1. |
- Albrecht, Franziska, et al.
(författare)
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Effects of a Highly Challenging Balance Training Program on Motor Function and Brain Structure in Parkinson's Disease
- 2021
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:4, s. 2057-2071
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is characterized by motor deficits and brain alterations having a detrimental impact on balance, gait, and cognition. Intensive physical exercise can induce changes in the neural system, potentially counteracting neurodegeneration in PD and improving clinical symptoms. Objective: This randomized controlled trial investigated effects of a highly challenging, cognitively demanding, balance and gait training (HiBalance) program in participants with PD on brain structure. Methods: 95 participants were assigned to either the HiBalance or an active control speech training program. The group-based interventions were performed in 1-hour sessions, twice per week over a 10-week period. Participants underwent balance, gait, cognitive function, and structural magnetic resonance imaging assessments before and after the interventions. Voxel-based morphometry was analyzed in 34 HiBalance and 31 active controls. Additionally, structural covariance networks were assessed. Results: There was no significant time by group interaction between the HiBalance and control training in balance, gait, or brain volume. Within-HiBalance-group analyses showed higher left putamen volumes post-training. In repeated measures correlation a positive linear, non-significant relationship between gait speed and putamen volume was revealed. In the HiBalance group we found community structure changes and stronger thalamic-cerebellar connectivity in structural covariance networks. Neither brain volume changes nor topology changes were found for the active controls after the training. Conclusion: Thus, subtle structural brain changes occur after balance and gait training. Future studies need to determine whether training modifications or other assessment methods lead to stronger effects.
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2. |
- Cedres, Nira, et al.
(författare)
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Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
- 2022
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 99:15, s. e1619-e1629
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals.Methods The contribution of amyloid and tau pathology was assessed through CSF levels of the Aβ42/40 ratio and phosphorylated tau (p-tau). CSF Aβ38 levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE ε4 carriership were also included in the analysis as variables of interest.Results We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of Aβ38 and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The Aβ42/40 ratio did not contribute notably to the models (IncMSE<3.0%). APOE ε4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T201 = −1.55; p = 0.123).Discussion In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.
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3. |
- 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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4. |
- Ferreira, Daniel, et al.
(författare)
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β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies
- 2020
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Ingår i: Neurology. - 1526-632X. ; 95:24, s. 3257-3268
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that β-amyloid and tau biomarker positivity increases with age, which is modified by APOE genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype. METHODS: We included 417 patients with DLB (age 45-93 years, 31% women). Positivity on β-amyloid (A+) and tau (T+) biomarkers was determined by CSF β-amyloid1-42 and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort. Patients were stratified into 4 groups: A-T-, A+T-, A-T+, and A+T+. RESULTS: A-T- was the largest group (39%), followed by A+T- (32%), A+T+ (15%), and A-T+ (13%). The percentage of A-T- decreased with age, and A+ and T+ increased with age in both women and men. A+ increased more in APOE ε4 carriers with age than in noncarriers. A+ was the main predictor of lower cognitive performance when considered together with T+. T+ was associated with a lower frequency of parkinsonism and probable REM sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype. CONCLUSIONS: Alzheimer disease pathologic changes are common in DLB and are associated with the clinical phenotype. β-Amyloid is associated with cognitive impairment, and tau pathology is associated with lower frequency of clinical features of DLB. These findings have important implications for diagnosis, prognosis, and disease monitoring, as well as for clinical trials targeting disease-specific proteins in DLB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with probable DLB, β-amyloid is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.
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5. |
- Lindberg, Olof, et al.
(författare)
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Atrophy of the posterior subiculum is associated with memory impairment, Tau- and Aβ pathology in non-demented individuals
- 2017
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 9:SEP
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is associated with atrophy of the cornu ammonis (CA) 1 and the subiculum subfield of the hippocampus (HC), and with deficits in episodic memory and spatial orientation. These deficits are mainly associated with the functionality of the posterior HC. We therefore hypothesized that key AD pathologies, i.e., β-amyloid and tau pathology would be particularly associated with the volume of the posterior subiculum in non-demented individuals. In our study we included 302 cognitively normal elderly participants (CN), 183 patients with subjective cognitive decline (SCD) and 171 patients with amnestic mild cognitive impairment (MCI), all of whom underwent 3T magnetic resonance images (MRI). The subicular subfield was segmented using Freesurfer 5.3 and divided into 10 volumetric segments moving from the most posterior (segment 1) to the most anterior part along the axis of the hippocampal head and body (segment 10). Cerebrospinal fluid (CSF) Aβ42 and phosphorylated tau (P-tau) were quantified using ELISA and were used as biomarkers for β-amyloid and tau pathology, respectively. In the total sample, tau-pathology and Aβ-pathology and (measured by elevated P-tau and low Aβ42 levels in CSF) and mild memory dysfunction were mostly associated with the volume changes of the posterior subiculum. Both SCD and MCI patients with elevated P-tau or low Aβ42 levels displayed predominantly posterior subicular atrophy in comparisons to control subjects with normal CSF biomarker levels. Finally, there was no main effect of Aβ42 or P-tau when comparing SCD with abnormal P-tau or Aβ42 with SCD with normal levels of these CSF-biomarkers. However, in the left subiculum there was a significant interaction revealing atrophy in the left posterior but not the anterior subiculum in participants with low Aβ42 levels. The same pattern was observed on the contralateral side in participants with elevated P-tau levels. In conclusion, AD pathologies and mild memory dysfunction are mainly associated with atrophy of the posterior parts of the subicular subfields of the HC in non-demented individuals. In light of these findings we suggest that segmentation of the HC subfields may benefit from considering the volume of the different anterior-posterior subsections of each subfield.
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6. |
- Mårtensson, Gustav, et al.
(författare)
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Medial temporal atrophy in preclinical dementia : Visual and automated assessment during six year follow-up
- 2020
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Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- Medial temporal lobe (MTL) atrophy is an important morphological marker of many dementias and is closely related to cognitive decline. In this study we aimed to characterize longitudinal progression of MTL atrophy in 93 individuals with subjective cognitive decline and mild cognitive impairment followed up over six years, and to assess if clinical rating scales are able to detect these changes. All MRI images were visually rated according to Scheltens’ scale of medial temporal atrophy (MTA) by two neuroradiologists and AVRA, a software for automated MTA ratings. The images were also segmented using FreeSurfer's longitudinal pipeline in order to compare the MTA ratings to volumes of the hippocampi and inferior lateral ventricles. We found that MTL atrophy rates increased with CSF biomarker abnormality, used to define preclinical stages of Alzheimer's Disease. Both AVRA's and the radiologists’ MTA ratings showed similar longitudinal trends as the subcortical volumes, suggesting that visual rating scales provide a valid alternative to automatic segmentations. Our results further showed that it took more than 8 years on average for individuals with mild cognitive impairment, and an Alzheimer's disease biomarker profile, to increase the MTA score by one. This suggests that discrete MTA ratings are too coarse for tracking individual MTL atrophy in short time spans. While the MTA scores from each radiologist showed strong correlations to subcortical volumes, the inter-rater agreement was low. We conclude that the main limitation of quantifying MTL atrophy with visual ratings in clinics is the subjectiveness of the assessment.
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7. |
- 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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8. |
- Pereira, Joana B., et al.
(författare)
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Amyloid and tau accumulate across distinct spatial networks and are differentially associated with brain connectivity
- 2019
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Ingår i: eLife. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)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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9. |
- 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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10. |
- Pereira, Joana B., et al.
(författare)
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Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer's disease
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 58, s. 14-29
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Tidskriftsartikel (refereegranskat)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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