Combined low plasma Aβ
            42
            /Aβ
            40
            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 Background 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 adults. Methods Participants (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. Results At 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]). Conclusions Combined 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 registration www.clinicaltrials.gov [NCT00672685].

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Associations of plasma neurofilament light chain and progranulin with frailty in older adults

Journal of the American Geriatrics Society ◽

10.1111/jgs.17604 ◽

2021 ◽

Author(s):

Wan‐Hsuan Lu ◽

Kelly Virecoulon Giudici ◽

Sophie Guyonnet ◽

Geetika Aggarwal ◽

Andrew D. Nguyen ◽

...

Keyword(s):

Older Adults ◽

Light Chain ◽

Neurofilament Light Chain ◽

Neurofilament Light

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Renal function is associated with blood neurofilament light chain level in older adults

Scientific Reports ◽

10.1038/s41598-020-76990-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Shoshin Akamine ◽

Noriko Marutani ◽

Daisuke Kanayama ◽

Shiho Gotoh ◽

Riki Maruyama ◽

...

Keyword(s):

Diabetes Mellitus ◽

Older Adults ◽

Renal Function ◽

Light Chain ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Precise Evaluation ◽

Patients With Diabetes ◽

Healthy Participants ◽

Chain Level

AbstractNeurofilament 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.

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

Scientific Reports ◽

10.1038/s41598-021-91038-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lingxiao He ◽

John E. Morley ◽

Geetika Aggarwal ◽

Andrew D. Nguyen ◽

Bruno Vellas ◽

...

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Light Chain ◽

Cognitive Functions ◽

Linear Models ◽

Cognitive Status ◽

Neurofilament Light Chain ◽

Cross Sectional ◽

Neurofilament Light ◽

State Examination

AbstractNeurofilament 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.

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Association of Serum Neurofilament Light Chain Concentration and MRI Findings in Older Adults: The Cardiovascular Health Study

Neurology ◽

10.1212/wnl.0000000000013229 ◽

2021 ◽

pp. 10.1212/WNL.0000000000013229

Author(s):

Alison E Fohner ◽

Traci M Bartz ◽

Russell P Tracy ◽

Hieab H.H. Adams ◽

Joshua C Bis ◽

...

Keyword(s):

Older Adults ◽

Brain Injury ◽

White Matter ◽

Light Chain ◽

Cardiovascular Health Study ◽

Mri Findings ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Brain Infarcts ◽

History Of

BACKGROUND AND OBJECTIVES:Neurofilament light chain (NfL) in blood is a sensitive but non-specific marker of brain injury. This study sought to evaluate associations between NfL concentration and MRI findings of vascular brain injury in older adults.METHODS:A longitudinal cohort study included two cranial MRI scans performed about 5 years apart and assessed for white matter hyperintensities (WMH) and infarcts. About one year before their second MRI, 1,362 participants (median age 77 years and 61.4% women) without a history of TIA or stroke had measurement of four biomarkers: NfL, total tau, glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L1. Most (n = 1,279) also had the first MRI scan, and some (n=633) had quantitative measurements of hippocampal and WMH. In primary analyses, we assessed associations of NfL with a 10-point white matter grade (WMG) and prevalent infarcts on second MRI and with worsening WMG and incident infarct comparing the two scans. A p-value <0.0125 (0.05/4) was considered significant for these analyses. We also assessed associations with hippocampal and WMH volume.RESULTS:In fully adjusted models, log2(NfL) concentration was associated with WMG (β=0.27; p=2.3x10-4) and worsening WMG (RR=1.24; p=0.0022), but less strongly with prevalent brain infarcts (RR=1.18; p=0.013) and not with incident brain infarcts (RR=1.18; p=0.18). Associations were also present with WMH volume (beta=2242.9, p=0.0036). For the other three biomarkers, the associations for log2(GFAP) concentration with WMG and worsening WMG were significant.DISCUSSION:Among older adults without a history of stroke, higher serum NfL concentration was associated with covert MRI findings of vascular brain injury, especially the burden of WMH and its worsening. Whether these results offer opportunities for the use of NfL as a non-invasive biomarker of WMH or to control vascular risk factors remains to be determined.

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