Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia

Inflammation is becoming increasingly recognised as a core feature of dementia with evidence indicating that its role may vary and adapt across different stages of the neurodegenerative process. This study aimed to investigate whether the associations of high-sensitivity C-reactive protein (hs-CRP)...

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Main Authors: Rachael Yu, Shawn D. Kong, Catriona Ireland, Genevieve Z. Steiner-Lim, Kimberley Bassett, Hannes Almgren, Dongang Wang, Chenyu Wang, Johannes C. Michaelian, Sharon L. Naismith
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Brain, Behavior, & Immunity - Health
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666354624002023
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author Rachael Yu
Shawn D. Kong
Catriona Ireland
Genevieve Z. Steiner-Lim
Kimberley Bassett
Hannes Almgren
Dongang Wang
Chenyu Wang
Johannes C. Michaelian
Sharon L. Naismith
author_facet Rachael Yu
Shawn D. Kong
Catriona Ireland
Genevieve Z. Steiner-Lim
Kimberley Bassett
Hannes Almgren
Dongang Wang
Chenyu Wang
Johannes C. Michaelian
Sharon L. Naismith
author_sort Rachael Yu
collection DOAJ
description Inflammation is becoming increasingly recognised as a core feature of dementia with evidence indicating that its role may vary and adapt across different stages of the neurodegenerative process. This study aimed to investigate whether the associations of high-sensitivity C-reactive protein (hs-CRP) with neuropsychological performance (verbal memory, executive function, processing speed) and cerebral white matter hyperintensities (WMHs) differed between older adults with subjective cognitive decline (SCD; n = 179) and mild cognitive impairment (MCI; n = 286). Fasting serum hs-CRP concentrations were grouped into low (<1.0 mg/L), moderate (1.0–3.0 mg/L), and high (>3.0–10.0 mg/L). Structural MRI scans were used to estimate WMH lesion volumes in the whole brain, as well as periventricular, deep white matter, and frontal regions. After adjusting for relevant demographic and clinical factors, multiple regression analyses revealed that in participants with SCD, high hs-CRP concentrations were significantly associated with poorer executive function (β[95% CI] = −.20[−.65, −.04], p = .025) and processing speed (β[95% CI] = −.19[−.53, .00], p = .048). Exploratory analyses suggested that this effect may be specific to APOE-ε4 non-carriers only. There were no significant associations between hs-CRP and neuropsychological outcomes in those with MCI. Hs-CRP was not associated with WMH volumes. Our findings suggest that hs-CRP may be involved in early disruptions to cerebral frontal-subcortical pathways, particularly in APOE-ε4 non-carriers, though this association may be independent of white matter lesions. In the earliest stages of cognitive decline where subjective complaints are paramount, addressing inflammation may offer potential benefits for supporting cognitive health.
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spelling doaj-art-a3475aa5970c4acebcf86453bc83723b2025-01-26T05:05:01ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-02-0143100924Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementiaRachael Yu0Shawn D. Kong1Catriona Ireland2Genevieve Z. Steiner-Lim3Kimberley Bassett4Hannes Almgren5Dongang Wang6Chenyu Wang7Johannes C. Michaelian8Sharon L. Naismith9Healthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, Faculty of Science, University of Sydney, NSW, 2050, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW, 2050, AustraliaHealthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, Faculty of Science, University of Sydney, NSW, 2050, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW, 2050, AustraliaHealthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, Faculty of Science, University of Sydney, NSW, 2050, AustraliaNICM Health Research Institute, Western Sydney University, AustraliaHealthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, Faculty of Science, University of Sydney, NSW, 2050, AustraliaHealthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, Faculty of Science, University of Sydney, NSW, 2050, Australia; School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, NSW, AustraliaSydney Neuroimaging Analysis Centre, Brain and Mind Centre, University of Sydney, NSW, 2050, AustraliaSydney Neuroimaging Analysis Centre, Brain and Mind Centre, University of Sydney, NSW, 2050, AustraliaHealthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, Faculty of Science, University of Sydney, NSW, 2050, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW, 2050, Australia; Corresponding author. Healthy Brain Ageing Program, Brain and Mind Centre, The University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia.Healthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, Faculty of Science, University of Sydney, NSW, 2050, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW, 2050, Australia; Corresponding author. Healthy Brain Ageing Program, Brain and Mind Centre, The University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia.Inflammation is becoming increasingly recognised as a core feature of dementia with evidence indicating that its role may vary and adapt across different stages of the neurodegenerative process. This study aimed to investigate whether the associations of high-sensitivity C-reactive protein (hs-CRP) with neuropsychological performance (verbal memory, executive function, processing speed) and cerebral white matter hyperintensities (WMHs) differed between older adults with subjective cognitive decline (SCD; n = 179) and mild cognitive impairment (MCI; n = 286). Fasting serum hs-CRP concentrations were grouped into low (<1.0 mg/L), moderate (1.0–3.0 mg/L), and high (>3.0–10.0 mg/L). Structural MRI scans were used to estimate WMH lesion volumes in the whole brain, as well as periventricular, deep white matter, and frontal regions. After adjusting for relevant demographic and clinical factors, multiple regression analyses revealed that in participants with SCD, high hs-CRP concentrations were significantly associated with poorer executive function (β[95% CI] = −.20[−.65, −.04], p = .025) and processing speed (β[95% CI] = −.19[−.53, .00], p = .048). Exploratory analyses suggested that this effect may be specific to APOE-ε4 non-carriers only. There were no significant associations between hs-CRP and neuropsychological outcomes in those with MCI. Hs-CRP was not associated with WMH volumes. Our findings suggest that hs-CRP may be involved in early disruptions to cerebral frontal-subcortical pathways, particularly in APOE-ε4 non-carriers, though this association may be independent of white matter lesions. In the earliest stages of cognitive decline where subjective complaints are paramount, addressing inflammation may offer potential benefits for supporting cognitive health.http://www.sciencedirect.com/science/article/pii/S2666354624002023InflammationC-reactive proteinDementiaSubjective cognitive decline (SCD)Mild cognitive impairment (MCI)White matter hyperintensities (WMH)
spellingShingle Rachael Yu
Shawn D. Kong
Catriona Ireland
Genevieve Z. Steiner-Lim
Kimberley Bassett
Hannes Almgren
Dongang Wang
Chenyu Wang
Johannes C. Michaelian
Sharon L. Naismith
Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia
Brain, Behavior, & Immunity - Health
Inflammation
C-reactive protein
Dementia
Subjective cognitive decline (SCD)
Mild cognitive impairment (MCI)
White matter hyperintensities (WMH)
title Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia
title_full Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia
title_fullStr Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia
title_full_unstemmed Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia
title_short Associations of high-sensitivity C-reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia
title_sort associations of high sensitivity c reactive protein with neuropsychological outcomes and cerebral white matter hyperintensities in older adults at risk of dementia
topic Inflammation
C-reactive protein
Dementia
Subjective cognitive decline (SCD)
Mild cognitive impairment (MCI)
White matter hyperintensities (WMH)
url http://www.sciencedirect.com/science/article/pii/S2666354624002023
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