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Plasma neurofilament light as a potential biomarker for cognitive decline in a longitudinal study of middle-aged urban adults.

ABSTRACT: 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.

SUBMITTER: Beydoun MA

PROVIDER: S-EPMC8380245 | 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 ].

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Plasma neurofilament light as a potential biomarker for cognitive decline in a longitudinal study of middle-aged urban adults.

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