AH, Cathey, J, Cating, R, Charron, K, Chavez, S, Chen, J, Chen, JC, Chen, JW, Cheng, C, Cheng, X, Christensen, BE, Church, KS, Cicone, NJ, Constance, P, Cooper, LA, Correia, CL, Coyne, J, Cram, WA, Curtis, A, Daigle, RJ, Dannemiller, S, Davenport, SA, Dawson, GS, De Meyst, KJL, Dell, S, Demirkan, S, Denison, CA, Desai, H, DeSimone, S, Diehl, LM, Dimes, R, Dong, B, Donnelly, A, du Pon, A, Duan, HK, Duffey, A, Dunn, RT, Durkin, MP, Dzuranin, AC, Eberle, RM, Ege, MS, El Mahdy, D, Esplin, A, Eulerich, M, Everaert, P, Farah, N, Farish, L, Favere-Marchesi, M, Fayard, D, Filosa, JR, Ford, M, Franz, DR, Fulmer, BP, Fulmer, S, Furner, ZZ, Gantman, S, Garner, S, Garrett, J, Geng, X, Golden, J, Goldman, W, Gomez, J, Gooley, M, Granitto, SP, Green, KY, Greenman, CL, Gupta, G, Guymon, RN, Hale, K, Harper, CJ, Hartt, SA, Hawk, H, Hawkins, SR, Hawkins, EM, Hay, DC, Heinzelmann, R, Henderson, CD, Hendricks, BE, Heninger, WG, Hill, MS, Holden, N, Holderness, DK, Holt, TP, Hoopes, JL, Hsieh, S-F, Huang, F, Huang, H-W, Huang, T-C, Huels, BW, Hunter, K, Hurley, PJ, Inger, K, Islam, S, Ison, I, Issa, H, Jackson, AB, Jackson, SC, Janvrin, DJ, Jimenez, PD, Johanson, D, Judd, JS, Kawada, BS, Kelton, AS, Kern, S, Kerr, JN, Keune, MB, Kim, M, Knox, BD, Kogan, G, Kotb, A, Krane, R, Kremin, J, Krieg, KS, Kugel, J, Kulset, EM, Kuruppu, C, LaDuca, G, Lamberton, BA, Lamboy-Ruiz, MA, Lang, B, Larocque, SA, Larson, MP, Lawson, BP, Lawson, JG, Lee, L, Lenk, MM, Li-Kuehne, M, Liljegren, J, Lin, Y-H, Liu, W-P, Liu, Z, Lock, B, Long, JH, Loraas, T, Lowensohn, S, Loy, TR, Lyngstadaas, H, Maas, W, MacGregor, JE, Madsen, DØ, Malone, CL, Margolin, M, Marshall, ME, Martin, RM, Mpofu, CM, McCoy, C, McGuigan, NC, McSwain, DN, Meckfessel, MD, Mellon, MJ, Melton, OS, Mercado, JM, Mitsuda, S, Modugu, K, Moehrle, S, Chaghervand, AM, Moffitt, K, Moon, JS, Muehlmann, B, Murray, J, Mwaungulu, ES, Myers, N, Naegle, JC, Ndicu, MJ, Nelson, AS, Nguyen, AL, Niederkofler, T, Nikbakht, E, O'Brien, AD, Ogunade, KM, O'Leary, D, Oler, MJ, Oler, DK, Olsen, KJ, Otalor, JI, Outlaw, KW, Ozlanski, ME, Parlier, J, Paterson, JS, Pearson, CA, Petersen, MJ, Petra, ST, Pickard, MD, Pickerd, J, Pinsker, R, Plante, C, Plečnik, JM, Price, RA, Quick, LA, Raedy, J, Raschke, R, Ravenscraft, J, Richardson, V, Rixom, BA, Robertson, JF, Rock, I, Romney, MA, Rozario, A, Ruff, MF, Rupley, K, Saeedi, A, Saiewitz, A, Salzsieder, LW, Sarkar, S, Saulls, M, Scanlan, TA, Schaefer, TJ, Schaupp, D, Schneider, GP, Seebeck, A, Sellers, RD, Seto, SC, Sevel, R-L, Shan, Y, Sherwood, MG, Singorahardjo, M, Skaftadottir, HK, Skomra, J, Smith, JL, Smith, DO, Smith, J, Snow, MC, Sommerfeldt, RD, Sorensen, KB, Sorensen, TL, Spieler, AC, Stallings, MA, Stallings, L, Stancill, A, Stanley, JD, Stefaniak, CM, Stephens, NM, Stewart, BW, Stratopoulos, TC, Street, DA, Subedi, M, Summers, SL, Sundkvist, CH, Synn, C, Tadesse, A, Tapis, GP, Tassin, K, Taylor, S, Teal, M, Teeter, R, Tharapos, M, Theis, JC, Thomas, J, Thompson, KS, Thornock, TA, Tietz, W, Travalent, AM, Trinkle, BS, Truelson, JM, Turner, MC, Vagner, B, Vakilzadeh, H, van der Geest, J, van Pelt, V, Vandervelde, SD, Vega, J, Vera-Muñoz, S, Villanueva, B, Vincent, NE, Wagener, M, Walton, S, Warne, RC, Watanabe, OV, Watson, D, Watson, MW, Weber, J, Weirich, T, West, AN, Wilford, AL, Wilson, AB, Winrow, B, Winrow, T, Winrow, TS, Wiseman, D, Witte, AL, Wood, BD, Wood, J, Woolley, D, Wright, NS, Wu, J, Xiong, X, Yatsenko, D, Yazzie, CE, Young, GM, Zhang, C, Zimmerman, AB, and Zoet, E

Abstract

ChatGPT, a language-learning model chatbot, has garnered considerable attention for its ability to respond to users’ questions. Using data from 14 countries and 186 institutions, we compare ChatGPT and student performance for 28,085 questions from accounting assessments and textbook test banks. As of January 2023, ChatGPT provides correct answers for 56.5 percent of questions and partially correct answers for an additional 9.4 percent of questions. When considering point values for questions, students significantly outperform ChatGPT with a 76.7 percent average on assessments compared to 47.5 percent for ChatGPT if no partial credit is awarded and 56.5 percent if partial credit is awarded. Still, ChatGPT performs better than the student average for 15.8 percent of assessments when we include partial credit. We provide evidence of how ChatGPT performs on different question types, accounting topics, class levels, open/closed assessments, and test bank questions. We also discuss implications for accounting education and research.

Published
2023

9. High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile

Author

Revelas, M, Thalamuthu, A, Zettergren, A, Oldmeadow, C, Najar, J, Seidu, NM, Armstrong, NJ, Riveros, C, Kwok, JB, Schofield, PR, Trollor, JN, Waern, M, Wright, MJ, Zetterberg, H, Ames, D, Belnnow, K, Brodaty, H, Scott, RJ, Skoog, I, Attia, JR, Sachdev, PS, Mather, KA, Revelas, M, Thalamuthu, A, Zettergren, A, Oldmeadow, C, Najar, J, Seidu, NM, Armstrong, NJ, Riveros, C, Kwok, JB, Schofield, PR, Trollor, JN, Waern, M, Wright, MJ, Zetterberg, H, Ames, D, Belnnow, K, Brodaty, H, Scott, RJ, Skoog, I, Attia, JR, Sachdev, PS, and Mather, KA

Abstract

Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual's polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40-69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55-85 years), Older Australian Twins Study (n = 539, 65-90 years) and Sydney Memory and Ageing Study (n = 925, 70-90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70-93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22-30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 × 10-42) and its components (p < 2.30 × 10-8). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p < 0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity.

Published
2023

10. Genetic and environmental influences on fruit and vegetable consumption and depression in older adults

Author

Matison, APP, Thalamuthu, A, Flood, VMM, Trollor, JNN, Catts, VSS, Wright, MJJ, Ames, D, Brodaty, H, Sachdev, PSS, Reppermund, S, Mather, KAA, Matison, APP, Thalamuthu, A, Flood, VMM, Trollor, JNN, Catts, VSS, Wright, MJJ, Ames, D, Brodaty, H, Sachdev, PSS, Reppermund, S, and Mather, KAA

Abstract

BACKGROUND: Prior work suggests that higher fruit and vegetable consumption may protect against depression in older adults. Better understanding of the influence of genetic and environmental factors on fruit and vegetable intakes may lead to the design of more effective dietary strategies to increase intakes. In turn this may reduce the occurrence of depression in older adults. OBJECTIVES: The primary aim of this study is to estimate the genetic and environmental influences on the consumption of fruit and vegetables in older adults. The secondary aim is an exploratory analysis into possible shared genetic influences on fruit and vegetable intakes and depression. METHODS: Analysis of observational data from 374 twins (67.1% female; 208 monozygotic (MZ); 166 dizygotic (DZ)) aged ≥ 65 years drawn from the Older Australian Twins Study. Dietary data were obtained using a validated food frequency questionnaire and depressive symptoms were measured using the 15-item short form Geriatric Depression Scale. The contribution of genetic and environmental influences on fruit and vegetable intake were estimated by comparing MZ and DZ twin intakes using structural equation modelling. A tri-variate twin model was used to estimate the genetic and environmental correlation between total fruit and vegetable intakes and depression. RESULTS: In this study, vegetable intake was moderately influenced by genetics (0.39 95%CI 0.22, 0.54). Heritability was highest for brassica vegetables (0.40 95%CI 0.24, 0.54). Overall fruit intake was not significantly heritable. No significant genetic correlations were detected between fruit and vegetable intake and depressive symptoms. CONCLUSIONS: Vegetable consumption, particularly bitter tasting brassica vegetables, was significantly influenced by genetics, although environmental influences were also apparent. Consumption of fruit was only influenced by the environment, with no genetic influence detected, suggesting strategies targeting the food envir

Published
2023

11. Study protocol for a randomized controlled trial of telephone-delivered cognitive behavior therapy compared with befriending for treating depression and anxiety in older adults with COPD

Author

Doyle C, Dunt D, Ames D, Fearn M, You E, and Bhar S

Subjects
chronic obstructive pulmonary disease (COPD), depression, anxiety, telephone, cognitive behaviour therapy (CBT), befriending, Diseases of the respiratory system, RC705-779
Abstract

Colleen Doyle,1 David Dunt,2 David Ames,3 Marcia Fearn,3 Emily (Chuanmei) You,1 Sunil Bhar41Australian Catholic University, Melbourne, VIC, Australia; 2Centre for Health Policy, The University of Melbourne, Melbourne, VIC, Australia; 3National Ageing Research Institute, Melbourne, VIC, Australia; 4Department of Psychological Sciences, Swinburne University of Technology, Hawthorn, VIC, AustraliaBackground: COPD is an umbrella term to describe chronic lung diseases that cause limitations in lung airflow, including emphysema and chronic bronchitis. The prevalence of depression and anxiety in people with COPD is high, although these comorbidities are often undiagnosed, untreated, or undertreated. There is a need to identify efficacious treatments for depression and anxiety in people with COPD. Cognitive behavior therapy (CBT) for the treatment of anxiety and depression has a strong evidence base. There has been some success delivering this treatment over the telephone in limited studies. The aim of this study is to evaluate the efficacy of both telephone-administered CBT and befriending on outcomes for patients with diagnosed COPD who have at least mild levels of depression and/or anxiety.Methods: The protocol described in this paper is of a pragmatic randomized controlled trial comparing eight sessions of telephone CBT to an active social control, referred to as befriending. Primary outcome measures will include depression and anxiety symptoms, and secondary outcome measures will include quality of life, self-efficacy, and COPD symptom severity. Participants’ satisfaction with the intervention and therapeutic alliance will also be assessed. Measures will be taken pre- and postdelivery of the intervention and again at 8 weeks following the intervention.Conclusion: People with COPD often have limitations to their mobility because of their breathlessness. They are often already attending many medical appointments and could be reluctant to attend for face-to-face psychological treatment. The results of this study should identify the relative efficacy of CBT delivered over the telephone to this population, which, if successful, may be a cost-effective and more palatable alternative to face-to-face treatment of depression or anxiety for this population.Keywords: chronic obstructive pulmonary disease (COPD), depression, anxiety, telephone, cognitive behavior therapy (CBT), befriending

Published
2016

13. Development of harmonized and co‐calibrated scores for memory, executive functioning, language, and visuospatial in the AIBL Study, ADNI, and NACC datasets

Author

Crane, PK, Trittschuh, EH, Mez, JB, Saykin, AJ, Sanders, RE, Gibbons, LE, Lee, ML, Scollard, P, Choi, S, Rainey‐Smith, S, Chooi, CK, Gavett, BE, Maruff, P, Ames, D, Culhane, JE, Gauthreaux, K, Chan, KCG, Biber, S, Stephens, K, Kukull, WA, Dumitrescu, L, Hohman, TJ, Mukherjee, S, Crane, PK, Trittschuh, EH, Mez, JB, Saykin, AJ, Sanders, RE, Gibbons, LE, Lee, ML, Scollard, P, Choi, S, Rainey‐Smith, S, Chooi, CK, Gavett, BE, Maruff, P, Ames, D, Culhane, JE, Gauthreaux, K, Chan, KCG, Biber, S, Stephens, K, Kukull, WA, Dumitrescu, L, Hohman, TJ, and Mukherjee, S

Abstract

Background The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study is a prospective study collecting extensive cognitive, clinical, fluid, and imaging biomarkers data from older adults living in Australia. Integration of outcomes between large prospective studies of AD will provide greater precision in models of AD brain‐behavior relationships, so it is important to align composite scores for cognitive domains between such studies. Methods Detailed methods for AIBL, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the National Alzheimer’s Coordinating Center (NACC) have been published. Briefly, AIBL participants had cognition assessed with an extensive neuropsychological test battery alongside health and biomarker assessments at entry and each 18‐months thereafter. Granular‐level cognitive data were obtained and an expert panel of two neuropsychologists and a behavioral neurologist categorized each element as assessing memory, executive functioning, language, visuospatial, or none of these, exactly as we have done previously. We also identified elements we had previously calibrated from other studies; after careful quality control and confirmation these served as anchors enabling co‐calibration. We used confirmatory factor analysis bi‐factor models to calibrate the AIBL battery with other studies. We used those calibrations to obtain co‐calibrated scores for all AIBL participants at every study visit. Here we show descriptive statistics for baseline visits, separately by diagnosis (normal cognition, mild cognitive impairment (MCI), dementia) for two enrollment waves for AIBL as well as for each phase of ADNI and across the Uniform Data Set (UDS) 1 & 2 (UDS1/2) and UDS3 time periods for NACC. Results Box plots for memory, executive functioning, language, and visuospatial for people with normal cognition are in Figure 1, MCI in Figure 2, and dementia in Figure 3. These figures show there is substantial cognitive variation across waves within these

Published
2022

14. Reproducibility in the absence of selective reporting: An illustration from large-scale brain asymmetry research

Author

Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, del Carmen Valdés Hernández, M, Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, and del Carmen Valdés Hernández, M

Published
2022

15. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author

Brouwer, RM, Klein, M, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alanaes, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Boen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bulow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivieres, S, Diaz-Caneja, CM, Doan, NT, Dohm, K, Froehner, JH, Goltermann, J, Grigis, A, Grotegerd, D, Han, LKM, Harris, MA, Hartman, CA, Heany, SJ, Heindel, W, Heslenfeld, DJ, Hohmann, S, Ittermann, B, Jansen, PR, Janssen, J, Jia, T, Jiang, J, Jockwitz, C, Karali, T, Keeser, D, Koevoets, MGJC, Lenroot, RK, Malchow, B, Mandl, RCW, Medel, V, Meinert, S, Morgan, CA, Muehleisen, TW, Nabulsi, L, Opel, N, de la Foz, VO-G, Overs, BJ, Paillere Martinot, M-L, Redlich, R, Marques, TR, Repple, J, Roberts, G, Roshchupkin, GV, Setiaman, N, Shumskaya, E, Stein, F, Sudre, G, Takahashi, S, Thalamuthu, A, Tordesillas-Gutierrez, D, van der Lugt, A, van Haren, NEM, Wardlaw, JM, Wen, W, Westeneng, H-J, Wittfeld, K, Zhu, AH, Zugman, A, Armstrong, NJ, Bonfiglio, G, Bralten, J, Dalvie, S, Davies, G, Di Forti, M, Ding, L, Donohoe, G, Forstner, AJ, Gonzalez-Penas, J, Guimaraes, JPOFT, Homuth, G, Hottenga, J-J, Knol, MJ, Kwok, JBJ, Le Hellard, S, Mather, KA, Milaneschi, Y, Morris, DW, Noethen, MM, Papiol, S, Rietschel, M, Santoro, ML, Steen, VM, Stein, JL, Streit, F, Tankard, RM, Teumer, A, van 't Ent, D, van der Meer, D, van Eijk, KR, Vassos, E, Vazquez-Bourgon, J, Witt, SH, Adams, HHH, Agartz, I, Ames, D, Amunts, K, Andreassen, OA, Arango, C, Banaschewski, T, Baune, BT, Belangero, SI, Bokde, ALW, Boomsma, DI, Bressan, RA, Brodaty, H, Buitelaar, JK, Cahn, W, Caspers, S, Cichon, S, Crespo-Facorro, B, Cox, SR, Dannlowski, U, Elvsashagen, T, Espeseth, T, Falkai, PG, Fisher, SE, Flor, H, Fullerton, JM, Garavan, H, Gowland, PA, Grabe, HJ, Hahn, T, Heinz, A, Hillegers, M, Hoare, J, Hoekstra, PJ, Ikram, MA, Jackowski, AP, Jansen, A, Jonsson, EG, Kahn, RS, Kircher, T, Korgaonkar, MS, Krug, A, Lemaitre, H, Malt, UF, Martinot, J-L, McDonald, C, Mitchell, PB, Muetzel, RL, Murray, RM, Nees, F, Nenadic, I, Oosterlaan, J, Ophoff, RA, Pan, PM, Penninx, BWJH, Poustka, L, Sachdev, PS, Salum, GA, Schofield, PR, Schumann, G, Shaw, P, Sim, K, Smolka, MN, Stein, DJ, Trollor, JN, van den Berg, LH, Veldink, JH, Walter, H, Westlye, LT, Whelan, R, White, T, Wright, MJ, Medland, SE, Franke, B, Thompson, PM, Hulshoff Pol, HE, Brouwer, RM, Klein, M, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alanaes, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Boen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bulow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivieres, S, Diaz-Caneja, CM, Doan, NT, Dohm, K, Froehner, JH, Goltermann, J, Grigis, A, Grotegerd, D, Han, LKM, Harris, MA, Hartman, CA, Heany, SJ, Heindel, W, Heslenfeld, DJ, Hohmann, S, Ittermann, B, Jansen, PR, Janssen, J, Jia, T, Jiang, J, Jockwitz, C, Karali, T, Keeser, D, Koevoets, MGJC, Lenroot, RK, Malchow, B, Mandl, RCW, Medel, V, Meinert, S, Morgan, CA, Muehleisen, TW, Nabulsi, L, Opel, N, de la Foz, VO-G, Overs, BJ, Paillere Martinot, M-L, Redlich, R, Marques, TR, Repple, J, Roberts, G, Roshchupkin, GV, Setiaman, N, Shumskaya, E, Stein, F, Sudre, G, Takahashi, S, Thalamuthu, A, Tordesillas-Gutierrez, D, van der Lugt, A, van Haren, NEM, Wardlaw, JM, Wen, W, Westeneng, H-J, Wittfeld, K, Zhu, AH, Zugman, A, Armstrong, NJ, Bonfiglio, G, Bralten, J, Dalvie, S, Davies, G, Di Forti, M, Ding, L, Donohoe, G, Forstner, AJ, Gonzalez-Penas, J, Guimaraes, JPOFT, Homuth, G, Hottenga, J-J, Knol, MJ, Kwok, JBJ, Le Hellard, S, Mather, KA, Milaneschi, Y, Morris, DW, Noethen, MM, Papiol, S, Rietschel, M, Santoro, ML, Steen, VM, Stein, JL, Streit, F, Tankard, RM, Teumer, A, van 't Ent, D, van der Meer, D, van Eijk, KR, Vassos, E, Vazquez-Bourgon, J, Witt, SH, Adams, HHH, Agartz, I, Ames, D, Amunts, K, Andreassen, OA, Arango, C, Banaschewski, T, Baune, BT, Belangero, SI, Bokde, ALW, Boomsma, DI, Bressan, RA, Brodaty, H, Buitelaar, JK, Cahn, W, Caspers, S, Cichon, S, Crespo-Facorro, B, Cox, SR, Dannlowski, U, Elvsashagen, T, Espeseth, T, Falkai, PG, Fisher, SE, Flor, H, Fullerton, JM, Garavan, H, Gowland, PA, Grabe, HJ, Hahn, T, Heinz, A, Hillegers, M, Hoare, J, Hoekstra, PJ, Ikram, MA, Jackowski, AP, Jansen, A, Jonsson, EG, Kahn, RS, Kircher, T, Korgaonkar, MS, Krug, A, Lemaitre, H, Malt, UF, Martinot, J-L, McDonald, C, Mitchell, PB, Muetzel, RL, Murray, RM, Nees, F, Nenadic, I, Oosterlaan, J, Ophoff, RA, Pan, PM, Penninx, BWJH, Poustka, L, Sachdev, PS, Salum, GA, Schofield, PR, Schumann, G, Shaw, P, Sim, K, Smolka, MN, Stein, DJ, Trollor, JN, van den Berg, LH, Veldink, JH, Walter, H, Westlye, LT, Whelan, R, White, T, Wright, MJ, Medland, SE, Franke, B, Thompson, PM, and Hulshoff Pol, HE

Abstract

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

Published
2022

16. Author Correction: Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s disease (Nature Communications, (2021), 12, 1, (721), 10.1038/s41467-021-21057-y)

Author

Roe, JM, Vidal-Piñeiro, D, Sørensen, Ø, Brandmaier, AM, Düzel, S, Gonzalez, HA, Kievit, RA, Knights, E, Kühn, S, Lindenberger, U, Mowinckel, AM, Nyberg, L, Park, DC, Pudas, S, Rundle, MM, Walhovd, KB, Fjell, AM, Westerhausen, R, Masters, CL, Bush, AI, Fowler, C, Darby, D, Pertile, K, Restrepo, C, Roberts, B, Robertson, J, Rumble, R, Ryan, T, Collins, S, Thai, C, Trounson, B, Lennon, K, Li, QX, Ugarte, FY, Volitakis, I, Vovos, M, Williams, R, Baker, J, Russell, A, Peretti, M, Milicic, L, Lim, L, Rodrigues, M, Taddei, K, Taddei, T, Hone, E, Lim, F, Fernandez, S, Rainey-Smith, S, Pedrini, S, Martins, R, Doecke, J, Bourgeat, P, Fripp, J, Gibson, S, Leroux, H, Hanson, D, Dore, V, Zhang, P, Burnham, S, Rowe, CC, Villemagne, VL, Yates, P, Pejoska, SB, Jones, G, Ames, D, Cyarto, E, Lautenschlager, N, Barnham, K, Cheng, L, Hill, A, Killeen, N, Maruff, P, Silbert, B, Brown, B, Sohrabi, H, Savage, G, Vacher, M, Roe, JM, Vidal-Piñeiro, D, Sørensen, Ø, Brandmaier, AM, Düzel, S, Gonzalez, HA, Kievit, RA, Knights, E, Kühn, S, Lindenberger, U, Mowinckel, AM, Nyberg, L, Park, DC, Pudas, S, Rundle, MM, Walhovd, KB, Fjell, AM, Westerhausen, R, Masters, CL, Bush, AI, Fowler, C, Darby, D, Pertile, K, Restrepo, C, Roberts, B, Robertson, J, Rumble, R, Ryan, T, Collins, S, Thai, C, Trounson, B, Lennon, K, Li, QX, Ugarte, FY, Volitakis, I, Vovos, M, Williams, R, Baker, J, Russell, A, Peretti, M, Milicic, L, Lim, L, Rodrigues, M, Taddei, K, Taddei, T, Hone, E, Lim, F, Fernandez, S, Rainey-Smith, S, Pedrini, S, Martins, R, Doecke, J, Bourgeat, P, Fripp, J, Gibson, S, Leroux, H, Hanson, D, Dore, V, Zhang, P, Burnham, S, Rowe, CC, Villemagne, VL, Yates, P, Pejoska, SB, Jones, G, Ames, D, Cyarto, E, Lautenschlager, N, Barnham, K, Cheng, L, Hill, A, Killeen, N, Maruff, P, Silbert, B, Brown, B, Sohrabi, H, Savage, G, and Vacher, M

Abstract

In this article the affiliation details for Ulman Lindenberger were incorrectly given as ‘Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany’ but should have been ‘Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany’, ‘Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany’. The original article has been corrected.

Published
2022

17. What constitutes 'good' home care for people with dementia? An investigation of the views of home care service recipients and providers

Author

Goh, AMY, Polacsek, M, Malta, S, Doyle, C, Hallam, B, Gahan, L, Low, LF, Cooper, C, Livingston, G, Panayiotou, A, Loi, SM, Omori, M, Savvas, S, Burton, J, Ames, D, Scherer, SC, Chau, N, Roberts, S, Winbolt, M, Batchelor, F, Dow, B, Goh, AMY, Polacsek, M, Malta, S, Doyle, C, Hallam, B, Gahan, L, Low, LF, Cooper, C, Livingston, G, Panayiotou, A, Loi, SM, Omori, M, Savvas, S, Burton, J, Ames, D, Scherer, SC, Chau, N, Roberts, S, Winbolt, M, Batchelor, F, and Dow, B

Abstract

BACKGROUND: Our objective was to explore what people receiving and providing care consider to be 'good' in-home care for people living with dementia. METHODS: We conducted 36 in-depth interviews and two focus groups with key stakeholders in Australia in the first quarter of 2018. Participants included those receiving care (4 people living with dementia, 15 family carers) or providing care (9 case managers, 5 service managers, 10 home care workers). Qualitative thematic analysis was guided by Braun and Clarke's six-step approach. RESULTS: Consensus was reached across all groups on five themes considered as important for good in-home dementia care: 1) Home care workers' understanding of dementia and its impact; 2) Home care workers' demonstrating person-centred care and empathy in their care relationship with their client; 3) Good relationships and communication between care worker, person with dementia and family carers; 4) Home care workers' knowing positive practical strategies for changed behaviours; 5) Effective workplace policies and workforce culture. The results contributed to the co-design of a dementia specific training program for home care workers. CONCLUSIONS: It is crucial to consider the views and opinions of each stakeholder group involved in providing/receiving dementia care from home care workers, to inform workforce training, education program design and service design. Results can be used to inform and empower home care providers, policy, and related decision makers to guide the delivery of improved home care services. TRIAL REGISTRATION: ACTRN 12619000251123 .

Published
2022

18. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author

Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., Räikkönen, K., Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., and Räikkönen, K.

Abstract

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Published
2022

19. Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

Author

Cadby, G, Giles, C, Melton, PE, Huynh, K, Mellett, NA, Thy, D, Anh, N, Cinel, M, Smith, A, Olshansky, G, Wang, T, Brozynska, M, Inouye, M, McCarthy, NS, Ariff, A, Hung, J, Hui, J, Beilby, J, Dube, M-P, Watts, GF, Shah, S, Wray, NR, Lim, WLF, Chatterjee, P, Martins, I, Laws, SM, Porter, T, Vacher, M, Bush, A, Rowe, CC, Villemagne, VL, Ames, D, Masters, CL, Taddei, K, Arnold, M, Kastenmueller, G, Nho, K, Saykin, AJ, Han, X, Kaddurah-Daouk, R, Martins, RN, Blangero, J, Meikle, PJ, Moses, EK, Cadby, G, Giles, C, Melton, PE, Huynh, K, Mellett, NA, Thy, D, Anh, N, Cinel, M, Smith, A, Olshansky, G, Wang, T, Brozynska, M, Inouye, M, McCarthy, NS, Ariff, A, Hung, J, Hui, J, Beilby, J, Dube, M-P, Watts, GF, Shah, S, Wray, NR, Lim, WLF, Chatterjee, P, Martins, I, Laws, SM, Porter, T, Vacher, M, Bush, A, Rowe, CC, Villemagne, VL, Ames, D, Masters, CL, Taddei, K, Arnold, M, Kastenmueller, G, Nho, K, Saykin, AJ, Han, X, Kaddurah-Daouk, R, Martins, RN, Blangero, J, Meikle, PJ, and Moses, EK

Abstract

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P < 1 × 10-3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.

Published
2022

20. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author

Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, Raikkonen, K, Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, and Raikkonen, K

Abstract

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Published
2022

21. Making modeling and software FAIR

Author

Barton, C.M., Ames, D., Chen, M., Frank, Karin, Jagers, H.R.A., Lee, A., Reis, S., Swantek, L., Barton, C.M., Ames, D., Chen, M., Frank, Karin, Jagers, H.R.A., Lee, A., Reis, S., and Swantek, L.

Abstract

no abstract

Published
2022

22. Managing mood disorders in patients attending pulmonary rehabilitation clinics

Author

Selvarajah S, Ames D, Dunt D, and Doyle C

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Colleen Doyle,1–3 David Dunt,2 David Ames,1 Suganya Selvarajah11National Ageing Research Institute, Royal Melbourne Hospital Royal Park Campus, Parkville, Victoria, Australia; 2Centre for Health Policy, Programs and Economics, University of Melbourne, Parkville, Victoria, Australia; 3Australian Catholic University, Fitzroy, Victoria, AustraliaBackground: There is good evidence for the positive benefits of pulmonary rehabilitation (PR) in the prevention of hospital admissions, lower mortality, and improved health-related quality of life. There is also increasing evidence about the impact of PR on mental health and, in particular, mood disorders. We aimed to identify how depression in chronic obstructive pulmonary disease (COPD) patients in Victoria, Australia, is being managed in PR, to identify the prevalence of depressive symptoms among COPD patients who attend PR, and to determine whether patients with depressive symptoms or anxiety symptoms dropped out of PR early.Method: Of 61 PR clinics, 44 were invited and 22 agreed to participate. Telephone interviews were conducted to see how depression and anxiety in COPD patients were being recognized and managed in these clinics. A total of 294 questionnaires were distributed to patients by clinic coordinators to determine the prevalence of anxiety/depression, as measured by the Hospital Anxiety and Depression Scale. Coordinators were contacted to provide information on whether respondents dropped out of rehabilitation early or continued with their treatment at 2–4 months post program.Results: Seven clinics were not aware of local guidelines on assessment/treatment/management of mood. Four clinics did not use any screening tools or other aids in the recognition and management of depression and/or anxiety. Overall, eight clinics participating in this study requested advice on suitable screening tools. The patient survey indicated that the mean depression score on the Hospital Anxiety and Depression Scale was 5.0 (standard deviation 3.0, range 1–13). The mean anxiety score was 5.5 (standard deviation 3.4, range 0–18). There was no evidence of a link between failure to complete rehabilitation and depression or anxiety scores, as only three of 105 patients failed to complete their rehabilitation.Discussion: Awareness of management guidelines for depression and anxiety in COPD patients was variable across the clinics recruited into our study. We found no link between compliance with rehabilitation and depression, but our sample had limitations.Conclusion: Future research needs to investigate how best to encourage more use of available guidelines regarding integrating psychological and psychosocial support to supplement the exercise and education that are currently offered routinely by all PR clinics studied in Victoria, Australia.Keywords: chronic obstructive pulmonary disease, depression, anxiety, pulmonary rehabilitation

Published
2013

33. Alzheimer's disease progression and risk factors: A standardized comparison between six large data sets

Author

Evans, S, McRae-McKee, K, Hadjichrysanthou, C, Wong, MM, Ames, D, Lopez, O, De Wolf, F, Anderson, RM, Australian Imaging Biomarkers and Lifestyle flagship study of ageing, Predictors of Cognitive Decline Among Normal Individuals (BIOCARD) study, Add Neuro Med Consortium, and Janssen Vaccines & Prevention B.V

Subjects
0301 basic medicine, medicine.medical_specialty, Epidemiology, Add Neuro Med Consortium, Disease, Markov model, 03 medical and health sciences, 0302 clinical medicine, Medicine, Dementia, Mixed regression, business.industry, Biological risk factors, Disease progression, Modeling, Mild cognitive impairment, Predictors of Cognitive Decline Among Normal Individuals (BIOCARD) study, Featured Article, medicine.disease, Clinical trial, Psychiatry and Mental health, 030104 developmental biology, Statistical analysis, Australian Imaging Biomarkers and Lifestyle flagship study of ageing, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study, Demography
Abstract

There exist a large number of cohort studies that have been used to identify genetic and biological risk factors for developing Alzheimer's disease (AD). However, there is a disagreement between studies as to how strongly these risk factors affect the rate of progression through diagnostic groups toward AD. We have calculated the probability of transitioning through diagnostic groups in six studies and considered how uncertainty around the strength of the effect of these risk factors affects estimates of the distribution of individuals in each diagnostic group in an AD clinical trial simulator. In this work, we identify the optimal choice of widely collected variables for comparing data sets and calculating probabilities of progression toward AD. We use the estimated transition probabilities to inform stochastic simulations of AD progression that are based on a Markov model and compare predicted incidence rates to those in a community-based study, the Cardiovascular Health Study.

Published
2019

38. Fifteen years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and observations from 2,359 older adults spanning the spectrum from cognitive normality to Alzheimer’s Disease

Author

Fowler, C., Rainey-Smith, S.R., Bird, S., Bomke, J., Bourgeat, P., Brown, B.M., Burnham, S.C., Bush, A.I., Chadunow, C., Collins, S., Doecke, J., Doré, V., Ellis, K.A., Evered, L., Fazlollahi, A., Fripp, J., Gardener, S.L., Gibson, S., Grenfell, R., Harrison, E., Head, R., Jin, L., Kamer, A., Lamb, F., Lautenschlager, N.T., Laws, S.M., Li, Q-X, Lim, L., Lim, Y.Y., Louey, A., Macaulay, S.L., Mackintosh, L., Martins, R.N., Maruff, P., Masters, C.L., McBride, S., Milicic, L., Peretti, M., Pertile, K., Porter, T., Radler, M., Rembach, A., Robertson, J., Rodrigues, M., Rowe, C.C., Rumble, R., Salvado, O., Savage, G., Silbert, B., Soh, M., Sohrabi, H.R., Taddei, K., Taddei, T., Thai, C., Trounson, B., Tyrrell, R., Vacher, M., Varghese, S., Villemagne, V.L., Weinborn, M., Woodward, M., Xia, Y., Ames, D., Fowler, C., Rainey-Smith, S.R., Bird, S., Bomke, J., Bourgeat, P., Brown, B.M., Burnham, S.C., Bush, A.I., Chadunow, C., Collins, S., Doecke, J., Doré, V., Ellis, K.A., Evered, L., Fazlollahi, A., Fripp, J., Gardener, S.L., Gibson, S., Grenfell, R., Harrison, E., Head, R., Jin, L., Kamer, A., Lamb, F., Lautenschlager, N.T., Laws, S.M., Li, Q-X, Lim, L., Lim, Y.Y., Louey, A., Macaulay, S.L., Mackintosh, L., Martins, R.N., Maruff, P., Masters, C.L., McBride, S., Milicic, L., Peretti, M., Pertile, K., Porter, T., Radler, M., Rembach, A., Robertson, J., Rodrigues, M., Rowe, C.C., Rumble, R., Salvado, O., Savage, G., Silbert, B., Soh, M., Sohrabi, H.R., Taddei, K., Taddei, T., Thai, C., Trounson, B., Tyrrell, R., Vacher, M., Varghese, S., Villemagne, V.L., Weinborn, M., Woodward, M., Xia, Y., and Ames, D.

Abstract

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer’s disease dementia (AD)) as an ‘Inception cohort’ who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an ‘Enrichment cohort’ (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

Published
2021

39. Longitudinal trajectories in cortical thickness and volume atrophy: Superior cognitive performance does not protect against brain atrophy in older adults

Author

Gardener, S.L., Weinborn, M., Sohrabi, H.R., Doecke, J.D., Bourgeat, P., Rainey-Smith, S.R., Shen, K-K, Fripp, J., Taddei, K., Maruff, P., Salvado, O., Savage, G., Ames, D., Masters, C.L., Rowe, C.C., Martins, R.N., O’Bryant, S., Gardener, S.L., Weinborn, M., Sohrabi, H.R., Doecke, J.D., Bourgeat, P., Rainey-Smith, S.R., Shen, K-K, Fripp, J., Taddei, K., Maruff, P., Salvado, O., Savage, G., Ames, D., Masters, C.L., Rowe, C.C., Martins, R.N., and O’Bryant, S.

Abstract

Background: Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable. Objective: Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years. Methods: Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70 + at baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30–44 years old, and in the unimpaired range for all other cognitive domains over the course of the study. Results: In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-β negative individuals in the analyses, again there were no significant differences between SCPs and TOAs. Conclusion: The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age.

Published
2021

40. Aggregation of abnormal memory scores and risk of incident Alzheimer’s disease dementia: A measure of objective memory impairment in amnestic mild cognitive impairment

Author

Bradfield, N.I., Ellis, K.A., Savage, G., Maruff, P., Burnham, S., Darby, D., Lautenschlager, N.T., Martins, R.N., Masters, C.L., Rainey-Smith, S.R., Robertson, J., Rowe, C., Woodward, M., Ames, D., Bradfield, N.I., Ellis, K.A., Savage, G., Maruff, P., Burnham, S., Darby, D., Lautenschlager, N.T., Martins, R.N., Masters, C.L., Rainey-Smith, S.R., Robertson, J., Rowe, C., Woodward, M., and Ames, D.

Abstract

Objectives: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia. Methods: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years. Results: Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status. Conclusions: Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.

Published
2021

41. Learning deficit in cognitively normal APOE ε4 carriers with LOW β‐amyloid

Author

Lim, Y.Y., Baker, J.E., Mills, A., Bruns, L., Fowler, C., Fripp, J., Rainey‐Smith, S.R., Ames, D., Masters, C.L., Maruff, P., Lim, Y.Y., Baker, J.E., Mills, A., Bruns, L., Fowler, C., Fripp, J., Rainey‐Smith, S.R., Ames, D., Masters, C.L., and Maruff, P.

Abstract

Introduction In cognitively normal (CN) adults, increased rates of amyloid beta (Aβ) accumulation can be detected in low Aβ (Aβ–) apolipoprotein E (APOE) ε4 carriers. We aimed to determine the effect of ε4 on the ability to benefit from experience (ie, learn) in Aβ– CNs. Methods Aβ– CNs (n = 333) underwent episodic memory assessments every 18 months for 108 months. A subset (n = 48) completed the Online Repeatable Cognitive Assessment‐Language Learning Test (ORCA‐LLT) over 6 days. Results Aβ– ε4 carriers showed significantly lower rates of improvement on episodic memory over 108 months compared to non‐carriers (d = 0.3). Rates of learning on the ORCA‐LLT were significantly slower in Aβ– ε4 carriers compared to non‐carriers (d = 1.2). Discussion In Aβ– CNs, ε4 is associated with a reduced ability to benefit from experience. This manifested as reduced practice effects (small to moderate in magnitude) over 108 months on the episodic memory composite, and a learning deficit (large in magnitude) over 6 days on the ORCA‐LLT. Alzheimer's disease (AD)–related cognitive abnormalities can manifest before preclinical AD thresholds.

Published
2021

42. SPON1 Is associated with Amyloid-β and APOE ε4-Related cognitive decline in cognitively normal adults

Author

Fernandez, S., Burnham, S.C., Milicic, L., Savage, G., Maruff, P., Peretti, M., Sohrabi, H.R., Lim, Y.Y., Weinborn, M., Ames, D., Masters, C.L., Martins, R.N., Rainey-Smith, S., Rowe, C.C., Salvado, O., Groth, D., Verdile, G., Villemagne, V.L., Porter, T., Laws, S.M., Fernandez, S., Burnham, S.C., Milicic, L., Savage, G., Maruff, P., Peretti, M., Sohrabi, H.R., Lim, Y.Y., Weinborn, M., Ames, D., Masters, C.L., Martins, R.N., Rainey-Smith, S., Rowe, C.C., Salvado, O., Groth, D., Verdile, G., Villemagne, V.L., Porter, T., and Laws, S.M.

Abstract

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer’s disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ɛ4 and rs11023139 in individuals with high amyloid-β burden. APOE ɛ4/rs11023139-A carriers declined significantly faster than APOE ɛ4/rs11023139-G_G carriers in measures of global cognition (p = 0.011) and verbal episodic memory (p = 0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ɛ4 cognitively normal older adults with a high neocortical amyloid-β burden.

Published
2021

43. Investigating olfactory gene variation and odour identification in older adults

Author

Raj, S., Thalamuthu, A., Armstrong, N.J., Wright, M.J., Kwok, J.B., Trollor, J.N., Ames, D., Schofield, P.R., Brodaty, H., Sachdev, P.S., Mather, K.A., Raj, S., Thalamuthu, A., Armstrong, N.J., Wright, M.J., Kwok, J.B., Trollor, J.N., Ames, D., Schofield, P.R., Brodaty, H., Sachdev, P.S., and Mather, K.A.

Abstract

Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour identification. In this study, we sought to find olfactory gene family variants associated with individual and overall odour identification and to examine the relationships between polygenic risk scores (PRS) for olfactory-related phenotypes and olfaction. Participants were Caucasian older adults from the Sydney Memory and Ageing Study and the Older Australian Twins Study with genome-wide genotyping data (n = 1395, mean age = 75.52 ± 6.45). The Brief-Smell Identification Test (BSIT) was administered in both cohorts. PRS were calculated from independent GWAS summary statistics for Alzheimer’s disease (AD), white matter hyperintensities (WMH), Parkinson’s disease (PD), hippocampal volume and smoking. Associations with olfactory receptor genes (n = 967), previously identified candidate olfaction-related SNPs (n = 36) and different PRS with BSIT scores (total and individual smells) were examined. All of the relationships were analysed using generalised linear mixed models (GLMM), adjusted for age and sex. Genes with suggestive evidence for odour identification were found for 8 of the 12 BSIT items. Thirteen out of 36 candidate SNPs previously identified from the literature were suggestively associated with several individual BSIT items but not total score. PRS for smoking, WMH and PD were negatively associated with chocolate identification. This is the first study to conduct genetic analyses with individual odorant identification, which found suggestive olfactory-related genes and genetic variants for multiple individual BSIT odours. Replication in independent and larger cohorts is needed.

Published
2021

44. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author

Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Andreassen, O.A., Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., and Andreassen, O.A.

Abstract

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Published
2021

45. Androgen receptor CAG repeat length as a moderator of the relationship between free testosterone levels and cognition

Author

Tan, S., Porter, T., Bucks, R.S., Weinborn, M., Milicic, L., Brown, A., Rainey-Smith, S.R., Taddei, K., Ames, D., Masters, C.L., Maruff, P., Savage, G., Rowe, C.C., Villemagne, V.L., Brown, B., Sohrabi, H.R., Laws, S.M., Martins, R.N., Tan, S., Porter, T., Bucks, R.S., Weinborn, M., Milicic, L., Brown, A., Rainey-Smith, S.R., Taddei, K., Ames, D., Masters, C.L., Maruff, P., Savage, G., Rowe, C.C., Villemagne, V.L., Brown, B., Sohrabi, H.R., Laws, S.M., and Martins, R.N.

Abstract

Age-related decrease in testosterone levels is a potential risk factor for cognitive decline in older men. However, observational studies and clinical trials have reported inconsistent results on the effects of testosterone on individual cognitive domains. Null findings may be attributed to factors that studies have yet to consider. In particular, individual variations in polyglutamine (CAG) length in the androgen receptor (AR) gene could alter androgenic activity in brain regions associated with cognitive processes including memory and executive functions. However, the role of AR CAG repeat length as a moderator of the relationship between testosterone levels and cognition has not been investigated. Therefore, we aimed to examine the relationship between baseline calculated free testosterone (cFT) levels, change in cFT levels over 18 months and CAG repeat length on cognitive performance in memory, executive function, language, attention and processing speed domains. These relationships were examined in 304 cognitively normal older male participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. In the attention and processing speed domain, a short CAG repeat length appears to exacerbate the effects of low baseline cFT levels that are also lower than expected at follow-up. These results highlight that individual variations in AR CAG repeat length should be considered in future studies and clinical trials that examine the complex relationship between testosterone and cognition.

Published
2021

46. Investigating olfactory gene variation and odour identification in older adults

Author

Raj, S, Thalamuthu, A, Armstrong, NJ, Wright, MJ, Kwok, JB, Trollor, JN, Ames, D, Schofield, PR, Brodaty, H, Sachdev, PS, Mather, KA, Raj, S, Thalamuthu, A, Armstrong, NJ, Wright, MJ, Kwok, JB, Trollor, JN, Ames, D, Schofield, PR, Brodaty, H, Sachdev, PS, and Mather, KA

Abstract

Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour identification. In this study, we sought to find olfactory gene family variants associated with individual and overall odour identification and to examine the relationships between polygenic risk scores (PRS) for olfactory-related phenotypes and olfaction. Participants were Caucasian older adults from the Sydney Memory and Ageing Study and the Older Australian Twins Study with genome-wide genotyping data (n = 1395, mean age = 75.52 ± 6.45). The Brief-Smell Identification Test (BSIT) was administered in both cohorts. PRS were calculated from independent GWAS summary statistics for Alzheimer’s disease (AD), white matter hyperintensities (WMH), Parkinson’s disease (PD), hippocampal volume and smoking. Associations with olfactory receptor genes (n = 967), previously identified candidate olfaction-related SNPs (n = 36) and different PRS with BSIT scores (total and individual smells) were examined. All of the relationships were analysed using generalised linear mixed models (GLMM), adjusted for age and sex. Genes with suggestive evidence for odour identification were found for 8 of the 12 BSIT items. Thirteen out of 36 candidate SNPs previously identified from the literature were suggestively associated with several individual BSIT items but not total score. PRS for smoking, WMH and PD were negatively associated with chocolate identification. This is the first study to conduct genetic analyses with individual odorant identification, which found suggestive olfactory-related genes and genetic variants for multiple individual BSIT odours. Replication in independent and larger cohorts is needed.

Published
2021

47. A Randomized Controlled Trial on the Effects of a 6-Month Home-Based Physical Activity Program with Individual Goal-Setting and Volunteer Mentors on Physical Activity, Adherence, and Physical Fitness in Inactive Older Adults at Risk of Cognitive Decline: The INDIGO Study

Author

Hauer, K, Cox, KL, Clare, L, Cyarto, E, Ellis, KA, Etherton-Beer, C, Southam, J, Ames, D, Flicker, L, Almeida, OP, LoGiudice, D, Liew, D, Vlaskovsky, P, Lautenschlager, NT, Hauer, K, Cox, KL, Clare, L, Cyarto, E, Ellis, KA, Etherton-Beer, C, Southam, J, Ames, D, Flicker, L, Almeida, OP, LoGiudice, D, Liew, D, Vlaskovsky, P, and Lautenschlager, NT

Abstract

BACKGROUND: Increasing physical activity (PA) in those who have memory concerns requires innovative approaches. OBJECTIVE: To compare in this randomized controlled trial (RCT) the effects on PA, adherence, and fitness of two approaches to deliver a 6-month home-based PA program in older, inactive individuals at risk of cognitive decline. METHODS: Individuals (n = 52) aged 60-85 years, inactive with mild cognitive impairment or subjective cognitive decline were recruited from the community and memory clinics. Randomization was to 6 months of 150 min/week moderate intensity PA with either: goal-setting with mentor support; or education and peer contact. A subset of participants (n = 36) continued for a further 6 months. PA, moderate and vigorous PA, and secondary outcomes, fitness, goal performance/satisfaction and self-efficacy were assessed at baseline, 6 and 12 months. Modelling of primary and secondary outcomes was conducted with linear mixed models. RESULTS: Participants were mean age (±sd) 70.1 (6.4) years. Six-month retention was 88.5%(n = 46). No significant between-group differences were observed for PA or fitness. Post-hoc combined group data showed a significant, moderate-large effect size increase in PA with time. PA increased by a mean 1,662 (943, 2383) steps/day (95%CI) and 1,320 (603, 2037) steps/day at 6 and 12 months (p < 0.001). Median (quartiles Q1-Q3) 6 and 6-12 month combined group adherence was 88.9 (74.4-95.7)%and 84.6 (73.9-95.4)%respectively. CONCLUSION: In this target group, no differences were detected between groups both intervention strategies were highly effective in increasing PA and fitness.

Published
2021

48. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author

Sonderby, IE, van der Meer, D, Moreau, C, Kaufmann, T, Walters, GB, Ellegaard, M, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB, Blangero, J, Boomsma, DI, Brodaty, H, Brouwer, RM, Buelow, R, Boen, R, Cahn, W, Calhoun, VD, Caspers, S, Ching, CRK, Cichon, S, Ciufolini, S, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Desrivieres, S, Doherty, JL, Donohoe, G, Draganski, B, Ehrlich, S, Eising, E, Espeseth, T, Fejgin, K, Fisher, SE, Fladby, T, Frei, O, Frouin, V, Fukunaga, M, Gareau, T, Ge, T, Glahn, DC, Grabe, HJ, Groenewold, NA, Gustafsson, O, Haavik, J, Haberg, AK, Hall, J, Hashimoto, R, Hehir-Kwa, JY, Hibar, DP, Hillegers, MHJ, Hoffmann, P, Holleran, L, Holmes, AJ, Homuth, G, Hottenga, J-J, Hulshoff Pol, HE, Ikeda, M, Jahanshad, N, Jockwitz, C, Johansson, S, Joensson, EG, Jorgensen, NR, Kikuchi, M, Knowles, EEM, Kumar, K, Le Hellard, S, Leu, C, Linden, DEJ, Liu, J, Lundervold, A, Lundervold, AJ, Maillard, AM, Martin, NG, Martin-Brevet, S, Mather, KA, Mathias, SR, McMahon, KL, McRae, AF, Medland, SE, Meyer-Lindenberg, A, Moberget, T, Modenato, C, Sanchez, JM, Morris, DW, Muehleisen, TW, Murray, RM, Nielsen, J, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, RA, Owen, MJ, Paus, T, Pausova, Z, Peralta, JM, Pike, GB, Prieto, C, Quinlan, EB, Reinbold, CS, Marques, TR, Rucker, JJH, Sachdev, PS, Sando, SB, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Silva, AI, Sisodiya, SM, Steen, VM, Stein, DJ, Strike, LT, Suzuki, IK, Tamnes, CK, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Uhlmann, A, Ulfarsson, MO, van 't Ent, D, van den Bree, MBM, Vanderhaeghen, P, Vassos, E, Wen, W, Wittfeld, K, Wright, MJ, Agartz, I, Djurovic, S, Westlye, LT, Stefansson, H, Stefansson, K, Jacquemont, S, Thompson, PM, Andreassen, OA, Sonderby, IE, van der Meer, D, Moreau, C, Kaufmann, T, Walters, GB, Ellegaard, M, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB, Blangero, J, Boomsma, DI, Brodaty, H, Brouwer, RM, Buelow, R, Boen, R, Cahn, W, Calhoun, VD, Caspers, S, Ching, CRK, Cichon, S, Ciufolini, S, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Desrivieres, S, Doherty, JL, Donohoe, G, Draganski, B, Ehrlich, S, Eising, E, Espeseth, T, Fejgin, K, Fisher, SE, Fladby, T, Frei, O, Frouin, V, Fukunaga, M, Gareau, T, Ge, T, Glahn, DC, Grabe, HJ, Groenewold, NA, Gustafsson, O, Haavik, J, Haberg, AK, Hall, J, Hashimoto, R, Hehir-Kwa, JY, Hibar, DP, Hillegers, MHJ, Hoffmann, P, Holleran, L, Holmes, AJ, Homuth, G, Hottenga, J-J, Hulshoff Pol, HE, Ikeda, M, Jahanshad, N, Jockwitz, C, Johansson, S, Joensson, EG, Jorgensen, NR, Kikuchi, M, Knowles, EEM, Kumar, K, Le Hellard, S, Leu, C, Linden, DEJ, Liu, J, Lundervold, A, Lundervold, AJ, Maillard, AM, Martin, NG, Martin-Brevet, S, Mather, KA, Mathias, SR, McMahon, KL, McRae, AF, Medland, SE, Meyer-Lindenberg, A, Moberget, T, Modenato, C, Sanchez, JM, Morris, DW, Muehleisen, TW, Murray, RM, Nielsen, J, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, RA, Owen, MJ, Paus, T, Pausova, Z, Peralta, JM, Pike, GB, Prieto, C, Quinlan, EB, Reinbold, CS, Marques, TR, Rucker, JJH, Sachdev, PS, Sando, SB, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Silva, AI, Sisodiya, SM, Steen, VM, Stein, DJ, Strike, LT, Suzuki, IK, Tamnes, CK, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Uhlmann, A, Ulfarsson, MO, van 't Ent, D, van den Bree, MBM, Vanderhaeghen, P, Vassos, E, Wen, W, Wittfeld, K, Wright, MJ, Agartz, I, Djurovic, S, Westlye, LT, Stefansson, H, Stefansson, K, Jacquemont, S, Thompson, PM, and Andreassen, OA

Abstract

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Published
2021

49. The Support Person's Preferences and Perspectives of Physical Activity Programs for Older Adults With Cognitive Impairment

Author

Chong, TWH, You, E, Ellis, KA, Cox, KL, Harrington, KD, Rainey-Smith, SR, Ames, D, Lautenschlager, NT, Chong, TWH, You, E, Ellis, KA, Cox, KL, Harrington, KD, Rainey-Smith, SR, Ames, D, and Lautenschlager, NT

Abstract

Objectives: Physical activity (PA) is beneficial for older adults' cognition. There is limited research investigating perspectives of support persons (SPs) of next-of-kins (NOKs) with cognitive impairment. This exploratory study aimed to investigate perspectives of SPs of older adults with Alzheimer's Dementia (AD) or Mild Cognitive Impairment (MCI). Methods: A telephone survey of 213 SPs of NOKs from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) was undertaken to quantitatively assess SPs' beliefs and knowledge about PA benefits, current PA level of their NOK, and PA program preferences. The contribution of age, gender, diagnosis and mental health symptoms was assessed using multiple logistic regression analyses. Results: Many SPs were aware of PA benefits for memory (64%) and believed it would help their NOK (72%). Older SP age was associated with less awareness of benefits (p = 0.016). SPs caring for male NOKs were more likely to believe that PA would be helpful than those caring for female NOKs (p = 0.049). NOK AD diagnosis (rather than MCI) (p = 0.014), older age (p = 0.005) and female gender (p = 0.043) were associated with lower PA levels. SPs were mixed regarding preference for their NOKs to participate in individual (45%) or group (54%) PA. Many SPs wanted to participate in PA with their NOK (63%). Conclusions: The results highlight that SPs have high levels of awareness of the cognitive benefits of PA, and describe their preferences regarding PA programs. The findings provide new information to inform targeted public health messaging, PA prescribers and providers, and future research directions.

Published
2021

50. Promoting Independence Through quality dementia Care at Home (PITCH): a research protocol for a stepped-wedge cluster-randomised controlled trial

Author

Savvas, S, Goh, AMY, Batchelor, F, Doyle, C, Wise, E, Tan, E, Panayiotou, A, Malta, S, Winbolt, M, Clarke, P, Burton, J, Low, L-F, Loi, SM, Fairhall, A, Polacsek, M, Stiles, J, Muliadi, F, Chau, N, Scherer, S, Ames, D, Sousa, TV, Dow, B, Savvas, S, Goh, AMY, Batchelor, F, Doyle, C, Wise, E, Tan, E, Panayiotou, A, Malta, S, Winbolt, M, Clarke, P, Burton, J, Low, L-F, Loi, SM, Fairhall, A, Polacsek, M, Stiles, J, Muliadi, F, Chau, N, Scherer, S, Ames, D, Sousa, TV, and Dow, B

Abstract

BACKGROUND: Home care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home. METHODS: This study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs' sense of competence in dementia care provision. DISCUSSION: Upskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs. TRIAL REGISTRATION: anzctr.org.au ; ACTRN12619000251123. Registered on 20 February 2019.

Published
2021

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