
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.19.608305
preprint
1
Article
An estimate of the longitudinal pace of aging from a single brain scan predicts dementia conversion, morbidity, and mortality
Whitman Ethan T.
Elliott Maxwell L.
Knodt Annchen R.
Abraham Wickliffe C.
Anderson Tim J.
Cutfield Nick
Hogan Sean
Ireland David
Melzer Tracy R.
Ramrakha Sandhya
Sugden Karen
Theodore Reremoana
Williams Benjamin S.
Caspi Avshalom
Moffitt Terrie E.
Hariri Ahmad R.
Alzheimer's Disease Neuroimaging Initiative
22 8 2024
2024.08.19.608305https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.19.608305
nihpp-2024.08.19.608305.pdf
To understand how aging affects functional decline and increases disease risk, it is necessary to develop accurate and reliable measures of how fast a person is aging. Epigenetic clocks measure aging but require DNA methylation data, which many studies lack. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain MRI: the Dunedin Pace of Aging Calculated from NeuroImaging or DunedinPACNI. Exporting this measure to the Alzheimer's Disease Neuroimaging Initiative and UK Biobank neuroimaging datasets revealed that faster DunedinPACNI predicted participants' cognitive impairment, accelerated brain atrophy, and conversion to diagnosed dementia. Underscoring close links between longitudinal aging of the body and brain, faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases, and mortality in older adults. Furthermore, DunedinPACNI followed the expected socioeconomic health gradient. When compared to brain age gap, an existing MRI aging biomarker, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a 'next generation' MRI measure that will be made publicly available to the research community to help accelerate aging research and evaluate the effectiveness of dementia prevention and anti-aging strategies.
==== Body
pmc
