Combined low plasma Aβ42/Aβ40 ratio and high neurofilament light chain levels are associated with both cognitive and physical function declines over time in non‐dementia older adults with memory complaints

Abstract

AbstractBackgroundAlthough brain amyloid deposition (Aβ) and plasma neurofilament light chain (NfL) are associated with cognitive decline, associations of combined plasma Aβ and NfL profiles with cognitive and physical functions in older adults remain unknown. The current study aimed to investigate prospective associations of combined plasma Aβ+ and NfL+ profiles with cognitive and physical functions in older adults.MethodPlasma Aβ and NfL levels, cognitive and physical function data (n=452 participants) collected from the Multidomain Alzheimer’s Preventive Trial (MAPT, www.clinicaltrials.gov [NCT00672685]) were used in this study. The MAPT recruited 1680 non‐dementia older adults with memory complaints for 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 moment 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.ResultAt the cross‐sectional level, no significant association was found between Aβ+NfL+ and cognitive or physical function. Evaluating longitudinal changes, participants with Aβ+NfL+ had more decline in the CCS and gait speed over time, compared to the other participants. After adjusting for APOE ɛ4 genotype, Aβ+NfL+ was associated with greater decline only in CCS.ConclusionCombined 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.