Effects of non-modifiable risk factors of Alzheimer’s disease on intracortical myelin content

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Abstract

Background

Non-modifiable risk factors of Alzheimer’s disease (AD) have lifelong effects on cortical integrity that could be mitigated if identified at early stages. However, it remains unknown whether cortical microstructure is affected in older individuals with non-modifiable AD risk factors and whether altered cortical tissue integrity produces abnormalities in brain functional networks in this AD-risk population.

Methods

Using relative T1w/T2w (rT1w/T2w) ratio maps, we have compared tissue integrity of normal-appearing cortical GM between controls and cognitively normal older adults with either APOE4 ( N = 50), with a first-degree family history (FH) of AD ( N = 52), or with the co-occurrence of both AD risk factors (APOE4+FH) ( N = 35). Additionally, individuals with only one risk factor (APOE4 or FH) were combined into one group ( N = 102) and compared with controls. The same number of controls matched in age, sex, and years of education was employed for each of these comparisons. Group differences in resting state functional connectivity (rs-FC) patterns were also investigated, using as FC seeds those cortical regions showing significant changes in rT1w/T2w ratios.

Results

Overall, individuals with non-modifiable AD risk factors exhibited significant variations in rT1w/T2w ratios compared to controls, being APOE4 and APOE4+FH at opposite ends of a continuum. The co-occurrence of APOE4 and FH was further accompanied by altered patterns of rs-FC.

Conclusions

These findings may have practical implications for early detection of cortical abnormalities in older populations with APOE4 and/or FH of AD and open new avenues to monitor changes in cortical tissue integrity associated with non-modifiable AD risk factors.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13195-022-01152-y.

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Most cited references 80

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An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.

Rahul Desikan, Florent Ségonne, Bruce Fischl … (2006)

In this study, we have assessed the validity and reliability of an automated labeling system that we have developed for subdividing the human cerebral cortex on magnetic resonance images into gyral based regions of interest (ROIs). Using a dataset of 40 MRI scans we manually identified 34 cortical ROIs in each of the individual hemispheres. This information was then encoded in the form of an atlas that was utilized to automatically label ROIs. To examine the validity, as well as the intra- and inter-rater reliability of the automated system, we used both intraclass correlation coefficients (ICC), and a new method known as mean distance maps, to assess the degree of mismatch between the manual and the automated sets of ROIs. When compared with the manual ROIs, the automated ROIs were highly accurate, with an average ICC of 0.835 across all of the ROIs, and a mean distance error of less than 1 mm. Intra- and inter-rater comparisons yielded little to no difference between the sets of ROIs. These findings suggest that the automated method we have developed for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable. This method may be useful for both morphometric and functional studies of the cerebral cortex as well as for clinical investigations aimed at tracking the evolution of disease-induced changes over time, including clinical trials in which MRI-based measures are used to examine response to treatment.

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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

E H Corder, A M Saunders, W J Strittmatter … (1993)

The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.

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Measuring the thickness of the human cerebral cortex from magnetic resonance images.

B Fischl, A M Dale (2000)

Accurate and automated methods for measuring the thickness of human cerebral cortex could provide powerful tools for diagnosing and studying a variety of neurodegenerative and psychiatric disorders. Manual methods for estimating cortical thickness from neuroimaging data are labor intensive, requiring several days of effort by a trained anatomist. Furthermore, the highly folded nature of the cortex is problematic for manual techniques, frequently resulting in measurement errors in regions in which the cortical surface is not perpendicular to any of the cardinal axes. As a consequence, it has been impractical to obtain accurate thickness estimates for the entire cortex in individual subjects, or group statistics for patient or control populations. Here, we present an automated method for accurately measuring the thickness of the cerebral cortex across the entire brain and for generating cross-subject statistics in a coordinate system based on cortical anatomy. The intersubject standard deviation of the thickness measures is shown to be less than 0.5 mm, implying the ability to detect focal atrophy in small populations or even individual subjects. The reliability and accuracy of this new method are assessed by within-subject test-retest studies, as well as by comparison of cross-subject regional thickness measures with published values.

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Author and article information

Contributors

Marina Fernandez-Alvarez: mferalv@upo.es

Mercedes Atienza: matirui@upo.es

Jose L. Cantero: jlcanlor@upo.es

Journal

Journal ID (nlm-ta): Alzheimers Res Ther

Journal ID (iso-abbrev): Alzheimers Res Ther

Title: Alzheimer's Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1758-9193

Publication date (Electronic): 31 December 2022

Publication date PMC-release: 31 December 2022

Publication date Collection: 2022

Volume: 14

Electronic Location Identifier: 202

Affiliations

[1 ]GRID grid.15449.3d, ISNI 0000 0001 2200 2355, Laboratory of Functional Neuroscience, , Pablo de Olavide University, ; Ctra. de Utrera Km 1, 41013 Seville, Spain

[2 ]GRID grid.418264.d, ISNI 0000 0004 1762 4012, CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, ; Madrid, Spain

Article

Publisher ID: 1152

DOI: 10.1186/s13195-022-01152-y

PMC ID: 9805254

PubMed ID: 36587227

SO-VID: 5eebd818-3f98-4b02-9458-b6345ed4b8b1

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 25 May 2022

Date accepted : 25 December 2022

Custom metadata

ScienceOpen disciplines: Neurology

Keywords: aging,alzheimer’s disease,apoe4,cortical microstructure integrity,family history,intracortical myelin,functional connectivity,t1w/t2w ratio maps

Data availability:

ScienceOpen disciplines: Neurology

Keywords: aging, alzheimer’s disease, apoe4, cortical microstructure integrity, family history, intracortical myelin, functional connectivity, t1w/t2w ratio maps

Effects of non-modifiable risk factors of Alzheimer’s disease on intracortical myelin content

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Abstract

Background

Methods

Results

Conclusions

Supplementary Information

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Karger: Neurology and Neuroscience

Most cited references 80

An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

Measuring the thickness of the human cerebral cortex from magnetic resonance images.

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