Dataset Information

Plasma A? and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults.

ABSTRACT: 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 ].

SUBMITTER: He L

PROVIDER: S-EPMC7545881 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Plasma Aβ and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults.

He Lingxiao L de Souto Barreto Philipe P Aggarwal Geetika G Nguyen Andrew D AD Morley John E JE Li Yan Y Bateman Randall J RJ Vellas Bruno B

Alzheimer's research & therapy 20201008 1

<h4>Background</h4>Cognition 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 a ...[more]

PMID: 33032662

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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: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.

Dataset Information

Plasma A? and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults.

Publications

Plasma Aβ and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults.

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