| 61. |
- Rydén, Lina, et al.
(författare)
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Atrial Fibrillation, Stroke, and Silent Cerebrovascular Disease : A Population-based MRI Study
- 2021
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 97:16, s. 1608-1619
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Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectivesAtrial fibrillation (AF) has been associated with cognitive decline and dementia. However, the mechanisms behind these associations are not clear. Examination of cerebrovascular pathology on MRI may shed light on how AF affects the brain. This study aimed to determine whether AF is associated with a broad range of cerebrovascular diseases beyond the well-known association with symptomatic stroke, including silent infarcts and markers of small vessel disease, i.e., cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and lacunes, in a population-based sample of 70-year-olds.MethodsData were obtained from the Gothenburg H70 Birth Cohort Studies, in which individuals are invited based on birthdate. This study has a cross-sectional design and includes individuals born in 1944 who underwent structural brain MRI in 2014 to 2017. AF diagnoses were based on self-report, ECG, and register data. Symptomatic stroke was based on self-report, proxy interviews, and register data. Brain infarcts and CMBs were assessed by a radiologist. WMH volumes were measured on fluid-attenuated inversion recovery images with the Lesion Segmentation Tool. Multivariable logistic regression was used to study the association between AF and infarcts/CMBs, and multivariable linear regression was used to study the association between AF and WMHs.ResultsA total of 776 individuals were included, and 65 (8.4%) had AF. AF was associated with symptomatic stroke (odds ratio [OR] 4.5, 95% confidence interval [CI] 2.1-9.5) and MRI findings of large infarcts (OR 5.0, 95% CI 1.5-15.9), lacunes (OR 2.7, 95% CI 1.2-5.6), and silent brain infarcts (OR 3.5; 95% CI 1.6-7.4). Among those with symptomatic stroke, individuals with AF had larger WMH volumes (0.0137 mL/total intracranial volume [TIV], 95% CI 0.0074-0.0252) compared to those without AF (0.0043 mL/TIV, 95% CI 0.0029-0.0064). There was no association between AF and WMH volumes among those without symptomatic stroke. In addition, AF was associated to CMBs in the frontal lobe.DiscussionAF was associated with a broad range of cerebrovascular pathologies. Further research is needed to establish whether cerebrovascular MRI markers can be added to current treatment guidelines to further personalize anticoagulant treatment in patients with AF and to further characterize the pathogenetic processes underlying the associations between AF and cerebrovascular diseases, as well as dementia.
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| 62. |
- Salvadó, Gemma, et al.
(författare)
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The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals
- 2022
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:7, s. 1383-1395
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3). Results: Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.
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| 63. |
- Samuelsson, Jessica, et al.
(författare)
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Associations between dietary patterns and structural neuroimaging measures of relevance for dementia : Alzheimer’s Association International Conference (AAIC)
- 2022
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Konferensbidrag (refereegranskat)abstract
- Associations between dietary patterns and structural neuroimaging measures of relevance for dementia Jessica Samuelsson, M.S.c¹, Anna Marseglia, PhD2, Olof Lindberg, PhD2, Eric Westman, PhD2, Silke Kern, MD, PhD¹, Felicia Ahlner M.S.c¹, Elisabet Rothenberg, PhD4, Ingmar Skoog, MD, PhD1,3*, Anna Zettergren, PhD¹* 1Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Sweden, 2 Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, 3Department of Psychiatry Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Region Västra Götaland, Mölndal, Sweden, 4Food and Meal Science, Kristianstad University, Kristianstad, Sweden Abstract Background: Diet is one of the lifestyle factors that could influence the risk of developing dementia, but effects of diet on the brain are not fully understood. Investigating associations between dietary patterns and structural neuroimaging measures of relevance for dementia could potentially increase this understanding. Methods: This study includes cross-sectional data from the population-based Gothenburg H70 Birth Cohort Studies based in Sweden, including 610 dementia-free 70-year-olds (born 1944, examined 2014-16) with dietary and magnetic resonance imaging (MRI) data (54 % women). Three dietary patterns were derived with principal component analysis, one labelled Western (e.g., refined cereal products, sweets, savory bakery/fast food), one Mediterranean (e.g., vegetables, fruits, whole grain cereal products) and one Low-fiber and high-alcohol (e.g., red meat/processed red meat, eggs, alcoholic beverages). Magnetic resonance imaging (MRI) measures of cortical thickness, white matter microstructure (based on diffusion tensor imaging), and a small vessel disease score (sum of white matter hyperintensities, lacunes,cerebral microbleeds, perivascular spaces) of relevance for dementia were included. Analyses (linear and ordinal regression models) were adjusted for sex, energy intake, educational level, physical activity level, smoking and body mass index. Results: Results from this study showed a positive association between higher adherence to the Mediterranean dietary pattern and higher white matter microstructural integrity (B 0.077; 95% CI 0.002 – 0.153), and that a higher adherence to the Low-fibre and high-alcohol dietary pattern was negatively associated with total mean cortical thickness (B -0.011; 95% CI -0.019 – -0.003) and an Alzheimer’s disease signature of cortical thickness (mean entorhinal, inferior temporal, middle temporal, and fusiform thickness) (B -0.013; 95% CI -0.024 – -0.001) in the fully adjusted models. No associations were found between the small vessel disease score and the dietary patterns. Nor were there any associations between the western dietary pattern and the MRI measures. Conclusions: The result from this study suggests that there may be an association between diet and dementia-related brain alterations. These findings could be of importance for dementia prevention strategies and for future intervention studies investigating the effect of dietary patterns in relation to dementia incidence.
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| 64. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 65. |
- Schöll, Michael, et al.
(författare)
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Glucose metabolism and PIB binding in carriers of a His163Tyr presenilin 1 mutation
- 2011
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 32:8, s. 1388-1399
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Tidskriftsartikel (refereegranskat)abstract
- Six young related pre-symptomatic carriers of a His 163Tyr mutation in the presenilin 1 gene who will develop early onset familial Alzheimer's disease (eoFAD), and a control group of 23 non-carriers underwent (18)F-fluorodeoxyglucose positron emission tomography (FDG PET). The mutation carriers were followed-up after 2 years. Multivariate analysis showed clear separation of carriers from non-carriers on both occasions, with the right thalamus being the region contributing most to group differentiation. Statistical parametric mapping (SPM) revealed in the carriers non-significantly lower thalamic cerebral glucos metabolism (CMRglc) at baseline and significantly decreased CMRglc in the right thalamus at follow-up. One mutation carrier was followed-up with FDG PET 10 years after baseline and showed reductions in cognition and CMRglc in the posterior cingulate and the frontal cortex. This subject was diagnosed with AD 1 year later and assessed with an additional FDG as well as an (11)C-PIB PET scan 12 years after baseline. Global cortical CMRglc and cognition were distinctly decreased. PIB binding was comparable with sporadic AD patterns but showing slightly higher striatal levels.
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| 66. |
- Seidu, Nazib, et al.
(författare)
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Association of CSF biomarkers with MRI brain changes in Alzheimer's disease
- 2024
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Ingår i: ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING. - 2352-8729. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- The relation between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and magnetic resonance imaging (MRI) measures is poorly understood in cognitively healthy individuals from the general population. Participants' (n = 226) mean age was 70.9 years (SD = 0.4). CSF concentrations of amyloid beta (A beta)1-42, total tau (t-tau), phosphorylated tau (p-tau), neurogranin, and neurofilament light, and volumes of hippocampus, amygdala, total basal forebrain (TBF), and cortical thickness were measured. Linear associations between CSF biomarkers and MRI measures were investigated. In A beta 1-42 positives, higher t-tau and p-tau were associated with smaller hippocampus (P = 0.001 and P = 0.003) and amygdala (P = 0.005 and P = 0.01). In A beta 1-42 negatives, higher t-tau, p-tau, and neurogranin were associated with larger TBF volume (P = 0.001, P = 0.001, and P = 0.01). No associations were observed between the CSF biomarkers and an AD signature score of cortical thickness. AD-specific biomarkers in cognitively healthy 70-year-olds may be related to TBF, hippocampus, and amygdala. Lack of association with cortical thickness might be due to early stage of disease.
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| 67. |
- Shams, Mana, et al.
(författare)
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Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 78:3, s. 1229-1236
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Tidskriftsartikel (refereegranskat)abstract
- Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma.Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels.This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models.No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratios (p<0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers.CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.
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| 68. |
- Simrén, Joel, 1996, et al.
(författare)
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The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease
- 2021
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:7, s. 1145-1156
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. Methods: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. Results: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. Discussion: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.
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| 69. |
- Sjöström, Henrik, et al.
(författare)
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Putaminal T1/T2-weighted ratio is increased in PSP compared to PD and healthy controls, a multi-cohort study
- 2024
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Ingår i: Parkinsonism and Related Disorders. - 1353-8020 .- 1873-5126. ; 121
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Differentiating Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is a common clinical problem. We aimed to apply the T1-/T2-weighted ratio imaging technique, based on standard clinical MRI, to reveal differences in neurodegeneration in three large cohorts. Methods: Three cohorts, with a total of 405 participants (269 PD, 44 PSP, 38 MSA, 54 controls), were combined and T1/T2-weighted ratio image analyses were carried out. A combination of automatic segmentation and atlas-based ROI were used in this study. The cohorts were combined using the ComBat batch correction procedure. Results: Group differences were found in the putamen (p = 0.040), with higher T1/T2-weighted ratio in this region in PSP compared to PD and healthy controls (p-values 0.010 and 0.007 respectively). Using putaminal T1/T2-weighted ratio for diagnostic separation, a fair performance was found in separating PSP from healthy controls, with an area under the receiver operating characteristic curve of 0.701. Conclusion: Different patterns of T1/T2-weighted ratio, reflecting differences in underlying pathophysiology, were found between the groups. Since T1/T2-weighted ratio can be applied to standard clinical MRI sequences to allow more quantitative analyses, this seems to be a promising biomarker for diagnostics and treatment evaluation of parkinsonian disorders for clinical trials.
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| 70. |
- Skillbäck, Tobias, et al.
(författare)
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Sex differences in CSF biomarkers for neurodegeneration and blood-brain barrier integrity.
- 2021
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Ingår i: Alzheimer's & dementia. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (QAlb) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand.Participants were derived from two Swedish samples: the population-based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, QAlb, n = 39252, age 0 to 95). In the population-based study, QAlb and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs). In the clinical cohort, QAlb and NfL sex differences were tested in relation to age.Men had higher QAlb and NfL concentrations and had higher QAlb and NfL concentrations from adolescence throughout life. NfL was not related to WML, but QAlb correlated positively with WMLs.The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.
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