Search

Your search keyword '"Brodaty, H"' showing total 1,618 results
Start Over Author "Brodaty, H"
1,618 results on '"Brodaty, H"'

201. Body mass index and waist circumference predict health-related quality of life, but not satisfaction with life, in the elderly

Author

Wang, L, Crawford, JD, Reppermund, S, Trollor, J, Campbell, L, Baune, BT, Sachdev, P, Brodaty, H, Samaras, K, Smith, E, Wang, L, Crawford, JD, Reppermund, S, Trollor, J, Campbell, L, Baune, BT, Sachdev, P, Brodaty, H, Samaras, K, and Smith, E

Abstract

Objectives: While obesity has been linked with lower quality of life in the general adult population, the prospective effects of present obesity on future quality of life amongst the elderly is unclear. This article investigates the cross-sectional and longitudinal relationships between obesity and aspects of quality of life in community-dwelling older Australians. Method: A 2-year longitudinal sample of community dwellers aged 70–90 years at baseline, derived from the Sydney Memory and Ageing Study (MAS), was chosen for the study. Of the 1037 participants in the original MAS sample, a baseline (Wave 1) sample of 926 and a 2-year follow-up (Wave 2) sample of 751 subjects were retained for these analyses. Adiposity was measured using body mass index (BMI) and waist circumference (WC). Quality of life was measured using the Assessment of Quality of Life (6 dimensions) questionnaire (AQoL-6D) as well as the Satisfaction with Life Scale (SWLS). Linear regression and analysis of covariance (ANCOVA) were used to examine linear and non-linear relationships between BMI and WC and measures of health-related quality of life (HRQoL) and satisfaction with life, adjusting for age, sex, education, asthma, osteoporosis, depression, hearing and visual impairment, mild cognitive impairment, physical activity, and general health. Where a non-linear relationship was found, established BMI or WC categories were used in ANCOVA. Results: Greater adiposity was associated with lower HRQoL but not life satisfaction. Regression modelling in cross-sectional analyses showed that higher BMI and greater WC were associated with lower scores for independent living, relationships, and pain (i.e. worse pain) on the AQoL-6D. In planned contrasts within a series of univariate analyses, obese participants scored lower in independent living and relationships, compared to normal weight and overweight participants. Longitudinal analyses found that higher baseline BMI and WC were associated with lower inde

Published
2018

203. Feasibility of LifeFul, a relationship and reablement-focused culture change program in residential aged care

Author

Low, LF, Venkatesh, S, Clemson, L, Merom, D, Casey, AN, Brodaty, H, Low, LF, Venkatesh, S, Clemson, L, Merom, D, Casey, AN, and Brodaty, H

Abstract

Background: The protective, custodial, task-oriented care provided in residential aged care facilitates decreases health and wellbeing of residents. The aim of the study was to conduct a feasibility study of LifeFul - a 12 month reablement program in residential aged care. Methods: LifeFul was developed based on systematic reviews of reablement and staff behaviour change in residential aged care, and in consultation with aged care providers, consumers and clinicians. LifeFul includes: engaging and supporting facility leaders to facilitate organisational change, procedural changes including dedicated rostering, assigning each resident a 'focus' carer and focusing on the psychosocial care of residents part of handovers and staff training. The study was conducted in three Australian residential aged care facilities. A pre-post mixed methods design was used to evaluate recruitment and retention, fidelity and adherence, acceptability, enablers and barriers and suitability of outcome measures for the program. Results: Eighty of 146 residents agreed to participate at baseline and 69 of these were followed up at 12 months. One hundred and four of 157 staff participated at baseline and 85 of 123 who were still working at the facilities participated at 12 months. Staff perceived the program to be acceptable, barriers included having insufficient time, having insufficient staff, negative attitudes, misunderstanding new procedures, and lack of sufficient leadership support. Quantitative data were promising in regards to residents' depression symptoms, functioning and social care related quality of life. Conclusion: It is feasible to deliver and evaluate LifeFul. The program could be improved through increased leadership training and support, and by focusing efforts on residents having a 'best week' rather than on completing a document each handover. Trial registration: Registered prospectively on 22nd January 2016 on ANZCTR369802.

Published
2018

204. Reliability and validity of a Mediterranean diet and culinary index (MediCul) tool in an older population with mild cognitive impairment

Author

Radd-Vagenas, S, Fiatarone Singh, MA, Inskip, M, Mavros, Y, Gates, N, Wilson, GC, Jain, N, Meiklejohn, J, Brodaty, H, Wen, W, Singh, N, Baune, BT, Suo, C, Baker, MK, Foroughi, N, Sachdev, PS, Valenzuela, M, Flood, VM, Radd-Vagenas, S, Fiatarone Singh, MA, Inskip, M, Mavros, Y, Gates, N, Wilson, GC, Jain, N, Meiklejohn, J, Brodaty, H, Wen, W, Singh, N, Baune, BT, Suo, C, Baker, MK, Foroughi, N, Sachdev, PS, Valenzuela, M, and Flood, VM

Abstract

Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test-retest reliability was assessed using intra-class correlation coefficients (ICC), Bland-Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland-Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test-retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=-2·30+0·17x) (95 % CI -0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.

Published
2018

205. Validity of the mediterranean diet and culinary index (Medicul) for online assessment of adherence to the ‘traditional’ diet and aspects of cuisine in older adults

Author

Radd-Vagenas, S, Singh, MAF, Daniel, K, Noble, Y, Jain, N, O’leary, F, Mavros, Y, Heffernan, M, Meiklejohn, J, Guerrero, Y, Chau, T, Sachdev, PS, Brodaty, H, Flood, VM, Radd-Vagenas, S, Singh, MAF, Daniel, K, Noble, Y, Jain, N, O’leary, F, Mavros, Y, Heffernan, M, Meiklejohn, J, Guerrero, Y, Chau, T, Sachdev, PS, Brodaty, H, and Flood, VM

Abstract

The Mediterranean diet is associated with multiple health benefits. Yet, no tool has been specifically developed to assess adherence to the ‘traditional’ Mediterranean diet and cuisine within a Western cohort, and validated for online use. We tested the reliability and validity of online administration of the Mediterranean Diet and Culinary Index (MediCul) among middle-aged and older adults. Participants were recruited in January–March 2017 from the 45 and Up Study, completing MediCul twice. Test-retest reliability was assessed using the paired t-test, intra-class correlation coefficient (ICC) and Bland-Altman plot. Validity was tested against a three-day food record (FR)-derived MediCul score using Bland-Altman and nutrient trends across the MediCul score tertiles. Participants (n = 84; 60% female; 65.4 years (SD = 5.9)), were overweight (BMI 26.1; SD = 4.0) with 1.7 (SD = 1.5) chronic illnesses/conditions. Sequential MediCul tool scores were 56.1/100.0 and 56.8/100.0, respectively (t = −1.019; p = 0.311). Reliability via ICC (ICC = 0.86, 95% CI: 0.789, 0.910, p < 0.0001) and Bland-Altman was good. In Bland-Altman validity analyses, the tool over-reported FR MediCul score by 5.6 points with no systematic bias ((y = 8.7 − 0.06*x) (95% CI: −0.278, 0.158, p = 0.584)). Nutrient trends were identified for MediCul consistent with expected Mediterranean patterns. Online MediCul administration demonstrated good reliability and moderate validity for assessing adherence to a ‘traditional’ Mediterranean pattern among older Australians.

Published
2018

206. Critical Contextual Elements in Facilitating and Achieving Success with a Person-Centred Care Intervention to Support Antipsychotic Deprescribing for Older People in Long-Term Care

Author

Chenoweth, L, Jessop, T, Harrison, F, Cations, M, Cook, J, Brodaty, H, Chenoweth, L, Jessop, T, Harrison, F, Cations, M, Cook, J, and Brodaty, H

Abstract

Antipsychotic and other tranquilising medicines are prescribed to help care staff manages behaviour in one-quarter of older people living in Australian long-term care homes. While these medicines pose significant health risks, particularly for people with dementia, reliance on their use occurs when staff are not educated to respond to resident behaviour using nonpharmacological approaches. The Halting Antipsychotic use in Long-Term care (HALT) single-arm study was undertaken to address this issue with 139 people 60 years and over with behaviours of concern for staff living in 24 care homes. A train-the-trainer approach delivered person-centred care education and support for 22 HALT (nurse) champions and 135 direct care staff, dementia management education for visiting general practitioners (GP) and pharmacists, use of an individualised deprescribing protocol for residents, and awareness-raising for the resident's family. The HALT champions completed open-ended questionnaires and semistructured interviews to identify the contextual elements they considered most critical to facilitating, educating care staff, and achieving success with the study intervention. They reported that person-centred approaches helped care staff to respond proactively to resident behaviours in the absence of antipsychotic medicines; the champions considered that this required strong managerial support, champion empowerment to lead change, reeducation of care staff, and the cooperation of families and GPs.

Published
2018

207. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), Deary, I.J. (Ian), Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), and Deary, I.J. (Ian)

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the c

Published
2018
Full Text
View/download PDF

208. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C, Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., Deary, I.J., Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S.J., Ware, E.B., Windham, B.G., Wright, M.J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Böhmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kähönen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C, Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikäinen, L-P, Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumaré, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P.L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hägg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Räikkönen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., van Duijn, C.M., Villringer, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16–102) and find 148 genome-wide significant independent loci (P < 5 × 10−8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Published
2018

209. The association of regional white matter lesions with cognition in a community-based cohort of older individuals

Author

Jiang, J., Paradise, M., Liu, T., Armstrong, N.J., Zhu, W., Kochan, N.A., Brodaty, H., Sachdev, P.S., Wen, W., Jiang, J., Paradise, M., Liu, T., Armstrong, N.J., Zhu, W., Kochan, N.A., Brodaty, H., Sachdev, P.S., and Wen, W.

Abstract

Emerging evidence from lesion-symptom mapping (LSM) studies suggested that regional white matter lesions (WML) on strategic white matter (WM) fiber tracts are significantly associated with specific cognitive domains, independent of global WML burden. However, previous LSM investigations were mostly carried out in disease cohorts, with little evidence from community-based older individuals, making findings difficult to generalize. Moreover, most LSM studies applied a threshold to the probabilistic atlas, leading to the loss of information and threshold-dependent findings. Furthermore, it is still unclear whether associations between regional WML and cognition are independent of global grey matter (GM) and WM volumes, which have also been linked to cognition. In the current study, we undertook a region of interest (ROI) LSM study to examine the relationship between regional WML on strategic WM tracts and cognitive performance in a large community-based cohort of older individuals (N = 461; 70–90 years). WML were extracted using a publicly available pipeline, UBO Detector (https://cheba.unsw.edu.au/group/neuroimaging-pipeline). Mapping of WML to the Johns Hopkins University WM atlas was undertaken using an automated TOolbox for Probabilistic MApping of Lesions (TOPMAL), which we introduce here, and is implemented in UBO Detector. The results show that different patterns of brain structural volumes in the ageing brain were associated with different cognitive domains. Regional WML were associated with processing speed, executive function, and global cognition, independent of total GM, WM and WML volumes. Moreover, regional WML explained more variance in executive function, compared to total GM, WM and WML volumes. The current study highlights the importance of studying regional WML in age-related cognitive decline.

Published
2018

210. Effectiveness of a peer-mediated educational intervention in improving general practitioner diagnostic assessment and management of dementia: a cluster randomised controlled trial

Author

Pond, D, Mate, K, Stocks, N, Gunn, J, Disler, P, Magin, P, Marley, J, Paterson, N, Horton, G, Goode, S, Weaver, N, Brodaty, H, Pond, D, Mate, K, Stocks, N, Gunn, J, Disler, P, Magin, P, Marley, J, Paterson, N, Horton, G, Goode, S, Weaver, N, and Brodaty, H

Abstract

OBJECTIVE: Test effectiveness of an educational intervention for general practitioners (GPs) on quality of life and depression outcomes for patients. DESIGN: Double-blind, cluster randomised controlled trial. SETTING: General practices in Australia between 2007 and 2010. PARTICIPANTS: General practices were randomly allocated to the waitlist (n=37) or intervention (n=66) group, in a ratio of 1:2. A total of 2030 (1478 intervention; 552 waitlist) community-dwelling participants aged 75 years or older were recruited via 168 GPs (113 intervention; 55 waitlist). INTERVENTIONS: A practice-based academic detailing intervention led by a peer educator that included: (1) training in use of the GP assessment of cognition dementia screening instrument; (2) training in diagnosis and management based on Royal Australian College of General Practitioners Dementia Guidelines; (3) addressing GPs' barriers to dementia diagnosis; and (4) a business case outlining a cost-effective dementia assessment approach. OUTCOME MEASURES: Primary outcome measures were patient quality of life and depression; secondary outcome measures were: (1) sensitivity and specificity of GP identification of dementia; (2) referral to medical specialists and/or support services; (3) patient satisfaction with care; and (4) carer quality of life, depression and satisfaction with care. RESULTS: The educational intervention had no significant effect on patient quality of life or depression scores after 12 months. There were however improvements in secondary outcome measures including sensitivity of GP judgement of dementia (p=0.002; OR 6.0, 95% CI 1.92 to 18.73), satisfaction with GP communication for all patients (p=0.024; mean difference 2.1, 95% CI 0.27 to 3.93) and for patients with dementia (p=0.007; mean difference 7.44, 95% CI 2.02 to 12.86) and enablement of carers (p=0.0185; mean difference 24.77, 95% CI 4.15 to 45.40). CONCLUSION: Practice-based academic detailing did not improve patient quality of life o

Published
2018

211. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

Author

Vojinovic, Dina, Adams, Hieab, Jian, XQ, Yang, Q, Smith, AV, Bis, JC, Teumer, A, Scholz, M, Armstrong, NJ, Hofer, E, Saba, Y, Luciano, M, Bernard, M, Trompet, S, Yang, JY, Gillespie, NA, van der Lee, Sven, Neumann, Alexander, Ahmad, Shahzad, Andreassen, OA, Ames, D, Amin, Najaf, Arfanakis, K, Bastin, ME, Becker, DM, Beiser, AS, Beyer, F, Brodaty, H, Bryan, RN, Bulow, R, Dale, AM, De Jager, PL, Deary, IJ, DeCarli, C, Fleischman, DA, Gottesman, RF, van der Grond, J, Gudnason, V, Harris, TB, Homuth, G, Knopman, DS, Kwok, JB, Lewis, CE, Li, S, Loeffler, M, Lopez, OL, Maillard, P, El Marroun, Hanan, Mather, KA, Mosley, TH, Muetzel, Ryan, Nauck, M, Nyquist, PA, Panizzon, MS, Pausova, Z, Psaty, BM, Rice, K, Rotter, JI, Royle, N, Satizabal, CL, Schmidt, R, Schofield, PR, Schreiner, PJ, Sidney, S, Stott, DJ, Thalamuthu, A, Uitterlinden, André, Hernandez, MCV, Vernooij, Meike, Wen, W, White, Tonya, Witte, AV, Wittfeld, K, Wright, MJ, Yanek, LR, Tiemeier, Henning, Kremen, WS, Bennett, DA, Jukema, JW, Paus, T, Wardlaw, JM, Schmidt, H, Sachdev, PS, Villringer, A, Grabe, HJ, Longstreth, WT, Duijn, Cornelia, Launer, LJ, Seshadri, S, Ikram, Arfan, Fornage, M, Vojinovic, Dina, Adams, Hieab, Jian, XQ, Yang, Q, Smith, AV, Bis, JC, Teumer, A, Scholz, M, Armstrong, NJ, Hofer, E, Saba, Y, Luciano, M, Bernard, M, Trompet, S, Yang, JY, Gillespie, NA, van der Lee, Sven, Neumann, Alexander, Ahmad, Shahzad, Andreassen, OA, Ames, D, Amin, Najaf, Arfanakis, K, Bastin, ME, Becker, DM, Beiser, AS, Beyer, F, Brodaty, H, Bryan, RN, Bulow, R, Dale, AM, De Jager, PL, Deary, IJ, DeCarli, C, Fleischman, DA, Gottesman, RF, van der Grond, J, Gudnason, V, Harris, TB, Homuth, G, Knopman, DS, Kwok, JB, Lewis, CE, Li, S, Loeffler, M, Lopez, OL, Maillard, P, El Marroun, Hanan, Mather, KA, Mosley, TH, Muetzel, Ryan, Nauck, M, Nyquist, PA, Panizzon, MS, Pausova, Z, Psaty, BM, Rice, K, Rotter, JI, Royle, N, Satizabal, CL, Schmidt, R, Schofield, PR, Schreiner, PJ, Sidney, S, Stott, DJ, Thalamuthu, A, Uitterlinden, André, Hernandez, MCV, Vernooij, Meike, Wen, W, White, Tonya, Witte, AV, Wittfeld, K, Wright, MJ, Yanek, LR, Tiemeier, Henning, Kremen, WS, Bennett, DA, Jukema, JW, Paus, T, Wardlaw, JM, Schmidt, H, Sachdev, PS, Villringer, A, Grabe, HJ, Longstreth, WT, Duijn, Cornelia, Launer, LJ, Seshadri, S, Ikram, Arfan, and Fornage, M

Abstract

The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (?genetic?=?-0.59, p-value?=?3.14?×?10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology

Published
2018

212. Variation in longitudinal trajectories of cortical sulci in normal elderly

Author

Shen, X, Liu, T, Tao, D, Fan, Y, Zhang, J, Li, S, Jiang, J, Zhu, W, Wang, Y, Brodaty, H, Sachdev, P, Wen, W, Shen, X, Liu, T, Tao, D, Fan, Y, Zhang, J, Li, S, Jiang, J, Zhu, W, Wang, Y, Brodaty, H, Sachdev, P, and Wen, W

Abstract

© 2017 Elsevier Inc. Sulcal morphology has been reported to change with age-related neurological diseases, but the trajectories of sulcal change in normal ageing in the elderly is still unclear. We conducted a study of sulcal morphological changes over seven years in 132 normal elderly participants aged 70–90 years at baseline, and who remained cognitively normal for the next seven years. We examined the fold opening and sulcal depth of sixteen (eight on each hemisphere) prominent sulci based on T1-weighted MRI using automated methods with visual quality control. The trajectory of each individual sulcus with respect to age was examined separately by linear mixed models. Fold opening was best modelled by cubic fits in five sulci, by quadratic models in six sulci and by linear models in five sulci, indicating an accelerated widening of a number of sulci in older age. Sulcal depth showed significant linear decline in three sulci and quadratic trend in one sulcus. Turning points of non-linear trajectories towards accelerated widening of the fold were found to be around the age between 75 and 80, indicating an accelerated atrophy of brain cortex starting in the age of late 70s. Our findings of cortical sulcal changes in normal ageing could provide a reference for studies of neurocognitive disorders, including neurodegenerative diseases, in the elderly.

Published
2018

213. Variation in longitudinal trajectories of cortical sulci in normal elderly

Author

Shen, X, Liu, T, Tao, D, Fan, Y, Zhang, J, Li, S, Jiang, J, Zhu, W, Wang, Y, Brodaty, H, Sachdev, P, and Wen, W

Subjects
Cerebral Cortex, Aged, 80 and over, Male, Aging, Neurology & Neurosurgery, Age Factors, Humans, Female, Longitudinal Studies, Atrophy, Magnetic Resonance Imaging, Aged
Abstract

© 2017 Elsevier Inc. Sulcal morphology has been reported to change with age-related neurological diseases, but the trajectories of sulcal change in normal ageing in the elderly is still unclear. We conducted a study of sulcal morphological changes over seven years in 132 normal elderly participants aged 70–90 years at baseline, and who remained cognitively normal for the next seven years. We examined the fold opening and sulcal depth of sixteen (eight on each hemisphere) prominent sulci based on T1-weighted MRI using automated methods with visual quality control. The trajectory of each individual sulcus with respect to age was examined separately by linear mixed models. Fold opening was best modelled by cubic fits in five sulci, by quadratic models in six sulci and by linear models in five sulci, indicating an accelerated widening of a number of sulci in older age. Sulcal depth showed significant linear decline in three sulci and quadratic trend in one sulcus. Turning points of non-linear trajectories towards accelerated widening of the fold were found to be around the age between 75 and 80, indicating an accelerated atrophy of brain cortex starting in the age of late 70s. Our findings of cortical sulcal changes in normal ageing could provide a reference for studies of neurocognitive disorders, including neurodegenerative diseases, in the elderly.

Published
2017

214. Associations between reaction time measures and white matter hyperintensities in very old age

Author

Haynes, BI, Bunce, D, Kochan, NA, Wen, W, Brodaty, H, and Sachdev, PS

Subjects
mental disorders, behavioral disciplines and activities
Abstract

In old age, a relationship has been reported between intraindividual variability (IIV) in reaction time and white matter integrity as evidenced by white matter hyperintensities (WMH). However, it is unclear how far such associations are due to incipient neurodegenerative pathology in the samples investigated. The present study examined the relationship between IIV and WMH in older individuals (N=526) drawn from the Sydney Memory and Ageing Study. Using a complex reaction time (RT) task, greater IIV and mean-RT were related to a higher WMH burden in the frontal lobe. Critically, significant associations remained having taken future dementia into account suggesting that they were not explained by incipient dementia. Additionally, independent measures of executive function accounted for the association between RT metrics and WHM. The results are consistent with the view that frontally-supported cognitive processes are involved in IIV-WMH relations, and that RT measures are sensitive to compromise in white matter structures in non-demented older individuals.

Published
2017

215. Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Author

Lipnicki, D.M. Crawford, J.D. Dutta, R. Thalamuthu, A. Kochan, N.A. Andrews, G. Lima-Costa, M.F. Castro-Costa, E. Brayne, C. Matthews, F.E. Stephan, B.C.M. Lipton, R.B. Katz, M.J. Ritchie, K. Scali, J. Ancelin, M.-L. Scarmeas, N. Yannakoulia, M. Dardiotis, E. Lam, L.C.W. Wong, C.H.Y. Fung, A.W.T. Guaita, A. Vaccaro, R. Davin, A. Kim, K.W. Han, J.W. Kim, T.H. Anstey, K.J. Cherbuin, N. Butterworth, P. Scazufca, M. Kumagai, S. Chen, S. Narazaki, K. Ng, T.P. Gao, Q. Reppermund, S. Brodaty, H. Lobo, A. Lopez-Anton, R. Santabárbara, J. Sachdev, P.S. Cohort Studies of Memory in an International Consortium (COSMIC)

Abstract

Background: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Conclusions: Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data. © 2017 Lipnicki et al.

Published
2017

216. Apathy associated with neurocognitive disorders: Recent progress and future directions

Author

Lanctôt, K.L. Agüera-Ortiz, L. Brodaty, H. Francis, P.T. Geda, Y.E. Ismail, Z. Marshall, G.A. Mortby, M.E. Onyike, C.U. Padala, P.R. Politis, A.M. Rosenberg, P.B. Siegel, E. Sultzer, D.L. Abraham, E.H.

Abstract

Introduction Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities. Methods The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs. Results Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches. Discussion Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention. © 2016 the Alzheimer's Association

Published
2017

219. Risk Factors for Mild Cognitive Impairment, Dementia and Mortality: The Sydney Memory and Ageing Study

Author

Lipnicki, DM, Crawford, J, Kochan, NA, Trollor, JN, Draper, B, Reppermund, S, Maston, K, Mather, KA, Brodaty, H, Sachdev, PS, Lipnicki, DM, Crawford, J, Kochan, NA, Trollor, JN, Draper, B, Reppermund, S, Maston, K, Mather, KA, Brodaty, H, and Sachdev, PS

Abstract

© 2016 AMDA - The Society for Post-Acute and Long-Term Care Medicine.Background: The nature and commonality of late-life risk factors for mild cognitive impairment (MCI), dementia, and mortality remain unclear. Our aim was to investigate potential risk factors, simultaneously in a single cohort including many individuals initially with normal cognition and followed for 6 years. Methods: We classified 873 community-dwelling individuals (70-90 years old and without dementia at baseline) from the Sydney Memory and Ageing Study as cognitively normal (CN), having MCI or dementia, or deceased 6 years after baseline. Associations with baseline demographic, lifestyle, health, and medical factors were investigated, including apolipoprotein (APOE) genotype, MCI at baseline, and reversion from MCI to CN within 2 years of baseline. Results: Eighty-three (9.5%) participants developed dementia and 114 (13%) died within 6 years; nearly 33% had MCI at baseline, of whom 28% reverted to CN within 2 years. A core set of baseline factors was associated with MCI and dementia at 6 years, including older age (per year: odds ratios and 95% confidence intervals = 1.08, 1.01-1.14 for MCI; 1.19, 1.09-1.31 for dementia), MCI at baseline (5.75, 3.49-9.49; 8.23, 3.93-17.22), poorer smelling ability (per extra test point: 0.89, 0.79-1.02; 0.80, 0.68-0.94), slower walking speed (per second: 1.12, 1.00-1.25; 1.21, 1.05-1.39), and being an . APOE ε4 carrier (1.84, 1.07-3.14; 3.63, 1.68-7.82). All except . APOE genotype were also associated with mortality (age: 1.11, 1.03-1.20; MCI: 3.87, 1.97-7.59; smelling ability: 0.83, 0.70-0.97; walking speed: 1.18, 1.03-1.34). Compared with stable CN participants, individuals reverting from MCI to CN after 2 years were at greater risk of future MCI (3.06, 1.63-5.72). Those who reverted exhibited some different associations between baseline risk factors and 6-year outcomes than individuals with stable MCI. Conclusion: A core group of late-life risk factors indic

Published
2017

221. Effects of MCI subtype and reversion on progression to dementia in a community sample

Author

Aerts, L, Heffernan, M, Kochan, NA, Crawford, JD, Draper, B, Trollor, JN, Sachdev, PS, Brodaty, H, Aerts, L, Heffernan, M, Kochan, NA, Crawford, JD, Draper, B, Trollor, JN, Sachdev, PS, and Brodaty, H

Abstract

OBJECTIVE: We sought to understand the trajectory of mild cognitive impairment (MCI) better by examining longitudinally different MCI subtypes and progression to dementia and reversion to normal cognition in a community sample. METHODS: We evaluated the stability of MCI subtypes and risk of dementia over 4 biennial assessments as part of an ongoing prospective cohort study, the Sydney Memory and Ageing Study. RESULTS: While prevalence of MCI and different MCI subtypes remains relatively stable across all assessments, reversion from MCI and transitions between different MCI subtypes were common. Up to 46.5% of participants classified with MCI at baseline reverted at some point during follow-up. The majority (83.8%) of participants with incident dementia were diagnosed with MCI 2 years prior to their dementia diagnosis. Both reverters and participants with stable MCI were at an increased risk of progression to dementia compared to those without MCI at baseline (HR 6.4, p = 0.02, and HR 24.7, p < 0.001, respectively); however, the risk of dementia in participants with MCI who did not revert was higher than in reverters (HR 2.5, p = 0.01). This effect was specific to amnestic subtypes (MCI reverters vs nonreverters: amnestic MCI HR 3.3, p = 0.006; nonamnestic MCI: HR 1.3, p = 0.67). CONCLUSION: Our findings indicate that the relevance of reversion for progression risk depends on the MCI subtype. Subtype specificity and longitudinal characterization are required for the reliable identification of individuals at high risk of developing dementia.

Published
2017

222. Operationalizing the Diagnostic Criteria for Mild Cognitive Impairment: The Salience of Objective Measures in Predicting Incident Dementia

Author

Brodaty, H, Aerts, L, Crawford, JD, Heffernan, M, Kochan, NA, Reppermund, S, Kang, K, Maston, K, Draper, B, Trollor, JN, Sachdev, PS, Brodaty, H, Aerts, L, Crawford, JD, Heffernan, M, Kochan, NA, Reppermund, S, Kang, K, Maston, K, Draper, B, Trollor, JN, and Sachdev, PS

Abstract

© 2017 American Association for Geriatric Psychiatry.Objective: Mild cognitive impairment (MCI) is considered an intermediate stage between normal aging and dementia. It is diagnosed in the presence of subjective cognitive decline and objective cognitive impairment without significant functional impairment, although there are no standard operationalizations for each of these criteria. The objective of this study is to determine which operationalization of the MCI criteria is most accurate at predicting dementia. Design: Six-year longitudinal study, part of the Sydney Memory and Ageing Study. Setting: Community-based. Participants: 873 community-dwelling dementia-free adults between 70 and 90 years of age. Persons from a non-English speaking background were excluded. Measurements: Seven different operationalizations for subjective cognitive decline and eight measures of objective cognitive impairment (resulting in 56 different MCI operational algorithms) were applied. The accuracy of each algorithm to predict progression to dementia over 6 years was examined for 618 individuals. Results: Baseline MCI prevalence varied between 0.4% and 30.2% and dementia conversion between 15.9% and 61.9% across different algorithms. The predictive accuracy for progression to dementia was poor. The highest accuracy was achieved based on objective cognitive impairment alone. Inclusion of subjective cognitive decline or mild functional impairment did not improve dementia prediction accuracy. Conclusions: Not MCI, but objective cognitive impairment alone, is the best predictor for progression to dementia in a community sample. Nevertheless, clinical assessment procedures need to be refined to improve the identification of pre-dementia individuals.

Published
2017

223. Suicidality: Prevention, detection and intervention

Author

Anderson, J, Mitchell, PB, Brodaty, H, Anderson, J, Mitchell, PB, and Brodaty, H

Abstract

© 2017 NPS MedicineWise. Australian suicide rates are increasing. GPs have a key role in the early detection and management of suicidality and the treatment of commonly associated mood disorders and substance misuse. Drugs are indicated for moderate to severe depression. They can also be considered for patients who have been unable to access, do not want or have not responded to psychological treatments. Selective serotonin reuptake inhibitors are less toxic than serotonin noradrenaline reuptake inhibitors. Tricyclic antidepressants are the most dangerous in overdose. Mood stabilising drugs can be prescribed, but in large quantities they are dangerous in overdose. In depressed adolescents psychological therapies are first-line treatments. When drugs are indicated, in older people selective serotonin reuptake inhibitors are generally well tolerated, but paroxetine and fluoxetine are best avoided.

Published
2017

224. Prospective memory function and cue salience in mild cognitive impairment: Findings from the Sydney Memory and Ageing Study

Author

Thompson, CL, Henry, JD, Rendell, PG, Withall, A, Kochan, NA, Sachdev, P, Brodaty, H, Thompson, CL, Henry, JD, Rendell, PG, Withall, A, Kochan, NA, Sachdev, P, and Brodaty, H

Abstract

© 2017 Informa UK Limited, trading as Taylor & Francis Group Objective: Prospective memory (PM) is crucial to the maintenance of functional independence in late adulthood and is consistently impaired in mild cognitive impairment (MCI). There remains a need for brief but valid measures of this construct that can be used as part of a comprehensive clinical assessment of cognition. Since the distinctiveness of PM cues is argued to determine the degree of strategic, controlled demands of PM paradigms, two variants of a brief measure were developed, one of which presented low-salience and the other high-salience PM cues. Method: A large cohort of older adults with normal cognition or MCI was assessed with one of the two variants of our brief, novel measure of PM. Participants were asked to remember to execute PM tasks where the target cue was either high or low in salience, while concurrently engaged in an ongoing task of olfactory assessment. Results: The task was able to discriminate between groups of participants with MCI or no cognitive impairment, albeit with a small effect size. The high-salience cue improved performance on the PM task; however, there was no interaction of cue salience with group. Conclusions: These results suggest that the temporal reliability and construct validity of very brief measures of the type used in this study need further exploration to determine their potential to provide meaningful insights into PM function. This measure may have utility as a brief screening tool, with identified deficits being followed up with a more comprehensive PM assessment.

Published
2017

225. Classifying MCI subtypes in community-dwelling elderly using cross-sectional and longitudinal MRI-based biomarkers

Author

Guan, H, Liu, T, Jiang, J, Tao, D, Zhang, J, Niu, H, Zhu, W, Wang, Y, Cheng, J, Kochan, NA, Brodaty, H, Sachdev, P, Wen, W, Guan, H, Liu, T, Jiang, J, Tao, D, Zhang, J, Niu, H, Zhu, W, Wang, Y, Cheng, J, Kochan, NA, Brodaty, H, Sachdev, P, and Wen, W

Abstract

Amnestic MCI (aMCI) and non-amnestic MCI (naMCI) are considered to differ in etiology and outcome. Accurately classifying MCI into meaningful subtypes would enable early intervention with targeted treatment. In this study, we employed structural magnetic resonance imaging (MRI) for MCI subtype classification. This was carried out in a sample of 184 community-dwelling individuals (aged 73-85 years). Cortical surface based measurements were computed from longitudinal and cross-sectional scans. By introducing a feature selection algorithm, we identified a set of discriminative features, and further investigated the temporal patterns of these features. A voting classifier was trained and evaluated via 10 iterations of cross-validation. The best classification accuracies achieved were: 77% (naMCI vs. aMCI), 81% (aMCI vs. cognitively normal (CN)) and 70% (naMCI vs. CN). The best results for differentiating aMCI from naMCI were achieved with baseline features. Hippocampus, amygdala and frontal pole were found to be most discriminative for classifying MCI subtypes. Additionally, we observed the dynamics of classification of several MRI biomarkers. Learning the dynamics of atrophy may aid in the development of better biomarkers, as it may track the progression of cognitive impairment.

Published
2017

226. Why aren't people with young onset dementia and their supporters using formal services? Results from the INSPIRED study

Author

Cations, M, Withall, A, Horsfall, R, Denham, N, White, F, Trollor, J, Loy, C, Brodaty, H, Sachdev, PS, Gonski, P, Demirkol, A, Cumming, RG, Draper, B, Cations, M, Withall, A, Horsfall, R, Denham, N, White, F, Trollor, J, Loy, C, Brodaty, H, Sachdev, PS, Gonski, P, Demirkol, A, Cumming, RG, and Draper, B

Abstract

BACKGROUND/AIMS: Despite reporting high levels of burden, supporters of people with young onset dementia (YOD) underuse formal community services. Previous quantitative studies in YOD are of limited utility in guiding service design because they did not consider important contextual barriers to service use. The aim of this study was to identify all relevant barriers and describe the service features considered most important to improving uptake by people with YOD and their supporters. METHODS: Eighty-six people with consensus-confirmed YOD (mean onset age 55.3 years) and/or their primary supporter participated in quantitative interviews, and 50 also participated in one of seven qualitative focus groups. Interview participants reported levels of community service use and reasons for non-use, functional impairment, behavioural and psychological symptoms, supporter burden, social network, and informal care provision. Focus group participants expanded on reasons for non-use and aspects of an ideal service. RESULTS: Although at least one community service was recommended to most participants (96.8%), 66.7% chose not to use one or more of these. Few of the clinical or demographic factors included here were related to service use. Qualitative analyses identified that lack of perceived need, availability, and YOD-specific barriers (including ineligibility, unaffordability, lack of security, lack of childcare) were commonly reported. Five aspects of an ideal service were noted: unique, flexibile, affordable, tailored, and promoting meaningful engagement. CONCLUSION: People with YOD and their families report that formal community services do not meet their personal and psychological needs. Researchers can provide ongoing assessment of program feasibility, suitability, and generalisability.

Published
2017

227. Midlife managerial experience is linked to late life hippocampal morphology and function

Author

Suo, C, Gates, N, Fiatarone Singh, M, Saigal, N, Wilson, GC, Meiklejohn, J, Sachdev, P, Brodaty, H, Wen, W, Singh, N, Baune, BT, Baker, M, Foroughi, N, Wang, Y, Valenzuela, MJ, Suo, C, Gates, N, Fiatarone Singh, M, Saigal, N, Wilson, GC, Meiklejohn, J, Sachdev, P, Brodaty, H, Wen, W, Singh, N, Baune, BT, Baker, M, Foroughi, N, Wang, Y, and Valenzuela, MJ

Abstract

© 2016 The Author(s)An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p = 0.024), mediated by larger hippocampal volume (p = 0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p < 0.05). Paradoxically, this group rated their memory proficiency worse (p = 0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p < 0.001). Finally, hierarchical regression modelling substantiated this double dissociation.

Published
2017

228. Performance-Based Assessment of Instrumental Activities of Daily Living: Validation of the Sydney Test of Activities of Daily Living in Memory Disorders (STAM)

Author

Reppermund, S, Birch, RC, Crawford, JD, Wesson, J, Draper, B, Kochan, NA, Trollor, JN, Luttenberger, K, Brodaty, H, Sachdev, PS, Reppermund, S, Birch, RC, Crawford, JD, Wesson, J, Draper, B, Kochan, NA, Trollor, JN, Luttenberger, K, Brodaty, H, and Sachdev, PS

Abstract

OBJECTIVES: The distinction between dementia and mild cognitive impairment (MCI) relies upon the evaluation of independence in instrumental activities of daily living (IADL). Self- and informant reports are prone to bias. Clinician-based performance tests are limited by long administration times, restricted access, or inadequate validation. To close this gap, we developed and validated a performance-based measure of IADL, the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). DESIGN: Prospective cohort study (Sydney Memory and Ageing Study). SETTING: Eastern Suburbs, Sydney, Australia. PARTICIPANTS: 554 community-dwelling individuals (54% female) aged 76 and older with normal cognition, MCI, or dementia. MEASUREMENTS: Activities of daily living were assessed with the STAM, administered by trained psychologists, and the informant-based Bayer-Activities of Daily Living Scale (B-ADL). Depressive symptoms were measured with the Geriatric Depression Scale (15-item version). Cognitive function was assessed with a comprehensive neuropsychological test battery. Consensus diagnoses of MCI and dementia were made independently of STAM scores. RESULTS: The STAM showed high interrater reliability (r = 0.854) and test-retest reliability (r = 0.832). It discriminated significantly between the diagnostic groups of normal cognition, MCI, and dementia with areas under the curves ranging from 0.723 to 0.948. A score of 26.5 discriminated between dementia and nondementia with a sensitivity of 0.831 and a specificity of 0.864. Correlations were low with education (r = 0.230) and depressive symptoms (r = -0.179), moderate with the B-ADL (r = -0.332), and high with cognition (ranging from r = 0.511 to r = 0.594). The mean time to complete the STAM was 16 minutes. CONCLUSIONS: The STAM has good psychometric properties. It can be used to differentiate between normal cognition, MCI, and dementia and can be a helpful tool for diagnostic classification both in clinical pract

Published
2017

229. Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks

Author

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

Abstract

AIM: To examine the relationships between two epigenetic clocks, aging and exceptional longevity. MATERIALS & METHODS: Participants were from three adult cohorts with blood DNA methylation data (Illumina 450 K, n = 275, 34-103 years). Epigenetic age (DNAmage) and age acceleration measures were calculated using the Hannum and Horvath epigenetic clocks. RESULTS: Across all cohorts, DNAmage was correlated with chronological age. In the long-lived cohort (Sydney Centenarian Study; 95+, n = 23), DNAmage was lower than chronological age for both clocks. Mean Sydney Centenarian Study Hannum age acceleration was negative, while the converse was observed for the Horvath model. CONCLUSION: Long-lived individuals have a young epigenetic age compared with their chronological age.

Published
2017

230. Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Author

Lipnicki, DM, Crawford, JD, Dutta, R, Thalamuthu, A, Kochan, NA, Andrews, G, Lima-Costa, MF, Castro-Costa, E, Brayne, C, Matthews, FE, Stephan, BCM, Lipton, RB, Katz, MJ, Ritchie, K, Scali, J, Ancelin, ML, Scarmeas, N, Yannakoulia, M, Dardiotis, E, Lam, LCW, Wong, CHY, Fung, AWT, Guaita, A, Vaccaro, R, Davin, A, Kim, KW, Han, JW, Kim, TH, Anstey, KJ, Cherbuin, N, Butterworth, P, Scazufca, M, Kumagai, S, Chen, S, Narazaki, K, Ng, TP, Gao, Q, Reppermund, S, Brodaty, H, Lobo, A, Lopez-Anton, R, Santabárbara, J, Sachdev, PS, Lipnicki, DM, Crawford, JD, Dutta, R, Thalamuthu, A, Kochan, NA, Andrews, G, Lima-Costa, MF, Castro-Costa, E, Brayne, C, Matthews, FE, Stephan, BCM, Lipton, RB, Katz, MJ, Ritchie, K, Scali, J, Ancelin, ML, Scarmeas, N, Yannakoulia, M, Dardiotis, E, Lam, LCW, Wong, CHY, Fung, AWT, Guaita, A, Vaccaro, R, Davin, A, Kim, KW, Han, JW, Kim, TH, Anstey, KJ, Cherbuin, N, Butterworth, P, Scazufca, M, Kumagai, S, Chen, S, Narazaki, K, Ng, TP, Gao, Q, Reppermund, S, Brodaty, H, Lobo, A, Lopez-Anton, R, Santabárbara, J, and Sachdev, PS

Abstract

© 2017 Lipnicki et al. Background: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (

Published
2017

231. A home-based, carer-enhanced exercise program improves balance and falls efficacy in community-dwelling older people with dementia

Author

Taylor, ME, Lord, SR, Brodaty, H, Kurrle, SE, Hamilton, S, Ramsay, E, Webster, L, Payne, NL, Close, JCT, Taylor, ME, Lord, SR, Brodaty, H, Kurrle, SE, Hamilton, S, Ramsay, E, Webster, L, Payne, NL, and Close, JCT

Abstract

Background: Older people with dementia are at increased risk of physical decline and falls. Balance and mood are significant predictors of falls in this population. The aim of this study was to determine the effect of a tailored home-based exercise program in community-dwelling older people with dementia. Methods: Forty-two participants with mild to moderate dementia were recruited from routine health services. All participants were offered a six-month home-based, carer-enhanced, progressive, and individually tailored exercise program. Physical activity, quality of life, physical, and psychological assessments were administered at the beginning and end of the trial. Results: Of 33 participants (78.6%) who completed the six-month reassessment ten (30%) reported falls and six (18%) multiple falls during the follow-up period. At reassessment, participants had better balance (sway on floor and foam), reduced concern about falls, increased planned physical activity, but worse knee extension strength and no change in depression scores. The average adherence to the prescribed exercise sessions was 45% and 22 participants (52%) were still exercising at trial completion. Those who adhered to ≥70% of prescribed sessions had significantly better balance at reassessment compared with those who adhered to <70% of sessions. Conclusions: This trial of a tailored home-based exercise intervention presents preliminary evidence that this intervention can improve balance, concern about falls, and planned physical activity in community-dwelling older people with dementia. Future research should determine whether exercise interventions are effective in reducing falls and elucidate strategies for enhancing uptake and adherence in this population.

Published
2017

232. Plasma apolipoproteins and physical and cognitive health in very old individuals

Author

Muenchhoff, J, Song, F, Poljak, A, Crawford, JD, Mather, KA, Kochan, NA, Yang, Z, Trollor, JN, Reppermund, S, Maston, K, Theobald, A, Kirchner-Adelhardt, S, Kwok, JB, Richmond, RL, McEvoy, M, Attia, J, Schofield, PW, Brodaty, H, Sachdev, PS, Muenchhoff, J, Song, F, Poljak, A, Crawford, JD, Mather, KA, Kochan, NA, Yang, Z, Trollor, JN, Reppermund, S, Maston, K, Theobald, A, Kirchner-Adelhardt, S, Kwok, JB, Richmond, RL, McEvoy, M, Attia, J, Schofield, PW, Brodaty, H, and Sachdev, PS

Abstract

Apolipoproteins play a crucial role in lipid metabolism with implications in cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We quantified 7 apolipoproteins in plasma in 1067 individuals aged 56–105 using immunoassays and explored relationships with APOE polymorphism ε2/3/4, vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH, and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends. Centenarians had the highest ApoE levels and the lowest frequency of APOE ε4 allele relative to younger groups. Apolipoprotein levels trended lower in APOE ε4 homozygotes and heterozygotes compared with noncarriers, with ApoE and ApoJ being significantly lower. Levels of all apolipoproteins except ApoH were higher in females. Sex- and age-related differences were apparent in the association of apolipoproteins with cognitive performance, as only women had significant negative associations of ApoB, ApoE, ApoH, and ApoJ in mid-life, whereas associations at older age were nonsignificant or positive. Our findings suggest levels of some apolipoproteins, especially ApoE, are associated with lifespan and cognitive function in exceptionally long-lived individuals.

Published
2017

233. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

Author

Guadalupe, T, Mathias, SR, vanErp, TGM, Whelan, CD, Zwiers, MP, Abe, Y, Abramovic, L, Agartz, I, Andreassen, OA, Arias-Vásquez, A, Aribisala, BS, Armstrong, NJ, Arolt, V, Artiges, E, Ayesa-Arriola, R, Baboyan, VG, Banaschewski, T, Barker, G, Bastin, ME, Baune, BT, Blangero, J, Bokde, ALW, Boedhoe, PSW, Bose, A, Brem, S, Brodaty, H, Bromberg, U, Brooks, S, Büchel, C, Buitelaar, J, Calhoun, VD, Cannon, DM, Cattrell, A, Cheng, Y, Conrod, PJ, Conzelmann, A, Corvin, A, Crespo-Facorro, B, Crivello, F, Dannlowski, U, de Zubicaray, GI, de Zwarte, SMC, Deary, IJ, Desrivières, S, Doan, NT, Donohoe, G, Dørum, ES, Ehrlich, S, Espeseth, T, Fernández, G, Flor, H, Fouche, J-P, Frouin, V, Fukunaga, M, Gallinat, J, Garavan, H, Gill, M, Suarez, AG, Gowland, P, Grabe, HJ, Grotegerd, D, Gruber, O, Hagenaars, S, Hashimoto, R, Hauser, TU, Heinz, A, Hibar, DP, Hoekstra, PJ, Hoogman, M, Howells, FM, Hu, H, Hulshoff Pol, HE, Huyser, C, Ittermann, B, Jahanshad, N, Jönsson, EG, Jurk, S, Kahn, RS, Kelly, S, Kraemer, B, Kugel, H, Kwon, JS, Lemaitre, H, Lesch, K-P, Lochner, C, Luciano, M, Marquand, AF, Martin, NG, Martínez-Zalacaín, I, Martinot, J-L, Mataix-Cols, D, Mather, K, McDonald, C, McMahon, KL, Medland, SE, Menchón, JM, Morris, DW, Mothersill, O, Maniega, SM, Mwangi, B, Nakamae, T, Nakao, T, Narayanaswaamy, JC, Nees, F, Nordvik, JE, Onnink, AMH, Opel, N, Ophoff, R, Paillère Martinot, M-L, Papadopoulos Orfanos, D, Pauli, P, Paus, T, Poustka, L, Reddy, JY, Renteria, ME, Roiz-Santiáñez, R, Roos, A, Royle, NA, Sachdev, P, Sánchez-Juan, P, Schmaal, L, Schumann, G, Shumskaya, E, Smolka, MN, Soares, JC, Soriano-Mas, C, Stein, DJ, Strike, LT, Toro, R, Turner, JA, Tzourio-Mazoyer, N, Uhlmann, A, Hernández, MV, van den Heuvel, OA, van der Meer, D, van Haren, NEM, Veltman, DJ, Venkatasubramanian, G, Vetter, NC, Vuletic, D, Walitza, S, Walter, H, Walton, E, Wang, Z, Wardlaw, J, Wen, W, Westlye, LT, Whelan, R, Wittfeld, K, Wolfers, T, Wright, MJ, Xu, J, Xu, X, Yun, J-Y, Zhao, J, Franke, B, Thompson, PM, Glahn, DC, Mazoyer, B, Fisher, SE, Francks, C, Guadalupe, T, Mathias, SR, vanErp, TGM, Whelan, CD, Zwiers, MP, Abe, Y, Abramovic, L, Agartz, I, Andreassen, OA, Arias-Vásquez, A, Aribisala, BS, Armstrong, NJ, Arolt, V, Artiges, E, Ayesa-Arriola, R, Baboyan, VG, Banaschewski, T, Barker, G, Bastin, ME, Baune, BT, Blangero, J, Bokde, ALW, Boedhoe, PSW, Bose, A, Brem, S, Brodaty, H, Bromberg, U, Brooks, S, Büchel, C, Buitelaar, J, Calhoun, VD, Cannon, DM, Cattrell, A, Cheng, Y, Conrod, PJ, Conzelmann, A, Corvin, A, Crespo-Facorro, B, Crivello, F, Dannlowski, U, de Zubicaray, GI, de Zwarte, SMC, Deary, IJ, Desrivières, S, Doan, NT, Donohoe, G, Dørum, ES, Ehrlich, S, Espeseth, T, Fernández, G, Flor, H, Fouche, J-P, Frouin, V, Fukunaga, M, Gallinat, J, Garavan, H, Gill, M, Suarez, AG, Gowland, P, Grabe, HJ, Grotegerd, D, Gruber, O, Hagenaars, S, Hashimoto, R, Hauser, TU, Heinz, A, Hibar, DP, Hoekstra, PJ, Hoogman, M, Howells, FM, Hu, H, Hulshoff Pol, HE, Huyser, C, Ittermann, B, Jahanshad, N, Jönsson, EG, Jurk, S, Kahn, RS, Kelly, S, Kraemer, B, Kugel, H, Kwon, JS, Lemaitre, H, Lesch, K-P, Lochner, C, Luciano, M, Marquand, AF, Martin, NG, Martínez-Zalacaín, I, Martinot, J-L, Mataix-Cols, D, Mather, K, McDonald, C, McMahon, KL, Medland, SE, Menchón, JM, Morris, DW, Mothersill, O, Maniega, SM, Mwangi, B, Nakamae, T, Nakao, T, Narayanaswaamy, JC, Nees, F, Nordvik, JE, Onnink, AMH, Opel, N, Ophoff, R, Paillère Martinot, M-L, Papadopoulos Orfanos, D, Pauli, P, Paus, T, Poustka, L, Reddy, JY, Renteria, ME, Roiz-Santiáñez, R, Roos, A, Royle, NA, Sachdev, P, Sánchez-Juan, P, Schmaal, L, Schumann, G, Shumskaya, E, Smolka, MN, Soares, JC, Soriano-Mas, C, Stein, DJ, Strike, LT, Toro, R, Turner, JA, Tzourio-Mazoyer, N, Uhlmann, A, Hernández, MV, van den Heuvel, OA, van der Meer, D, van Haren, NEM, Veltman, DJ, Venkatasubramanian, G, Vetter, NC, Vuletic, D, Walitza, S, Walter, H, Walton, E, Wang, Z, Wardlaw, J, Wen, W, Westlye, LT, Whelan, R, Wittfeld, K, Wolfers, T, Wright, MJ, Xu, J, Xu, X, Yun, J-Y, Zhao, J, Franke, B, Thompson, PM, Glahn, DC, Mazoyer, B, Fisher, SE, and Francks, C

Abstract

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

Published
2017

234. Novel genetic loci associated with hippocampal volume

Author

Hibar, D.P. (Derrek), Adams, H.H.H. (Hieab), Jahanshad, N. (Neda), Chauhan, G. (Ganesh), Stein, J.L., Hofer, E. (Edith), Rentería, M.E. (Miguel), Bis, J.C. (Joshua), Arias-Vásquez, A. (Alejandro), Ikram, M.K. (M. Kamran), Desrivières, S. (Sylvane), Vernooij, M.W. (Meike), Abramovic, L. (Lucija), Alhusaini, S. (Saud), Amin, N. (Najaf), Andersson, M. (Micael), Arfanakis, K. (Konstantinos), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Athanasiu, L. (Lavinia), Axelsson, T. (Tomas), Beecham, A.H. (Ashley), Beiser, A. (Alexa), Bernard, M. (Manon), Blanton, S.H. (Susan H.), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brickman, A.M. (Adam M.), Carmichael, O. (Owen), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Chouraki, V. (Vincent), Cuellar-Partida, G. (Gabriel), Crivello, F. (Fabrice), Braber, A. (Anouk) den, Doan, N.T. (Nhat Trung), Ehrlich, S.M. (Stefan), Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Gottesman, R.F. (Rebecca), Grimm, O. (Oliver), Griswold, M.D. (Michael), Guadalupe, T. (Tulio), Gutman, B.A. (Boris A.), Hass, J. (Johanna), Haukvik, U.K. (Unn), Hoehn, D. (David), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Jørgensen, K.N. (Kjetil N.), Karbalai, N. (Nazanin), Kasperaviciute, D. (Dalia), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Luciano, M. (Michelle), MacAre, C. (Christine), Marquand, A.F. (Andre F.), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), McKay, D.R. (David R.), Milaneschi, Y. (Yuri), Muñoz Maniega, S. (Susana), Nho, K. (Kwangsik), Nugent, A.C. (Allison), Nyquist, P. (Paul), Loohuis, L.M.O. (Loes M. Olde), Oosterlaan, J. (Jaap), Papmeyer, M. (Martina), Pirpamer, L. (Lukas), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Richards, J.S. (Jennifer S.), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rommelse, N. (Nanda), Ropele, S. (Stefan), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rundek, T. (Tatjana), Sämann, P.G. (Philipp), Saremi, A. (Arvin), Satizabal, C.L. (Claudia), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shen, L. (Li), Shin, J. (Jean), Shumskaya, E. (Elena), Smith, A.V. (Albert Vernon), Sprooten, R. (Roy), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Tordesillas-Gutierrez, D. (Diana), Toro, R. (Roberto), Trabzuni, D. (Danyah), Trompet, S. (Stella), Vaidya, D. (Dhananjay), van der Grond, J. (Jeroen), Lee, S.J. (Sven) van der, Van Der Meer, D. (Dennis), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Van Rooij, D. (Daan), Walton, E. (Esther), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Windham, B.G. (Gwen), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Wolfers, T. (Thomas), Yanek, L.R. (Lisa), Yang, J. (Jingyun), Zijdenbos, A.P., Zwiers, M.P. (Marcel), Agartz, I. (Ingrid), Almasy, L. (Laura), Ames, D.J. (David), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Arepalli, S. (Sampath), Assareh, A.A., Barral, S. (Sandra), Bastin, M.E. (Mark), Becker, D.M. (Diane M.), Becker, J.T. (James), Bennett, D.A. (David A.), Blangero, J. (John), Bokhoven, H. (Hans) van, Boomsma, D.I. (Dorret), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cavalleri, G. (Gianpiero), Cheng, C.-Y. (Ching-Yu), Cichon, S. (Sven), Cookson, M.R. (Mark), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Dale, A.M. (Anders), Davies, G.E. (Gareth), Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Jager, P.L. (Philip) de, Zubicaray, G.I. (Greig) de, Deary, I.J. (Ian), Debette, S. (Stéphanie), DeCarli, C. (Charles), Delanty, N., Depondt, C. (Chantal), DeStefano, A.L. (Anita), Dillman, A. (Allissa), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drevets, D.A. (Douglas), Duggirala, R. (Ravi), Dyer, M.D. (Matthew), Enzinger, C. (Christian), Erk, S., Espeseth, T. (Thomas), Fedko, I.O. (Iryna O.), Fernández, G. (Guillén), Ferrucci, L. (Luigi), Fisher, S.E. (Simon), Fleischman, D. (Debra), Ford, I. (Ian), Fornage, M. (Myriam), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Fukunaga, M. (Masaki), Gibbs, J.R. (J. Raphael), Glahn, D.C. (David), Gollub, R.L. (Randy), Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Gruber, O. (Oliver), Gudnason, V. (Vilmundur), Guelfi, S. (Sebastian), Håberg, A.K. (Asta K.), Hansell, N.K. (Narelle), Hardy, J. (John), Hartman, C.A. (C.), Hashimoto, R. (Ryota), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Le Hellard, S. (Stephanie), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Holsboer, F. (Florian), Homuth, G. (Georg), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Huentelman, M.J. (Matthew), Pol, H.H., Ikeda, M. (Masashi), Jack, C.R. (Clifford R.), Jenkinson, S. (Sarah), Johnson, R. (Robert), Jönsson, E.G. (Erik G.), Jukema, J.W., Kahn, R. (René), Kanai, R. (Ryota), Kloszewska, I. (Iwona), Knopman, D.S. (David S.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Lemaître, H. (Herve), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Lopez, O.L. (Oscar L.), Lovestone, S. (Simon), Martinez, O. (Oliver), Martinot, J.-L. (Jean-Luc), Mattay, V.S. (Venkata S.), McDonald, C. (Colm), McIntosh, A.M. (Andrew), McMahon, F.J. (Francis J.), McMahon, K.L. (Katie L.), Mecocci, P. (Patrizia), Melle, I. (Ingrid), Meyer-Lindenberg, A. (Andreas), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant W.), Morris, D.W. (Derek W), Mosley, T.H. (Thomas H.), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (B.), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nichols, T.E. (Thomas), Niessen, W.J. (Wiro), Nöthen, M.M. (Markus), Nyberg, L. (Lars), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Paus, T. (Tomas), Pausova, Z. (Zdenka), Penninx, B.W.J.H. (Brenda), Pike, G.B. (G. Bruce), Potkin, S.G. (Steven), Psaty, B.M. (Bruce), Reppermund, S., Rietschel, M. (Marcella), Roffman, J.L. (Joshua), Seiferth, N. (Nina), Rotter, J.I. (Jerome I.), Ryten, M. (Mina), Sacco, R.L. (Ralph L.), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, C.J. (Christopher), Sigursson, S. (Sigurdur), Simmons, A. (Andrew), Singleton, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soininen, H. (H.), Steen, V.M. (Vidar), Stott, D.J. (David J.), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Tsolaki, M. (Magda), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Hernández, M.C.V. (Maria C. Valdés), Brug, M.P. (Marcel) van der, Lugt, A. (Aad) van der, Wee, N.J. (Nic) van der, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Vardarajan, B.N. (Badri), Vellas, B. (Bruno), Veltman, D.J. (Dick), Völzke, H. (Henry), Walter, H.J. (Henrik), Wardlaw, J. (Joanna), Wassink, A.M.J. (Annemarie), Weale, M.E. (Michael), Weinberger, D.R. (Daniel R.), Weiner, M.W. (Michael W.), Wen, W. (Wei), Westman, E. (Eric), White, T.J.H. (Tonya), Wong, T.Y. (Tien Y.), Wright, C.B. (Clinton B.), Zielke, R.H. (Ronald H.), Zonderman, A.B., Martin, N.G. (Nicholas), Duijn, C.M. (Cornelia) van, Wright, M.J. (Margaret), Longstreth Jr, W.T., Schumann, G. (Gunter), Grabe, H.J. (Hans Jörgen), Franke, B. (Barbara), Launer, L.J. (Lenore), Medland, S.E. (Sarah), Seshadri, S. (Sudha), Thompson, P.M. (Paul), Ikram, M.K. (Kamran), Hibar, D.P. (Derrek), Adams, H.H.H. (Hieab), Jahanshad, N. (Neda), Chauhan, G. (Ganesh), Stein, J.L., Hofer, E. (Edith), Rentería, M.E. (Miguel), Bis, J.C. (Joshua), Arias-Vásquez, A. (Alejandro), Ikram, M.K. (M. Kamran), Desrivières, S. (Sylvane), Vernooij, M.W. (Meike), Abramovic, L. (Lucija), Alhusaini, S. (Saud), Amin, N. (Najaf), Andersson, M. (Micael), Arfanakis, K. (Konstantinos), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Athanasiu, L. (Lavinia), Axelsson, T. (Tomas), Beecham, A.H. (Ashley), Beiser, A. (Alexa), Bernard, M. (Manon), Blanton, S.H. (Susan H.), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brickman, A.M. (Adam M.), Carmichael, O. (Owen), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Chouraki, V. (Vincent), Cuellar-Partida, G. (Gabriel), Crivello, F. (Fabrice), Braber, A. (Anouk) den, Doan, N.T. (Nhat Trung), Ehrlich, S.M. (Stefan), Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Gottesman, R.F. (Rebecca), Grimm, O. (Oliver), Griswold, M.D. (Michael), Guadalupe, T. (Tulio), Gutman, B.A. (Boris A.), Hass, J. (Johanna), Haukvik, U.K. (Unn), Hoehn, D. (David), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Jørgensen, K.N. (Kjetil N.), Karbalai, N. (Nazanin), Kasperaviciute, D. (Dalia), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Luciano, M. (Michelle), MacAre, C. (Christine), Marquand, A.F. (Andre F.), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), McKay, D.R. (David R.), Milaneschi, Y. (Yuri), Muñoz Maniega, S. (Susana), Nho, K. (Kwangsik), Nugent, A.C. (Allison), Nyquist, P. (Paul), Loohuis, L.M.O. (Loes M. Olde), Oosterlaan, J. (Jaap), Papmeyer, M. (Martina), Pirpamer, L. (Lukas), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Richards, J.S. (Jennifer S.), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rommelse, N. (Nanda), Ropele, S. (Stefan), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rundek, T. (Tatjana), Sämann, P.G. (Philipp), Saremi, A. (Arvin), Satizabal, C.L. (Claudia), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shen, L. (Li), Shin, J. (Jean), Shumskaya, E. (Elena), Smith, A.V. (Albert Vernon), Sprooten, R. (Roy), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Tordesillas-Gutierrez, D. (Diana), Toro, R. (Roberto), Trabzuni, D. (Danyah), Trompet, S. (Stella), Vaidya, D. (Dhananjay), van der Grond, J. (Jeroen), Lee, S.J. (Sven) van der, Van Der Meer, D. (Dennis), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Van Rooij, D. (Daan), Walton, E. (Esther), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Windham, B.G. (Gwen), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Wolfers, T. (Thomas), Yanek, L.R. (Lisa), Yang, J. (Jingyun), Zijdenbos, A.P., Zwiers, M.P. (Marcel), Agartz, I. (Ingrid), Almasy, L. (Laura), Ames, D.J. (David), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Arepalli, S. (Sampath), Assareh, A.A., Barral, S. (Sandra), Bastin, M.E. (Mark), Becker, D.M. (Diane M.), Becker, J.T. (James), Bennett, D.A. (David A.), Blangero, J. (John), Bokhoven, H. (Hans) van, Boomsma, D.I. (Dorret), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cavalleri, G. (Gianpiero), Cheng, C.-Y. (Ching-Yu), Cichon, S. (Sven), Cookson, M.R. (Mark), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Dale, A.M. (Anders), Davies, G.E. (Gareth), Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Jager, P.L. (Philip) de, Zubicaray, G.I. (Greig) de, Deary, I.J. (Ian), Debette, S. (Stéphanie), DeCarli, C. (Charles), Delanty, N., Depondt, C. (Chantal), DeStefano, A.L. (Anita), Dillman, A. (Allissa), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drevets, D.A. (Douglas), Duggirala, R. (Ravi), Dyer, M.D. (Matthew), Enzinger, C. (Christian), Erk, S., Espeseth, T. (Thomas), Fedko, I.O. (Iryna O.), Fernández, G. (Guillén), Ferrucci, L. (Luigi), Fisher, S.E. (Simon), Fleischman, D. (Debra), Ford, I. (Ian), Fornage, M. (Myriam), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Fukunaga, M. (Masaki), Gibbs, J.R. (J. Raphael), Glahn, D.C. (David), Gollub, R.L. (Randy), Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Gruber, O. (Oliver), Gudnason, V. (Vilmundur), Guelfi, S. (Sebastian), Håberg, A.K. (Asta K.), Hansell, N.K. (Narelle), Hardy, J. (John), Hartman, C.A. (C.), Hashimoto, R. (Ryota), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Le Hellard, S. (Stephanie), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Holsboer, F. (Florian), Homuth, G. (Georg), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Huentelman, M.J. (Matthew), Pol, H.H., Ikeda, M. (Masashi), Jack, C.R. (Clifford R.), Jenkinson, S. (Sarah), Johnson, R. (Robert), Jönsson, E.G. (Erik G.), Jukema, J.W., Kahn, R. (René), Kanai, R. (Ryota), Kloszewska, I. (Iwona), Knopman, D.S. (David S.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Lemaître, H. (Herve), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Lopez, O.L. (Oscar L.), Lovestone, S. (Simon), Martinez, O. (Oliver), Martinot, J.-L. (Jean-Luc), Mattay, V.S. (Venkata S.), McDonald, C. (Colm), McIntosh, A.M. (Andrew), McMahon, F.J. (Francis J.), McMahon, K.L. (Katie L.), Mecocci, P. (Patrizia), Melle, I. (Ingrid), Meyer-Lindenberg, A. (Andreas), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant W.), Morris, D.W. (Derek W), Mosley, T.H. (Thomas H.), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (B.), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nichols, T.E. (Thomas), Niessen, W.J. (Wiro), Nöthen, M.M. (Markus), Nyberg, L. (Lars), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Paus, T. (Tomas), Pausova, Z. (Zdenka), Penninx, B.W.J.H. (Brenda), Pike, G.B. (G. Bruce), Potkin, S.G. (Steven), Psaty, B.M. (Bruce), Reppermund, S., Rietschel, M. (Marcella), Roffman, J.L. (Joshua), Seiferth, N. (Nina), Rotter, J.I. (Jerome I.), Ryten, M. (Mina), Sacco, R.L. (Ralph L.), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, C.J. (Christopher), Sigursson, S. (Sigurdur), Simmons, A. (Andrew), Singleton, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soininen, H. (H.), Steen, V.M. (Vidar), Stott, D.J. (David J.), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Tsolaki, M. (Magda), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Hernández, M.C.V. (Maria C. Valdés), Brug, M.P. (Marcel) van der, Lugt, A. (Aad) van der, Wee, N.J. (Nic) van der, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Vardarajan, B.N. (Badri), Vellas, B. (Bruno), Veltman, D.J. (Dick), Völzke, H. (Henry), Walter, H.J. (Henrik), Wardlaw, J. (Joanna), Wassink, A.M.J. (Annemarie), Weale, M.E. (Michael), Weinberger, D.R. (Daniel R.), Weiner, M.W. (Michael W.), Wen, W. (Wei), Westman, E. (Eric), White, T.J.H. (Tonya), Wong, T.Y. (Tien Y.), Wright, C.B. (Clinton B.), Zielke, R.H. (Ronald H.), Zonderman, A.B., Martin, N.G. (Nicholas), Duijn, C.M. (Cornelia) van, Wright, M.J. (Margaret), Longstreth Jr, W.T., Schumann, G. (Gunter), Grabe, H.J. (Hans Jörgen), Franke, B. (Barbara), Launer, L.J. (Lenore), Medland, S.E. (Sarah), Seshadri, S. (Sudha), Thompson, P.M. (Paul), and Ikram, M.K. (Kamran)

Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Published
2017
Full Text
View/download PDF

235. Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks

Author

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

Abstract

Aim: To examine the relationships between two epigenetic clocks, aging and exceptional longevity. Materials & methods: Participants were from three adult cohorts with blood DNA methylation data (Illumina 450 K, n = 275, 34-103 years). Epigenetic age (DNAmage) and age acceleration measures were calculated using the Hannum and Horvath epigenetic clocks. Results: Across all cohorts, DNAmage was correlated with chronological age. In the long-lived cohort (Sydney Centenarian Study; 95+, n = 23), DNAmage was lower than chronological age for both clocks. Mean Sydney Centenarian Study Hannum age acceleration was negative, while the converse was observed for the Horvath model. Conclusion: Long-lived individuals have a young epigenetic age compared with their chronological age.

Published
2017

236. Novel genetic loci associated with hippocampal volume

Author

Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., Ikram, M.A., Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., and Ikram, M.A.

Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Published
2017

237. A pilot study on the feasibility of training nurses to formulate multicomponent oral health interventions in a residential aged care facility

Author

Deutsch, A, Siegel, E, Cations, M, Wright, C, Naganathan, V, Brodaty, H, Deutsch, A, Siegel, E, Cations, M, Wright, C, Naganathan, V, and Brodaty, H

Abstract

OBJECTIVES: This 10 weeks feasibility study investigated whether residential care nurses with 12 hours advanced oral health training in assessments and saliva testing could formulate, implement and monitor individualised oral care plans of early dementia residents. METHOD: Four trained lead advocate nurses using SXI-D, OHIP14, oral health assessment tool (OHAT) assessments and a modified saliva test formulated nurse scheduled comprehensive oral care plans (NSCOCPs) by selecting and scheduling preventive products and procedures multiple times throughout the day to alkalise the mouth of 8 residents as an adjunct to assisted brushing and high-fluoride toothpaste. RESULTS: Nurse assessments, saliva tests and care plans were validated against oral health therapist (OHT) findings. Care plan agreement between Nurse and OHT intervention selection and scheduling was high (75%-88%). Untrained nurse compliance was very high, 86%-99% for the 4930 scheduled interventions. Untrained nurses delivered multiple scheduled interventions by following NSCOCPs despite initially not understanding the reason for each of 9 interventions categories. NSCOCPs could track and monitor whether a recommended intervention had been completed by general nursing staff over 3 nursing shifts. CONCLUSION: The role of nurses may have to be expanded beyond traditional roles to meet the growth and changes in oral health needs in residential facilities. Intensive training of a few lead advocate nurses to assess risk and formulate individualised NSCOCPs provides a method to transfer knowledge to untrained staff and deliver multicomponent preventive interventions soon after entry into residential care where timely visits by dental professionals to examine residents and prescribe preventive interventions are infrequent or unlikely.

Published
2017

238. Novel genetic loci associated with hippocampal volume

Author

Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Nhat, TD, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jorgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, AF, Matarin, M, Mather, KA, Mattheisen, M, McKay, DR, Milaneschi, Y, Maniega, SM, Nho, K, Nugent, AC, Nyquist, P, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pirpamer, L, Puetz, B, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santianez, R, Rommelse, N, Ropele, S, Rose, EJ, Royle, NA, Rundek, T, Saemann, PG, Saremi, A, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Trompet, S, Vaidya, D, Van der Grond, J, Van der Lee, SJ, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Wolfers, T, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Craen, AJM, De Geus, EJC, De Jager, PL, De Zubicaray, GI, Deary, IJ, Debette, S, DeCarli, C, Delanty, N, Depondt, C, DeStefano, A, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Enzinger, C, Erk, S, Espeseth, T, Fedko, IO, Fernandez, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Fornage, M, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Goring, HHH, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Haberg, AK, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Huentelman, M, Pol, HEH, Ikeda, M, Jack, CR, Jenkinson, M, Johnson, R, Joensson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaitre, H, Liu, X, Longo, DL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Muhleisen, TW, Mueller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nothen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schmidt, H, Schofield, PR, Sigursson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Toga, AW, Traynor, BJ, Troncoso, J, Tsolaki, M, Tzourio, C, Uitterlinden, AG, Hernandez, MCV, Van der Brug, M, van der Lugt, A, van der Wee, NJA, Van Haren, NEM, van't Ent, D, Van Tol, M-J, Vardarajan, BN, Vellas, B, Veltman, DJ, Voelzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, RH, Zonderman, AB, Martin, NG, Van Duijn, CM, Wright, MJ, Longstreth, WT, Schumann, G, Grabe, HJ, Franke, B, Launer, LJ, Medland, SE, Seshadri, S, Thompson, PM, Ikram, MA, Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Nhat, TD, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jorgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, AF, Matarin, M, Mather, KA, Mattheisen, M, McKay, DR, Milaneschi, Y, Maniega, SM, Nho, K, Nugent, AC, Nyquist, P, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pirpamer, L, Puetz, B, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santianez, R, Rommelse, N, Ropele, S, Rose, EJ, Royle, NA, Rundek, T, Saemann, PG, Saremi, A, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Trompet, S, Vaidya, D, Van der Grond, J, Van der Lee, SJ, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Wolfers, T, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Craen, AJM, De Geus, EJC, De Jager, PL, De Zubicaray, GI, Deary, IJ, Debette, S, DeCarli, C, Delanty, N, Depondt, C, DeStefano, A, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Enzinger, C, Erk, S, Espeseth, T, Fedko, IO, Fernandez, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Fornage, M, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Goring, HHH, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Haberg, AK, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Huentelman, M, Pol, HEH, Ikeda, M, Jack, CR, Jenkinson, M, Johnson, R, Joensson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaitre, H, Liu, X, Longo, DL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Muhleisen, TW, Mueller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nothen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schmidt, H, Schofield, PR, Sigursson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Toga, AW, Traynor, BJ, Troncoso, J, Tsolaki, M, Tzourio, C, Uitterlinden, AG, Hernandez, MCV, Van der Brug, M, van der Lugt, A, van der Wee, NJA, Van Haren, NEM, van't Ent, D, Van Tol, M-J, Vardarajan, BN, Vellas, B, Veltman, DJ, Voelzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, RH, Zonderman, AB, Martin, NG, Van Duijn, CM, Wright, MJ, Longstreth, WT, Schumann, G, Grabe, HJ, Franke, B, Launer, LJ, Medland, SE, Seshadri, S, Thompson, PM, and Ikram, MA

Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Published
2017

239. An evaluation of the additional benefit of population screening for dementia beyond a passive case-finding approach

Author

Mate, KE, Magin, PJ, Brodaty, H, Stocks, NP, Gunn, J, Disler, PB, Marley, JE, Pond, CD, Mate, KE, Magin, PJ, Brodaty, H, Stocks, NP, Gunn, J, Disler, PB, Marley, JE, and Pond, CD

Abstract

OBJECTIVE: General practitioners (GPs) fail to identify more than 50% of dementia cases using the existing passive case-finding approach. Using data from the "Ageing in General Practice" study, we sought to establish the additional benefit of screening all patients over the age of 75 for dementia beyond those patients already identified by passive case-finding. METHOD: Patients were classified as "case-finding" (n = 425) or "screening" (n = 1006) based on their answers to four subjective memory related questions or their GP's clinical judgement of their dementia status. Cognitive status of each patient was formally assessed by a research nurse using the Cambridge Cognition Examination (CAMCOG-R). Patients then attended their usual GP for administration of the GP assessment of Cognition (GPCOG) dementia screening instrument, and follow-up care and/or referral as necessary in light of the outcome. RESULTS: The prevalence of dementia was significantly higher in the case-finding group (13.6%) compared to the screening group (4.6%; p < 0.01). The GPCOG had a positive predictive value (PPV) of 61% in the case-finding group and 39% in the screening group; negative predictive value was >95% in both groups. GPs and their patients both found the GPCOG to be an acceptable cognitive assessment tool. The dementia cases missed via case-finding were younger (p = 0.024) and less cognitively impaired (p = 0.020) than those detected. CONCLUSION: There is a very limited benefit of screening for dementia, as most people with dementia could be detected using a case-finding approach, and considerable potential for social and economic harm because of the low PPV associated with screening.

Published
2017

240. Halting Antipsychotic Use in Long-Term care (HALT): A single-arm longitudinal study aiming to reduce inappropriate antipsychotic use in long-term care residents with behavioral and psychological symptoms of dementia

Author

Jessop, T, Harrison, F, Cations, M, Draper, B, Chenoweth, L, Hilmer, S, Westbury, J, Low, LF, Heffernan, M, Sachdev, P, Close, J, Blennerhassett, J, Marinkovich, M, Shell, A, Brodaty, H, Jessop, T, Harrison, F, Cations, M, Draper, B, Chenoweth, L, Hilmer, S, Westbury, J, Low, LF, Heffernan, M, Sachdev, P, Close, J, Blennerhassett, J, Marinkovich, M, Shell, A, and Brodaty, H

Abstract

© 2017 International Psychogeriatric Association. Background: Inappropriate use of antipsychotic medications to manage Behavioral and Psychological Symptoms of Dementia (BPSD) continues despite revised guidelines and evidence for the associated risks and side effects. The aim of the Halting Antipsychotic Use in Long-Term care (HALT) project is to identify residents of long-term care (LTC) facilities on antipsychotic medications, and undertake an intervention to deprescribe (or cease) these medicines and improve non-pharmacological behavior management. Methods: LTC facilities will be recruited across Sydney, Australia. Resident inclusion criteria will be aged over 60 years, on regular antipsychotic medication, and without a primary psychotic illness or very severe BPSD, as measured using the Neuropsychiatric Inventory (NPI). Data collection will take place one month and one week prior to commencement of deprescribing; and 3, 6 and 12 months later. During the period prior to deprescribing, training will be provided for care staff on how to reduce and manage BPSD using person-centered approaches, and general practitioners of participants will be provided academic detailing. The primary outcome measure will be reduction of regular antipsychotic medication without use of substitute psychotropic medications. Secondary outcome measures will be NPI total and domain scores, Cohen-Mansfield Agitation Inventory scores and adverse events, including falls and hospitalizations. Conclusion: While previous studies have described strategies to minimize inappropriate use of antipsychotic medications in people with dementia living in long-term care, sustainability and a culture of prescribing for BPSD in aged care remain challenges. The HALT project aims to evaluate the feasibility of a multi-disciplinary approach for deprescribing antipsychotics in this population.

Published
2017

241. Evidence-based occupational therapy for people with dementia and their families: What clinical practice guidelines tell us and implications for practice

Author

Laver, K, Cumming, R, Dyer, S, Agar, M, Anstey, KJ, Beattie, E, Brodaty, H, Broe, T, Clemson, L, Crotty, M, Dietz, M, Draper, B, Flicker, L, Friel, M, Heuzenroeder, L, Koch, S, Kurrle, S, Nay, R, Pond, D, Thompson, J, Santalucia, Y, Whitehead, C, Yates, M, Laver, K, Cumming, R, Dyer, S, Agar, M, Anstey, KJ, Beattie, E, Brodaty, H, Broe, T, Clemson, L, Crotty, M, Dietz, M, Draper, B, Flicker, L, Friel, M, Heuzenroeder, L, Koch, S, Kurrle, S, Nay, R, Pond, D, Thompson, J, Santalucia, Y, Whitehead, C, and Yates, M

Abstract

© 2016 Occupational Therapy Australia Background/aim: The first evidence-based Clinical Practice Guidelines and Principles of Care for People with Dementia in Australia have been released. The Guidelines detail a number of important evidence-based recommendations for occupational therapists. The aim of this paper is (1) to provide an overview of Guideline development, and (2) to describe the evidence supporting a recommendation for occupational therapy. Common characteristics of effective occupational therapy programmes for people with dementia are described. Methods: Guideline development involved adaptation of existing high-quality guidelines developed overseas and 17 systematic reviews to ensure that the most recent high-quality evidence was included. One of the systematic reviews involved examining the evidence for interventions to promote independence in people with dementia. Specifically, we looked at the evidence for occupational therapy and its effect on activities of daily living, quality of life and carer impact. Results: A total of 109 recommendations are included in the Guidelines. Occupational therapy was found to significantly increase independence in activities of daily living and improve quality of life. Effective occupational therapy programmes involve: environmental assessment, problem solving strategies, carer education and interactive carer skills training. Conclusion: Occupational therapists working with people with dementia in community settings should ensure that their time is spent on those aspects of intervention that are shown to be effective.

Published
2017

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

Author

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

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

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

Published
2015

250. Genetic contributions to variation in general cognitive function:a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Author

Davies, G., Armstrong, N., Bis, J. C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C. A., Kirin, M., Lahti, J., van der Lee, S. J., Le Hellard, S., Liu, T., Marioni, R. E., Oldmeadow, C., Postmus, I., Smith, A. V., Smith, J. A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S. E., Hill, W. D., Liewald, D. C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A. A., Au, R., Becker, J. T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B. M., Campbell, H., Corley, J., De Jager, P. L., Dufouil, C., Eriksson, J. G., Espeseth, T., Faul, J. D., Ford, I., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Heiss, G., Hofman, A., Holliday, E. G., Huffman, J., Kardia, S. L. R., Kochan, N., Knopman, D. S., Kwok, J. B., Lambert, J-C, Lee, T., Li, G., Li, S-C, Loitfelder, M., Lopez, O. L., Lundervold, A. J., Lundquist, Anders, Mather, K. A., Mirza, S. S., Nyberg, Lars, Oostra, B. A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B. M., Redmond, P., Reppermund, S., Rotter, J. I., Schmidt, H., Schuur, M., Schofield, P. W., Scott, R. J., Steen, V. M., Stott, D. J., Van Swieten, J. C., Taylor, K. D., Trollor, J., Trompet, S., Uitterlinden, A. G., Weinstein, G., Widen, E., Windham, B. G., Jukema, J. W., Wright, A. F., Wright, M. J., Yang, Q., Amieva, H., Attia, J. R., Bennett, D. A., Brodaty, H., de Craen, A. J. M., Hayward, C., Ikram, M. A., Lindenberger, U., Nilsson, Lars-Göran, Porteous, D. J., Raikkonen, K., Reinvang, I., Rudan, I., Sachdev, P. S., Schmidt, R., Schofield, P. R., Srikanth, V., Starr, J. M., Turner, S. T., Weir, D. R., Wilson, J. F., Van Duijn, C., Launer, L., Fitzpatrick, A. L., Seshadri, S., Jr, T. H. Mosley, Deary, I. J., Epidemiology, Neurology, Radiology & Nuclear Medicine, Clinical Genetics, and Internal Medicine

Subjects
Male, Neurologi, SUSCEPTIBILITY LOCI, Neuropsychological Tests, Polymorphism, Single Nucleotide, IDENTIFIES VARIANTS, APOLIPOPROTEIN-E, Cohort Studies, Cognition, OLD-AGE, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, HUMAN INTELLIGENCE, Aged, TYPE-4 ALLELE, Aged, 80 and over, TEST BATTERIES, Middle Aged, Atherosclerosis, CPG-BINDING PROTEIN-2, ALZHEIMERS-DISEASE, Phenotype, Scotland, Neurology, Female, Cognition Disorders, Immediate Communication, HUMAN HEIGHT, HMGN1 Protein, Genome-Wide Association Study
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

Catalog

Books, media, physical & digital resources
See catalog results