Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults.
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ABSTRACT:
SUBMITTER: He L
PROVIDER: S-EPMC8238930 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Cognition is closely associated with physical function. Although high brain amyloid-? (A?) deposition and neurofilament light chain (NfL) are associated with cognitive and gait speed decline, relationships of combined plasma A? and NfL profiles with cognitive and physical functions in older adults remain unknown. The research aim of this study was to investigate the prospective associations of combined plasma A? and NfL profiles with cognitive and physical functions in older adults. METHODS:Participants (n?=?452, aged 76?±?5?years) who had both plasma A? and NfL data collected from the Multidomain Alzheimer's Preventive Trial (MAPT, May 2008 to April 2016) were included in the current study. These participants were from four MAPT groups (multidomain interventions [physical activity and nutritional counselling, and cognitive training], omega-3 supplementation, multidomain plus omega-3 supplementation and control group) and had received a 3-year intervention, followed by a 2-year observational follow-up. Cognitive function was evaluated as Mini-Mental State Examination and composite cognitive score (CCS, a mean Z-score combining four cognitive tests). Physical function was evaluated as gait speed (4-m usual-pace walk test) and chair-stand time (5-time maximal chair-stand test). Cognitive and physical function data measured at the time of and after blood A? and NfL tests were used for analysis. Participants with plasma A?42/A?40 ratios lower than 0.107 and NfL levels greater than 93.04?pg/ml were classified as A?+ and NfL+. Multivariable regressions and mixed-effects linear models were used for the analysis. RESULTS:At the cross-sectional level, no significant association was found between A?+NfL+ and cognitive or physical function after controlling for age, sex, body mass index, education level and MAPT group. Evaluating longitudinal changes, participants with A?+NfL+ had greater annual declines in the CCS (??=?-?0.11, 95%CI [-?0.17, -?0.05]) and gait speed (??=?-?0.03, 95%CI [-?0.05, -?0.005]). After adjusting for APOE ?4 genotype, A?+NfL+ was associated with a greater decline only in the CCS (??=?-?0.09, 95%CI [-?0.15, -?0.02]). CONCLUSIONS:Combined low plasma A?42/A?40 ratio and high plasma NfL level was associated with greater declines in cognition and gait speed over time, providing further evidence of the links between cognitive and physical function. TRIAL REGISTRATION:www.clinicaltrials.gov [ NCT00672685 ].
| S-EPMC7545881 | biostudies-literature
Project description:ImportanceLittle is known about the association of serum neurofilament light chain (NfL) concentrations and physical activity with the rate of cognitive decline in older adults.ObjectiveTo examine the association of physical activity and NfL concentrations with cognitive decline in older adults over time.Design, setting, and participantsThis cohort study used data from the Chicago Health and Aging Project (CHAP), a population-based cohort study that recruited participants through door-to-door census in 4 Chicago-area communities and collected data between 1993 and 2012 in cycles of 3 years. Participants in CHAP who had 2 or more cognitive function assessments and at least 1 blood sample collected for NfL measurement were selected for inclusion in the current study. Data were analyzed from January to December 2021.ExposuresSelf-reported physical activity (minutes per week) and serum NfL concentration (pg/mL).Main outcomes and measuresAssociations of baseline physical activity and NfL concentrations with changes in global cognitive function over time as evaluated using the East Boston Memory Test for episodic memory, the Symbol Digit Modalities Test for perceptual speed, and the Mini-Mental State Examination. Mixed-effects regression analyses were conducted to examine associations at baseline and longitudinally.ResultsThe study sample included 1158 participants (695 [60%] African American; 728 [63%] female), with a mean (SD) age of 77.4 (6.0) years and a mean educational level of 12.6 (3.5) years. Among participants with high NfL concentrations (>25 pg/mL), those who engaged in medium physical activity (<150 minutes per week) had a 12% slower rate of global cognitive decline (SD units, or β, -0.065; 95% CI, -0.099 to -0.032) and participants who engaged in high physical activity (≥150 minutes per week) had a 36% slower rate of decline (β, -0.048; 95% CI, -0.080 to -0.016) than did participants with low physical activity (no reported participation) (β, -0.075; 95% CI, -0.108 to -0.041). For participants with low NfL concentrations (≤25 pg/mL), those who took part in medium physical activity had 43% slower global cognitive decline (β, -0.025; 95% CI, -0.043 to -0.007) and individuals who participated in high physical activity had 30% slower decline (β, -0.031; 95% CI, -0.048 to -0.014) than did those who participated in low physical activity (β, -0.046; 95% CI, -0.066 to -0.025).Conclusions and relevanceThe findings suggest that physical activity is associated with diminished cognitive decline among older adults with increased serum NfL concentrations. The results support the potential use of blood biomarkers in measuring the benefits of health behaviors, such as physical activity, and early intervention for older adults at risk for cognitive decline.
| S-EPMC8941360 | biostudies-literature
Project description:BackgroundNeurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration.ObjectivesTo determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) and (2) predict future motor or cognitive decline in PD.MethodsSix hundred and fifteen participants with neurodegenerative diseases, including 152 PD and 200 healthy control participants, provided a plasma and/or cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the Kruskal-Wallis rank test. Within PD, cross-sectional associations between NfL and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and Mattis Dementia Rating Scale (DRS-2) scores were assessed by linear regression; longitudinal analyses were performed using linear mixed-effects models and Cox regression.ResultsPlasma and CSF NfL levels correlated substantially (Spearman r = 0.64, P < 0.001); NfL was highest in neurocognitive disorders. PD participants with high plasma NfL were more likely to develop incident cognitive impairment (HR 5.34, P = 0.005).ConclusionsPlasma NfL is a useful prognostic biomarker for PD, predicting clinical conversion to mild cognitive impairment or dementia. © 2021 International Parkinson and Movement Disorder Society.
| S-EPMC8688198 | biostudies-literature
Project description:Evidence suggests that lightly myelinated cortical regions are vulnerable to aging and Alzheimer's disease (AD). However, it remains unknown whether plasma markers of amyloid and neurodegeneration are related to deficits in intracortical myelin content, and whether this relationship, in turn, is associated with altered patterns of resting-state functional connectivity (rs-FC). To shed light into these questions, plasma levels of amyloid-β fragment 1-42 (Aβ1-42) and neurofilament light chain (NfL) were measured using ultra-sensitive single-molecule array (Simoa) assays, and the intracortical myelin content was estimated with the ratio T1-weigthed/T2-weighted (T1w/T2w) in 133 cognitively normal older adults. We assessed: (i) whether plasma Aβ1-42 and/or NfL levels were associated with intracortical myelin content at different cortical depths and (ii) whether cortical regions showing myelin reductions also exhibited altered rs-FC patterns. Surface-based multiple regression analyses revealed that lower plasma Aβ1-42 and higher plasma NfL were associated with lower myelin content in temporo-parietal-occipital regions and the insular cortex, respectively. Whereas the association with Aβ1-42 decreased with depth, the NfL-myelin relationship was most evident in the innermost layer. Older individuals with higher plasma NfL levels also exhibited altered rs-FC between the insula and medial orbitofrontal cortex. Together, these findings establish a link between plasma markers of amyloid/neurodegeneration and intracortical myelin content in cognitively normal older adults, and support the role of plasma NfL in boosting aberrant FC patterns of the insular cortex, a central brain hub highly vulnerable to aging and neurodegeneration.
| S-EPMC9247578 | biostudies-literature
Project description:Plasma neurofilament light (NfL) is a marker for neurodegenerative diseases. Few studies have examined the association of NfL with middle-aged changes in cognitive performance, and no studies have examined differential NfL effects by race. Using data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 625, Agev1: 30-66 y, 41.6% male, 56.3% African American, 27.8% below poverty), we investigated the associations of initial NfL levels and annualized change with cognitive performance over time in global mental status, verbal and visual memory, fluency, attention, and executive function. We used ordinary least squares and mixed-effects regressions stratified by race, while exploring differential associations by age group, sex, and poverty status. Over a mean follow-up of 4.3 years, we found initial NfL level was associated with a faster decline on normalized mental status scores in Whites only and in those >50 years old. Annualized increase in NfL was associated with a greater decline in verbal fluency in men. In other exploratory analyses, annualized increase in NfL was associated with a slower decline in verbal memory among individuals living above poverty; in the older group (>50 years), first-visit NfL was linked with better performance at baseline in global mental status and verbal memory. In summary, first-visit NfL was primarily associated with the global mental status decline among Whites, while exhibiting inconsistent relationships in some exploratory analyses. Plasma NfL levels can be detected and quantified in non-demented middle-aged adults and changes can be analyzed over time. More longitudinal studies are needed to address the clinical utility of this biomarker for early cognitive defects.
| S-EPMC8380245 | biostudies-literature
Project description:People with Down syndrome (DS) are at high risk of developing Alzheimer disease (AD) with aging. The diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. Plasma neurofilament light chain (NfL) is one of the established biomarkers of AD, suggesting that it may be useful as an indicator of dementia in DS patients. The aims of this study were: 1) to examine whether plasma levels of NfL in DS patients are correlated with decreased adaptive behavior scores one year after sample collection, and 2) to compare plasma levels of NfL in adults with DS and an age-matched healthy control population. In this study, plasma levels of NfL in 24 patients with DS and 24 control participants were measured by the single-molecule immunoarray (Simoa) method. We observed significantly increased plasma NfL levels in the DS compared with the control group. There was a significant correlation between age and levels of plasma NfL in both groups. This age-dependent elevation was steeper in the DS compared with the control group. Moreover, elevated plasma NfL was associated with decreased adaptive behavior scores one year later, after age-adjustment. Previously reported blood-based biomarkers available in Simoa for DS, plasma total tau and phosphorylated tau, were not significantly correlated with the annual decrement of adaptive behavior scores after age-adjustment. These results suggest that plasma NfL has the potential to serve as an objective biomarker to predict dementia in adult DS patients.
| S-EPMC6450630 | biostudies-literature
Project description:Neurofilament light chain (NfL) is a novel biomarker of neurodegenerative diseases. It is detectable in the peripheral blood, allowing low-invasive assessment of early signs of neurodegeneration. The level of NfL gradually increases with age; however, what other factors affect it remains unclear. The present study examined the association between blood NfL level and renal function among healthy participants undergoing a health check (n = 43, serum NfL) and patients with diabetes mellitus (n = 188, plasma NfL). All participants were 60 years of age or older; none were diagnosed with dementia. In each group, levels of blood NfL and serum creatinine significantly correlated (coefficient r = 0.50, 0.56). These associations remained statistically significant even after adjustment for age, sex, and body mass index. These findings indicate that blood NfL level might be partially affected by renal function. We recommend measuring renal function for a more precise evaluation of neuroaxonal damage, in particular, among older adults.
| S-EPMC7683708 | biostudies-literature
Project description:ObjectiveTo evaluate cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL) levels in genetic frontotemporal dementia (FTD) as a potential biomarker in the presymptomatic stage and during the conversion into the symptomatic stage. Additionally, to correlate NfL levels to clinical and neuroimaging parameters.MethodsIn this multicenter case-control study, we investigated CSF NfL in 174 subjects (48 controls, 40 presymptomatic carriers and 86 patients with microtubule-associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72) mutations), and serum NfL in 118 subjects (39 controls, 44 presymptomatic carriers, 35 patients). In 55 subjects both CSF and serum was determined. In two subjects CSF was available before and after symptom onset (converters). Additionally, NfL levels were correlated with clinical parameters, survival, and regional brain atrophy.ResultsCSF NfL levels in patients (median 6762 pg/mL, interquartile range 3186-9309 pg/mL) were strongly elevated compared with presymptomatic carriers (804 pg/mL, 627-1173 pg/mL, P < 0.001), resulting in a good diagnostic performance to discriminate both groups. Serum NfL correlated highly with CSF NfL (r s = 0.87, P < 0.001) and was similarly elevated in patients. Longitudinal samples in the converters showed a three- to fourfold increase in CSF NfL after disease onset. Additionally, NfL levels in patients correlated with disease severity, brain atrophy, annualized brain atrophy rate and survival.InterpretationNfL in both serum and CSF has the potential to serve as a biomarker for clinical disease onset and has a prognostic value in genetic FTD.
| S-EPMC4999594 | biostudies-literature
Project description:CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-?, are increasingly being used to define and stage Alzheimer's disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer's disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-?40 and amyloid-?42 were measured using the Simoa NF-light® and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer's disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE ?4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer's disease dementia. A log2 higher baseline amyloid-?42 plasma level was associated with a lower risk of developing all-cause or Alzheimer's disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P?<?0.0001] and 0.59 (95% CI, 0.43-0.79; P?=?0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38-1.83); P?<?0.0001] or Alzheimer's disease [adjusted HR 1.50 (95% CI, 1.26-1.78); P?<?0.0001]. Combining the lowest quartile group of amyloid-?42 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3-40.4); P?<?0.002] and with Alzheimer's disease [adjusted HR 15.7 (95% CI, 2.1-117.4); P?<?0.0001], compared to the highest quartile group of amyloid-?42 and lowest of NfL. Total-tau and amyloid-?40 levels were not associated with all-cause or Alzheimer's disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer's disease compared to those who remained dementia-free (P?<?0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer's disease diagnosis. Amyloid-?42 levels began to decrease in Alzheimer's disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-?42 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer's disease dementia. These data indicate that plasma NfL and amyloid-?42 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer's disease dementia.
| S-EPMC7174054 | biostudies-literature
Project description:Plasma neurofilament light (NFL) has been proposed as a blood-based biomarker for neurodegeneration in Alzheimer's disease (AD) and parkinsonian disorders. However, the relationship between plasma NFL and cognitive decline in dementia due to Parkinson's disease (PD) remains to be elucidated. In this research, 119 AD, 56 mild cognitive impairment (MCI), 26 non-demented PD (PDND), and 23 Parkinson's disease dementia (PDD) patients, as well as 59 cognitively healthy controls (HC) were recruited. Each subject underwent a battery of neuropsychological testing. Plasma NFL levels were measured in duplicate using an NF-Light assay and transferred onto the Simoa platform with a home-brew kit. Plasma NFL was significantly increased in the AD group, compared with the control, MCI, PDND, and PDD groups. Plasma NFL was significantly higher in the PDD group, compared with the PDND group. High plasma NFL correlated with poor cognition in AD and PD, but not with motor symptoms in PD. Plasma NFL may represent a biomarker of cognitive decline in AD and PD, with more specificity for AD.
| S-EPMC6255914 | biostudies-literature