| 1. |
- Baldacci, Filippo, et al.
(författare)
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Two-level diagnostic classification using cerebrospinal fluid YKL-40 in Alzheimer's disease.
- 2017
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 13:9, s. 993-1003
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) YKL-40 in discriminating (1) clinical Alzheimer's disease (AD) from cognitively healthy controls (HCs) and frontotemporal dementia (FTD) (level I) and (2) patients stratified by different pathophysiological profiles from HCs and FTD following a novel unbiased/descriptive categorization based on CSF biomarkers, independent of cognitive impairment severity (level II).YKL-40 was compared among HCs (n=21), mild cognitive impairment (n=41), AD (n=35), and FTD (n=9) (level I) and among HCs (n=21), AD pathophysiology (tau and amyloid-β) negative (n=15), tau positive (n=15), amyloid-β positive (n=13), AD pathophysiology positive (n=33), and FTD (n=9) (level II).Level I: YKL-40 discriminated AD from HC and FTD (area under the receiver operating characteristic curves [AUROCs]=0.69, 0.71). Level II: YKL-40 discriminated tau-positive individuals and AD pathophysiology-positive individuals from HC, AD pathophysiology-positive patients from FTD (AUROCs=0.76, 0.72, 0.73).YKL-40 demonstrates fair performance in distinguishing tau-positive patients from HCs, suggesting it may aid clinical diagnosis and support a biomarker-guided pathophysiological stratification.
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| 2. |
- Blennow, Kaj, 1958, et al.
(författare)
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Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease.
- 2015
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 11:1, s. 58-69
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Tidskriftsartikel (refereegranskat)abstract
- Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD.
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| 3. |
- Bollack, Ariane, et al.
(författare)
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Investigating reliable amyloid accumulation in Centiloids : Results from the AMYPAD Prognostic and Natural History Study
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:5, s. 3429-3441
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: To support clinical trial designs focused on early interventions, our study determined reliable early amyloid-β (Aβ) accumulation based on Centiloids (CL) in pre-dementia populations. METHODS: A total of 1032 participants from the Amyloid Imaging to Prevent Alzheimer's Disease–Prognostic and Natural History Study (AMYPAD-PNHS) and Insight46 who underwent [18F]flutemetamol, [18F]florbetaben or [18F]florbetapir amyloid-PET were included. A normative strategy was used to define reliable accumulation by estimating the 95th percentile of longitudinal measurements in sub-populations (NPNHS = 101/750, NInsight46 = 35/382) expected to remain stable over time. The baseline CL threshold that optimally predicts future accumulation was investigated using precision-recall analyses. Accumulation rates were examined using linear mixed-effect models. RESULTS: Reliable accumulation in the PNHS was estimated to occur at >3.0 CL/year. Baseline CL of 16 [12,19] best predicted future Aβ-accumulators. Rates of amyloid accumulation were tracer-independent, lower for APOE ε4 non-carriers, and for subjects with higher levels of education. DISCUSSION: Our results support a 12–20 CL window for inclusion into early secondary prevention studies. Reliable accumulation definition warrants further investigations.
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| 4. |
- Bradley, Patrick, et al.
(författare)
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Taking stock: A multistakeholder perspective on improving the delivery of care and the development of treatments for Alzheimer's disease.
- 2015
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 11:4, s. 455-461
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Tidskriftsartikel (refereegranskat)abstract
- Health-care stakeholders increasingly recognize that the scientific and economic challenges associated with Alzheimer's disease (AD) are simply too great for individual stakeholder groups to address solely from within their own silos. In the necessary spirit of collaboration, we present in this perspective a set of multicountry multistakeholder recommendations to improve the organization of existing AD and dementia care and the development of new treatments. In brief, the five recommendations are (1) health-care systems must make choices regarding the patient populations to be diagnosed and treated, (2) health-care systems should use an evidence-based standard of care, (3) increased collaboration between public and private institutions is needed to enhance research, (4) reimbursement end points need to be agreed on and validated, and (5) innovative business models should be used to spur the introduction of new medicines.
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| 5. |
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| 6. |
- Festari, Cristina, et al.
(författare)
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European consensus for the diagnosis of MCI and mild dementia : Preparatory phase
- 2023
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:5, s. 1729-1741
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. Methods: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. Results: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). Discussion: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers’ use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. Highlights: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.
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| 7. |
- Hampel, Harald, et al.
(författare)
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Alzheimer's disease biomarker-guided diagnostic workflow using the added value of six combined cerebrospinal fluid candidates: Aβ1-42, total-tau, phosphorylated-tau, NFL, neurogranin, and YKL-40.
- 2018
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 14:4, s. 492-501
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Tidskriftsartikel (refereegranskat)abstract
- The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n=41), Alzheimer's disease dementia (ADD; n=35), frontotemporal dementia (FTD; n=9), and cognitively healthy controls (HC; n=21), using 10-fold cross-validation.The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified.The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid β peptide + phosphorylated tau+neurofilament light chain] for distinguishing between ADD patients and HC (AUROC=0.86), t-tau for distinguishing between ADD and FTD patients (AUROC=0.82), and t-tau for distinguishing between FTD patients and HC (AUROC=0.78).Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor.
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| 8. |
- Leyhe, Thomas, et al.
(författare)
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A common challenge in older adults: Classification, overlap, and therapy of depression and dementia.
- 2017
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 13:1, s. 59-71
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Tidskriftsartikel (refereegranskat)abstract
- Late-life depression is frequently associated with cognitive impairment. Depressive symptoms are often associated with or even precede a dementia syndrome. Moreover, depressive disorders increase the risk of persistence for mild cognitive impairment and dementia. Here, we present both the current state of evidence and future perspectives regarding the integration and value of clinical assessments, neuropsychological, neurochemical, and neuroimaging biomarkers for the etiological classification of the dementia versus the depression syndrome and for the prognosis of depression relating to dementia risk. Finally, we summarize the existing evidence for both pharmacotherapy and psychotherapy of depression in demented patients. There is an urgent need for large-scale collaborative research to elucidate the role and interplay of clinical and biological features in elderly individuals with depressive disorders who are at elevated risk for developing dementia. To overcome barriers for successful drug development, we propose the introduction of the precision medicine paradigm to this research field.
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| 9. |
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| 10. |
- Vergallo, Andrea, et al.
(författare)
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Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers.
- 2018
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 14:12, s. 1623-1631
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Tidskriftsartikel (refereegranskat)abstract
- Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls.The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD).We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations.Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.
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