02580nas a2200229 4500008004100000022001400041245019900055210006900254260001600323520178300339100002002122700001802142700001702160700001602177700002202193700001902215700002302234700002102257700001602278700002002294856003602314 2023 eng d a1758-535X00aEvaluation of Associations of Growth Differentiation Factor-11, Growth Differentiation Factor-8 and their Binding Proteins Follistatin and Follistatin-like protein-3 with Dementia and Cognition.0 aEvaluation of Associations of Growth Differentiation Factor11 Gr c2023 Jan 203 a

BACKGROUND: Studies using heterochronic parabiosis discovered that circulating factors mediate brain aging in animal models.

METHODS: We assessed Growth Differentiation Factor (GDF)-11 and GDF-8 using mass spectrometry and inhibitors follistatin and follistatin-like protein-3 (FSTL-3) with ELISA in in the Cardiovascular Health Study (N=1506) and the Health ABC study (N=1237). CLL-11 and Beta 2 microglobulin (B2M) were measured with ELISA in a subset of 400 individuals in Health ABC. Associations were assessed with cognitive function, brain magnetic resonance imaging (MRI) findings (CHS only) and incident dementia using correlations, linear regression and Cox proportional hazards models.

RESULTS: In CHS, levels of GDF-11, GDF-8 and follistatin were not correlated cross sectionally with the 3MSE or DSST, brain MRI findings of white matter hyperintensity, atrophy or small infarcts, nor were they associated with incident dementia. FSTL-3 was modestly correlated with poorer cognitive function, greater white matter hyperintensities and atrophy on MRI as well as with incident dementia with an adjusted HR of 1.72 (95% CI=1.13, 2.61) per doubling of FSTL-3. FSTL-3 was not associated with cognition or dementia in Health ABC, but GDF-8 was associated with both. The adjusted HR for incident dementia was 1.50 (95%CI 1.07, 2.10) per doubling of GDF-8.

CONCLUSIONS: Total GDF-11 level was not related to cognition or dementia in older adults. Associations of GDF-8 with cognitive outcomes in Health ABC were not expected, but consistent with animal models. Associations of FSTL-3 with cognition, brain abnormalities, and incident dementia in CHS implicates TGF-B superfamily inhibition in the pathogenesis of dementia.

1 aNewman, Anne, B1 aPatel, Sheena1 aKizer, Jorge1 aLee, Se-Jin1 aBhasin, Shalinder1 aCawthon, Peggy1 aLeBrasseur, Nathan1 aTracy, Russel, P1 aGanz, Peter1 aCummings, Steve uhttps://chs-nhlbi.org/node/9290