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2. Sexual dimorphism of physical activity on cognitive aging: Role of immune functioning

Author

Casaletto, KB, Lindbergh, C, Memel, M, Staffaroni, A, Elahi, F, Weiner-Light, S, You, M, Fonseca, C, Karydas, A, Jacobs, E, Dubal, DB, Yaffe, K, and Kramer, JH

Subjects
Biological Psychology, Clinical and Health Psychology, Psychology, Brain Disorders, Physical Activity, Neurosciences, Prevention, Aging, Behavioral and Social Science, Basic Behavioral and Social Science, Clinical Research, Neurodegenerative, Mental Health, Aged, Brain, Cognitive Aging, Exercise, Female, Humans, Male, Sex Characteristics, Inflammation, Gender, Cognitive aging, Brain aging, Lifestyle, Chemokines, Immunology, Neurology & Neurosurgery, Biological psychology
Abstract

ObjectiveExercise is one of the most potent strategies available to support cognitive health with age, yet substantial variability exists. Sexual dimorphism is evident for brain and immune functioning, the latter being implicated as important pathway for exercise. We examined the moderating role of sex on the relationship between physical activity and systemic inflammatory and brain health outcomes in support of more personalized approaches to behavioral interventions.MethodsOur discovery cohort included 45 typically aging women matched on age (±5y) and education (±2y) to 45 men (mean age = 72.5; Clinical Dementia Rating = 0) who completed self-reported current physical activity (Physical Activity Scale for Elderly), blood draw, neuropsychological evaluation, and brain MRI. An independent sample of 45 typically aging women and 36 men who completed the same measures comprised a replication cohort. Plasma was analyzed for 11 proinflammatory cytokine and chemokine markers via MesoScale Discovery.ResultsDiscovery cohort: Reported physical activity did not differ between sexes (150 vs. 157, p = 0.72). There was a significant interaction between sex and physical activity on chemokine markers MDC, MIP-1b, MCP-4, and eotaxin-3 (ps

Published
2020

3. Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration

Author

Casaletto, KB, Staffaroni, AM, Wolf, A, Appleby, B, Brushaber, D, Coppola, G, Dickerson, B, Domoto‐Reilly, K, Elahi, FM, Fields, J, Fong, JC, Forsberg, L, Ghoshal, N, Graff‐Radford, N, Grossman, M, Heuer, HW, Hsiung, G‐Y, Huey, ED, Irwin, D, Kantarci, K, Kaufer, D, Kerwin, D, Knopman, D, Kornak, J, Kramer, JH, Litvan, I, Mackenzie, IR, Mendez, M, Miller, B, Rademakers, R, Ramos, EM, Rascovsky, K, Roberson, ED, Syrjanen, JA, Tartaglia, MC, Weintraub, S, Boeve, B, Boxer, AL, Rosen, H, Yaffe, K, and Study, the ARTFL LEFFTDS

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Basic Behavioral and Social Science, Rare Diseases, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Neurodegenerative, Clinical Research, Brain Disorders, Prevention, Frontotemporal Dementia (FTD), Behavioral and Social Science, Biomedical Imaging, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease, Neurosciences, Acquired Cognitive Impairment, Dementia, Neurological, Aged, Atrophy, Cognition, Exercise, Female, Frontotemporal Lobar Degeneration, Humans, Leisure Activities, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, cognitive activity, cognitive reserve, exercise, frontotemporal dementia, physical activity, ARTFL/LEFFTDS Study, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionLeisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsA total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans.ResultsGreater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates.DiscussionActive lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Published
2020

4. Contributions to lateral balance control in ambulatory older adults

Author

Sparto, Patrick J, Newman, AB, Simonsick, EM, Caserotti, P, Strotmeyer, ES, Kritchevsky, SB, Yaffe, K, Rosano, C, and For the Health ABC Study

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rehabilitation, Clinical Research, Behavioral and Social Science, Aging, 2.1 Biological and endogenous factors, Aetiology, Accidental Falls, Aged, 80 and over, Body Mass Index, Feedback, Sensory, Female, Humans, Lower Extremity, Male, Perception, Postural Balance, Posture, Pressure, Psychomotor Performance, Balance, Visual feedback, Posturography, Executive function, Health ABC Study, Public Health and Health Services, Cognitive Sciences, Geriatrics, Clinical sciences
Abstract

BackgroundIn older adults, impaired control of standing balance in the lateral direction is associated with the increased risk of falling. Assessing the factors that contribute to impaired standing balance control may identify areas to address to reduce falls risk.AimTo investigate the contributions of physiological factors to standing lateral balance control.MethodsTwo hundred twenty-two participants from the Pittsburgh site of the Health, Aging and Body Composition Study had lateral balance control assessed using a clinical sensory integration balance test (standing on level and foam surface with eyes open and closed) and a lateral center of pressure tracking test using visual feedback. The center of pressure was recorded from a force platform. Multiple linear regression models examined contributors of lateral control of balance performance, including concurrently measured tests of lower extremity sensation, knee extensor strength, executive function, and clinical balance tests. Models were adjusted for age, body mass index, and sex.ResultsLarger lateral sway during the sensory integration test performed on foam was associated with longer repeated chair stands time. During the lateral center of pressure tracking task, the error in tracking increased at higher frequencies; greater error was associated with worse executive function. The relationship between sway performance and physical and cognitive function differed between women and men.DiscussionContributors to control of lateral balance were task-dependent. Lateral standing performance on an unstable surface may be more dependent upon general lower extremity strength, whereas visual tracking performance may be more dependent upon cognitive factors.ConclusionsLateral balance control in ambulatory older adults is associated with deficits in strength and executive function.

Published
2018

12. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author

Ibrahim-Verbaas, CA, Bressler, J, Debette, S, Schuur, M, Smith, AV, Bis, JC, Davies, G, Trompet, S, Smith, JA, Wolf, C, Chibnik, LB, Liu, Y, Vitart, V, Kirin, M, Petrovic, K, Polasek, O, Zgaga, L, Fawns-Ritchie, C, Hoffmann, P, Karjalainen, J, Lahti, J, Llewellyn, DJ, Schmidt, CO, Mather, KA, Chouraki, V, Sun, Q, Resnick, SM, Rose, LM, Oldmeadow, C, Stewart, M, Smith, BH, Gudnason, V, Yang, Q, Mirza, SS, Jukema, JW, deJager, PL, Harris, TB, Liewald, DC, Amin, N, Coker, LH, Stegle, O, Lopez, OL, Schmidt, R, Teumer, A, Ford, I, Karbalai, N, Becker, JT, Jonsdottir, MK, Au, R, Fehrmann, RSN, Herms, S, Nalls, M, Zhao, W, Turner, ST, Yaffe, K, Lohman, K, van Swieten, JC, Kardia, SLR, Knopman, DS, Meeks, WM, Heiss, G, Holliday, EG, Schofield, PW, Tanaka, T, Stott, DJ, Wang, J, Ridker, P, Gow, AJ, Pattie, A, Starr, JM, Hocking, LJ, Armstrong, NJ, McLachlan, S, Shulman, JM, Pilling, LC, Eiriksdottir, G, Scott, RJ, Kochan, NA, Palotie, A, Hsieh, Y-C, Eriksson, JG, Penman, A, Gottesman, RF, Oostra, BA, Yu, L, DeStefano, AL, Beiser, A, Garcia, M, Rotter, JI, Nöthen, MM, Hofman, A, Slagboom, PE, Westendorp, RGJ, Buckley, BM, Wolf, PA, Uitterlinden, AG, Psaty, BM, Grabe, HJ, Bandinelli, S, and Chasman, DI

Subjects
Biological Psychology, Clinical and Health Psychology, Psychology, Human Genome, Neurosciences, Genetics, Clinical Research, Aging, Aetiology, 2.1 Biological and endogenous factors, Aged, Aged, 80 and over, Cell Adhesion Molecules, Cognition, Cohort Studies, Executive Function, Female, Genetic Association Studies, Genetic Variation, Genome-Wide Association Study, Genomics, Humans, Introns, Male, Middle Aged, Neuropsychological Tests, Polymorphism, Single Nucleotide, White People, gamma-Aminobutyric Acid, Generation Scotland, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

Published
2016

13. Cognitive function in a middle aged cohort is related to higher quality dietary pattern 5 and 25 years earlier: The cardia study

Author

Zhu, N, Jacobs, David R, Meyer, KA, He, K, Launer, L, Reis, JP, Yaffe, K, Sidney, S, Whitmer, RA, and Steffen, LM

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Nutrition and Dietetics, Clinical Research, Prevention, Cardiovascular, Heart Disease - Coronary Heart Disease, Behavioral and Social Science, Nutrition, Heart Disease, Aetiology, Prevention of disease and conditions, and promotion of well-being, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, 2.3 Psychological, social and economic factors, Adolescent, Adult, Black People, Body Mass Index, Cognition, Cohort Studies, Coronary Artery Disease, Diet, Executive Function, Feeding Behavior, Female, Humans, Male, Memory, Middle Aged, Nutrition Surveys, Psychomotor Performance, Risk, Stroop Test, Time Factors, White People, Young Adult, Cohort study, epidemiology, middle age, diet pattern, cognitive tests, Clinical Sciences, Nutrition & Dietetics, Nutrition and dietetics, Health services and systems
Abstract

BackgroundPreserving cognitive function is an important public health issue. We investigated whether dietary pattern associates with cognitive function in middle-age.MethodsWe studied 2435 participants in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study of black and white men and women aged 18-30 in 1985-86 (year 0, Y0). We hypothesized that a higher A Priori Diet Quality Score, measured at Y0 and Y20, is associated with better cognitive function measured at Y25. The diet score incorporated 46 food groups (each in servings/day) as the sum of quintile ranks of food groups rated beneficial, 0 for food groups rated neutral, and reversed quintile ranks for food groups rated adverse; higher score indicated better diet quality. Y25 cognitive testing included verbal memory (Rey Auditory-Verbal Learning Test (RAVLT)), psychomotor speed (Digit Symbol Substitution Test (DSST)) and executive function (Stroop).ResultsPer 10-unit higher diet score at Y20, the RAVLT was 0.32 words recalled higher, the DSST was 1.76 digits higher, and the Stroop was 1.00 seconds+errors lower (better performance) after adjusting for race, sex, age, clinic, and energy intake. Further adjustment for physical activity, smoking, education, and body mass index attenuated the association slightly. Diet score at Y0 and increase in diet score over 20 years were also positively associated with each cognitive test.ConclusionsA higher quality dietary pattern was associated with better cognitive function 5 years and even 25 years later in apparently healthy middle-aged adults.

Published
2015

15. Neuropathologic features associated with Alzheimer disease diagnosis

Author

Middleton, LE, Grinberg, LT, Miller, B, Kawas, C, and Yaffe, K

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Acquired Cognitive Impairment, Dementia, Neurodegenerative, Alzheimer's Disease, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Detection, screening and diagnosis, Aetiology, 4.2 Evaluation of markers and technologies, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Aged, Aged, 80 and over, Alzheimer Disease, Cross-Sectional Studies, Databases, Factual, Female, Humans, Male, Neurofibrillary Tangles, Plaque, Amyloid, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age.MethodsWe conducted a cross-sectional analysis of 2,014 older adults (≥70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made ≤1 year before death, n = 419) or AD (at ≥65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group.ResultsIn a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70-74 years: c statistic, 95% confidence interval: 0.93, 0.89-0.96; 75-84 years: 0.95, 0.87-0.95; ≥85 years: 0.83, 0.80-0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004).ConclusionClinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old.

Published
2011

17. Arousal Intensity Predicts Incident Dementia in Sleep Apnea: The Multiethnic Study of Atherosclerosis (MESA)

Author

Labarca, G.P., primary, Esmaeili, N., additional, Gell, L., additional, Hu, W.-H., additional, Messineo, L., additional, Vena, D., additional, Sumner, J., additional, Yang, H.C., additional, Wang, T.-Y., additional, Michos, E., additional, Sofer, T., additional, Kwon, Y., additional, Yaffe, K., additional, Ensrud, K., additional, Stone, K.L., additional, Sands, S.A., additional, White, D., additional, Wellman, A., additional, Redline, S.S., additional, and Azarbarzin, A., additional

Published
2023
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18. Multivariate prediction of cognitive performance from the sleep electroencephalogram.

Author

Ujma, P.P., Bódizs, R., Dresler, M., Simor, P., Purcell, S., Stone, K.L., Yaffe, K., Redline, S., Ujma, P.P., Bódizs, R., Dresler, M., Simor, P., Purcell, S., Stone, K.L., Yaffe, K., and Redline, S.

Abstract

Contains fulltext : 296183.pdf (Publisher’s version ) (Open Access), Human cognitive performance is a key function whose biological foundations have been partially revealed by genetic and brain imaging studies. The sleep electroencephalogram (EEG) is tightly linked to structural and functional features of the central nervous system and serves as another promising biomarker. We used data from MrOS, a large cohort of older men and cross-validated regularized regression to link sleep EEG features to cognitive performance in cross-sectional analyses. In independent validation samples 2.5-10% of variance in cognitive performance can be accounted for by sleep EEG features, depending on the covariates used. Demographic characteristics account for more covariance between sleep EEG and cognition than health variables, and consequently reduce this association by a greater degree, but even with the strictest covariate sets a statistically significant association is present. Sigma power in NREM and beta power in REM sleep were associated with better cognitive performance, while theta power in REM sleep was associated with worse performance, with no substantial effect of coherence and other sleep EEG metrics. Our findings show that cognitive performance is associated with the sleep EEG (r = 0.283), with the strongest effect ascribed to spindle-frequency activity. This association becomes weaker after adjusting for demographic (r = 0.186) and health variables (r = 0.155), but its resilience to covariate inclusion suggest that it also partially reflects trait-like differences in cognitive ability.

Published
2023

23. List of Contributors

Author

Ashbrook, L., primary, Braley, T.J., additional, Cheung, J., additional, Cowan, R.P., additional, Day, J.W., additional, During, E.H., additional, Fisher, R.S., additional, Guilleminault, C., additional, Kawai, M., additional, Kimbrough, D.J., additional, Meskill, G.J., additional, Miglis, M.G., additional, Mignot, E., additional, Najjar, R.P., additional, O’Hare, M., additional, Peters, B.R., additional, Razavi, B., additional, Ruoff, C.M., additional, Sakamuri, S., additional, Schneider, L., additional, Sha, S.J., additional, Yaffe, K., additional, and Zeitzer, J.M., additional

Published
2017
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24. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author

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

Abstract

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

Published
2022

25. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, and Gravel, S

Abstract

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Published
2022

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

Author

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

Abstract

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

Published
2022

29. Associations between modifiable risk factors and white matter of the aging brain: insights from diffusion tensor imaging studies

Author

Wassenaar, TM, Yaffe, K, van der Werf, YD, Sexton, CE, Anatomy and neurosciences, and Amsterdam Neuroscience - Brain Imaging

Subjects
Sleep Wake Disorders, Aging, Clinical Sciences, Cardiovascular, Article, Clinical Research, 2.3 Psychological, Risk Factors, Modifiable-risk factor, Behavioral and Social Science, Diabetes Mellitus, Humans, Obesity, Aetiology, Hearing Loss, Nutrition, Depressive Disorder, Neurology & Neurosurgery, Prevention, White matter, Smoking, Neurosciences, Modifiable– risk factor, Diffusion tensor imaging, Mental Health, Cross-Sectional Studies, Diffusion Tensor Imaging, Social Isolation, Hypertension, Biomedical Imaging, social and economic factors, Mind and Body
Abstract

There is increasing interest in factors that may modulate white matter (WM) breakdown and, consequentially, age-related cognitive and behavioral deficits. Recent diffusion tensor imaging studies have examined the relationship of such factors with WM microstructure. This review summarizes the evidence regarding the relationship between WM microstructure and recognized modifiable factors, including hearing loss, hypertension, diabetes, obesity, smoking, depressive symptoms, physical (in) activity, and social isolation, as well as sleep disturbances, diet, cognitive training, and meditation. Current cross-sectional evidence suggests a clear link between loss of WM integrity (lower fractional anisotropy and higher mean diffusivity) and hypertension, obesity, diabetes, and smoking; a relationship that seems to hold for hearing loss, social isolation, depressive symptoms, and sleep disturbances. Physical activity, cognitive training, diet, and meditation, on the other hand, may protect WM with aging. Preliminary evidence from cross-sectional studies of treated risk factors suggests that modification of factors could slow down negative effects on WM microstructure. Careful intervention studies are needed for this literature to contribute to public health initiatives going forward., Highlights • Both aging and dementia are associated with breakdown of white matter (WM) microstructure. • We review a range of modifiable factors that could prevent or slow age-related WM decline. • Risk factors are consistently related with lower fractional anisotropy and higher mean diffusivity. • Treatment of risk factors may slow WM decline. • Careful longitudinal and intervention studies are now needed.

Published
2019

31. Executive function, memory, and gait speed decline in well-functioning older adults

Author

Watson, N.L., Rosano, C., Boudreau, R.M., Simonsick, E.M., Ferrucci, L., Sutton-Tyrrell, K., Hardy, S.E., Atkinson, H.H., Yaffe, K., Satterfield, S., Harris, T.B., and Newman, A.B.

Subjects
Aged -- Physiological aspects, Gait -- Evaluation, Cognition disorders -- Diagnosis, Cognition disorders -- Demographic aspects, Health, Seniors
Abstract

Background. In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time. Methods. Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 [+ or -] 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up. Results. Poorer performance in each cognitive task was cross-sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p =.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics. Conclusions. In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging. Key Words: Aging--Cognitive function--Gait speed. doi: 10.1093/gerona/glq111

Published
2010

33. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

Author

Maas, A, Menon, D, Adelson, P, Andelic, N, Bell, M, Belli, A, Bragge, P, Brazinova, A, Büki, A, Chesnut, R, CITERIO, GIUSEPPE, Coburn, M, Cooper, D, Crowder, A, Czeiter, E, Czosnyka, M, Diaz arrastia, R, Dreier, J, Duhaime, A, Ercole, A, Van Essen, T, Feigin, V, Gao, G, Giacino, J, Gonzalez lara, L, Gruen, R, Gupta, D, Hartings, J, Hill, S, Jiang, J, Ketharanathan, N, Kompanje, E, Lanyon, L, Laureys, S, Lecky, F, Levin, H, Lingsma, H, Maegele, M, Majdan, M, Manley, G, Marsteller, J, Mascia, L, Mcfadyen, C, Mondello, S, Newcombe, V, Palotie, A, Parizel, P, Peul, W, Piercy, J, Polinder, S, Puybasset, L, Rasmussen, T, Rossaint, R, Smielewski, P, Söderberg, J, Stanworth, S, Stein, M, Von Steinbüchel, N, Stewart, W, Steyerberg, E, Stocchetti, N, Synnot, A, Te Ao, B, Tenovuo, O, Theadom, A, Tibboel, D, Videtta, W, Wang, K, Williams, W, Wilson, L, Yaffe, K, Adams, H, Agnoletti, V, Allanson, J, Amrein, K, Andaluz, N, Anke, A, Antoni, A, Van As, A, Audibert, G, Azaševac, A, Azouvi, P, Azzolini, M, Baciu, C, Badenes, R, Barlow, K, Bartels, R, Bauerfeind, U, Beauchamp, M, Beer, D, Beer, R, Belda, F, Bellander, B, Bellier, R, Benali, H, Benard, T, Beqiri, V, Beretta, L, Bernard, F, Bertolini, G, Bilotta, F, Blaabjerg, M, Den Boogert, H, Boutis, K, Bouzat, P, Brooks, B, Brorsson, C, Bullinger, M, Burns, E, Calappi, E, Cameron, P, Carise, E, Castaño león, A, Causin, F, Chevallard, G, Chieregato, A, Christie, B, Cnossen, M, Coles, J, Collett, J, Della Corte, F, Craig, W, Csato, G, Csomos, A, Curry, N, Dahyot fizelier, C, Dawes, H, Dematteo, C, Depreitere, B, Dewey, D, Van Dijck, J, Đilvesi, Đ, Dippel, D, Dizdarevic, K, Donoghue, E, Duek, O, Dulière, G, Dzeko, A, Eapen, G, Emery, C, English, S, Esser, P, Ezer, E, Fabricius, M, Feng, J, Fergusson, D, Figaji, A, Fleming, J, Foks, K, Francony, G, Freedman, S, Freo, U, Frisvold, S, Gagnon, I, Galanaud, D, Gantner, D, Giraud, B, Glocker, B, Golubovic, J, Gómez López, P, Gordon, W, Gradisek, P, Gravel, J, Griesdale, D, Grossi, F, Haagsma, J, Håberg, A, Haitsma, I, Van Hecke, W, Helbok, R, Helseth, E, Van Heugten, C, Hoedemaekers, C, Höfer, S, Horton, L, Hui, J, Huijben, J, Hutchinson, P, Jacobs, B, Van Der Jagt, M, Jankowski, S, Janssens, K, Jelaca, B, Jones, K, Kamnitsas, K, Kaps, R, Karan, M, Katila, A, Kaukonen, K, De Keyser, V, Kivisaari, R, Kolias, A, Kolumbán, B, Kolundžija, K, Kondziella, D, Koskinen, L, Kovács, N, Kramer, A, Kutsogiannis, D, Kyprianou, T, Lagares, A, Lamontagne, F, Latini, R, Lauzier, F, Lazar, I, Ledig, C, Lefering, R, Legrand, V, Levi, L, Lightfoot, R, Lozano, A, Macdonald, S, Major, S, Manara, A, Manhes, P, Maréchal, H, Martino, C, Masala, A, Masson, S, Mattern, J, Mcfadyen, B, Mcmahon, C, Meade, M, Melegh, B, Menovsky, T, Moore, L, Morgado Correia, M, Morganti kossmann, M, Muehlan, H, Mukherjee, P, Murray, L, Van Der Naalt, J, Negru, A, Nelson, D, Nieboer, D, Noirhomme, Q, Nyirádi, J, Oddo, M, Okonkwo, D, Oldenbeuving, A, Ortolano, F, Osmond, M, Payen, J, Perlbarg, V, Persona, P, Pichon, N, Piippo karjalainen, A, Pili floury, S, Pirinen, M, Ple, H, Poca, M, Posti, J, Van Praag, D, Ptito, A, Radoi, A, Ragauskas, A, Raj, R, Real, R, Reed, N, Rhodes, J, Robertson, C, Rocka, S, Røe, C, Røise, O, Roks, G, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossi, S, Rueckert, D, De Ruiter, G, Sacchi, M, Sahakian, B, Sahuquillo, J, Sakowitz, O, Salvato, G, Sánchez porras, R, Sándor, J, Sangha, G, Schäfer, N, Schmidt, S, Schneider, K, Schnyer, D, Schöhl, H, Schoonman, G, Schou, R, Sir, Ö, Skandsen, T, Smeets, D, Sorinola, A, Stamatakis, E, Stevanovic, A, Stevens, R, Sundström, N, Taccone, F, Takala, R, Tanskanen, P, Taylor, M, Telgmann, R, Temkin, N, Teodorani, G, Thomas, M, Tolias, C, Trapani, T, Turgeon, A, Vajkoczy, P, Valadka, A, Valeinis, E, Vallance, S, Vámos, Z, VARGIOLU, ALESSIA, Vega, E, Verheyden, J, Vik, A, Vilcinis, R, Vleggeert lankamp, C, Vogt, L, Volovici, V, Voormolen, D, Vulekovic, P, Vande Vyvere, T, Van Waesberghe, J, Wessels, L, Wildschut, E, Williams, G, Winkler, M, Wolf, S, Wood, G, Xirouchaki, N, Younsi, A, Zaaroor, M, Zelinkova, V, Zemek, R, Zumbo, F, Citerio, G, Vargiolu, A, Zumbo, F., Maas, Andrew I R, Menon, David K, Adelson, P David, Andelic, Nada, Bell, Michael J, Belli, Antonio, Bragge, Peter, Brazinova, Alexandra, Büki, Andrá, Chesnut, Randall M, Citerio, Giuseppe, Coburn, Mark, Cooper, D Jamie, Crowder, A Tamara, Czeiter, Endre, Czosnyka, Marek, Diaz-Arrastia, Ramon, Dreier, Jens P, Duhaime, Ann-Christine, Ercole, Ari, van Essen, Thomas A, Feigin, Valery L, Gao, Guoyi, Giacino, Joseph, Gonzalez-Lara, Laura E, Gruen, Russell L, Gupta, Deepak, Hartings, Jed A, Hill, Sean, Jiang, Ji-yao, Ketharanathan, Naomi, Kompanje, Erwin J O, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Levin, Harvey, Lingsma, Hester F, Maegele, Marc, Majdan, Marek, Manley, Geoffrey, Marsteller, Jill, Mascia, Luciana, Mcfadyen, Charle, Mondello, Stefania, Newcombe, Virginia, Palotie, Aarno, Parizel, Paul M, Peul, Wilco, Piercy, Jame, Polinder, Suzanne, Puybasset, Loui, Rasmussen, Todd E, Rossaint, Rolf, Smielewski, Peter, Söderberg, Jeannette, Stanworth, Simon J, Stein, Murray B, von Steinbüchel, Nicole, Stewart, William, Steyerberg, Ewout W, Stocchetti, Nino, Synnot, Anneliese, Te Ao, Braden, Tenovuo, Olli, Theadom, Alice, Tibboel, Dick, Videtta, Walter, Wang, Kevin K W, Williams, W Huw, Wilson, Lindsay, Yaffe, Kristine, InTBIR Participants, Investigator, Beretta, Luigi, InTBIR Participants Investigators, Menon, David [0000-0002-3228-9692], Czosnyka, Marek [0000-0003-2446-8006], Ercole, Ari [0000-0001-8350-8093], Newcombe, Virginia [0000-0001-6044-9035], Smielewski, Peter [0000-0001-5096-3938], Apollo - University of Cambridge Repository, Maas A.I.R., Menon D.K., David Adelson P.D., Andelic N., Bell M.J., Belli A., Bragge P., Brazinova A., Buki A., Chesnut R.M., Citerio G., Coburn M., Jamie Cooper D., Tamara Crowder A., Czeiter E., Czosnyka M., Diaz-Arrastia R., Dreier J.P., Duhaime A.-C., Ercole A., van Essen T.A., Feigin V.L., Gao G., Giacino J., Gonzalez-Lara L.E., Gruen R.L., Gupta D., Hartings J.A., Hill S., Jiang J.-Y., Ketharanathan N., Kompanje E.J.O., Lanyon L., Laureys S., Lecky F., Levin H., Lingsma H.F., Maegele M., Majdan M., Manley G., Marsteller J., Mascia L., McFadyen C., Mondello S., Newcombe V., Palotie A., Parizel P.M., Peul W., Piercy J., Polinder S., Puybasset L., Rasmussen T.E., Rossaint R., Smielewski P., Soderberg J., Stanworth S.J., Stein M.B., von Steinbuchel N., Stewart W., Steyerberg E.W., Stocchetti N., Synnot A., Te Ao B., Tenovuo O., Theadom A., Tibboel D., Videtta W., Wang K.K.W., Huw Williams W., Wilson L., Yaffe K., Adams H., Allanson J., Coles J., Hutchinson P.J., Kolias A.G., Sahakian B.J., Stamatakis E., Williams G., Agnoletti V., Martino C., Masala A., Teodorani G., Zumbo F., Amrein K., Ezer E., Kolumban B., Kovacs N., Melegh B., Nyiradi J., Sorinola A., Vamos Z., Andaluz N., Anke A., Frisvold S.K., Antoni A., van As A.B., Figaji A., Audibert G., Azasevac A., Dilvesi D., Golubovic J., Jelaca B., Karan M., Kolundzija K., Negru A., Vulekovic P., Azouvi P., Azzolini M.L., Beretta L., Baciu C., Beqiri V., Chevallard G., Chieregato A., Sacchi M., Badenes R., Belda F.J., Bilotta F., Lozano A., Barlow K.M., Schneider K.J., Bartels R., den Boogert H., Hoedemaekers C., Sir O., Bauerfeind U., Lefering R., Schafer N., Beauchamp M., Gravel J., Beer D., Beer R., Helbok R., Hofer S., Bellander B.-M., Nelson D., Bellier R., Benard T., Carise E., Dahyot-Fizelier C., Giraud B., Benali H., Bernard F., Bertolini G., Masson S., Blaabjerg M., Rosenlund C., Schou R.F., Boutis K., Bouzat P., Francony G., Manhes P., Payen J.-F., Brooks B., Dewey D., Emery C.A., Freedman S., Kramer A., Brorsson C., Koskinen L.-O., Sundstrom N., Bullinger M., Burns E., Calappi E., Ortolano F., Cameron P., Castano-Leon A.M., Gomez Lopez P.A., Lagares A., Causin F., Freo U., Persona P., Rossi S., Christie B., Cnossen M., Dippel D., Foks K., Haagsma J.A., Haitsma I., Huijben J.A., van der Jagt M., Nieboer D., Volovici V., Voormolen D.C., Collett J., Dawes H., Esser P., van Heugten C., Della Corte F., Grossi F., Craig W., Csato G., Csomos A., Curry N., Dematteo C., Meade M., Depreitere B., van Dijck J., de Ruiter G.C.W., Vleggeert-Lankamp C., Dizdarevic K., Donoghue E., Gantner D., Murray L., Trapani T., Vallance S., Duek O., Lazar I., Duliere G.-L., Marechal H., Dzeko A., Eapen G., Jankowski S., English S., Fergusson D., Osmond M., Fabricius M., Kondziella D., Feng J., Hui J., Fleming J., Latini R., Gagnon I., Ptito A., Galanaud D., Glocker B., Kamnitsas K., Ledig C., Rueckert D., Gordon W.A., Gradisek P., Griesdale D., Haberg A.K., van Hecke W., Smeets D., Verheyden J., Vyvere T.V., Helseth E., Roe C., Roise O., Horton L., Jacobs B., van der Naalt J., Janssens K., De Keyser V., Menovsky T., Van Praag D., Jones K.M., Kaps R., Katila A., Posti J., Takala R., Kaukonen K.-M., Kivisaari R., Piippo-Karjalainen A., Raj R., Tanskanen P., Kutsogiannis D., Kyprianou T., Lamontagne F., Lauzier F., Moore L., Turgeon A., Legrand V., Levi L., Zaaroor M., Lightfoot R., Macdonald S., Major S., Vajkoczy P., Wessels L., Winkler M.K.L., Wolf S., Manara A., Thomas M., Mattern J., Sakowitz O., Vogt L., Younsi A., McFadyen B., McMahon C., Correia M.M., Morganti-Kossmann M.C., Rosenfeld J.V., Muehlan H., Schmidt S., Mukherjee P., Noirhomme Q., Oddo M., Okonkwo D.O., Oldenbeuving A.W., Roks G., Schoonman G.G., Perlbarg V., Pichon N., Pili-Floury S., Pirinen M., Ples H., Poca M.A., Radoi A., Sahuquillo J., Ragauskas A., Rocka S., Real R.G.L., Telgmann R., Reed N., Rhodes J., Robertson C., Rosand J., Rosenthal G., Salvato G., Sanchez-Porras R., Sandor J., Sangha G., Schnyer D., Schohl H., Skandsen T., Stevanovic A., van Waesberghe J.V., Stevens R.D., Taccone F.S., Taylor M.S., Zelinkova V., Temkin N., Tolias C.M., Valadka A.B., Valeinis E., Vargiolu A., Vega E., Vik A., Vilcinis R., Wildschut E., Wood G., Xirouchaki N., Zemek R., Maas, A, Menon, D, Adelson, P, Andelic, N, Bell, M, Belli, A, Bragge, P, Brazinova, A, Büki, A, Chesnut, R, Citerio, G, Coburn, M, Cooper, D, Crowder, A, Czeiter, E, Czosnyka, M, Diaz arrastia, R, Dreier, J, Duhaime, A, Ercole, A, Van Essen, T, Feigin, V, Gao, G, Giacino, J, Gonzalez lara, L, Gruen, R, Gupta, D, Hartings, J, Hill, S, Jiang, J, Ketharanathan, N, Kompanje, E, Lanyon, L, Laureys, S, Lecky, F, Levin, H, Lingsma, H, Maegele, M, Majdan, M, Manley, G, Marsteller, J, Mascia, L, Mcfadyen, C, Mondello, S, Newcombe, V, Palotie, A, Parizel, P, Peul, W, Piercy, J, Polinder, S, Puybasset, L, Rasmussen, T, Rossaint, R, Smielewski, P, Söderberg, J, Stanworth, S, Stein, M, Von Steinbüchel, N, Stewart, W, Steyerberg, E, Stocchetti, N, Synnot, A, Te Ao, B, Tenovuo, O, Theadom, A, Tibboel, D, Videtta, W, Wang, K, Williams, W, Wilson, L, Yaffe, K, Adams, H, Agnoletti, V, Allanson, J, Amrein, K, Andaluz, N, Anke, A, Antoni, A, Van As, A, Audibert, G, Azaševac, A, Azouvi, P, Azzolini, M, Baciu, C, Badenes, R, Barlow, K, Bartels, R, Bauerfeind, U, Beauchamp, M, Beer, D, Beer, R, Belda, F, Bellander, B, Bellier, R, Benali, H, Benard, T, Beqiri, V, Beretta, L, Bernard, F, Bertolini, G, Bilotta, F, Blaabjerg, M, Den Boogert, H, Boutis, K, Bouzat, P, Brooks, B, Brorsson, C, Bullinger, M, Burns, E, Calappi, E, Cameron, P, Carise, E, Castaño león, A, Causin, F, Chevallard, G, Chieregato, A, Christie, B, Cnossen, M, Coles, J, Collett, J, Della Corte, F, Craig, W, Csato, G, Csomos, A, Curry, N, Dahyot fizelier, C, Dawes, H, Dematteo, C, Depreitere, B, Dewey, D, Van Dijck, J, Đilvesi, Đ, Dippel, D, Dizdarevic, K, Donoghue, E, Duek, O, Dulière, G, Dzeko, A, Eapen, G, Emery, C, English, S, Esser, P, Ezer, E, Fabricius, M, Feng, J, Fergusson, D, Figaji, A, Fleming, J, Foks, K, Francony, G, Freedman, S, Freo, U, Frisvold, S, Gagnon, I, Galanaud, D, Gantner, D, Giraud, B, Glocker, B, Golubovic, J, Gómez López, P, Gordon, W, Gradisek, P, Gravel, J, Griesdale, D, Grossi, F, Haagsma, J, Håberg, A, Haitsma, I, Van Hecke, W, Helbok, R, Helseth, E, Van Heugten, C, Hoedemaekers, C, Höfer, S, Horton, L, Hui, J, Huijben, J, Hutchinson, P, Jacobs, B, Van Der Jagt, M, Jankowski, S, Janssens, K, Jelaca, B, Jones, K, Kamnitsas, K, Kaps, R, Karan, M, Katila, A, Kaukonen, K, De Keyser, V, Kivisaari, R, Kolias, A, Kolumbán, B, Kolundžija, K, Kondziella, D, Koskinen, L, Kovács, N, Kramer, A, Kutsogiannis, D, Kyprianou, T, Lagares, A, Lamontagne, F, Latini, R, Lauzier, F, Lazar, I, Ledig, C, Lefering, R, Legrand, V, Levi, L, Lightfoot, R, Lozano, A, Macdonald, S, Major, S, Manara, A, Manhes, P, Maréchal, H, Martino, C, Masala, A, Masson, S, Mattern, J, Mcfadyen, B, Mcmahon, C, Meade, M, Melegh, B, Menovsky, T, Moore, L, Morgado Correia, M, Morganti kossmann, M, Muehlan, H, Mukherjee, P, Murray, L, Van Der Naalt, J, Negru, A, Nelson, D, Nieboer, D, Noirhomme, Q, Nyirádi, J, Oddo, M, Okonkwo, D, Oldenbeuving, A, Ortolano, F, Osmond, M, Payen, J, Perlbarg, V, Persona, P, Pichon, N, Piippo karjalainen, A, Pili floury, S, Pirinen, M, Ple, H, Poca, M, Posti, J, Van Praag, D, Ptito, A, Radoi, A, Ragauskas, A, Raj, R, Real, R, Reed, N, Rhodes, J, Robertson, C, Rocka, S, Røe, C, Røise, O, Roks, G, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossi, S, Rueckert, D, De Ruiter, G, Sacchi, M, Sahakian, B, Sahuquillo, J, Sakowitz, O, Salvato, G, Sánchez porras, R, Sándor, J, Sangha, G, Schäfer, N, Schmidt, S, Schneider, K, Schnyer, D, Schöhl, H, Schoonman, G, Schou, R, Sir, Ö, Skandsen, T, Smeets, D, Sorinola, A, Stamatakis, E, Stevanovic, A, Stevens, R, Sundström, N, Taccone, F, Takala, R, Tanskanen, P, Taylor, M, Telgmann, R, Temkin, N, Teodorani, G, Thomas, M, Tolias, C, Trapani, T, Turgeon, A, Vajkoczy, P, Valadka, A, Valeinis, E, Vallance, S, Vámos, Z, Vargiolu, A, Vega, E, Verheyden, J, Vik, A, Vilcinis, R, Vleggeert lankamp, C, Vogt, L, Volovici, V, Voormolen, D, Vulekovic, P, Vande Vyvere, T, Van Waesberghe, J, Wessels, L, Wildschut, E, Williams, G, Winkler, M, Wolf, S, Wood, G, Xirouchaki, N, Younsi, A, Zaaroor, M, Zelinkova, V, Zemek, R, Zumbo, F, Pediatric Surgery, Intensive Care, and Public Health

Subjects
medicine.medical_specialty, EVIDENCE-BASED MEDICINE, Treatment outcome, Poison control, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], EMERGENCY-DEPARTMENT VISITS, Review, PLACEBO-CONTROLLED TRIAL, Middle income country, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, 0302 clinical medicine, Intensive care, Brain Injuries, Traumatic, Journal Article, medicine, traumatic barin injury, Humans, 030212 general & internal medicine, Clinical care, Neurologic disease, Psychiatry, DIAGNOSTIC MANAGEMENT STRATEGIES, business.industry, RANDOMIZED CONTROLLED-TRIAL, ACUTE SUBDURAL-HEMATOMA, SEVERE HEAD-INJURY, ROAD TRAFFIC INJURIES, brain injury, Hospital care, 3. Good health, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Brain Injuries, Health care cost, PATIENT-REPORTED OUTCOMES, Human medicine, Neurology (clinical), business, Humanities, 030217 neurology & neurosurgery, GLASGOW COMA SCALE
Abstract

Executive summary A concerted effort to tackle the global health problem posed by traumatic brain injury (TBI) is long overdue. TBI is a public health challenge of vast, but insufficiently recognised, proportions. Worldwide, more than 50 million people have a TBI each year, and it is estimated that about half the world’s population will have one or more TBIs over their lifetime. TBI is the leading cause of mortality in young adults and a major cause of death and disability across all ages in all countries, with a disproportionate burden of disability and death occurring in low-income and middle-income countries (LMICs). It has been estimated that TBI costs the global economy approximately $US400 billion annually. Deficiencies in prevention, care, and research urgently need to be addressed to reduce the huge burden and societal costs of TBI. This Commission highlights priorities and provides expert recommendations for all stakeholders— policy makers, funders, health-care professionals, researchers, and patient representatives—on clinical and research strategies to reduce this growing public health problem and improve the lives of people with TBI. The epidemiology of TBI is changing: in high-income countries, the number of elderly people with TBI is increasing, mainly due to falls, while in LMICs, the burden of TBI from road traffic incidents is increasing. Data on the frequency of TBI and TBI-related deaths and on the economic impact of brain trauma are often incomplete and vary between countries. Improved, accurate epidemiological monitoring and robust healtheconomic data collection are needed to inform healthcare policy and prevention programmes. Highly developed and coordinated systems of care are crucial for management of patients with TBI. However, in practice, implementation of such frameworks varies greatly and disconnects exist in the chain of care. Optimisation of systems of care should be high on the policy agenda and could yield substantial gains in terms of both patient outcomes and costs to society. TBI is a complex condition, and strong evidence to support treatment guidelines and recommendations is scarce. Most multicentre clinical trials of medical and surgical interventions have failed to show efficacy, despite promising preclinical results. At the bedside, treatment strategies are generally based on guidelines that promote a one-size-fits-all approach and are insufficiently targeted to the needs of individual patients. Attempts to individualise treatment are challenging owing to the diversity of TBI, and are hampered by the use of simplistic methods to characterise its initial type and severity. Advances in genomics, blood biomarkers, magnetic resonance imaging (MRI), and pathophysiological monitoring, combined with informatics to integrate data from multiple sources, offer new research avenues to improve disease characterisation and monitoring of disease evolution. These tools can also aid understanding of disease mechanisms and facilitate targeted treatment strategies for individual patients. Individualised management in the postacute phase and evaluation of the effectiveness of treatment and care processes depend on accurate quantification of outcomes. In practice, however, the use of simplistic methods hinders efforts to quantify outcomes after TBI of all severities. Development and validation of multidimensional approaches will be essential to improve measurement of clinical outcomes, for both research and patient care. In particular, we need to find better ways to characterise the currently under-recognised risk of long-term disabling sequelae in patients with relatively mild injuries. Prognostic models are important to help clinicians to provide reliable information to patients and relatives, and to facilitate comparative audit of care between centres and countries. There is an urgent need for further development, validation, and implementation of prognostic models in TBI, particularly for less severe TBI. This multitude of challenges in TBI—encompassing systems of care, clinical management, and research strategy—demands novel approaches to the generation of new evidence and its implementation in clinical practice. Comparative effectiveness research (CER) offers opportunities to capitalise on the diversity of TBI and systems of care and enables assessment of therapies in real-world conditions; high-quality CER studies can provide strong evidence to support guideline recommendations. The global challenges posed by TBI necessitate global collaborations and a change in research culture to endorse broad data sharing. This Commission covers a range of topics that need to be addressed to confront the global burden of TBI and reduce its effects on individuals and society: epidemiology (section 1); health economics (section 2); prevention (section 3); systems of care (section 4); clinical management (section 5); characterisation of TBI (section 6); outcome assessment (section 7); prognosis (section 8); and new directions for acquiring and implementing evidence (section 9). Table 1 summarises key messages from the Commission and provides recommendations to advance clinical care and research in TBI. We must increase awareness of the scale of the challenge posed by TBI. If we are to tackle the individual and societal burden of TBI, these efforts need to go beyond a clinical and research audience and address the public, politicians, and other stakeholders. We need to develop and implement policies for better prevention and systems of care in order to improve outcomes for individuals with TBI. We also need a commitment to substantial long-term investment in TBI research across a range of disciplines to determine best practice and facilitate individualised management strategies. A combination of innovative research methods and global collaboration, and ways to effectively translate progress in basic and clinical research into clinical practice and public health policy, will be vital for progress in the field.

Published
2017

34. Erratum: stematic review and meta-analysis of individual participant data (Clin Epidemiol. 2018, 10, 363–379)

Author

Eurelings L. S. M., van Dalen J. W., Ter Riet G., Moll van Charante E. P., Richard E., van Gool W. A., Almeida O. P., Alexandre T. S., Baune B. T., Bickel H., Cacciatore F., Cooper C., de Craen T. A. J. M., Degryse J. -M., Di Bari M., Duarte Y. A., Feng L., Ferrara N., Flicker L., Gallucci M., Guaita A., Harrison S. L., Katz M. J., Lebrao M. L., Leung J., Lipton R. B., Mengoni M., Ng T. P., Ostbye T., Panza F., Polito L., Sander D., Solfrizzi V., Syddall H. E., van der Mast R. C., Vaes B., Woo J., Yaffe K., Gao S., Ho S. C., Lindsay J., Sham A., Reppermund S., Unverzagt F. W., Eurelings, L. S. M., van Dalen, J. W., Ter Riet, G., Moll van Charante, E. P., Richard, E., van Gool, W. A., Almeida, O. P., Alexandre, T. S., Baune, B. T., Bickel, H., Cacciatore, F., Cooper, C., de Craen, T. A. J. M., Degryse, J. -M., Di Bari, M., Duarte, Y. A., Feng, L., Ferrara, N., Flicker, L., Gallucci, M., Guaita, A., Harrison, S. L., Katz, M. J., Lebrao, M. L., Leung, J., Lipton, R. B., Mengoni, M., Ng, T. P., Ostbye, T., Panza, F., Polito, L., Sander, D., Solfrizzi, V., Syddall, H. E., van der Mast, R. C., Vaes, B., Woo, J., Yaffe, K., Gao, S., Ho, S. C., Lindsay, J., Sham, A., Reppermund, S., and Unverzagt, F. W.

Abstract

Page 363, affiliations section, “On behalf of the ICARA Study Group” should instead read “and the ICARA study group”.

Published
2019

37. Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia

Author

Lee, C.M., Woodward, M., Batty, G.D., Beiser, A.S., Bell, S., Berr, C., Bjertness, E., Chalmers, J., Clarke, R., Dartigues, J.F., Davis-Plourde, K., Debette, S., Angelantonio, E. Di, Feart, C., Frikke-Schmidt, R., Gregson, J., Haan, M.N., Hassing, L.B., Hayden, K.M., Hoevenaar-Blom, M.P., Kaprio, J., Kivimäki, M., Lappas, G., Larson, E.B., LeBlanc, E.S., Lee, A., Lui, L.Y., Charante, E.P.M. van, Ninomiya, T., Nordestgaard, L.T., Ohara, T., Ohkuma, T., Palviainen, T., Peres, K., Peters, R, Qizilbash, N., Richard, E., Rosengren, A., Seshadri, S., Shipley, M., Singh-Manoux, A., Strand, B.H., Gool, W.A. van, Vuoksimaa, E., Yaffe, K., Huxley, R.R., Lee, C.M., Woodward, M., Batty, G.D., Beiser, A.S., Bell, S., Berr, C., Bjertness, E., Chalmers, J., Clarke, R., Dartigues, J.F., Davis-Plourde, K., Debette, S., Angelantonio, E. Di, Feart, C., Frikke-Schmidt, R., Gregson, J., Haan, M.N., Hassing, L.B., Hayden, K.M., Hoevenaar-Blom, M.P., Kaprio, J., Kivimäki, M., Lappas, G., Larson, E.B., LeBlanc, E.S., Lee, A., Lui, L.Y., Charante, E.P.M. van, Ninomiya, T., Nordestgaard, L.T., Ohara, T., Ohkuma, T., Palviainen, T., Peres, K., Peters, R, Qizilbash, N., Richard, E., Rosengren, A., Seshadri, S., Shipley, M., Singh-Manoux, A., Strand, B.H., Gool, W.A. van, Vuoksimaa, E., Yaffe, K., and Huxley, R.R.

Abstract

Contains fulltext : 218833.pdf (publisher's version ) (Open Access), Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m(2) ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m(2) ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.

Published
2020

38. Risk Factors for Incident Dementia Among Older Cubans.

Author

Peeters, G.M.E.E., Sanchez, A., Guerra, J., Lawlor, B., Kenny, R.A., Yaffe, K., Rodriguez, J., Peeters, G.M.E.E., Sanchez, A., Guerra, J., Lawlor, B., Kenny, R.A., Yaffe, K., and Rodriguez, J.

Abstract

Contains fulltext : 229314.pdf (publisher's version ) (Open Access)

Published
2020

39. Future Directions for Dementia Risk Reduction and Prevention Research: An International Research Network on Dementia Prevention Consensus

Author

Anstey, KJ, Peters, R, Zheng, L, Barnes, DE, Brayne, C, Brodaty, H, Chalmers, J, Clare, L, DIxon, RA, Dodge, H, Lautenschlager, NT, Middleton, LE, Qiu, C, Rees, G, Shahar, S, Yaffe, K, Anstey, KJ, Peters, R, Zheng, L, Barnes, DE, Brayne, C, Brodaty, H, Chalmers, J, Clare, L, DIxon, RA, Dodge, H, Lautenschlager, NT, Middleton, LE, Qiu, C, Rees, G, Shahar, S, and Yaffe, K

Abstract

In the past decade a large body of evidence has accumulated on risk factors for dementia, primarily from Europe and North America. Drawing on recent integrative reviews and a consensus workshop, the International Research Network on Dementia Prevention developed a consensus statement on priorities for future research. Significant gaps in geographical location, representativeness, diversity, duration, mechanisms, and research on combinations of risk factors were identified. Future research to inform dementia risk reduction should fill gaps in the evidence base, take a life-course, multi-domain approach, and inform population health approaches that improve the brain-health of whole communities.

Published
2020

40. Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia

Author

Lee, CMY, Woodward, M, Batty, GD, Beiser, AS, Bell, S, Berr, C, Bjertness, E, Chalmers, J, Clarke, R, Dartigues, JF, Davis-Plourde, K, Debette, S, Di Angelantonio, E, Feart, C, Frikke-Schmidt, R, Gregson, J, Haan, MN, Hassing, LB, Hayden, KM, Hoevenaar-Blom, MP, Kaprio, J, Kivimaki, M, Lappas, G, Larson, EB, LeBlanc, ES, Lee, A, Lui, LY, Moll van Charante, EP, Ninomiya, T, Nordestgaard, LT, Ohara, T, Ohkuma, T, Palviainen, T, Peres, K, Peters, R, Qizilbash, N, Richard, E, Rosengren, A, Seshadri, S, Shipley, M, Singh-Manoux, A, Strand, BH, van Gool, WA, Vuoksimaa, E, Yaffe, K, Huxley, RR, Lee, CMY, Woodward, M, Batty, GD, Beiser, AS, Bell, S, Berr, C, Bjertness, E, Chalmers, J, Clarke, R, Dartigues, JF, Davis-Plourde, K, Debette, S, Di Angelantonio, E, Feart, C, Frikke-Schmidt, R, Gregson, J, Haan, MN, Hassing, LB, Hayden, KM, Hoevenaar-Blom, MP, Kaprio, J, Kivimaki, M, Lappas, G, Larson, EB, LeBlanc, ES, Lee, A, Lui, LY, Moll van Charante, EP, Ninomiya, T, Nordestgaard, LT, Ohara, T, Ohkuma, T, Palviainen, T, Peres, K, Peters, R, Qizilbash, N, Richard, E, Rosengren, A, Seshadri, S, Shipley, M, Singh-Manoux, A, Strand, BH, van Gool, WA, Vuoksimaa, E, Yaffe, K, and Huxley, RR

Abstract

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta‐analysis. Compared with body mass index–defined lower‐normal weight (18.5‐22.4 kg/m2), the risk of all‐cause dementia was higher among underweight individuals but lower among those with upper‐normal (22.5‐24.9 kg/m2) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all‐cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non‐linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.

Published
2020

41. The necessity of diplomacy in brain health

Author

Dawson, WD, Bobrow, K, Ibanez, A, Booi, L, Pintado-Caipa, M, Yamamoto, S, Tarnanas, I, Evans, T, Comas-Herrera, A, Cummings, J, Kaye, J, Yaffe, K, Miller, BL, Eyre, Harris, Dawson, WD, Bobrow, K, Ibanez, A, Booi, L, Pintado-Caipa, M, Yamamoto, S, Tarnanas, I, Evans, T, Comas-Herrera, A, Cummings, J, Kaye, J, Yaffe, K, Miller, BL, and Eyre, Harris

Published
2020

43. Emphysema on Chest Imaging and Mid-Life Cognition

Author

Henkle, B.E., primary, Kalhan, R., additional, Colangelo, L., additional, Pistenmaa Aaron, C., additional, Dransfield, M.T., additional, Jacobs, D., additional, Putman, R.K., additional, Sidney, S., additional, Thyagarajan, B., additional, Washko, G.R., additional, Yaffe, K., additional, and Kunisaki, K.M., additional

Published
2020
Full Text
View/download PDF

44. 0652 A Novel Cognitive-Behavioral Therapy to Increase PAP Adherence in Veterans With Posttraumatic Stress Disorder: Preliminary Results

Author

Kinoshita, L, primary, Blank, E, primary, Chen, M, primary, Doudell, K, primary, Day, Y, primary, Alipio Jocson, V, primary, Lazzeroni, L, primary, Noda, A, primary, Hernandez, B, primary, Holty, J, primary, Kuschner, W, primary, Kushida, C, primary, Yaffe, K, primary, Cheng, J, primary, and Yesavage, J A, primary

Published
2020
Full Text
View/download PDF

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