| 41. |
- Oberg, Johanna, et al.
(author)
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Age related changes in brain metabolites observed by 1H MRS in APP/PS1 mice
- 2008
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:9, s. 1423-1433
-
Journal article (peer-reviewed)abstract
- Translational biomarkers in Alzheimer's disease based on non-invasive in vivo methods are highly warranted. (1)H magnetic resonance spectroscopy (MRS) is non-invasive and applicable in vivo in both humans and experimental animals. In vivo(1)H MRS and 3D MRI were performed on brains of double transgenic (tg) mice expressing a double mutant human beta-amyloid precursor protein APP(K670N,M671L) and human mutated presenilin gene PS1M146L, and wild-type (wt) littermates at 2.5, 6.5 and 9 months of age using a 9.4T magnet. For quantification, LCModel was used, and the data were analyzed using multivariate data analysis (MVDA). MVDA evidenced a significant separation, which became more pronounced with age, between tg and wt mice at all time points. While myo-inositol and guanidoacetate were important for group separation in young mice, N-acetylaspartate, glutamate and macrolipids were important for separation of aged tg and wt mice. Volume segmentation revealed that brain and hippocampus were readily smaller in tg as compared to wt mice at the age of 2.5 months. Amyloid plaques were seen in 6.5 and 9 months, but not in 2.5 months old animals. In conclusion, differences in brain metabolites could be accurately depicted in tg and wt mice in vivo by combining MRS with MVDA. First differences in metabolite content were readily seen at 2.5 months, when volume defects in tg mice were present, but no amyloid plaques.
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| 42. |
- Olsson, Eric, et al.
(author)
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Diabetes and glucose disturbances in patients with psychosis in Sweden
- 2015
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In: BMJ Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 3
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication.METHOD:We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ(2) test, and factors associated with antidiabetic treatment were evaluated with logistic regression.RESULTS:Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1-6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness.CONCLUSIONS:The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.
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| 43. |
- Pereira, Joana B., et al.
(author)
-
Abnormal structural brain connectome in individuals with preclinical Alzheimer's disease
- 2018
-
In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:10, s. 3638-3649
-
Journal article (peer-reviewed)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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| 44. |
- Pereira, Joana B., et al.
(author)
-
Amyloid and tau accumulate across distinct spatial networks and are differentially associated with brain connectivity
- 2019
-
In: eLife. - 2050-084X. ; 8
-
Journal article (peer-reviewed)abstract
- The abnormal accumulation of amyloid-β and tau targets specific spatial networks in Alzheimer’s disease. However, the relationship between these networks across different disease stages and their association with brain connectivity has not been explored. In this study, we applied a joint independent component analysis to18F-Flutemetamol (amyloid-β) and18F-Flortaucipir (tau) PET images to identify amyloid-β and tau networks across different stages of Alzheimer’s disease. We then assessed whether these patterns were associated with resting-state functional networks and white matter tracts. Our analyses revealed nine patterns that were linked across tau and amyloid-β data. The amyloid-β and tau patterns showed a fair to moderate overlap with distinct functional networks but only tau was associated with white matter integrity loss and multiple cognitive functions. These findings show that amyloid-β and tau have different spatial affinities, which can be used to understand how they accumulate in the brain and potentially damage the brain’s connections.
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| 45. |
- Pereira, Joana B., et al.
(author)
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Amyloid network topology characterizes the progression of Alzheimer's disease during the predementia stages
- 2018
-
In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:1, s. 340-349
-
Journal article (peer-reviewed)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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| 46. |
- Pereira, Joana B., et al.
(author)
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Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer's disease
- 2017
-
In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 58, s. 14-29
-
Journal article (peer-reviewed)abstract
- The aggregation and deposition of amyloid-β (Aβ) peptides into plaques is an early event in Alzheimer's disease (AD), which is followed by different aspects of neurodegeneration that can be measured in the cerebrospinal fluid (CSF) or plasma using neurofilament light (NFL), neurogranin (Ng), total Tau (T-Tau), and phosphorylated tau (P-Tau) levels. The relationship between these biomarkers and regional brain atrophy across the different stages of AD remains largely unexplored. In this study, we assessed whether NFL, Ng, T-Tau, and P-Tau levels in CSF and NFL in plasma are associated with cortical thinning and subcortical volume loss in cognitively normal, mild cognitive impairment, and AD subjects with and without Aβ pathology. Our main findings showed that CSF NFL levels were associated with brain atrophy in all groups, but plasma NFL only correlated with atrophy in symptomatic cases. In contrast, Ng was associated with regional brain atrophy only in individuals with Aβ pathology. Altogether, our main findings suggest that Ng is strongly associated with Aβ pathology, whereas NFL is more unspecific.
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| 47. |
- Pereira, Joana B., et al.
(author)
-
Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease
- 2020
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 139
-
Journal article (peer-reviewed)abstract
- Objectives: Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. Methods: We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. Results: Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p =.003) and those who already had PDD (p <.001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p =.004). Baseline and longitudinal Ch4 volumes were associated with cognition (p <.002) and longitudinal Ch4 atrophy predicted future dementia (p =.009). Conclusions: Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.
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| 48. |
- Peter, Moa G., et al.
(author)
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Lifelong olfactory deprivation-dependent cortical reorganization restricted to orbitofrontal cortex
- 2023
-
In: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 44:18, s. 6459-6470
-
Journal article (peer-reviewed)abstract
- Prolonged sensory deprivation has repeatedly been linked to cortical reorganization. We recently demonstrated that individuals with congenital anosmia (CA, complete olfactory deprivation since birth) have seemingly normal morphology in piriform (olfactory) cortex despite profound morphological deviations in the orbitofrontal cortex (OFC), a finding contradictory to both the known effects of blindness on visual cortex and to the sparse literature on brain morphology in anosmia. To establish whether these unexpected findings reflect the true brain morphology in CA, we first performed a direct replication of our previous study to determine if lack of results was due to a deviant control group, a confound in cross sectional studies. Individuals with CA (n = 30) were compared to age and sex matched controls (n = 30) using voxel- and surface-based morphometry. The replication results were near identical to the original study: bilateral clusters of group differences in the OFC, including CA atrophy around the olfactory sulci and volume increases in the medial orbital gyri. Importantly, no group differences in piriform cortex were detected. Subsequently, to assess any subtle patterns of group differences not detectable by our mass-univariate analysis, we explored the data from a multivariate perspective. Combining the newly collected data with data from the replicated study (CA = 49, control = 49), we performed support vector machine classification based on gray matter volume. In line with the mass-univariate analyses, the multivariate analysis could accurately differentiate between the groups in bilateral OFC, whereas the classification accuracy in piriform cortex was at chance level. Our results suggest that despite lifelong olfactory deprivation, piriform (olfactory) cortex is morphologically unaltered and the morphological deviations in CA are confined to the OFC.
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| 49. |
- Peter, Moa G., et al.
(author)
-
Morphological changes in secondary, but not primary, sensory cortex in individuals with life-long olfactory sensory deprivation
- 2020
-
In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 218
-
Journal article (peer-reviewed)abstract
- Individuals with congenital sensory deprivation usually demonstrate altered brain morphology in areas associated with early processing of the absent sense. Here, we aimed to establish whether this also applies to individuals born without a sense of smell (congenital anosmia) by comparing cerebral morphology between 33 individuals with isolated congenital anosmia and matched controls. We detected no morphological alterations in the primary olfactory (piriform) cortex. However, individuals with anosmia demonstrated gray matter volume atrophy in bilateral olfactory sulci, explained by decreased cortical area, curvature, and sulcus depth. They further demonstrated increased gray matter volume and cortical thickness in the medial orbital gyri; regions closely associated with olfactory processing, sensory integration, and value-coding. Our results suggest that a lifelong absence of sensory input does not necessarily lead to morphological alterations in primary sensory cortex and extend previous findings with divergent morphological alterations in bilateral orbitofrontal cortex, indicating influences of different developmental processes.
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| 50. |
- Peter, Moa G., et al.
(author)
-
Normal Olfactory Functional Connectivity Despite Lifelong Absence of Olfactory Experiences
- 2021
-
In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 31:1, s. 159-168
-
Journal article (peer-reviewed)abstract
- Congenital blindness is associated with atypical morphology and functional connectivity within and from visual cortical regions; changes that are hypothesized to originate from a lifelong absence of visual input and could be regarded as a general (re) organization principle of sensory cortices. Challenging this is the fact that individuals with congenital anosmia (lifelong olfactory sensory loss) display little to no morphological changes in the primary olfactory cortex. To determine whether olfactory input from birth is essential to establish and maintain normal functional connectivity in olfactory processing regions, akin to the visual system, we assessed differences in functional connectivity within the olfactory cortex between individuals with congenital anosmia (n=33) and matched controls (n=33). Specifically, we assessed differences in connectivity between core olfactory processing regions as well as differences in regional homogeneity and homotopic connectivity within the primary olfactory cortex. In contrast to congenital blindness, none of the analyses indicated atypical connectivity in individuals with congenital anosmia. In fact, post-hoc Bayesian analysis provided support for an absence of group differences. These results suggest that a lifelong absence of olfactory experience has a limited impact on the functional connectivity in the olfactory cortex, a finding that indicates a clear difference between sensory modalities in how sensory cortical regions develop.
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