Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia

Kirsty E McAleese; Sean J Colloby; Alan J Thomas; Safa Al-Sarraj; Olaf Ansorge; James Neal; Federico Roncaroli; Seth Love; Paul T Francis; Johannes Attems

doi:10.1002/alz.12291

Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia

Kirsty E McAleese^*
, Sean J Colloby
, Alan J Thomas
, Safa Al-Sarraj
, Olaf Ansorge
, James Neal
, Federico Roncaroli
, Seth Love
, Paul T Francis
, Johannes Attems

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

90 Citations (Scopus)

141 Downloads (Pure)

Abstract

INTRODUCTION: The aged brain frequently exhibits multiple pathologies, rather than a single hallmark pathology (pure pathology [PurP]), ranging from low/intermediate levels of additional pathology (LowP) to mixed severe pathology (mixed SevP). We investigated the frequency of PurP, LowP, and mixed SevP, and the impact of additional LowP on cognition.

METHODS: Data came from 670 cases from the Brains for Dementia research program. Cases were categorized into PurP, mixed SevP, or a main disease with additional LowP; 508 cases had a clinical dementia rating.

RESULTS: 69.9% of cases had LowP, 22.7% had PurP, and 7.5% had mixed SevP. Additional LowP increased the likelihood of having mild dementia versus mild cognitive impairment (MCI) by almost 20-fold (odds ratio = 19.5).

DISCUSSION: Most aged individuals have multiple brain pathologies. The presence of one additional LowP can significantly worsen cognitive decline, increasing the risk of transitioning from MCI to dementia 20-fold. Multimorbidity should be considered in dementia research and clinical studies.

Original language	English
Pages (from-to)	1121-1133
Number of pages	13
Journal	Alzheimer's and Dementia
Volume	17
Issue number	7
Early online date	4 Mar 2021
DOIs	https://doi.org/10.1002/alz.12291
Publication status	Published - Jul 2021

Bibliographical note

Funding Information:
informationThe funders had no role in study design, data analysis, data interpretation, or writing of the manuscript. All data are freely available upon request to DPUK and UKBBNid numbers of cases used are provided. All authors had full access to all the data and responsibility for writing the manuscript. The corresponding author has full access to all data in the study and had final responsibility for the decision to submit for publication. KEM is funded by the Alzheimer's Society (grant number AS-JF-18-01). BDR is funded by the Alzheimer's Society, Alzheimer's Research UK, and the Medical Research Council.Consent for clinical assessment, brain donation and storage, neuropathological assessment, and data use for research had been obtained in accordance with ethics approval 13/SC/0516 granted by the Oxford C Committee of the National Research Ethics Service. For ethical, legal, and recruitment details please see Francis et?al.21. We remain profoundly grateful to the participants, study participants, and nominated representatives for their engagement with, and commitment to, BDR. We are thankful for the constant support by the BDR Deputy director Mrs Debbie Lett and BDR Senior manager Nicky Barnett. We also thank the UK Medical Research Council's Dementias Platform UK (DPUK) initiative for access to the data and infrastructural support and the National Institute for Health Research Clinical Research Network (study identifier: 6271) who has enabled some assessments of BDR participants to be undertaken by the Clinical Research Network.

Publisher Copyright:
© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association

Research Groups and Themes

Cerebrovascular and Dementia Research Group

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title = "Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia",

abstract = "INTRODUCTION: The aged brain frequently exhibits multiple pathologies, rather than a single hallmark pathology (pure pathology [PurP]), ranging from low/intermediate levels of additional pathology (LowP) to mixed severe pathology (mixed SevP). We investigated the frequency of PurP, LowP, and mixed SevP, and the impact of additional LowP on cognition.METHODS: Data came from 670 cases from the Brains for Dementia research program. Cases were categorized into PurP, mixed SevP, or a main disease with additional LowP; 508 cases had a clinical dementia rating.RESULTS: 69.9\% of cases had LowP, 22.7\% had PurP, and 7.5\% had mixed SevP. Additional LowP increased the likelihood of having mild dementia versus mild cognitive impairment (MCI) by almost 20-fold (odds ratio = 19.5).DISCUSSION: Most aged individuals have multiple brain pathologies. The presence of one additional LowP can significantly worsen cognitive decline, increasing the risk of transitioning from MCI to dementia 20-fold. Multimorbidity should be considered in dementia research and clinical studies.",

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note = "Funding Information: informationThe funders had no role in study design, data analysis, data interpretation, or writing of the manuscript. All data are freely available upon request to DPUK and UKBBNid numbers of cases used are provided. All authors had full access to all the data and responsibility for writing the manuscript. The corresponding author has full access to all data in the study and had final responsibility for the decision to submit for publication. KEM is funded by the Alzheimer's Society (grant number AS-JF-18-01). BDR is funded by the Alzheimer's Society, Alzheimer's Research UK, and the Medical Research Council.Consent for clinical assessment, brain donation and storage, neuropathological assessment, and data use for research had been obtained in accordance with ethics approval 13/SC/0516 granted by the Oxford C Committee of the National Research Ethics Service. For ethical, legal, and recruitment details please see Francis et?al.21. We remain profoundly grateful to the participants, study participants, and nominated representatives for their engagement with, and commitment to, BDR. We are thankful for the constant support by the BDR Deputy director Mrs Debbie Lett and BDR Senior manager Nicky Barnett. We also thank the UK Medical Research Council's Dementias Platform UK (DPUK) initiative for access to the data and infrastructural support and the National Institute for Health Research Clinical Research Network (study identifier: 6271) who has enabled some assessments of BDR participants to be undertaken by the Clinical Research Network. Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association",

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journal = "Alzheimer's and Dementia",

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T1 - Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia

AU - McAleese, Kirsty E

AU - Colloby, Sean J

AU - Thomas, Alan J

AU - Al-Sarraj, Safa

AU - Ansorge, Olaf

AU - Neal, James

AU - Roncaroli, Federico

AU - Love, Seth

AU - Francis, Paul T

AU - Attems, Johannes

N1 - Funding Information: informationThe funders had no role in study design, data analysis, data interpretation, or writing of the manuscript. All data are freely available upon request to DPUK and UKBBNid numbers of cases used are provided. All authors had full access to all the data and responsibility for writing the manuscript. The corresponding author has full access to all data in the study and had final responsibility for the decision to submit for publication. KEM is funded by the Alzheimer's Society (grant number AS-JF-18-01). BDR is funded by the Alzheimer's Society, Alzheimer's Research UK, and the Medical Research Council.Consent for clinical assessment, brain donation and storage, neuropathological assessment, and data use for research had been obtained in accordance with ethics approval 13/SC/0516 granted by the Oxford C Committee of the National Research Ethics Service. For ethical, legal, and recruitment details please see Francis et?al.21. We remain profoundly grateful to the participants, study participants, and nominated representatives for their engagement with, and commitment to, BDR. We are thankful for the constant support by the BDR Deputy director Mrs Debbie Lett and BDR Senior manager Nicky Barnett. We also thank the UK Medical Research Council's Dementias Platform UK (DPUK) initiative for access to the data and infrastructural support and the National Institute for Health Research Clinical Research Network (study identifier: 6271) who has enabled some assessments of BDR participants to be undertaken by the Clinical Research Network. Publisher Copyright: © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association

PY - 2021/7

Y1 - 2021/7

N2 - INTRODUCTION: The aged brain frequently exhibits multiple pathologies, rather than a single hallmark pathology (pure pathology [PurP]), ranging from low/intermediate levels of additional pathology (LowP) to mixed severe pathology (mixed SevP). We investigated the frequency of PurP, LowP, and mixed SevP, and the impact of additional LowP on cognition.METHODS: Data came from 670 cases from the Brains for Dementia research program. Cases were categorized into PurP, mixed SevP, or a main disease with additional LowP; 508 cases had a clinical dementia rating.RESULTS: 69.9% of cases had LowP, 22.7% had PurP, and 7.5% had mixed SevP. Additional LowP increased the likelihood of having mild dementia versus mild cognitive impairment (MCI) by almost 20-fold (odds ratio = 19.5).DISCUSSION: Most aged individuals have multiple brain pathologies. The presence of one additional LowP can significantly worsen cognitive decline, increasing the risk of transitioning from MCI to dementia 20-fold. Multimorbidity should be considered in dementia research and clinical studies.

AB - INTRODUCTION: The aged brain frequently exhibits multiple pathologies, rather than a single hallmark pathology (pure pathology [PurP]), ranging from low/intermediate levels of additional pathology (LowP) to mixed severe pathology (mixed SevP). We investigated the frequency of PurP, LowP, and mixed SevP, and the impact of additional LowP on cognition.METHODS: Data came from 670 cases from the Brains for Dementia research program. Cases were categorized into PurP, mixed SevP, or a main disease with additional LowP; 508 cases had a clinical dementia rating.RESULTS: 69.9% of cases had LowP, 22.7% had PurP, and 7.5% had mixed SevP. Additional LowP increased the likelihood of having mild dementia versus mild cognitive impairment (MCI) by almost 20-fold (odds ratio = 19.5).DISCUSSION: Most aged individuals have multiple brain pathologies. The presence of one additional LowP can significantly worsen cognitive decline, increasing the risk of transitioning from MCI to dementia 20-fold. Multimorbidity should be considered in dementia research and clinical studies.

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DO - 10.1002/alz.12291

M3 - Article (Academic Journal)

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SN - 1552-5260

VL - 17

SP - 1121

EP - 1133

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 7

ER -

Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia

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