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Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults.

ABSTRACT: Neurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer's Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and composite cognitive score (CCS) over a 4-year period. Plasma NfL was measured at the first or the second year of the MAPT. Mixed-effects linear models were performed to evaluate cross-sectional and longitudinal associations. In the whole population, higher plasma NfL was cross-sectionally associated with lower cognitive functions (MMSE: β = - 0.007, 95% CI [- 0.013, - 0.001]; CCS: β = - 0.003, 95% CI [- 0.006, - 0.001]). In adults with MCI, but not NC, higher plasma NfL was associated with lower CCS at the cross-sectional level (β = - 0.003, 95% CI [- 0.005, - 0.0002]). The upper quartile NfL group further demonstrated more over time decline in CCS (β = - 0.07, 95% CI [- 0.12, - 0.01]) under the MCI status. Plasma NfL can be a promising biomarker of progressive cognition decline in older adults with MCI.

SUBMITTER: He L

PROVIDER: S-EPMC8238930 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults.

He Lingxiao L Morley John E JE Aggarwal Geetika G Nguyen Andrew D AD Vellas Bruno B de Souto Barreto Philipe P

Scientific reports 20210628 1

Neurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer's Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and c ...[more]

PMID: 34183688

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Project description:BackgroundCognition is closely associated with physical function. Although high brain amyloid-β (Aβ) deposition and neurofilament light chain (NfL) are associated with cognitive and gait speed decline, relationships of combined plasma Aβ 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 Aβ and NfL profiles with cognitive and physical functions in older adults.MethodsParticipants (n = 452, aged 76 ± 5 years) who had both plasma Aβ 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 Aβ and NfL tests were used for analysis. Participants with plasma Aβ42/Aβ40 ratios lower than 0.107 and NfL levels greater than 93.04 pg/ml were classified as Aβ+ and NfL+. Multivariable regressions and mixed-effects linear models were used for the analysis.ResultsAt the cross-sectional level, no significant association was found between Aβ+NfL+ and cognitive or physical function after controlling for age, sex, body mass index, education level and MAPT group. Evaluating longitudinal changes, participants with Aβ+NfL+ had greater annual declines in the CCS (β = - 0.11, 95%CI [- 0.17, - 0.05]) and gait speed (β = - 0.03, 95%CI [- 0.05, - 0.005]). After adjusting for APOE ɛ4 genotype, Aβ+NfL+ was associated with a greater decline only in the CCS (β = - 0.09, 95%CI [- 0.15, - 0.02]).ConclusionsCombined low plasma Aβ42/Aβ40 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 registrationwww.clinicaltrials.gov [ NCT00672685 ].

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.

Project description:BackgroundAnalysis of selected research cohorts has highlighted an association between plasma neurofilament light (NfL) protein and cross-sectional cognitive impairment as well as longitudinal cognitive decline. However, the findings have yielded inconsistent results regarding its possible application in clinical practice. Despite its potential prognostic significance, the role of plasma NfL in daily clinical practice with unselected patients suffering from cognitive impairment remains largely unexplored.MethodsThis retrospective, cross-sectional and longitudinal monocentric study enrolled 320 patients with Alzheimer's disease ([AD], n = 158), dementia with Lewy body ([DLB], n = 30), frontotemporal dementia ([FTD], n = 32), non-neurodegenerative diseases ([NND], n = 59) or subjective cognitive decline ([SCD], n = 41). Plasma NfL levels were measured at baseline on the Simoa platform. AD, DLB, and FTD patients were also analyzed altogether as a 'degenerative conditions' subgroup, whereas SCD and NND were grouped as a 'non-degenerative conditions' subgroup. We assessed the relationship between plasma NfL levels and cross-sectional cognitive performance, including global cognition and six specific cognitive domains. A subset of 239 patients had follow-up mini-mental state examinations (MMSE) up to 60 months. Models were adjusted on age, education level, glomerular filtration rate and body mass index.ResultsIn 320 patients, baseline plasma NfL levels were negatively associated with global cognition (β=-1.28 (-1.81 ; -0.75) P < 0.001), memory (β=-1.48 (-2.38 ; -0.59), P = 0.001), language (β=-1.72(-2.49 ; -0.95) P < 0.001), praxis (β=-2.02 (-2.91 ; -1.13) P < 0.001) and executive functions (β=-0.81, P < 0.001). Across diagnosis, plasma NfL levels were negatively associated with cross-sectional global cognition in all but the SCD subgroup, specifically with executive functions and memory in AD (respectively β=-0.71(-1.21 ; -0.211), P = 0.005 and β=-1.29 (-2.17 ; -0.42), P = 0.004), and with attention in LBD (β=-0.81(-1.16 ; -0.002), P = 0.03). Linear mixed-effects models showed that plasma NfL predicted MMSE decline in the global population (βPlasmaNfLxTime=-0.15 (-0.26 ; -0.04), P = 0.006), as in the neurodegenerative condition subgroup (βPlasmaNfLxTime=-0.21 (-0.37 ; - 0.06), P = 0.007), but not in non-neurodegenerative condition subgroup.ConclusionIn our clinical cohort, plasma NfL was associated with faster cognitive decline in neurodegenerative dementia, which corroborates data obtained in research cohorts. Yet, plasma NfL was not predictive of accelerated cognitive decline in individuals without neurodegeneration, suggesting its use as a neurodegeneration-specific predictive biomarker.

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Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults.

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Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults.

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