Higher cortical thickness/volume in Alzheimer's-related regions: protective factor or risk factor?

McKenna E Williams; Jeremy A Elman; Tyler R Bell; Anders M Dale; Lisa T Eyler; Christine Fennema-Notestine; Carol E Franz; Nathan A Gillespie; Donald J Hagler Jr; Michael J Lyons; Linda K McEvoy; Michael C Neale; Matthew S Panizzon; Chandra A Reynolds; Mark Sanderson-Cimino; William S Kremen

doi:10.1016/j.neurobiolaging.2023.05.004

Higher cortical thickness/volume in Alzheimer's-related regions: protective factor or risk factor?

Neurobiol Aging. 2023 Sep:129:185-194. doi: 10.1016/j.neurobiolaging.2023.05.004. Epub 2023 May 9.

Authors

McKenna E Williams¹, Jeremy A Elman², Tyler R Bell², Anders M Dale³, Lisa T Eyler⁴, Christine Fennema-Notestine⁵, Carol E Franz², Nathan A Gillespie⁶, Donald J Hagler Jr⁷, Michael J Lyons⁸, Linda K McEvoy⁷, Michael C Neale⁶, Matthew S Panizzon², Chandra A Reynolds⁹, Mark Sanderson-Cimino¹⁰, William S Kremen²

Affiliations

¹ Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA; Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. Electronic address: mewillia@health.ucsd.edu.
² Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
³ Department of Radiology, University of California San Diego, La Jolla, CA, USA; Department of Neuroscience, University of California San Diego, La Jolla, CA, USA.
⁴ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Desert Pacific Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA.
⁵ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Radiology, University of California San Diego, La Jolla, CA, USA.
⁶ Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA.
⁷ Department of Radiology, University of California San Diego, La Jolla, CA, USA.
⁸ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
⁹ Department of Psychology, University of California Riverside, Riverside, CA, USA.
¹⁰ Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA; Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

PMID: 37343448
PMCID: PMC10676195
DOI: 10.1016/j.neurobiolaging.2023.05.004

Abstract

Some evidence suggests a biphasic pattern of changes in cortical thickness wherein higher, rather than lower, thickness is associated with very early Alzheimer's disease (AD) pathology. We examined whether integrating information from AD brain signatures based on mean diffusivity (MD) can aid in the interpretation of cortical thickness/volume as a risk factor for future AD-related changes. Participants were 572 men in the Vietnam Era Twin Study of Aging who were cognitively unimpaired at baseline (mean age = 56 years; range = 51-60). Individuals with both high thickness/volume signatures and high MD signatures at baseline had lower cortical thickness/volume in AD signature regions and lower episodic memory performance 12 years later compared to those with high thickness/volume and low MD signatures at baseline. Groups did not differ in level of young adult cognitive reserve. Our findings are in line with a biphasic model in which increased cortical thickness may precede future decline and establish the value of examining cortical MD alongside cortical thickness to identify subgroups with differential risk for poorer brain and cognitive outcomes.

Keywords: Alzheimer’s disease; Cortical thickness; Mean diffusivity; Neuroimaging; Signatures.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Aging / pathology
Alzheimer Disease* / pathology
Brain / pathology
Humans
Magnetic Resonance Imaging
Male
Protective Factors
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding