Abstract
Several studies have reported associations between brain iron deposits and cognitive status, and cardiovascular and neurodegenerative diseases in older individuals, but the mechanisms underlying these associations remain unclear. We explored the associations between regional brain iron deposits and different factors of cognitive ability (fluid intelligence, speed and memory) in a large sample (n = 662) of individuals with a mean age of 73 years. Brain iron deposits in the corpus striatum were extracted automatically. Iron deposits in other parts of the brain (i.e., white matter, thalamus, brainstem and cortex), brain tissue volume and white matter hyperintensities (WMH) were assessed separately and semi-automatically. Overall, 72.8 % of the sample had iron deposits. The total volume of iron deposits had a small but significant negative association with all three cognitive ability factors in later life (mean r = −0.165), but no relation to intelligence in childhood (r = 0.043, p = 0.282). Regression models showed that these iron deposit associations were still present after control for a variety of vascular health factors, and were separable from the association of WMH with cognitive ability. Iron deposits were also associated with cognition across the lifespan, indicating that they are relevant for cognitive ability only at older ages. Iron deposits might be an indicator of small vessel disease that affects the neuronal networks underlying higher cognitive functioning.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-015-9837-2) contains supplementary material, which is available to authorized users.
Highlights
As people grow older, iron accumulates, mainly in the form of hemosiderin, in several brain regions and cell types (Valdés Hernández et al 2012; Ward et al 2014)
With data from only 143 individuals, it had relatively low statistical power, increasing the chances of erroneous results. It did not analyse other variables, such as vascular risk factors, and white matter hyperintensities (WMH) that could be potentially related to brain iron deposition
We investigate a second hypothesis, related to WMH: hyperintensities observed in the white matter and subcortical grey matter on fluid attenuation inversion recovery (FLAIR) and T2W structural magnetic resonance images (MRI); which are common in older brains and may have similar associations with indicators of cognitive ability as brain iron deposits (Valdés Hernández et al 2013a; Wardlaw et al 2013)
Summary
Iron accumulates, mainly in the form of hemosiderin, in several brain regions and cell types (Valdés Hernández et al 2012; Ward et al 2014). With data from only 143 individuals, it had relatively low statistical power, increasing the chances of erroneous results It did not analyse other variables, such as vascular risk factors, and white matter hyperintensities (WMH) that could be potentially related to brain iron deposition. We investigate a second hypothesis, related to WMH: hyperintensities observed in the white matter and subcortical grey matter on fluid attenuation inversion recovery (FLAIR) and T2W structural MRI; which are common in older brains and may have similar associations with indicators of cognitive ability as brain iron deposits (Valdés Hernández et al 2013a; Wardlaw et al 2013). We estimate models that test whether iron deposits relate to lifetime cognitive ability, using the age-11 intelligence data in our sample as a control variable. If iron deposits relate to cognition across the life course, we would expect still to find an association between iron deposit volume and cognitive ability at old age when we account for childhood intelligence like we found before on a smaller sample
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