An estimate of the longitudinal pace of aging from a single brain scan predicts dementia conversion, morbidity, and mortality

Whitman, E. T.; Elliott, M. L.; Knodt, A. R.; Abraham, W. C.; Anderson, T. J.; Cutfield, N.; Hogan, S.; Ireland, D.; Melzer, T. R.; Ramrakha, S.; Sugden, K.; Theodore, R.; Williams, B. S.; Caspi, A.; Moffitt, T. E.; Hariri, A. R.; Alzheimer's Disease Neuroimaging Initiative,

doi:10.1101/2024.08.19.608305

bioRxiv · 10.1101/2024.08.19.608305

An estimate of the longitudinal pace of aging from a single brain scan predicts dementia conversion, morbidity, and mortality

Whitman, E. T.·Elliott, M. L.·Knodt, A. R.·Abraham, W. C.·Anderson, T. J.·Cutfield, N.·Hogan, S.·Ireland, D.·Melzer, T. R.·Ramrakha, S.·Sugden, K.·Theodore, R.·Williams, B. S.·Caspi, A.·Moffitt, T. E.·Hariri, A. R.·Alzheimer's Disease Neuroimaging Initiative,

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Abstract

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 Alzheimers Disease Neuroimaging Initiative and UK Biobank 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 an established socioeconomic health gradient with people of lower socioeconomic status showing faster DunedinPACNI. Associations between DunedinPACNI and cognitive impairment were replicated in BrainLat, a sample of Latin American patients with dementia. 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.

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Whitman, E. T., Elliott, M. L., Knodt, A. R., Abraham, W. C., Anderson, T. J., Cutfield, N., Hogan, S., Ireland, D., Melzer, T. R., Ramrakha, S., Sugden, K., Theodore, R., Williams, B. S., Caspi, A., Moffitt, T. E., Hariri, A. R., Alzheimer's Disease Neuroimaging Initiative,. 2024-08-22. An estimate of the longitudinal pace of aging from a single brain scan predicts dementia conversion, morbidity, and mortality. https://doi.org/10.1101/2024.08.19.608305

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