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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- Piras, F, et al.
(författare)
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White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group
- 2021
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1, s. 173-
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Tidskriftsartikel (refereegranskat)abstract
- Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
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- Assogna, M., et al.
(författare)
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Association of Choroid Plexus Volume With Serum Biomarkers, Clinical Features, and Disease Severity in Patients With Frontotemporal Lobar Degeneration Spectrum
- 2023
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Ingår i: NEUROLOGY. - 0028-3878. ; 101:12
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Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectivesChoroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study, we investigated ChP volume in a large cohort of patients with frontotemporal lobar degeneration (FTLD) spectrum to explore a possible link between ChP volume and other disease-specific biomarkers.MethodsParticipants included patients meeting clinical criteria for a probable syndrome in the FTLD spectrum. Structural brain MRI imaging, serum neurofilament light (NfL), serum phosphorylated-Tau181 (p-Tau181), and cognitive and behavioral data were collected. MRI ChP volumes were obtained from an ad-hoc segmentation model based on a Gaussian Mixture Models algorithm.ResultsThree-hundred and sixteen patients within FTLD spectrum were included in this study, specifically 135 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD), 75 primary progressive aphasia, 46 progressive supranuclear palsy, and 60 corticobasal syndrome. In addition, 82 age-matched healthy participants were recruited as controls (HCs). ChP volume was significantly larger in patients with FTLD compared with HC, across the clinical subtype. Moreover, we found a significant difference in ChP volume between HC and patients stratified for disease-severity based on CDR plus NACC FTLD, including patients at very early stage of the disease. Interestingly, ChP volume correlated with serum NfL, cognitive/behavioral deficits, and with patterns of cortical atrophy. Finally, ChP volume seemed to discriminate HC from patients with FTLD better than other previously identified brain structure volumes.DiscussionConsidering the clinical, pathologic, and genetic heterogeneity of the disease, ChP could represent a potential biomarker across the FTLD spectrum, especially at the early stage of disease. Further longitudinal studies are needed to establish its role in disease onset and progression.Classification of EvidenceThis study provides Class III evidence that choroid plexus volume, as measured on MRI scan, can assist in differentiating patients with FTLD from healthy controls and in characterizing disease severity.
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| 8. |
- Bruin, WB, et al.
(författare)
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Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters
- 2020
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 342-
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Tidskriftsartikel (refereegranskat)abstract
- No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
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