scholarly journals Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer’s Disease in the FIT-AD Trial

2021 ◽  
pp. 1-11
Author(s):  
Danni Li ◽  
Lin Zhang ◽  
Nathaniel W. Nelson ◽  
Michelle M. Mielke ◽  
Fang Yu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Daily Living ◽  
Short Term ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Linear Mixed Effects ◽  
Future Studies ◽  
Rate Of Decline ◽  
And Function

Background: Utilities of blood-based biomarkers in Alzheimer’s disease (AD) clinical trials remain unknown. Objective: To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial. Methods: Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes. Results: Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of –0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of –0.04638 [0.003], p = 0.01635; standardized estimate of –0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of –0.01492, p = 0.01082). Conclusion: This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.

scholarly journals Plasma P-tau 181, P-tau 217 and Other Blood-Based Alzheimer's Disease Biomarkers in a Multi-Ethnic, Community Study

2020 ◽  
Author(s):  
Adam M. Brickman ◽  
Jennifer J Manly ◽  
Lawrence Honig ◽  
Danurys Sanchez ◽  
Dolly Reyes-Dumeyer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ethnic Community ◽  
Community Study ◽  
Community Studies ◽  
Operating Characteristics ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Clinical Diagnoses ◽  
Washington Heights

Introduction. Blood-based Alzheimer's disease (AD) biomarkers provide opportunities for community studies and across ethnic groups. We investigated blood biomarker concentrations in the Washington Heights, Inwood, Columbia Aging Project (WHICAP), a multi-ethnic community study of aging and dementia. Methods. We measured plasma Aβ40, Aβ42,T-tau, P-tau181 and P-tau217, and neurofilament light chain (NfL) in 113 autopsied participants, (29% with high AD neuropathological changes) and in 300 clinically evaluated individuals (42% with clinical AD). Receiver operating characteristics were used to evaluate each biomarker. We also investigated biomarkers as predictors of incident clinical AD. Results. P-tau181, P-tau217 and NfL concentrations were elevated in pathologically and clinically diagnosed AD. Decreased Aβ42/Aβ40 ratio and increased P-tau217 and P-tau181 were associated with subsequent AD diagnosis. Discussion. Blood-based AD biomarker concentrations are associated with pathological and clinical diagnoses and can predict future development of clinical AD, providing evidence that they can be incorporated into multi-ethnic, community-based studies.

scholarly journals Tracking neurodegeneration in frontotemporal dementia and Alzheimer’s disease: A comparative study of plasma tau and neurofilament light chain

2020 ◽  
Vol 16 (S5) ◽  
Author(s):  
Ignacio Illán‐Gala ◽  
Alberto Lleó ◽  
Anna M. Karydas ◽  
Adam M. Staffaroni ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Comparative Study ◽  
Frontotemporal Dementia ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals ASSOCIATION OF VASCULAR RISK AND ALZHEIMER’S DISEASE PATHOLOGY WITH NEURODEGENERATION AND COGNITIVE DECLINE

2021 ◽  
Author(s):  
João Pedro Ferrari- Souza ◽  
Wagner Brum ◽  
Lucas Hauschild ◽  
Lucas Da Ros ◽  
Pâmela Lukasewicz Ferreira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Mixed Effects Models ◽  
Vascular Risk ◽  
Clinical Progression ◽  
Neurofilament Light ◽  
Linear Mixed Effects Models ◽  
Linear Mixed Effects

Background: It is not fully understood how vascular risk factors (VRFs) are associated with Alzheimer’s disease (AD) pathology to promote neurodegeneration and cognitive decline. Objective: Investigate whether VRF burden synergistically interacts with AD pathology to accelerate neurodegeneration and cognitive decline in cognitively unimpaired (CU) individuals. Methods: We assessed 503 CU participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Individuals were dichotomized as having an elevated VRF burden if ≥ 2 VRFs (V+) and as presenting biological AD if CSF p-tau181 ≥ 24 pg/mL and CSF Aβ1-42 ≤ 976.6 pg/mL [(AT)+]. Neurodegeneration was assessed with plasma neurofilament light (NfL) and cognition with the modified version of the Preclinical Alzheimer’s Cognitive Composite. Results: Linear mixed-effects models demonstrated that an elevated VRF burden interacted with AD pathology to promote higher rates of neurodegeneration (β=5.68, p=.005) and cognitive decline (β=- 0.43, p=.019). Survival analysis demonstrated that only (AT)+V+ individuals had a significantly greater risk of clinical progression to cognitive impairment (adjusted Hazard Ratio=3.5, p <.001). Conclusion: Our results suggest that VRF burden and AD pathology synergistically lead to neurodegeneration and cognitive decline, favoring the onset of cognitive impairment. These findings support that the clinical evaluation of VRF burden might improve the clinical assessment especially of subjects at higher risk for developing cognitive impairment.

scholarly journals Plasma tau and neurofilament light in frontotemporal lobar degeneration and Alzheimer's disease

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011226
Author(s):  
Ignacio Illán-Gala ◽  
Alberto Lleo ◽  
Anna Karydas ◽  
Adam M. Staffaroni ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Severity ◽  
Cortical Thickness ◽  
Frontotemporal Lobar Degeneration ◽  
Amyloid Pet ◽  
Class Iii ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T Tau

ObjectiveTo test the hypothesis that plasma total tau (t-tau) and neurofilament light chain (NfL) concentrations may have a differential role in the study of frontotemporal lobar degeneration syndromes (FTLD-S) and clinically-diagnosed Alzheimer's disease (AD-S), we determined their diagnostic and prognostic value in FTLD-S and AD-S and their sensitivity to pathologic diagnoses.MethodsWe measured plasma t-tau and NfL with the Simoa platform in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-Tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD) and 98 participants with amyloid PET. We compared cross-sectional and longitudinal biomarker concentrations between groups, their correlation with clinical measures of disease severity, progression and survival and cortical thickness.ResultsPlasma NfL, but not plasma t-tau discriminated FTLD-S from HC and AD-S from HC. Both plasma NfL and t-tau were poor discriminators between FLTD-S and AD-S. In pathology confirmed cases, plasma NfL was higher in FTLD than AD and in FTLD-TDP compared to FTLD-Tau, after accounting for age and disease severity. Plasma NfL, but not plasma t-tau, predicted clinical decline and survival and correlated with regional cortical thickness in both FTLD-S and AD-S. The combination of plasma NfL with plasma t-tau did not outperform plasma NfL alone.ConclusionsPlasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S.Classification of evidenceThis study provides Class III evidence that plasma NfL has superior diagnostic and prognostic performance than plasma t-tau in FTLD and AD.

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