Cognition and brain iron deposition in whole grey matter regions and hippocampal subfields

Holly Spence; Chris J. McNeil; Gordon D. Waiter

doi:10.1111/ejn.15838

Cognition and brain iron deposition in whole grey matter regions and hippocampal subfields

Holly Spence^* (Corresponding Author), Chris J. McNeil, Gordon D. Waiter

^*Corresponding author for this work

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Abstract

Regional brain iron accumulation is observed in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and is associated with cognitive decline. We explored associations between age, cognition and iron content in grey matter regions and hippocampal subfields in 380 participants of the Aberdeen children of the 1950s cohort and their first-generation relatives (aged 26–72 years). Participants underwent cognitive assessment at the time of MRI scanning. Quantitative susceptibility mapping of these MRI data was used to assess iron content in grey matter regions and in hippocampal subfields. Principle component analysis was performed on cognitive test scores to create a general cognition score. Spline analysis was used with the Akaike information criterion to determine if order 1, 2 or 3 natural splines were optimal for assessing non-linear relationships between regional iron and age. Multivariate linear models were used to assess associations between regional iron and cognition. Higher iron correlated with older age in the left putamen across all ages and in the right putamen of only participants over 58. Whereas a decrease in iron with older age was observed in the right thalamus and left pallidum across all ages. Right amygdala iron levels were associated with poorer general cognition scores and poorer immediate recall scores. Iron was not associated with any measures of cognitive performance in other regions of interest. Our results suggest that, whilst iron in some regions was associated with cognitive performance, there is an overall lack of association between regional iron content and cognitive ability in cognitively healthy individuals.

Original language	English
Pages (from-to)	6039-6054
Number of pages	16
Journal	European Journal of Neuroscience
Volume	56
Issue number	11
Early online date	10 Oct 2022
DOIs	https://doi.org/10.1111/ejn.15838
Publication status	Published - Dec 2022

Bibliographical note

ACKNOWLEDGEMENTS
We are grateful to the Aberdeen Children of the 1950's (ACONF) subset of Generation Scotland GS:SFHS who took part in the STRADL study, supported and funded by the Wellcome Trust Strategic Award ‘Stratifying Resilience and Depression Longitudinally’ (STRADL) [104036/Z/14/Z]. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. HS is supported by the Roland Sutton Academic Trust [0076/R/19]. We also thank the STRADL project team.

Research Funding
Chief Scientist Office. Grant Number: CZD/16/6
Roland Sutton Academic Trust. Grant Number: 0076/R/19
Scottish Funding Council. Grant Number: HR03006
Wellcome Trust. Grant Number: 104036/Z/14/Z

Data Availability Statement

The data collected in the STRADL study have been incorporated in the larger Generation Scotland dataset. Non-identifiable information from the Generation Scotland cohort is available to researchers in the United Kingdom and to international collaborators through application to the Generation Scotland Access Committee (access@generationscotland.org). Generation Scotland operates a managed data access process including an online application form, and proposals are reviewed by the Generation Scotland Access Committee.

Keywords

cognition
hippocampal subfields
iron
MRI
QSM

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10.1111/ejn.15838Licence: CC BY

Spence_etal_EJN_Cognition_and_brain_VOR
© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 2.19 MBLicence: CC BY

https://onlinelibrary.wiley.com/doi/abs/10.1111/ejn.15838

Cite this

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title = "Cognition and brain iron deposition in whole grey matter regions and hippocampal subfields",

abstract = "Regional brain iron accumulation is observed in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and is associated with cognitive decline. We explored associations between age, cognition and iron content in grey matter regions and hippocampal subfields in 380 participants of the Aberdeen children of the 1950s cohort and their first-generation relatives (aged 26–72 years). Participants underwent cognitive assessment at the time of MRI scanning. Quantitative susceptibility mapping of these MRI data was used to assess iron content in grey matter regions and in hippocampal subfields. Principle component analysis was performed on cognitive test scores to create a general cognition score. Spline analysis was used with the Akaike information criterion to determine if order 1, 2 or 3 natural splines were optimal for assessing non-linear relationships between regional iron and age. Multivariate linear models were used to assess associations between regional iron and cognition. Higher iron correlated with older age in the left putamen across all ages and in the right putamen of only participants over 58. Whereas a decrease in iron with older age was observed in the right thalamus and left pallidum across all ages. Right amygdala iron levels were associated with poorer general cognition scores and poorer immediate recall scores. Iron was not associated with any measures of cognitive performance in other regions of interest. Our results suggest that, whilst iron in some regions was associated with cognitive performance, there is an overall lack of association between regional iron content and cognitive ability in cognitively healthy individuals.",

keywords = "cognition, hippocampal subfields, iron, MRI, QSM",

author = "Holly Spence and McNeil, {Chris J.} and Waiter, {Gordon D.}",

note = "ACKNOWLEDGEMENTS We are grateful to the Aberdeen Children of the 1950's (ACONF) subset of Generation Scotland GS:SFHS who took part in the STRADL study, supported and funded by the Wellcome Trust Strategic Award {\textquoteleft}Stratifying Resilience and Depression Longitudinally{\textquoteright} (STRADL) [104036/Z/14/Z]. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. HS is supported by the Roland Sutton Academic Trust [0076/R/19]. We also thank the STRADL project team. Research Funding Chief Scientist Office. Grant Number: CZD/16/6 Roland Sutton Academic Trust. Grant Number: 0076/R/19 Scottish Funding Council. Grant Number: HR03006 Wellcome Trust. Grant Number: 104036/Z/14/Z",

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AU - McNeil, Chris J.

AU - Waiter, Gordon D.

N1 - ACKNOWLEDGEMENTS We are grateful to the Aberdeen Children of the 1950's (ACONF) subset of Generation Scotland GS:SFHS who took part in the STRADL study, supported and funded by the Wellcome Trust Strategic Award ‘Stratifying Resilience and Depression Longitudinally’ (STRADL) [104036/Z/14/Z]. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. HS is supported by the Roland Sutton Academic Trust [0076/R/19]. We also thank the STRADL project team. Research Funding Chief Scientist Office. Grant Number: CZD/16/6 Roland Sutton Academic Trust. Grant Number: 0076/R/19 Scottish Funding Council. Grant Number: HR03006 Wellcome Trust. Grant Number: 104036/Z/14/Z

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N2 - Regional brain iron accumulation is observed in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and is associated with cognitive decline. We explored associations between age, cognition and iron content in grey matter regions and hippocampal subfields in 380 participants of the Aberdeen children of the 1950s cohort and their first-generation relatives (aged 26–72 years). Participants underwent cognitive assessment at the time of MRI scanning. Quantitative susceptibility mapping of these MRI data was used to assess iron content in grey matter regions and in hippocampal subfields. Principle component analysis was performed on cognitive test scores to create a general cognition score. Spline analysis was used with the Akaike information criterion to determine if order 1, 2 or 3 natural splines were optimal for assessing non-linear relationships between regional iron and age. Multivariate linear models were used to assess associations between regional iron and cognition. Higher iron correlated with older age in the left putamen across all ages and in the right putamen of only participants over 58. Whereas a decrease in iron with older age was observed in the right thalamus and left pallidum across all ages. Right amygdala iron levels were associated with poorer general cognition scores and poorer immediate recall scores. Iron was not associated with any measures of cognitive performance in other regions of interest. Our results suggest that, whilst iron in some regions was associated with cognitive performance, there is an overall lack of association between regional iron content and cognitive ability in cognitively healthy individuals.

AB - Regional brain iron accumulation is observed in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and is associated with cognitive decline. We explored associations between age, cognition and iron content in grey matter regions and hippocampal subfields in 380 participants of the Aberdeen children of the 1950s cohort and their first-generation relatives (aged 26–72 years). Participants underwent cognitive assessment at the time of MRI scanning. Quantitative susceptibility mapping of these MRI data was used to assess iron content in grey matter regions and in hippocampal subfields. Principle component analysis was performed on cognitive test scores to create a general cognition score. Spline analysis was used with the Akaike information criterion to determine if order 1, 2 or 3 natural splines were optimal for assessing non-linear relationships between regional iron and age. Multivariate linear models were used to assess associations between regional iron and cognition. Higher iron correlated with older age in the left putamen across all ages and in the right putamen of only participants over 58. Whereas a decrease in iron with older age was observed in the right thalamus and left pallidum across all ages. Right amygdala iron levels were associated with poorer general cognition scores and poorer immediate recall scores. Iron was not associated with any measures of cognitive performance in other regions of interest. Our results suggest that, whilst iron in some regions was associated with cognitive performance, there is an overall lack of association between regional iron content and cognitive ability in cognitively healthy individuals.

KW - cognition

KW - hippocampal subfields

KW - iron

KW - MRI

KW - QSM

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DO - 10.1111/ejn.15838

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SN - 0953-816X

VL - 56

SP - 6039

EP - 6054

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

IS - 11

ER -

Cognition and brain iron deposition in whole grey matter regions and hippocampal subfields

Abstract

Bibliographical note

Data Availability Statement

Keywords

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