학술논문
Sex Modulates the Pathological Aging Effect on Caudate Functional Connectivity in Mild Cognitive Impairment
Document Type
article
Author
Zhengshi Yang; Jessica Z. K. Caldwell; Jeffrey L. Cummings; Aaron Ritter; Jefferson W. Kinney; Dietmar Cordes; The Alzheimer's Disease Neuroimaging Initiative (ADNI); Michael Weiner; Paul Aisen; Ronald Petersen; Clifford R. Jack; William Jagust; John Q. Trojanowki; Arthur W. Toga; Laurel Beckett; Robert C. Green; Andrew J. Saykin; John Morris; Enchi Liu; Tom Montine; Anthony Gamst; Ronald G. Thomas; Michael Donohue; Sarah Walter; Devon Gessert; Tamie Sather; Danielle Harvey; John Kornak; Anders Dale; Matthew Bernstein; Joel Felmlee; Nick Fox; Paul Thompson; Norbert Schuff; Gene Alexander; Charles DeCArli; Dan Bandy; Robert A. Koeppe; Norm Foster; Eric M. Reiman; Kewei Chen; Chet Mathis; Nigel J. Cairns; Lisa Taylor-Reinwald; J. Q. Trojanowki; Les Shaw; Virginia M.Y. Lee; Magdalena Korecka; Karen Crawford; Scott Neu; Tatiana M. Foroud; Steven Potkin; Li Shen; Zaven Khachaturian; Richard Frank; Peter J. Snyder; Susan Molchan; Jeffrey Kaye; Joseph Quinn; Betty Lind; Sara Dolen; Lon S. Schneider; Sonia Pawluczyk; Bryan M. Spann; James Brewer; Helen Vanderswag; Judith L. Heidebrink; Joanne L. Lord; Kris Johnson; Rachelle S. Doody; Javier Villanueva-Meyer; Munir Chowdhury; Yaakov Stern; Lawrence S. Honig; Karen L. Bell; John C. Morris; Beau Ances; Maria Carroll; Sue Leon; Mark A. Mintun; Stacy Schneider; Daniel Marson; Randall Griffith; David Clark; Hillel Grossman; Effie Mitsis; Aliza Romirowsky; Leyla deToledo-Morrell; Raj C. Shah; Ranjan Duara; Daniel Varon; Peggy Roberts; Marilyn Albert; Chiadi Onyike; Stephanie Kielb; Henry Rusinek; Mony J de Leon; Lidia Glodzik; P. Murali Doraiswamy; Jeffrey R. Petrella; Edward R. Coleman; Steven E. Arnold; Jason H. Karlawish; David Wolk; Charles D. Smith; Greg Jicha; Peter Hardy; Oscar L. Lopez; MaryAnn Oakley; Donna M. Simpson; Anton P. Porsteinsson; Bonnie S. Goldstein; Kim Martin; Kelly M. Makino; M. Saleem Ismail; Connie Brand; Ruth A. Mulnard; Gaby Thai; Catherine Mc-Adams-Ortiz; Ramon Diaz-Arrastia; Kristen Martin-Cook; Michael DeVous; Allan I. Levey; James J. Lah; Janet S. Cellar; Jeffrey M. Burns; Heather S Anderson; Russell H. Swerdlow; Liana Apostolova; Po H. Lu; George Bartzokis; Daniel H.S. Silverman; Neill R Graff-Radford; Francine Parfitt; Heather Johnson; Martin Farlow; Scott Herring; Ann M. Hake; Christopher H. van Dyck; Richard E. Carson; Martha G. MacAvoy; Howard Chertkow; Howard Bergman; Chris Hosein; Sandra Black; Bojana Stefanovic; Curtis Caldwell; Ging-Yuek Robin Hsiung; Howard Feldman; Michele Assaly; Andrew KertesZ; John Rogers; Dick Trost; Charles Bernick; Donna Munic; Diana Kerwin; Marek-Marsel Mesulam; Kristine Lipowski; Chuang-Kuo Wu; Nancy Johnson; Carl Sadowsky; Walter Martinez; Teresa Villena; Raymond Scott Turner; Kathleen Johnson; Brigid Reynolds; Reisa A. Sperling; Keith A. Johnson; Gad Marshall; Meghan Frey; Allyson Rosen; Jared Tinklenberg; Marwan Sabbagh; Christine Belden; Sandra Jacobson; Neil Kowall; Ronald Killiany; Andrew E. Budson; Alexander Norbash; Patricia Lynn Johnson; Thomas O. Obisesan; Saba Wolday; Salome K. Bwayo; Alan Lerner; Leon Hudson; Paula Ogrocki; Evan Fletcher; Owen Carmichael; John Olichney; Charles DeCarli; Smita Kittur; Michael Borrie; T-Y Lee; Rob Bartha; Sterling Johnson; Sanjay Asthana; Cynthia M. Carlsson; Steven G. Potkin; Adrian Preda; Dana Nguyen; Pierre Tariot; Adam Fleisher; Stephanie Reeder; Vernice Bates; Horacio Capote; Michelle Rainka; Barry A. Hendin; Douglas W. Scharre; Maria Kataki; Earl A. Zimmerman; Dzintra Celmins; Alice D. Brown; Godfrey D. Pearlson; Karen Blank; Karen Anderson; Robert B. Santulli; Eben S. Schwartz; Kaycee M. Sink; Jeff D. Williamson; Pradeep Garg; Franklin Watkins; Brian R. Ott; Henry Querfurth; Geoffrey Tremont; Stephen Salloway; Paul Malloy; Stephen Correia; Howard J. Rosen; Bruce L. Miller; Jacobo Mintzer; Crystal Flynn Longmire; Kenneth Spicer
Source
Frontiers in Psychiatry, Vol 13 (2022)
Subject
Language
English
ISSN
1664-0640
Abstract
PurposeTo assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process.Materials and MethodsTwo hundred and seventy-seven functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson's correlation was used to characterize the functional connectivity (FC) between caudate nuclei and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4, and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status, and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region's connectivity with caudate nuclei. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI.ResultsThe MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P = 6.23 × 10−7, right: P = 3.37 × 10−8), but not for men (P > 0.3 for bilateral caudate nuclei). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI.ConclusionSex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.