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Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status

INTRODUCTION: Choroid plexus (CP)-related mechanisms have been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease. In this pilot study, we aimed to elucidate the association between longitudinal changes in CP volume, sex and cognitive impairment. METHODS: We...

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Autores principales: Novakova Martinkova, Julie, Ferretti, Maria Teresa, Ferrari, Alberto, Lerch, Ondrej, Matuskova, Veronika, Secnik, Juraj, Hort, Jakub
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031049/
https://www.ncbi.nlm.nih.gov/pubmed/36970283
http://dx.doi.org/10.3389/fpsyt.2023.1039239
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author Novakova Martinkova, Julie
Ferretti, Maria Teresa
Ferrari, Alberto
Lerch, Ondrej
Matuskova, Veronika
Secnik, Juraj
Hort, Jakub
author_facet Novakova Martinkova, Julie
Ferretti, Maria Teresa
Ferrari, Alberto
Lerch, Ondrej
Matuskova, Veronika
Secnik, Juraj
Hort, Jakub
author_sort Novakova Martinkova, Julie
collection PubMed
description INTRODUCTION: Choroid plexus (CP)-related mechanisms have been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease. In this pilot study, we aimed to elucidate the association between longitudinal changes in CP volume, sex and cognitive impairment. METHODS: We assessed longitudinal changes in CP volume in a cohort of n = 613 subjects across n = 2,334 datapoints from ADNI 2 and ADNI-GO, belonging to cognitively unimpaired (CN), stable mild cognitive impairment (MCI), clinically diagnosed Alzheimer’s disease dementia (AD) or convertor (to either AD or MCI) subgroups. CP volume was automatically segmented and used as a response variable in linear mixed effect models with random intercept clustered by patient identity. Temporal effects of select variables were assessed by interactions and subgroup analyses. RESULTS: We found an overall significant increase of CP volume in time (14.92 mm(3) per year, 95% confidence interval, CI (11.05, 18.77), p < 0.001). Sex-disaggregated results showed an annual rate of increase 9.48 mm(3) in males [95% CI (4.08, 14.87), p < 0.001], and 20.43 mm(3) in females [95% CI (14.91, 25.93), p < 0.001], indicating more than double the rate of increase in females, which appeared independent of other temporal variables. The only diagnostic group with a significant CP increase as compared to CN was the convertors group, with an increase of 24.88 mm(3)/year [95% CI (14, 35.82), p < 0.001]. ApoE exhibited a significant temporal effect, with the E4 homozygote group’s CP increasing at more than triple the rate of non-carrier or heterozygote groups [40.72, 95% CI (25.97, 55.46), p < 0.001 vs. 12.52, 95% CI (8.02, 17.02), p < 0.001 for ApoE E4 homozygotes and E4 non-carriers, respectively], and may have modified the diagnostic group relationship. CONCLUSION: Our results contribute to potential mechanisms for sex differences in cognitive impairment with a novel finding of twice the annual choroid plexus enlargement in females and provide putative support for CP-related mechanisms of cognitive deterioration and its relationship to ApoE E4.
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spelling pubmed-100310492023-03-23 Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status Novakova Martinkova, Julie Ferretti, Maria Teresa Ferrari, Alberto Lerch, Ondrej Matuskova, Veronika Secnik, Juraj Hort, Jakub Front Psychiatry Psychiatry INTRODUCTION: Choroid plexus (CP)-related mechanisms have been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease. In this pilot study, we aimed to elucidate the association between longitudinal changes in CP volume, sex and cognitive impairment. METHODS: We assessed longitudinal changes in CP volume in a cohort of n = 613 subjects across n = 2,334 datapoints from ADNI 2 and ADNI-GO, belonging to cognitively unimpaired (CN), stable mild cognitive impairment (MCI), clinically diagnosed Alzheimer’s disease dementia (AD) or convertor (to either AD or MCI) subgroups. CP volume was automatically segmented and used as a response variable in linear mixed effect models with random intercept clustered by patient identity. Temporal effects of select variables were assessed by interactions and subgroup analyses. RESULTS: We found an overall significant increase of CP volume in time (14.92 mm(3) per year, 95% confidence interval, CI (11.05, 18.77), p < 0.001). Sex-disaggregated results showed an annual rate of increase 9.48 mm(3) in males [95% CI (4.08, 14.87), p < 0.001], and 20.43 mm(3) in females [95% CI (14.91, 25.93), p < 0.001], indicating more than double the rate of increase in females, which appeared independent of other temporal variables. The only diagnostic group with a significant CP increase as compared to CN was the convertors group, with an increase of 24.88 mm(3)/year [95% CI (14, 35.82), p < 0.001]. ApoE exhibited a significant temporal effect, with the E4 homozygote group’s CP increasing at more than triple the rate of non-carrier or heterozygote groups [40.72, 95% CI (25.97, 55.46), p < 0.001 vs. 12.52, 95% CI (8.02, 17.02), p < 0.001 for ApoE E4 homozygotes and E4 non-carriers, respectively], and may have modified the diagnostic group relationship. CONCLUSION: Our results contribute to potential mechanisms for sex differences in cognitive impairment with a novel finding of twice the annual choroid plexus enlargement in females and provide putative support for CP-related mechanisms of cognitive deterioration and its relationship to ApoE E4. Frontiers Media S.A. 2023-03-08 /pmc/articles/PMC10031049/ /pubmed/36970283 http://dx.doi.org/10.3389/fpsyt.2023.1039239 Text en Copyright © 2023 Novakova Martinkova, Ferretti, Ferrari, Lerch, Matuskova, Secnik and Hort. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Novakova Martinkova, Julie
Ferretti, Maria Teresa
Ferrari, Alberto
Lerch, Ondrej
Matuskova, Veronika
Secnik, Juraj
Hort, Jakub
Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status
title Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status
title_full Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status
title_fullStr Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status
title_full_unstemmed Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status
title_short Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status
title_sort longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and apoe e4 homozygote status
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031049/
https://www.ncbi.nlm.nih.gov/pubmed/36970283
http://dx.doi.org/10.3389/fpsyt.2023.1039239
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