Abstract
Background and purposeSeveral studies have reported associations between brain iron deposits (IDs), white matter hyperintensities (WMHs) and cognitive ability in older individuals. Whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of total brain tissue damage represented by WMHs visible on structural magnetic resonance imaging (MRI) was examined.MethodsData from 676 community‐dwelling individuals from the Lothian Birth Cohort 1936, with Mini‐Mental State Examination scores >24, who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years were analysed. Brain IDs were assessed automatically following manual editing. WMHs were assessed semi‐automatically. Brain microbleeds were visually counted. Structural equation modelling was used to test for mediation.ResultsOverall, 72.8% of the sample had IDs with a median total volume of 0.040 ml (i.e. 0.004% of the total brain volume). The total volume of IDs, significantly and negatively associated with general cognitive function (standardized β = −0.17, P < 0.01), was significantly and positively associated with WMH volume (std β = 0.13, P = 0.03). WMH volume had a significant negative association with general cognitive function, independent of IDs (std β = −0.13, P < 0.01). The association between cognition and IDs in the brain stem (and minimally the total brain iron load) was partially and significantly mediated by WMH volume (P = 0.03).ConclusionsThe negative association between brain IDs and cognitive ability in the elderly is partially mediated by WMHs, with this mediation mainly arising from the iron deposition load in the brain stem. IDs might be an indicator of small vessel disease that predisposes to white matter damage, affecting the neuronal networks underlying higher cognitive functioning.
Highlights
As people age, iron accumulates in several brain regions and cell types [1,2].This accumulation, in the corpus striatum and substantia nigra, is reported to be associated with cognitive decline and neurodegeneration [3,4].Iron may accumulate in tissue via dysfunctional brain iron regulatory mechanisms [5]
iron deposits (IDs) were identified in 477 participants (70.8% of the sample), in the brainstem in 87 participants (12.9%) and elsewhere in 51 participants (7.6%)
IDs were present in 72.8% of the sample (490 participants)
Summary
Iron accumulates in several brain regions and cell types [1,2].This accumulation, in the corpus striatum and substantia nigra, is reported to be associated with cognitive decline and neurodegeneration [3,4].Iron may accumulate in tissue via dysfunctional brain iron regulatory mechanisms [5]. Changes in glial cell function could alter the exportation of iron leading to its accumulation in tissue (Fig. 1), which, if prominent, can be identifiable in structural magnetic resonance imaging (MRI). If dysfunctional, can fail to clear these haemosiderin micropools from tissue resulting in their accumulation These are radiologically identified as round hypointensities of less than 10 mm diameter on T2*-weighted gradient echo MRI. Several studies have reported associations between brain iron deposits (IDs), white matter hyperintensities (WMHs) and cognitive ability in older individuals. Whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of total brain tissue damage represented by WMHs visible on structural magnetic resonance imaging (MRI) was examined. IDs might be an indicator of small vessel disease that predisposes to white matter damage, affecting the neuronal networks underlying higher cognitive functioning
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