Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohort
Abstract Background White matter hyperintensities (WMH) of presumed vascular origin have been associated with an increased risk of Alzheimer’s disease (AD). This study aims to describe the patterns of WMH associated with dementia risk estimates and individual risk factors in a cohort of middle-aged/...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13195-018-0460-1 |
| _version_ | 1828891616306266112 |
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| author | Gemma Salvadó Anna Brugulat-Serrat Carole H. Sudre Oriol Grau-Rivera Marc Suárez-Calvet Carles Falcon Karine Fauria M. Jorge Cardoso Frederik Barkhof José Luis Molinuevo Juan Domingo Gispert for the ALFA Study |
| author_facet | Gemma Salvadó Anna Brugulat-Serrat Carole H. Sudre Oriol Grau-Rivera Marc Suárez-Calvet Carles Falcon Karine Fauria M. Jorge Cardoso Frederik Barkhof José Luis Molinuevo Juan Domingo Gispert for the ALFA Study |
| author_sort | Gemma Salvadó |
| collection | DOAJ |
| description | Abstract Background White matter hyperintensities (WMH) of presumed vascular origin have been associated with an increased risk of Alzheimer’s disease (AD). This study aims to describe the patterns of WMH associated with dementia risk estimates and individual risk factors in a cohort of middle-aged/late middle-aged individuals (mean 58 (interquartile range 51–64) years old). Methods Magnetic resonance imaging and AD risk factors were collected from 575 cognitively unimpaired participants. WMH load was automatically calculated in each brain lobe and in four equidistant layers from the ventricular surface to the cortical interface. Global volumes and regional patterns of WMH load were analyzed as a function of the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) dementia risk score, as well as family history of AD and Apolipoprotein E (APOE) genotype. Additional analyses were performed after correcting for the effect of age and hypertension. Results The studied cohort showed very low WMH burden (median 1.94 cm3) and 20-year dementia risk estimates (median 1.47 %). Even so, higher CAIDE scores were significantly associated with increased global WMH load. The main drivers of this association were age and hypertension, with hypercholesterolemia and body mass index also displaying a minor, albeit significant, influence. Regionally, CAIDE scores were positively associated with WMH in anterior areas, mostly in the frontal lobe. Age and hypertension showed significant association with WMH in almost all regions analyzed. The APOE-ε2 allele showed a protective effect over global WMH with a pattern that comprised juxtacortical temporo-occipital and fronto-parietal deep white matter regions. Participants with maternal family history of AD had higher WMH load than those without, especially in temporal and occipital lobes. Conclusions WMH load is associated with AD risk factors even in cognitively unimpaired subjects with very low WMH burden and dementia risk estimates. Our results suggest that tight control of modifiable risk factors in middle-age/late middle-age could have a significant impact on late-life dementia. |
| first_indexed | 2024-12-13T13:21:26Z |
| format | Article |
| id | doaj.art-2336f348041b411fbe5533e547086076 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-13T13:21:26Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-2336f348041b411fbe5533e5470860762022-12-21T23:44:24ZengBMCAlzheimer’s Research & Therapy1758-91932019-01-0111111410.1186/s13195-018-0460-1Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohortGemma Salvadó0Anna Brugulat-Serrat1Carole H. Sudre2Oriol Grau-Rivera3Marc Suárez-Calvet4Carles Falcon5Karine Fauria6M. Jorge Cardoso7Frederik Barkhof8José Luis Molinuevo9Juan Domingo Gispert10for the ALFA StudyBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationEngineering and Imaging Sciences, King’s College LondonBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationEngineering and Imaging Sciences, King’s College LondonCentre for Medical Imaging Computing, Faculty of Engineering, University College LondonBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationAbstract Background White matter hyperintensities (WMH) of presumed vascular origin have been associated with an increased risk of Alzheimer’s disease (AD). This study aims to describe the patterns of WMH associated with dementia risk estimates and individual risk factors in a cohort of middle-aged/late middle-aged individuals (mean 58 (interquartile range 51–64) years old). Methods Magnetic resonance imaging and AD risk factors were collected from 575 cognitively unimpaired participants. WMH load was automatically calculated in each brain lobe and in four equidistant layers from the ventricular surface to the cortical interface. Global volumes and regional patterns of WMH load were analyzed as a function of the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) dementia risk score, as well as family history of AD and Apolipoprotein E (APOE) genotype. Additional analyses were performed after correcting for the effect of age and hypertension. Results The studied cohort showed very low WMH burden (median 1.94 cm3) and 20-year dementia risk estimates (median 1.47 %). Even so, higher CAIDE scores were significantly associated with increased global WMH load. The main drivers of this association were age and hypertension, with hypercholesterolemia and body mass index also displaying a minor, albeit significant, influence. Regionally, CAIDE scores were positively associated with WMH in anterior areas, mostly in the frontal lobe. Age and hypertension showed significant association with WMH in almost all regions analyzed. The APOE-ε2 allele showed a protective effect over global WMH with a pattern that comprised juxtacortical temporo-occipital and fronto-parietal deep white matter regions. Participants with maternal family history of AD had higher WMH load than those without, especially in temporal and occipital lobes. Conclusions WMH load is associated with AD risk factors even in cognitively unimpaired subjects with very low WMH burden and dementia risk estimates. Our results suggest that tight control of modifiable risk factors in middle-age/late middle-age could have a significant impact on late-life dementia.http://link.springer.com/article/10.1186/s13195-018-0460-1VascularLesionsAgingBrainPrevention |
| spellingShingle | Gemma Salvadó Anna Brugulat-Serrat Carole H. Sudre Oriol Grau-Rivera Marc Suárez-Calvet Carles Falcon Karine Fauria M. Jorge Cardoso Frederik Barkhof José Luis Molinuevo Juan Domingo Gispert for the ALFA Study Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohort Alzheimer’s Research & Therapy Vascular Lesions Aging Brain Prevention |
| title | Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohort |
| title_full | Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohort |
| title_fullStr | Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohort |
| title_full_unstemmed | Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohort |
| title_short | Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohort |
| title_sort | spatial patterns of white matter hyperintensities associated with alzheimer s disease risk factors in a cognitively healthy middle aged cohort |
| topic | Vascular Lesions Aging Brain Prevention |
| url | http://link.springer.com/article/10.1186/s13195-018-0460-1 |
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