| 1. |
- Ally, M., et al.
(författare)
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Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer's disease
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p-tau)181+231.Methods: Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross-sectional and longitudinal outcomes.Results: Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia.Discussion: Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.
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| 2. |
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| 3. |
- Chong, J. R., et al.
(författare)
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Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of cognitively impaired patients with concomitant cerebral small vessel disease
- 2023
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionPlasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non-dementia cohorts with cerebral small vessel disease (CSVD). However, studies of AD in populations with high prevalence of concomitant CSVD to evaluate associations of brain atrophy, CSVD, and amyloid beta (A beta) burden on plasma NfL are lacking. MethodsAssociations were tested between plasma NfL and brain A beta, medial temporal lobe atrophy (MTA) as well as neuroimaging features of CSVD, including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds. ResultsWe found that participants with either MTA (defined as MTA score >= 2; neurodegeneration [N]+WMH-) or WMH (cut-off for log-transformed WMH volume at 50th percentile; N-WMH+) manifested increased plasma NfL levels. Participants with both pathologies (N+WMH+) showed the highest NfL compared to N+WMH-, N-WMH+, and N-WMH- individuals. DiscussionPlasma NfL has potential utility in stratifying individual and combined contributions of AD pathology and CSVD to cognitive impairment.
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| 4. |
- Coath, W., et al.
(författare)
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Operationalizing the centiloid scale for F-18 florbetapir PET studies on PET/MRI
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONThe Centiloid scale aims to harmonize amyloid beta (A beta) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized tomography (CT) data and are influenced by scanner differences, we investigated the Centiloid transformation with data from Insight 46 acquired with PET/magnetic resonanceimaging (MRI). METHODSWe transformed standardized uptake value ratios (SUVRs) from 432 florbetapir PET/MRI scans processed using whole cerebellum (WC) and white matter (WM) references, with and without partial volume correction. Gaussian-mixture-modelling-derived cutpoints for A beta PET positivity were converted. RESULTSThe Centiloid cutpoint was 14.2 for WC SUVRs. The relationship between WM and WC uptake differed between the calibration and testing datasets, producing implausibly low WM-based Centiloids. Linear adjustment produced a WM-based cutpoint of 18.1. DISCUSSIONTransformation of PET/MRI florbetapir data to Centiloids is valid. However, further understanding of the effects of acquisition or biological factors on the transformation using a WM reference is needed. HIGHLIGHTSCentiloid conversion of amyloid beta positron emission tomography (PET) data aims to standardize results.Centiloid values can be influenced by differences in acquisition.We converted florbetapir PET/magnetic resonance imaging data from a large birth cohort.Whole cerebellum referenced values could be reliably transformed to Centiloids. White matter referenced values may be less generalizable between datasets.
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| 6. |
- Giangrande, C., et al.
(författare)
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Harmonization and standardization of biofluid-based biomarker measurements for AT(N) classification in Alzheimer's disease
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Fluid biomarkers are currently measured in cerebrospinal fluid and blood for Alzheimer's disease diagnosis and are promising targets for drug development and for patients' follow-up in clinical trials. These biomarkers have been grouped in an unbiased research framework, the amyloid (A & beta;), tau, and neurodegeneration (AT[N]) biomarker system to aid patients' early diagnosis and stratification. Metrological approaches relying on mass spectrometry have been used for the development of reference materials and reference measurement procedures. Despite their excellent performances as clinical tools, fluid biomarkers often present an important between-laboratory variation. Standardization efforts were carried out on the biomarkers currently included in the AT(N) classification system, involving the collaboration of national metrology institutes, clinicians, researchers, and in vitro diagnostic providers. This article provides an overview of current activities towards standardization. These reference methods and reference materials may be used for recalibration of immunoassays and the establishment of standardized cutoff values allowing a better stratification of Alzheimer's disease patients. HighlightsThe AT(N) biomarker system allows stratifying AD patients on the basis of biomarker profiles.Fluid biomarker measurements often present an important between-laboratory variation preventing the establishment of standardized cutoff values.Overview on the standardization initiatives involving the fluid biomarkers currently included in the AT(N) framework.
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| 7. |
- Pascoal, Tharick A., et al.
(författare)
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Discriminative accuracy of the A/T/N scheme to identify cognitive impairment due to Alzheimer's disease
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The optimal combination of amyloid-β/tau/neurodegeneration (A/T/N) biomarker profiles for the diagnosis of Alzheimer's disease (AD) dementia is unclear. Methods: We examined the discriminative accuracy of A/T/N combinations assessed with neuroimaging biomarkers for the differentiation of AD from cognitively unimpaired (CU) elderly and non-AD neurodegenerative diseases in the TRIAD, BioFINDER-1 and BioFINDER-2 cohorts (total n = 832) using area under the receiver operating characteristic curves (AUC). Results: For the diagnosis of AD dementia (vs. CU elderly), T biomarkers performed as well as the complete A/T/N system (AUC range: 0.90–0.99). A and T biomarkers in isolation performed as well as the complete A/T/N system in differentiating AD dementia from non-AD neurodegenerative diseases (AUC range; A biomarker: 0.84–1; T biomarker: 0.83–1). Discussion: In diagnostic settings, the use of A or T neuroimaging biomarkers alone can reduce patient burden and medical costs compared with using their combination, without significantly compromising accuracy.
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| 8. |
- Pelak, Victoria S., et al.
(författare)
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Consensus recommendations for clinical assessment tools for the diagnosis of posterior cortical atrophy syndrome from the Atypical AD PIA of ISTAART
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Delay in diagnosis of posterior cortical atrophy (PCA) syndrome is common, and the lack of familiarity with assessment tools for identifying visual cortical dysfunction is a contributing factor. We propose recommendations for the approach to the evaluation of PCA clinical features during the office visit, the neuropsychological evaluation, and the research setting. A recommended screening battery for eye clinics is also proposed. METHODS: Recommendations were developed using results from a web-based survey of members of Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Atypical Alzheimer's Disease Professional Interest Area (PIA), literature review, and consensus by the PCA assessment working party of the Atypical Alzheimer's Disease PIA. RESULTS: Survey results revealed robust agreement for assessment tool preferences for PCA features, and many respondents indicated that they reserve assessment tools for use only when PCA is suspected. For some PCA features, curated tools were preferred over validated battery tools, particularly for the office visit. Consensus recommendations superseded survey preferences for two core cognitive features within the 2017 PCA diagnostic criteria. DISCUSSION: These consensus recommendations provide an evaluation framework for PCA clinical features and can facilitate timely and accurate recognition and diagnosis of PCA. Broader use of these tools should be sought, and development and validation of novel PCA clinical outcome assessments are needed to improve our understanding of atypical AD and other dementias and support the inclusion of those with PCA in treatment trials.
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| 9. |
- Sunde, A. L., et al.
(författare)
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Preanalytical stability of plasma biomarkers for Alzheimer's disease pathology
- 2023
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionPlasma tests have demonstrated high diagnostic accuracy for identifying Alzheimer's disease pathology. To facilitate the transition to clinical utility, we assessed whether plasma storage duration and temperature affect the biomarker concentrations. MethodsPlasma samples from 13 participants were stored at +4 degrees C and +18 degrees C. Concentrations of six biomarkers were measured after 2, 4, 6, 8, 10, and 24 h by single molecule array assays. ResultsPhosphorylated tau 181 (p-tau181), phosphorylated tau 231 (p-tau231), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) concentrations were unchanged both when stored at +4 degrees C and +18 degrees C. Amyloid-beta 40 (A beta 40) and amyloid-beta 42 (A beta 42) concentrations were stable for 24 h at +4 degrees C but declined when stored at +18 degrees C for longer than 6 h. This decline did not affect the A beta 42/A beta 40 ratio. DiscussionPlasma samples can be stored for 24 h at +4 degrees C or +18 degrees C and result in valid assay results for p-tau181, p-tau231, A beta 42/A beta 40 ratio, GFAP, and NfL. HIGHLIGHTSPlasma samples were stored for 24 h at +4 degrees C and +18 degrees C, mimicking clinical practice.Concentrations for Alzheimer's disease biomarkers were measured at six time-points.p-tau181, p-tau231, NfL, and GFAP concentrations were unchanged during the experiment.Storage at +18 degrees C affected A beta 40 and A beta 42 concentrations while storage at +4 degrees C did not. The A beta 42/A beta 40 ratio was unaffected.These plasma tests seem suitable for use in general practice.
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| 10. |
- Tian, Na, et al.
(författare)
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Triglyceride-glucose index, Alzheimer's disease plasma biomarkers, and dementia in older adults : The MIND-China study
- 2023
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - 2352-8729. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Population-based studies have rarely explored the associations of the triglyceride–glucose (TyG) index, a surrogate marker of insulin resistance, with dementia and plasma biomarkers for amyloid beta (Aβ) and neurodegeneration.Methods: This population-based study included 5199 participants (age ≥ 65 years); of these, plasma Aβ, total tau, and neurofilament light chain (NfL) were measured in 1287 persons. Dementia and subtypes were diagnosed following the international criteria. TyG index was calculated as ln(fasting triglyceride(mg/dL) × fasting glucose[mg/dL]/2). Data were analyzed using logistic and general linear regression models.Results: Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were diagnosed in 301, 195, and 95 individuals, respectively. A high TyG index was significantly associated with increased likelihoods of dementia and AD; the significant association with dementia remained among participants without cardiovascular disease or diabetes. In the biomarker subsample, a high TyG index was correlated with elevated plasma Aβ, but not with total tau or NfL.Discussion: High TyG index is associated with dementia, possibly via Aβ pathology.
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