Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community‐based sample of 70‐year‐olds

Dittrich, Anna; Ashton, Nicholas J.; Zetterberg, Henrik; Blennow, Kaj; Simrén, Joel; Geiger, Fiona; Zettergren, Anna; Shams, Sara; Machado, Alejandra; Westman, Eric; Schöll, Michael; Skoog, Ingmar; Kern, Silke

doi:10.1002/dad2.12295

Cited by 14 publications

(23 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 Dementia had an estimated global prevalence of 57 million people in 2019, a number expected to increase to 153 million by 2050. 1 CKD has previously been associated with blood-based biomarkers of neurodegeneration (phosphorylated tau [p-tau], amyloid beta 42/40(Aβ42/40), and neurofilament light protein [NfL]) [5][6][7][8][9] and different neurodegenerative conditions including dementia 10 and polyneuropathy. 11 This association has previously been examined in the clinical context of different patient groups, including patients from memory clinics.…”

Section: Discussionmentioning

confidence: 99%

“…Some authors suggest that CKD and kidney function could alter a biomarkers' normal reference range and should be considered when used in clinical screening and diagnosis in cognitively healthy populations or in clinical studies of neurodegeneration. 6,7,18,19 Plasma neurofilament light protein (P-NfL) is a promising biomarker of neurodegeneration for use in a primary care setting because it is analyzed from blood and not CSF. P-NfL segregates depression from dementia in older individuals, and while only mildly elevated in patients with AD, it is an efficient marker for ruling out underlying neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23] Studies on the influence of several comorbidities and different blood-based biomarkers have reported an influence of kidney function on P-NfL. 6,7,9 However, studies specifically focused on the interaction between kidney function and different neurodegenerative markers in a community-based setting of older individuals with CKD and normal kidney function are currently few. The Alzheimer Association has specifically highlighted the need for studies on the influence of kidney disease on the diagnostic performance of P-NfL as one of the top research priorities in its recent statement paper on the use of blood-based biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“…25 The mean cortical thickness and mean lateral ventricular and hippocampal volumes were quantified using FreeSurfer 6.0.0 through the TheHiveDB, 38 and the mean volume between the left and right sides was calculated for ventricles and hippocampus. 6 Total white matter lesion volumes were measured using the open-source segmentation toolbox LST 2.0.15 implemented in the SPM software as previously described. 39 All volumes were normalized by ratio to total intracranial volume, as previously described.…”

Section: Mrimentioning

confidence: 99%

See 3 more Smart Citations

Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background and objectives:Studies associate chronic kidney disease (CKD) with neurodegeneration. This study investigated the relation between kidney function, blood, cerebrospinal fluid (CSF), and structural brain MRI markers of neurodegeneration, in a sample including individuals with and without CKD.Methods: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 CSF collected. The primary endpoint of the present study was to determine any association between CKD and P-NfL. Secondary endpoints included cross-sectional associations between CKD, eGFR and cerebrospinal fluid (CSF)- and MRI-derived markers of neurodegeneration and Alzheimer’s disease (AD) pathology (MRI: cortical thickness, hippocampal volume, lateral ventricle volume, white matter lesion volume; CSF: β-amyloid (Aβ) 42, Aβ42/40, Aβ42/p-tau, t-tau, p-tau, 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.Results: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 cerebrospinal fluid (CSF) were analysed in 313 participants. 558 individuals returned for a re-examination of eGFR (75% response rate, age 76 (76; 77), 48% males, 76 new cases of CKD). Participants with CKD had higher P-NfL levels than those with normal kidney function (median; 18.8 versus 14.0 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; 2.08 (1.14: 4.50)).Discussion: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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Mrimentioning

confidence: 99%

See 2 more Smart Citations

Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Details of CSF sampling and analyses are provided in Rydberg Sterner et al [19][20][21] . Plasma NFL concentration was measured at the Clinical Neurochemistry Laboratory, University of Gothenburg (Mölndal, Sweden) using the NF-Light Advantage kit on a Simoa HD-1 instrument (Quanterix, Billerica, MA, USA) 22,23 .…”

Section: Gothenburg H70 Birth Cohortmentioning

confidence: 99%

Assessing the clinical application of deep-learning-derived CT volumetric measures in neurodegenerative disease diagnostics

Srikrishna

Ashton

Moscoso

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Existing bio fluid and imaging biomarkers used in research and clinical diagnostics of neurodegenerative diseases are often expensive or invasive and are mainly available in specialised care centres. CT is an affordable and widely available imaging modality predominantly used to evaluate structural abnormalities, but not for the volumetric quantification of neurodegeneration. Previously, we developed a deep learning model trained on MRI segmentations from individuals with paired CT and MR scans, which achieved high accuracy and robust tissue classification based on brain CT images. Purpose: To explore the diagnostic utility of deep-learning-derived CT-based atrophy measures and study their association with relevant cognitive, biochemical, and other imaging markers of neurodegenerative diseases. Materials and methods: In this retrospective study, we analysed 917 CT and 744 MR scans from cognitively healthy participants of the Gothenburg H70 Birth Cohort (70.4 ± 2.6 years) and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore (73 Alzheimer's disease, 20 vascular dementia, 22 cognitively normal; 74.0 ± 8.2 years). We tested associations between six CT-derived volumetric measures with clinical diagnosis, fluid and imaging biomarkers, and cognition. Results: In the Memory Clinic Cohort, deep-learning-derived CT-based atrophy measures differentiated cognitively healthy individuals from Alzheimers disease (AUC 0.88; 95% CI: 0.79-0.96) and vascular dementia (AUC 0.91; 95% CI: 0.81-1.00) patients with high accuracy levels comparable to MR-derived measures. Additionally, CT-based measures distinguished early, prodromal Alzheimers disease (AUC= 0.73, 95% CI: 0.62, 0.85) and prodromal vascular dementia patients from healthy individuals (CT-GM: AUC= 0.7, 95% CI: 0.51, 0.81). CT-derived volumes were significantly associated with measures of cognition and biochemical markers of neurodegeneration, notably plasma-derived neurofilament light (ρ=-0.43, p <0.001, in the Memory Clinic Cohort). Conclusion: Our findings provide strong evidence for the potential of deep-learning-derived CT-based atrophy measures in aiding neurodegenerative disease diagnostics in primary care settings.

show abstract

CT‐based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration

Srikrishna,

Ashton,

Moscoso

et al. 2023

Alzheimer's & Dementia

Self Cite

View full text Add to dashboard Cite

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.HIGHLIGHTS Computed 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.

show abstract

Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community‐based sample of 70‐year‐olds

Cited by 14 publications

References 47 publications

Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration

Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration

Assessing the clinical application of deep-learning-derived CT volumetric measures in neurodegenerative disease diagnostics

CT‐based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration

Contact Info

Product

Resources

About