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Genetic, vascular, and amyloid components of cerebral blood flow in a preclinical population

Padrela BE, Lorenzini L, Collij LE, García DV, Coomans E, Ingala S, Tomassen J, Deckers Q, Shekari M, Geus EJ, van de Giessen E, Kate MT, Visser PJ, Barkhof F, Petr J, Braber AD, Mutsaerts HJ

Abstracto

Aging-related cognitive decline can be accelerated by a combination of genetic factors, cardiovascular and cerebrovascular dysfunction, and amyloid-β burden. Whereas cerebral blood flow (CBF) has been studied as a potential early biomarker of cognitive decline, its normal variability in healthy elderly is less known. In this study, we investigated the contribution of genetic, vascular, and amyloid-β components of CBF in a cognitively unimpaired (CU) population of monozygotic older twins. We included 134 participants who underwent arterial spin labeling (ASL) MRI and [18F]flutemetamol amyloid-PET imaging at baseline and after a four-year follow-up. Generalized estimating equations were used to investigate the associations of amyloid burden and white matter hyperintensities with CBF. We showed that, in CU individuals, CBF: 1) has a genetic component, as within-pair similarities in CBF values were moderate and significant (ICC > 0.40); 2) is negatively associated with cerebrovascular damage; and 3) is positively associated with the interaction between cardiovascular risk scores and early amyloid-β burden, which may reflect a vascular compensatory response of CBF to early amyloid-β accumulation. These findings encourage future studies to account for multiple interactions with CBF in disease trajectory analyses.

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Referencia

Padrela BE, Lorenzini L, Collij LE, García DV, Coomans E, Ingala S, Tomassen J, Deckers Q, Shekari M, Geus EJ, van de Giessen E, Kate MT, Visser PJ, Barkhof F, Petr J, Braber AD, Mutsaerts HJ. Genetic, vascular, and amyloid components of cerebral blood flow in a preclinical population. J Cereb Blood Flow Metab. 2023 May 26:271678X231178993. doi: 10.1177/0271678X231178993. Epub ahead of print. PMID: 37231665.