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- Dittrich, Anna, 1972, et al.
(författare)
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Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration: The H70 Birth Cohort Study in Gothenburg.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 101:3, s. e277-e288
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Tidskriftsartikel (refereegranskat)abstract
- Studies associate chronic kidney disease (CKD) with neurodegeneration. This study investigated the relationship between kidney function, blood, CSF, and structural brain MRI markers of neurodegeneration in a sample including individuals with and without CKD.Participants from the Gothenburg H70 Birth Cohort Study, with data on plasma neurofilament light (P-NfL), estimated glomerular filtration rate (eGFR), and structural brain MRI were included. Participants were invited to also have the CSF collected. The primary endpoint of this study was to determine any association between CKD and P-NfL. Secondary endpoints included cross-sectional associations between CKD, eGFR, and CSF-derived and MRI-derived markers of neurodegeneration and Alzheimer disease (AD) pathology (MRI: cortical thickness, hippocampal volume, lateral ventricle volume, and white matter lesion volume; CSF: β-amyloid (Aβ) 42, Aβ42/40, Aβ42/p-tau, t-tau, p-tau, and NfL). Participants with P-NfL and eGFR at baseline were re-examined on eGFR, 5.5 (5.3-6.1) years (median; IQR) after the first visit, and the predictive value of P-NfL levels on incident CKD was estimated longitudinally, using a Cox proportional hazards model.We included 744 participants, 668 without CKD (age 71 [70-71] years, 50% males) and 76 with CKD (age 71 [70-71] years, 39% males). Biomarkers from the CSF were analyzed in 313 participants. A total of 558 individuals returned for a re-examination of eGFR (75% response rate, age 76 [76; 77] years, 48% males, 76 new cases of CKD). Participants with CKD had higher P-NfL levels than those with normal kidney function (median; 18.8 vs 14.1 pg/mL, p < 0.001), while MRI and CSF markers were similar between the groups. P-NfL was independently associated with CKD after adjustment for confounding variables, including hypertension and diabetes (OR; 3.231, p < 0.001), in a logistic regression model. eGFR and CSF Aβ 42/40: R = 0.23, p = 0.004 correlated in participants with Aβ42 pathology. P-NfL levels in the highest quartile were associated with incident CKD at follow-up (HR; 2.39 [1.21: 4.72]).In a community-based cohort of 70-year olds, P-NfL was associated with both prevalent and incident CKD, while CSF and/or imaging measures did not differ by CKD status. Participants with CKD and dementia presented similar levels of P-NfL.
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| 2. |
- Dittrich, Anna, 1972, et al.
(författare)
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Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community-based sample of 70-year-olds
- 2022
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light protein (NfL) in cerebrospinal fluid (CSF) and plasma (P) are suggested to be interchangeable markers of neurodegeneration. However, evidence is scarce from community-based samples. NfL was examined in a small-scale sample of 287 individuals from the Gothenburg H70 Birth cohort 1944 study, using linear models in relation to CSF and magnetic resonance imaging (MRI) biomarker evidence of neurodegeneration. CSF-NfL and P-NfL present distinct associations with biomarker evidence of Alzheimer's disease (AD) pathology and neurodegeneration. P-NfL was associated with several markers that are characteristic of AD, including smaller hippocampal volumes, amyloid beta (A beta)(42), A beta(42/40), and A beta(42)/t-tau (total tau). CSF-NfL demonstrated associations with measures of synaptic and neurodegeneration, including t-tau, phosphorylated tau (p-tau), and neurogranin. Our findings suggest that P-NfL and CSF-NfL may exert different effects on markers of neurodegeneration in a small-scale community-based sample of 70-year-olds.
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| 3. |
- Srikrishna, Meera, et al.
(författare)
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CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 20:1, s. 629-640
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONCranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep-learning-based model that produced accurate and robust cranial CT tissue classification.MATERIALS AND METHODSWe analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT-based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition.RESULTSCTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR-based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration.DISCUSSIONThese findings suggest the potential future use of CT-based volumetric measures as an informative first-line examination tool for neurodegenerative disease diagnostics after further validation.HIGHLIGHTSComputed tomography (CT)-based volumetric measures can distinguish between patients with neurodegenerative disease and healthy controls, as well as between patients with prodromal dementia and controls.CT-based volumetric measures associate well with relevant cognitive, biochemical, and neuroimaging markers of neurodegenerative diseases.Model performance, in terms of brain tissue classification, was consistent across two cohorts of diverse nature.Intermodality agreement between our automated CT-based and established magnetic resonance (MR)-based image segmentations was stronger than the agreement between visual CT and MR imaging assessment.
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