White matter hyperintensities are common in midlife and already associated with cognitive decline

d'Arbeloff, T.; Elliott, M. L.; Knodt, A. R.; Melzer, T. R.; Keenan, R.; Ireland, D.; Ramrakha, S.; Poiulton, R.; Anderson, T.; Caspi, A.; Moffitt, T. E.; Hariri, A. R.

doi:10.1101/687111

bioRxiv · 10.1101/687111

White matter hyperintensities are common in midlife and already associated with cognitive decline

d'Arbeloff, T.·Elliott, M. L.·Knodt, A. R.·Melzer, T. R.·Keenan, R.·Ireland, D.·Ramrakha, S.·Poiulton, R.·Anderson, T.·Caspi, A.·Moffitt, T. E.·Hariri, A. R.

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Abstract

White matter hyperintensities (WMHs) proliferate as the brain ages and are associated with increased risk for cognitive decline as well as Alzheimers disease and related dementias. As such, WMHs have been targeted as a surrogate biomarker in intervention trials with older adults. However, it is unclear at what stage of aging WMHs begin to relate to cognition and if they may be a viable target for early prevention. In a population-representative birth cohort of 843 45-year-olds we measured WMHs using T2-weighted MRI, and we assessed cognitive decline from childhood to midlife. We found that WMHs were common at age 45 and that WMH volume was modestly associated with both lower childhood ({beta}=-0.08, p=0.013) and adult IQ ({beta}=-0.15, p<0.001). Moreover, WMH volume was associated with greater cognitive decline from childhood to midlife ({beta}=-0.09, p<0.001). Our results demonstrate that a link between WMHs and early signs of cognitive decline is detectable decades before clinical symptoms of dementia emerge. Thus, WMHs may be a useful surrogate biomarker for identifying individuals in midlife at risk for future accelerated cognitive decline and selecting participants for dementia prevention trials.

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d'Arbeloff, T., Elliott, M. L., Knodt, A. R., Melzer, T. R., Keenan, R., Ireland, D., Ramrakha, S., Poiulton, R., Anderson, T., Caspi, A., Moffitt, T. E., Hariri, A. R.. 2019-06-29. White matter hyperintensities are common in midlife and already associated with cognitive decline. https://doi.org/10.1101/687111

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