Latent change-on-change between amyloid accumulation and cognitive decline

Hannah M Klinger; Brian C Healy; Bernard J Hanseeuw; Rich N Jones; Rory Boyle; Diana L Townsend; Michael J Properzi; Gillian T Coughlan; Mabel Seto; Colin Birkenbihl; Michelle E Farrell; Kathryn V Papp; Jasmeer P Chhatwal; Hyun-Sik Yang; Aaron P Schultz; Rebecca E Amariglio; Heidi I L Jacobs; Julie C Price; Keith A Johnson; Dorene M Rentz; Reisa A Sperling; Rachel F Buckley

doi:10.1002/alz.14326

Latent change-on-change between amyloid accumulation and cognitive decline

Alzheimers Dement. 2024 Oct 29. doi: 10.1002/alz.14326. Online ahead of print.

Authors

Hannah M Klinger¹, Brian C Healy¹, Bernard J Hanseeuw^{2

3}, Rich N Jones⁴, Rory Boyle¹, Diana L Townsend¹, Michael J Properzi¹, Gillian T Coughlan¹, Mabel Seto^{1

5}, Colin Birkenbihl¹, Michelle E Farrell¹, Kathryn V Papp⁵, Jasmeer P Chhatwal^{1

5}, Hyun-Sik Yang¹, Aaron P Schultz^{1

6}, Rebecca E Amariglio⁵, Heidi I L Jacobs², Julie C Price², Keith A Johnson², Dorene M Rentz⁵, Reisa A Sperling^{1

5}, Rachel F Buckley^{1

5

7}

Affiliations

¹ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Department of Neurology, Cliniques Universitaires Saint-Luc, Institute of Neurosciences, UCLouvain, Belgium.
⁴ Department of Psychiatry and Human Behavior, Brown University, Warren Alpert Medical School, Providence, Rhode Island, USA.
⁵ Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
⁷ Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.

PMID: 39470175
DOI: 10.1002/alz.14326

Abstract

Introduction: While the influence of cross-sectional β-amyloid (Aβ) on longitudinal changes in cognition is well established, longitudinal change-on-change between Aβ and cognition is less explored.

Methods: A series of bivariate latent change score models (LCSM) examined the relationship between changes in ¹¹C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) and the Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) while adjusting for covariates, including cross-sectional medial temporal lobe (MTL) tau-PET burden. We selected 352 clinically normal older participants with up to 9 years of PiB-PET and PACC-5 data from the Harvard Aging Brain Study (HABS).

Results: Aβ accumulation was associated with subsequent cognitive decline beyond the effects of cross-sectional Aβ burden. Within this model including covariates such as age, sex, and apolipoprotein ε4 (APOEε4) status, we found no evidence supporting previously published associations between cross-sectional tau-PET and cognitive intercept/slope.

Discussion: Short-term Aβ changes are significantly associated with cognitive decline in clinically normal older adults and may eclipse the effect of cross-sectional Aβ and MTL tau.

Highlights: Aβ accumulation is associated with subsequent cognitive decline. High Aβ burden is not the sole metric signaling impending cognitive decline. Contrary to prior work, MTL tau-PET and cognition were not associated in our models. Models of bivariate latent Aβ and cognitive change may eclipse the effects of MTL tau.

Keywords: Alzheimer's disease; amyloid accumulation; change‐on‐change; cognitive decline; latent change score models; structural equation models.

Abstract

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