| 1. |
- Ferreira, Daniel, et al.
(författare)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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| 2. |
- Nordenskjöld, Richard, et al.
(författare)
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Intracranial volume estimated with commonly used methods could introduce bias in studies including brain volume measurements
- 2013
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 83, s. 355-360
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Tidskriftsartikel (refereegranskat)abstract
- In brain volumetric studies, intracranial volume (ICV) is often used as an estimate of pre-morbid brain size as well as to compensate for inter-subject variations in head size. However, if the estimated ICV is biased by for example gender or atrophy, it could introduce errors in study results. To evaluate how two commonly used methods for ICV estimation perform, computer assisted reference segmentations were created and evaluated. Segmentations were created for 399 MRI volumes from 75-year-old subjects, with 53 of these subjects having an additional scan and segmentation created at age 80. ICV estimates from Statistical Parametric Mapping (SPM, version 8) and Freesurfer (FS, version 5.1.0) were compared to the reference segmentations, and bias related to skull size (approximated with the segmentation measure), gender or atrophy were tested for. The possible ICV related effect on associations between normalized hippocampal volume and factors gender, education and cognition was evaluated by normalizing hippocampal volume with different ICV measures. Excellent agreement was seen for inter- (r=0.999) and intra- (r=0.999) operator reference segmentations. Both SPM and FS overestimated ICV. SPM showed bias associated with gender and atrophy while FS showed bias dependent on skull size. All methods showed good correlation between time points in the longitudinal data (reference: 0.998, SPM: 0.962, FS: 0.995). Hippocampal volume showed different associations with cognition and gender depending on which ICV measure was used for hippocampal volume normalization. These results show that the choice of method used for ICV estimation can bias results in studies including brain volume measurements.
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| 3. |
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| 4. |
- Nordenskjöld, Richard, et al.
(författare)
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Intracranial volume normalization methods : Considerations when investigating gender differences in regional brain volume
- 2015
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123 .- 0925-4927. ; 231:3, s. 227-235
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Tidskriftsartikel (refereegranskat)abstract
- Intracranial volume (ICV) normalization of regional brain volumes (v) is common practice in volumetric studies of the aging brain. Multiple normalization methods exist and this study aimed to investigate when each method is appropriate to use in gender dimorphism studies and how differences in v are affected by the choice of method. A new method based on weighted ICV matching is also presented. Theoretical reasoning and simulated experiments were followed by an evaluation using real data comprising 400 subjects, all 75 years old, whose ICV was segmented with a gold standard method. The presented method allows good visualization of volume relation between gender groups. A different gender dimorphism in volume was found depending on the normalization method used for both simulated and real data. Method performance was also seen to depend on the slope (B) and intercept (m) from the linear relation between v and ICV (v=B·ICV+m) as well as gender distribution in the cohort. A suggested work-flow for selecting ICV normalization method when investigating gender related differences in regional brain volume is presented.
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| 5. |
- Voevodskaya, Olga, et al.
(författare)
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The effects of intracranial volume adjustment approaches on multiple regional MRI volumes in healthy aging and Alzheimer's disease
- 2014
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 6, s. 264-
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Tidskriftsartikel (refereegranskat)abstract
- In neurodegeneration research, normalization of regional volumes by intracranial volume (ICV) is important to estimate the extent of disease-driven atrophy. There is little agreement as to whether raw volumes, volume-to-ICV fractions or regional volumes from which the ICV factor has been regressed out should be used for volumetric brain imaging studies. Using multiple regional cortical and subcortical volumetric measures generated by Freesurfer (51 in total), the main aim of this study was to elucidate the implications of these adjustment approaches. Magnetic resonance imaging (MRI) data were analyzed from two large cohorts, the population-based PIVUS cohort (N = 406, all subjects age 75) and the Alzheimer disease Neuroimaging Initiative (ADNI) cohort (N = 724). Further, we studied whether the chosen ICV normalization approach influenced the relationship between hippocampus and cognition in the three diagnostic groups of the ADNI cohort (Alzheimer's disease, mild cognitive impairment, and healthy individuals). The ability of raw vs. adjusted hippocampal volumes to predict diagnostic status was also assessed. In both cohorts raw volumes correlate positively with ICV, but do not scale directly proportionally with it. The correlation direction is reversed for all volume-to-ICV fractions, except the lateral and third ventricles. Most gray matter fractions are larger in females, while lateral ventricle fractions are greater in males. Residual correction effectively eliminated the correlation between the regional volumes and ICV and removed gender differences. The association between hippocampal volumes and cognition was not altered by ICV normalization. Comparing prediction of diagnostic status using the different approaches, small but significant differences were found. The choice of normalization approach should be carefully considered when designing a volumetric brain imaging study.
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