Fully characterizing age differences in the brain is a key task for combating aging-related cognitive decline. Using propensity score matching on 2 independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age of 92 years (n = 42) to very similar participants at mean age of 73 years (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in gray and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural aging, in which brains from the 8th and 10th decades of life differ widely despite the same cognitive, socioeconomic, and brain-volumetric starting points.

VL - 62 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29149632?dopt=Abstract ER - TY - JOUR T1 - Novel genetic loci underlying human intracranial volume identified through genome-wide association. JF - Nat Neurosci Y1 - 2016 A1 - Adams, Hieab H H A1 - Hibar, Derrek P A1 - Chouraki, Vincent A1 - Stein, Jason L A1 - Nyquist, Paul A A1 - Renteria, Miguel E A1 - Trompet, Stella A1 - Arias-Vasquez, Alejandro A1 - Seshadri, Sudha A1 - Desrivières, Sylvane A1 - Beecham, Ashley H A1 - Jahanshad, Neda A1 - Wittfeld, Katharina A1 - van der Lee, Sven J A1 - Abramovic, Lucija A1 - Alhusaini, Saud A1 - Amin, Najaf A1 - Andersson, Micael A1 - Arfanakis, Konstantinos A1 - Aribisala, Benjamin S A1 - Armstrong, Nicola J A1 - Athanasiu, Lavinia A1 - Axelsson, Tomas A1 - Beiser, Alexa A1 - Bernard, Manon A1 - Bis, Joshua C A1 - Blanken, Laura M E A1 - Blanton, Susan H A1 - Bohlken, Marc M A1 - Boks, Marco P A1 - Bralten, Janita A1 - Brickman, Adam M A1 - Carmichael, Owen A1 - M Mallar Chakravarty A1 - Chauhan, Ganesh A1 - Chen, Qiang A1 - Ching, Christopher R K A1 - Cuellar-Partida, Gabriel A1 - Braber, Anouk Den A1 - Doan, Nhat Trung A1 - Ehrlich, Stefan A1 - Filippi, Irina A1 - Ge, Tian A1 - Giddaluru, Sudheer A1 - Goldman, Aaron L A1 - Gottesman, Rebecca F A1 - Greven, Corina U A1 - Grimm, Oliver A1 - Griswold, Michael E A1 - Guadalupe, Tulio A1 - Hass, Johanna A1 - Haukvik, Unn K A1 - Hilal, Saima A1 - Hofer, Edith A1 - Hoehn, David A1 - Holmes, Avram J A1 - Hoogman, Martine A1 - Janowitz, Deborah A1 - Jia, Tianye A1 - Kasperaviciute, Dalia A1 - Kim, Sungeun A1 - Klein, Marieke A1 - Kraemer, Bernd A1 - Lee, Phil H A1 - Liao, Jiemin A1 - Liewald, David C M A1 - Lopez, Lorna M A1 - Luciano, Michelle A1 - Macare, Christine A1 - Marquand, Andre A1 - Matarin, Mar A1 - Mather, Karen A A1 - Mattheisen, Manuel A1 - Mazoyer, Bernard A1 - McKay, David R A1 - McWhirter, Rebekah A1 - Milaneschi, Yuri A1 - Mirza-Schreiber, Nazanin A1 - Muetzel, Ryan L A1 - Maniega, Susana Muñoz A1 - Nho, Kwangsik A1 - Nugent, Allison C A1 - Loohuis, Loes M Olde A1 - Oosterlaan, Jaap A1 - Papmeyer, Martina A1 - Pappa, Irene A1 - Pirpamer, Lukas A1 - Pudas, Sara A1 - Pütz, Benno A1 - Rajan, Kumar B A1 - Ramasamy, Adaikalavan A1 - Richards, Jennifer S A1 - Risacher, Shannon L A1 - Roiz-Santiañez, Roberto A1 - Rommelse, Nanda A1 - Rose, Emma J A1 - Royle, Natalie A A1 - Rundek, Tatjana A1 - Sämann, Philipp G A1 - Satizabal, Claudia L A1 - Schmaal, Lianne A1 - Schork, Andrew J A1 - Shen, Li A1 - Shin, Jean A1 - Shumskaya, Elena A1 - Smith, Albert V A1 - Sprooten, Emma A1 - Strike, Lachlan T A1 - Teumer, Alexander A1 - Thomson, Russell A1 - Tordesillas-Gutierrez, Diana A1 - Toro, Roberto A1 - Trabzuni, Daniah A1 - Vaidya, Dhananjay A1 - Van der Grond, Jeroen A1 - Van der Meer, Dennis A1 - van Donkelaar, Marjolein M J A1 - van Eijk, Kristel R A1 - van Erp, Theo G M A1 - Van Rooij, Daan A1 - Walton, Esther A1 - Westlye, Lars T A1 - Whelan, Christopher D A1 - Windham, Beverly G A1 - Winkler, Anderson M A1 - Woldehawariat, Girma A1 - Wolf, Christiane A1 - Wolfers, Thomas A1 - Xu, Bing A1 - Yanek, Lisa R A1 - Yang, Jingyun A1 - Zijdenbos, Alex A1 - Zwiers, Marcel P A1 - Agartz, Ingrid A1 - Aggarwal, Neelum T A1 - Almasy, Laura A1 - Ames, David A1 - Amouyel, Philippe A1 - Andreassen, Ole A A1 - Arepalli, Sampath A1 - Assareh, Amelia A A1 - Barral, Sandra A1 - Bastin, Mark E A1 - Becker, Diane M A1 - Becker, James T A1 - Bennett, David A A1 - Blangero, John A1 - van Bokhoven, Hans A1 - Boomsma, Dorret I A1 - Brodaty, Henry A1 - Brouwer, Rachel M A1 - Brunner, Han G A1 - Buckner, Randy L A1 - Buitelaar, Jan K A1 - Bulayeva, Kazima B A1 - Cahn, Wiepke A1 - Calhoun, Vince D A1 - Cannon, Dara M A1 - Cavalleri, Gianpiero L A1 - Chen, Christopher A1 - Cheng, Ching-Yu A1 - Cichon, Sven A1 - Cookson, Mark R A1 - Corvin, Aiden A1 - Crespo-Facorro, Benedicto A1 - Curran, Joanne E A1 - Czisch, Michael A1 - Dale, Anders M A1 - Davies, Gareth E A1 - de Geus, Eco J C A1 - De Jager, Philip L A1 - de Zubicaray, Greig I A1 - Delanty, Norman A1 - Depondt, Chantal A1 - DeStefano, Anita L A1 - Dillman, Allissa A1 - Djurovic, Srdjan A1 - Donohoe, Gary A1 - Drevets, Wayne C A1 - Duggirala, Ravi A1 - Dyer, Thomas D A1 - Erk, Susanne A1 - Espeseth, Thomas A1 - Evans, Denis A A1 - Fedko, Iryna O A1 - Fernández, Guillén A1 - Ferrucci, Luigi A1 - Fisher, Simon E A1 - Fleischman, Debra A A1 - Ford, Ian A1 - Foroud, Tatiana M A1 - Fox, Peter T A1 - Francks, Clyde A1 - Fukunaga, Masaki A1 - Gibbs, J Raphael A1 - Glahn, David C A1 - Gollub, Randy L A1 - Göring, Harald H H A1 - Grabe, Hans J A1 - Green, Robert C A1 - Gruber, Oliver A1 - Gudnason, Vilmundur A1 - Guelfi, Sebastian A1 - Hansell, Narelle K A1 - Hardy, John A1 - Hartman, Catharina A A1 - Hashimoto, Ryota A1 - Hegenscheid, Katrin A1 - Heinz, Andreas A1 - Le Hellard, Stephanie A1 - Hernandez, Dena G A1 - Heslenfeld, Dirk J A1 - Ho, Beng-Choon A1 - Hoekstra, Pieter J A1 - Hoffmann, Wolfgang A1 - Hofman, Albert A1 - Holsboer, Florian A1 - Homuth, Georg A1 - Hosten, Norbert A1 - Hottenga, Jouke-Jan A1 - Pol, Hilleke E Hulshoff A1 - Ikeda, Masashi A1 - Ikram, M Kamran A1 - Jack, Clifford R A1 - Jenkinson, Mark A1 - Johnson, Robert A1 - Jönsson, Erik G A1 - Jukema, J Wouter A1 - Kahn, René S A1 - Kanai, Ryota A1 - Kloszewska, Iwona A1 - Knopman, David S A1 - Kochunov, Peter A1 - Kwok, John B A1 - Lawrie, Stephen M A1 - Lemaître, Herve A1 - Liu, Xinmin A1 - Longo, Dan L A1 - Longstreth, W T A1 - Lopez, Oscar L A1 - Lovestone, Simon A1 - Martinez, Oliver A1 - Martinot, Jean-Luc A1 - Mattay, Venkata S A1 - McDonald, Colm A1 - McIntosh, Andrew M A1 - McMahon, Katie L A1 - McMahon, Francis J A1 - Mecocci, Patrizia A1 - Melle, Ingrid A1 - Meyer-Lindenberg, Andreas A1 - Mohnke, Sebastian A1 - Montgomery, Grant W A1 - Morris, Derek W A1 - Mosley, Thomas H A1 - Mühleisen, Thomas W A1 - Müller-Myhsok, Bertram A1 - Nalls, Michael A A1 - Nauck, Matthias A1 - Nichols, Thomas E A1 - Niessen, Wiro J A1 - Nöthen, Markus M A1 - Nyberg, Lars A1 - Ohi, Kazutaka A1 - Olvera, Rene L A1 - Ophoff, Roel A A1 - Pandolfo, Massimo A1 - Paus, Tomas A1 - Pausova, Zdenka A1 - Penninx, Brenda W J H A1 - Pike, G Bruce A1 - Potkin, Steven G A1 - Psaty, Bruce M A1 - Reppermund, Simone A1 - Rietschel, Marcella A1 - Roffman, Joshua L A1 - Romanczuk-Seiferth, Nina A1 - Rotter, Jerome I A1 - Ryten, Mina A1 - Sacco, Ralph L A1 - Sachdev, Perminder S A1 - Saykin, Andrew J A1 - Schmidt, Reinhold A1 - Schofield, Peter R A1 - Sigurdsson, Sigurdur A1 - Simmons, Andy A1 - Singleton, Andrew A1 - Sisodiya, Sanjay M A1 - Smith, Colin A1 - Smoller, Jordan W A1 - Soininen, Hilkka A1 - Srikanth, Velandai A1 - Steen, Vidar M A1 - Stott, David J A1 - Sussmann, Jessika E A1 - Thalamuthu, Anbupalam A1 - Tiemeier, Henning A1 - Toga, Arthur W A1 - Traynor, Bryan J A1 - Troncoso, Juan A1 - Turner, Jessica A A1 - Tzourio, Christophe A1 - Uitterlinden, Andre G A1 - Hernández, Maria C Valdés A1 - van der Brug, Marcel A1 - van der Lugt, Aad A1 - van der Wee, Nic J A A1 - van Duijn, Cornelia M A1 - van Haren, Neeltje E M A1 - Van T Ent, Dennis A1 - van Tol, Marie-Jose A1 - Vardarajan, Badri N A1 - Veltman, Dick J A1 - Vernooij, Meike W A1 - Völzke, Henry A1 - Walter, Henrik A1 - Wardlaw, Joanna M A1 - Wassink, Thomas H A1 - Weale, Michael E A1 - Weinberger, Daniel R A1 - Weiner, Michael W A1 - Wen, Wei A1 - Westman, Eric A1 - White, Tonya A1 - Wong, Tien Y A1 - Wright, Clinton B A1 - Zielke, H Ronald A1 - Zonderman, Alan B A1 - Deary, Ian J A1 - DeCarli, Charles A1 - Schmidt, Helena A1 - Martin, Nicholas G A1 - De Craen, Anton J M A1 - Wright, Margaret J A1 - Launer, Lenore J A1 - Schumann, Gunter A1 - Fornage, Myriam A1 - Franke, Barbara A1 - Debette, Stéphanie A1 - Medland, Sarah E A1 - Ikram, M Arfan A1 - Thompson, Paul M AB -Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

VL - 19 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27694991?dopt=Abstract ER - TY - JOUR T1 - Progression of White Matter Disease and Cortical Thinning Are Not Related in Older Community-Dwelling Subjects. JF - Stroke Y1 - 2016 A1 - Dickie, David Alexander A1 - Sherif Karama A1 - Ritchie, Stuart J A1 - Cox, Simon R A1 - Sakka, Eleni A1 - Royle, Natalie A A1 - Aribisala, Benjamin S A1 - Hernández, Maria Valdés A1 - Maniega, Susana Muñoz A1 - Pattie, Alison A1 - Corley, Janie A1 - Starr, John M A1 - Bastin, Mark E A1 - Evans, Alan C A1 - Deary, Ian J A1 - Wardlaw, Joanna M KW - Aged KW - Cardiovascular Diseases KW - Cerebral Cortex KW - Cognition Disorders KW - Cross-Sectional Studies KW - Diabetes Mellitus KW - Disease Progression KW - Female KW - Humans KW - Hypercholesterolemia KW - Hypertension KW - Independent Living KW - Leukoencephalopathies KW - Linear Models KW - Longitudinal Studies KW - Magnetic Resonance Imaging KW - Male KW - Organ Size KW - Risk Factors KW - Scotland KW - Smoking KW - White Matter AB -**BACKGROUND AND PURPOSE: **We assessed cross-sectional and longitudinal relationships between whole brain white matter hyperintensity (WMH) volume and regional cortical thickness.

**METHODS: **We measured WMH volume and regional cortical thickness on magnetic resonance imaging at ≈73 and ≈76 years in 351 community-dwelling subjects from the Lothian Birth Cohort 1936. We used multiple linear regression to calculate cross-sectional and longitudinal associations between regional cortical thickness and WMH volume controlling for age, sex, Mini Mental State Examination, education, intelligence quotient at age 11, and vascular risk factors.

**RESULTS: **We found cross-sectional associations between WMH volume and cortical thickness within and surrounding the Sylvian fissure at 73 and 76 years (rho=-0.276, Q=0.004). However, we found no significant longitudinal associations between (1) baseline WMH volume and change in cortical thickness; (2) baseline cortical thickness and change in WMH volume; or (3) change in WMH volume and change in cortical thickness.

**CONCLUSIONS: **Our results show that WMH volume and cortical thinning both worsen with age and are associated cross-sectionally within and surrounding the Sylvian fissure. However, changes in WMH volume and cortical thinning from 73 to 76 years are not associated longitudinally in these relatively healthy older subjects. The underlying cause(s) of WMH growth and cortical thinning have yet to be fully determined.

People with larger brains tend to score higher on tests of general intelligence (g). It is unclear, however, how much variance in intelligence other brain measurements would account for if included together with brain volume in a multivariable model. We examined a large sample of individuals in their seventies (n = 672) who were administered a comprehensive cognitive test battery. Using structural equation modelling, we related six common magnetic resonance imaging-derived brain variables that represent normal and abnormal features-brain volume, cortical thickness, white matter structure, white matter hyperintensity load, iron deposits, and microbleeds-to g and to fluid intelligence. As expected, brain volume accounted for the largest portion of variance (~ 12%, depending on modelling choices). Adding the additional variables, especially cortical thickness (+~ 5%) and white matter hyperintensity load (+~ 2%), increased the predictive value of the model. Depending on modelling choices, all neuroimaging variables together accounted for 18-21% of the variance in intelligence. These results reveal which structural brain imaging measures relate to g over and above the largest contributor, total brain volume. They raise questions regarding which other neuroimaging measures might account for even more of the variance in intelligence.

VL - 51 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26240470?dopt=Abstract ER -