Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Danai Dima ,Katie L Mcmahon ,Bernd Krämer ,Stefan Borgwardt ,Erik G Jönsson ,Jan K Buitelaar ,Jim Lagopoulos ,Gunter Schümann ,O Grimm ,Christopher R K Ching ,Jaap Oosterlaan ,José M Menchón ,Nancy C Andreasen ,Salvador Sarró ,Ben J Harrison ,Klaus‐Peter Lesch ,Randy L Buckner ,Alessandro Bertolino ,Paul Pauli ,Paul M Thompson ,Erlend S Dørum ,Víctor Ortiz‐García De La Foz ,Simon E Fisher ,Fabrice Crivello ,Giulio Pergola ,Tobias Banaschewski ,Marcus V Zanetti ,Joshua L Roffman ,Simon Červenka ,Efstathios Papachristou ,Ian B Hickie ,Dara M Cannon ,Tomohiro Nakao ,David C Glahn ,Norbert Hosten ,Daniel H Wolf ,Thomas H Wassink ,Amanda Worker ,Annette Conzelmann ,Kathryn I Alpert ,Ignacio Martínez‐Zalacaín ,Lachlan T Strike ,Nynke A Groenewold ,Hilleke E Hulshoff Pol ,Neda Jahanshad ,Edith Pomarol‐Clotet ,Neeltje E.m Van Haren ,Hans‐Jörgen Grabe ,И С Лебедева ,Anthony James ,Andrew M Mcintosh ,Ruben C Gur ,Jessica A Turner ,Jilly Naaijen ,John A Joska ,Sarah E Medland ,F Xavier Castellanos ,Pieter J Hoekstra ,Dick J Veltman ,Patricia Conrod ,Yulyia Yoncheva ,Iris Sommer ,Christopher G Davey ,Perminder S Sachdev ,Jonna Kuntsi ,Anne Uhlmann ,Matthew D Sacchet ,Tiffany M Chaim‐Avancini ,Esther Walton ,Sean N Hatton ,Annabella Di Giorgio ,Susanne Erk ,Aristotle N Voineskos ,Henry Brodaty ,Raymond Salvador ,Dominik Grotegerd ,Andreas Meyer‐Lindenberg ,Christine Löchner ,Martine Hoogman ,Theo G.m Van Erp ,Micael Andersson ,Ryota Kanai ,Daniel Brandeis ,Maurício H Serpa ,Andreas Heinz ,Vincent Calhoun ,Laura Koenders ,Ian H Gotlib ,Won Hee Lee ,Eveline A Crone ,Dennis Van’t Ent ,Benedicto Crespo‐Facorro ,Christian K Tamnes ,Dag Alnæs ,Greig I De Zubicaray ,Fleur M Howells ,Joaquim Radúa ,Patricia Gruner ,Thomas Espeseth ,Amirhossein Modabbernia ,Suzanne C Swagerman ,Nic J.a Van Der Wee ,Aurora Bonvino ,Kun Yang ,Rachel M Brouwer ,Jan Egil Nordvik ,Sanne Koops ,Henry Völzke ,Andrew J Saykin ,Philip Asherson ,Bernard Mazoyer ,Alan Breier ,Anders M Dale ,Lars Nyberg ,Ingrid Agartz ,Avram J Holmes ,Georg C Ziegler ,Rachel E Gur ,René S Kahn ,Lei Wang ,Brenna C Mcdonald ,Moji Aghajani ,Sophie Maingault ,Genevieve Mcphilemy ,Katharina Wittfeld ,Terry L Jernigan ,María J Portella ,John D West ,Carles Soriano‐Mas ,Xavier Caseras ,Lieuwe De Haan ,Ramona Baur‐Streubel ,T P Klyushnik ,Dan J Stein ,David Mataix–Cols ,Chaim Huyser ,Vincent P Clark ,Wen Wang ,Paola Fuentes‐Claramonte ,Sarah Baumeister ,Knut Schnell ,Josiane Bourque ,Jean-Paul Fouché ,Anouk Den Braber ,Dorret I Boomsma ,Julian N Trollor ,Colm Mcdonald ,Viktoria Chubar ,Steven G Potkin ,Odile A Van Den Heuvel ,Pedro Rosa ,Jiyang Jiang ,Sarah Hohmann ,Lars T Westlye ,Kang Sim ,Oliver Gruber ,Theophilus N Akudjedu ,Geraldo F Busatto ,Ilya M Veer ,Erick J Canales‐Rodríguez ,Theodore D Satterthwaite ,Eco J C De Geus ,Derrek P Hibar ,Yang Wang ,Sophia I Thomopoulos ,Helena Fatouros‐Bergman ,Dirk J Heslenfeld ,Lianne Schmaal ,Núria Bargalló ,Gaëlle E Doucet ,Catharine A Hartman ,Marieke Klein ,Pascual Sánchez‐Juan ,Nhat Trung Doan ,Henk Temmingh ,Thomas Frodl ,Luisa Lázaro ,Anton Albajes‐Eizagirre ,Henrik Walter ,Lara M Wierenga ,Andreas Reif ,Yannis Paloyelis ,Beng‐Choon Ho ,Daniel A Rinker ,Barbara Franke ,Alexander Tomyshev ,Diana Tordesillas‐Gutiérrez ,Jordan W Smoller ,Marise W J Machielsen ,Dennis Van Den Meer ,Erin W Dickie ,Steven Williams ,Pablo Najt ,Bernd Weber ,Nicholas G Martin ,Ole A Andreassen ,Margaret J Wright ,Stefan Ehrlich ,Heather C Whalley ,Andrew Kalnin ,Sophia Frangou

doi:10.1002/hbm.25320

Abstract

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to examine age‐related trajectories inferred from cross‐sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter‐individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age‐related morphometric patterns.

Highlights

Over the last 20 years, studies using structural magnetic resonance imaging (MRI) have confirmed that brain morphometric measures change with age
We formed the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium (Thompson et al, 2014, 2017) to perform large-scale analyses of brain morphometric data extracted from MRI images using standardized protocols and unified quality control procedures, harmonized and validated across all participating sites
Using data from 18,605 individuals aged 3–90 years from the ENIGMA Lifespan working group we delineated the association between age and subcortical volumes from early to late life in order to (a) identify periods of volume change or stability, (b) provide normative, age-adjusted centile curves of subcortical volumes and (c) quantify inter-individual variability in subcortical volumes which is considered a major source of inter-study differences (Dickie et al, 2013; Raz, Ghisletta, Rodrigue, Kennedy, & Lindenberger, 2010)

Summary

| INTRODUCTION

Over the last 20 years, studies using structural magnetic resonance imaging (MRI) have confirmed that brain morphometric measures change with age. Most published studies are constrained by small sample sizes, restricted age coverage and methodological variability These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain structures. The role of subcortical structures extends beyond normal cognition because changes in the volume of these regions have been reliably identified in developmental (Ecker, Bookheimer, & Murphy, 2015; Krain & Castellanos, 2006), psychiatric (Hibar et al, 2016; Kempton et al, 2011; Schmaal et al, 2016; van Erp et al, 2016) and degenerative disorders (Risacher et al, 2009). Using data from 18,605 individuals aged 3–90 years from the ENIGMA Lifespan working group we delineated the association between age and subcortical volumes from early to late life in order to (a) identify periods of volume change or stability, (b) provide normative, age-adjusted centile curves of subcortical volumes and (c) quantify inter-individual variability in subcortical volumes which is considered a major source of inter-study differences (Dickie et al, 2013; Raz, Ghisletta, Rodrigue, Kennedy, & Lindenberger, 2010)

| MATERIALS AND METHODS

Findings

| DISCUSSION