Altered brain white matter integrity in healthy carriers of the
            <i>APOE</i>
            ε4 allele

Persson, Jonas; Lind, John; Larsson, Anne; Ingvar, Martin; Cruts, Marc; Broeckhoven, Christine Van; Adolfsson, Rolf; Nilsson, Lars‐Göran; Nyberg, Lars

doi:10.1212/01.wnl.0000204180.25361.48

Cited by 154 publications

(146 citation statements)

References 28 publications

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“…Our study showed a selective regional atrophy of transcallosal prefrontal connections in the APOE ε4 carriers. This finding is consistent with a recent diffusion tensor imaging study that showed a decline in fractional anisotropy (FA) in the entire CC (15) in healthy APOE ε4 carriers relative to noncarriers. Furthermore, measurement of transverse relaxation rates also showed a steeper slope of agerelated decline in relaxation rates in the frontal lobe and in the genu of the CC in APOE ε4 carriers, suggesting that the ε4 allele may affect frontal WM integrity by accelerating age-related changes (16).…”

Section: Discussionsupporting

confidence: 92%

“…Previous neuroimaging studies of the effect of APOE on the WM have been mainly focused on its association with vascular events and/or the degree of WM ischemic lesions in the ε4 allele carriers, showing a strong correlation between the APOE ε4 allele and WM changes (12)(13)(14). Recent studies using diffusion tensor imaging (DTI) and transverse relaxation times suggested a deleterious effect of the APOE ε4 allele on the corpus callosum (CC) integrity (15,16). Although evidence in support of a global effect of APOE ε4 on the brain has been accumulating, the impact of the APOE ε4 allele on specific neural pathways is still unclear.…”

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confidence: 99%

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Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE ϵ4 carriers

Filippini

Zarei

Beckmann

et al. 2009

Magnetic Resonance Imaging

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Purpose:To investigate the possible effect of the APOE ε4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy ε4 allele carriers compared with noncarriers. Materials and Methods:A total of 211 subjects, ages 27 to 83 years, 51 ε4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE ε4 gene on the gray matter. Results:We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE ε4 carriers compared withthe noncarriers particularly in the prefrontal region (P ϭ 0.02). No gray matter differences were observed between the two groups.Conclusion: APOE ε4 polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE ε4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE ϵ4 carriers

Filippini

Zarei

Beckmann

et al. 2009

Magnetic Resonance Imaging

View full text Add to dashboard Cite

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“…This is supported by findings of a bilateral reduction in hippocampal activation during episodic retrieval in older adults (Cabeza et al, 2004;Daselaar et al, 2006). The present findings suggest that the hippocampal component of age-related episodic memory deficits might not only be due to grey matter shrinkage (Raz et al, 2005), but also reflect alterations in hippocampal WM connections (see also Persson et al, 2006).…”

Section: Discussionsupporting

confidence: 86%

Age-related differences in white matter microstructure: Region-specific patterns of diffusivity

Burzynska¹,

Preuschhof²,

Bäckman³

et al. 2010

NeuroImage

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348

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We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of agerelated decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

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“…To summarize briefly: it has been hypothesized that interhemispheric connections of the corpus callosum provide inhibition between functionally homologous areas in the left and right hemisphere (Gazzaniga, 2000). Differences in corpus callosum anatomy such as reduced volume or reduced microstructural integrity are related to lower lateralization of function in typical participants and patient groups (Hinkley et al., 2016; Just, Cherkassky, Keller, Kana, & Minshew, 2007; Persson et al., 2006). In turn, lower lateralization is associated with lower performance on cognitive tasks, including executive function tasks (Hinkley et al., 2012; Just et al., 2007; Nagel, Herting, Maxwell, Bruno, & Fair, 2013).…”

Section: Discussionmentioning

confidence: 99%

Differences in brain morphology and working memory capacity across childhood

Bathelt

Gathercole

Johnson

et al. 2017

Developmental Science

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Working memory (WM) skills are closely associated with learning progress in key areas such as reading and mathematics across childhood. As yet, however, little is known about how the brain systems underpinning WM develop over this critical developmental period. The current study investigated whether and how structural brain correlates of components of the working memory system change over development. Verbal and visuospatial short‐term and working memory were assessed in 153 children between 5.58 and 15.92 years, and latent components of the working memory system were derived. Fractional anisotropy and cortical thickness maps were derived from T1‐weighted and diffusion‐weighted MRI and processed using eigenanatomy decomposition. There was a greater involvement of the corpus callosum and posterior temporal white matter in younger children for performance associated with the executive part of the working memory system. For older children, this was more closely linked with the thickness of the occipitotemporal cortex. These findings suggest that increasing specialization leads to shifts in the contribution of neural substrates over childhood, moving from an early dependence on a distributed system supported by long‐range connections to later reliance on specialized local circuitry. Our findings demonstrate that despite the component factor structure being stable across childhood, the underlying brain systems supporting working memory change. Taking the age of the child into account, and not just their overall score, is likely to be critical for understanding the nature of the limitations on their working memory capacity.

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Altered brain white matter integrity in healthy carriers of the APOE ε4 allele

Cited by 154 publications

References 28 publications

Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE ϵ4 carriers

Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE ϵ4 carriers

Age-related differences in white matter microstructure: Region-specific patterns of diffusivity

Differences in brain morphology and working memory capacity across childhood

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