| 1. |
- Hahn, Andreas, et al.
(författare)
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Association Between Earliest Amyloid Uptake and Functional Connectivity in Cognitively Unimpaired Elderly
- 2019
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 29, s. 2173-2182
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in cognitive performance have been noted in nondemented subjects with elevated accumulation of amyloid-β (Aβ) fibrils. However, it is not yet understood whether brain function is already influenced by Aβ deposition during the very earliest stages of the disease. We therefore investigated associations between [18F]Flutemetamol PET, resting-state functional connectivity, gray and white matter structure and cognitive performance in 133 cognitively normal elderly that exhibited normal global Aβ PET levels. [18F]Flutemetamol uptake in regions known to accumulate Aβ fibrils early in preclinical AD (i.e., mainly certain parts of the default-mode network) was positively associated with dynamic but not static functional connectivity (r = 0.77). Dynamic functional connectivity was further related to better cognitive performance (r = 0.21-0.72). No significant associations were found for Aβ uptake with gray matter volume or white matter diffusivity. The findings demonstrate that the earliest accumulation of Aβ fibrils is associated with increased functional connectivity, which occurs before any structural alterations. The enhanced functional connectivity may reflect a compensatory mechanism to maintain high cognitive performance in the presence of increasing amyloid accumulation during the earliest phases of AD.
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| 2. |
- Harper, Luke, et al.
(författare)
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Prenatal Gyrification Pattern Affects Age at Onset in Frontotemporal Dementia
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 32:18, s. 3937-3944
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Tidskriftsartikel (refereegranskat)abstract
- The paracingulate sulcus is a tertiary sulcus formed during the third trimester. In healthy individuals paracingulate sulcation is more prevalent in the left hemisphere. The anterior cingulate and paracingulate gyri are focal points of neurodegeneration in behavioral variant frontotemporal dementia (bvFTD). This study aims to determine the prevalence and impact of paracingulate sulcation in bvFTD. Structural magnetic resonance images of individuals with bvFTD (n = 105, mean age 66.9 years), Alzheimer's disease (n = 92, 73.3), and healthy controls (n = 110, 62.4) were evaluated using standard protocol for hemispheric paracingulate sulcal presence. No difference in left hemisphere paracingulate sulcal frequency was observed between groups; 0.72, 0.79, and 0.70, respectively, in the bvFTD, Alzheimer's disease, and healthy control groups, (P = 0.3). A significant impact of right (but not left) hemispheric paracingulate sulcation on age at disease onset was identified in bvFTD (mean 60.4 years where absent vs. 63.8 where present [P = 0.04, Cohen's d = 0.42]). This relationship was not observed in Alzheimer's disease. These findings demonstrate a relationship between prenatal neuronal development and the expression of a neurodegenerative disease providing a gross morphological example of brain reserve.
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| 3. |
- Pereira, Joana B., et al.
(författare)
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Abnormal structural brain connectome in individuals with preclinical Alzheimer's disease
- 2018
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:10, s. 3638-3649
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease has a long preclinical phase during which amyloid pathology and neurodegeneration accumulate in the brain without producing overt cognitive deficits. It is currently unclear whether these early disease stages are associated with a progressive disruption in the communication between brain regions that subsequently leads to cognitive decline and dementia. In this study we assessed the organization of structural networks in cognitively normal (CN) individuals harboring amyloid pathology (A+N-), neurodegeneration (A-N+), or both (A+N+) from the prospective and longitudinal Swedish BioFINDER study. We combined graph theory with diffusion tensor imaging to investigate integration, segregation, and centrality measures in the brain connectome in the previous groups. At baseline, our findings revealed a disrupted network topology characterized by longer paths, lower efficiency, increased clustering and modularity in CN A-N+ and CN A+N+, but not in CN A+N-. After 2 years, CN A+N+ showed significant abnormalities in all global network measures, whereas CN A-N+ only showed abnormalities in the global efficiency. Network connectivity and organization were associated with memory in CN A+N+ individuals. Altogether, our findings suggest that amyloid pathology is not sufficient to disrupt structural network topology, whereas neurodegeneration is.
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| 4. |
- Pereira, Joana B., et al.
(författare)
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Amyloid network topology characterizes the progression of Alzheimer's disease during the predementia stages
- 2018
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:1, s. 340-349
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence showing that the accumulation of the amyloid-β (Aβ) peptide into extracellular plaques is a central event in Alzheimer's disease (AD). These abnormalities can be detected as lowered levels of Aβ42 in the cerebrospinal fluid (CSF) and are followed by increased amyloid burden on positron emission tomography (PET) several years before the onset of dementia. The aim of this study was to assess amyloid network topology in nondemented individuals with early stage Aβ accumulation, defined as abnormal CSF Aβ42 levels and normal Florbetapir PET (CSF+/PET-), and more advanced Aβ accumulation, defined as both abnormal CSF Aβ42 and Florbetapir PET (CSF+/PET+). The amyloid networks were built using correlations in the mean 18F-florbetapir PET values between 72 brain regions and analyzed using graph theory analyses. Our findings showed an association between early amyloid stages and increased covariance as well as shorter paths between several brain areas that overlapped with the default-mode network (DMN). Moreover, we found that individuals with more advanced amyloid accumulation showedmore widespread changes in brain regions both within and outside the DMN. These findings suggest that amyloid network topology could potentially be used to assess disease progression in the predementia stages of AD.
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