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

He, Lingxiao ; Morley, John E. ; Aggarwal, Geetika ; [et al.]

Springer Science and Business Media LLC ; 2021

In: Scientific Reports Vol. 11, No. 1 ( 2021-06-28)

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In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-06-28)

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.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-021-91038-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2615211-3

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2

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Physical Activity, Body Mass Index, and Blood Progranulin in Older Adults: Cross-Sectional Associations in the MAPT Study

Raffin, Jérémy ; Angioni, Davide ; Giudici, Kelly V ; [et al.]

Oxford University Press (OUP) ; 2022

In: The Journals of Gerontology: Series A Vol. 77, No. 6 ( 2022-06-01), p. 1141-1149

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In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 77, No. 6 ( 2022-06-01), p. 1141-1149

Abstract: Physical activity (PA) has been shown to moderate the negative effects of obesity on pro-inflammatory cytokines but its relationship with the adipokine progranulin (PGRN) remains poorly investigated. This study aimed to examine the cross-sectional main and interactive associations of body mass index (BMI) and PA level with circulating PGRN in older adults. Five-hundred and twelve participants aged 70 years and older involved in the Multidomain Alzheimer Preventive Trial (MAPT) study who underwent plasma PGRN measurements (ng/mL) were included. Self-reported PA levels were assessed using questionnaires. People were classified into 3 BMI categories: normal weight, overweight, or obesity. Further categorization using PA tertiles was used to define highly active, moderately active, and low active individuals. Multiple linear regressions were performed in order to test the associations of BMI, PA level, and their interaction with PGRN levels. Multiple linear regressions adjusted by age, sex, diabetes mellitus status, total cholesterol, creatinine level, and MAPT group demonstrated significant interactive associations of BMI status and continuous PA such that in people without obesity, higher PA levels were associated with lower PGRN concentrations, while an opposite pattern was found in individuals with obesity. In addition, continuous BMI was positively associated with circulating PGRN in highly active individuals but not in their less active peers. This cross-sectional study demonstrated reverse patterns in older adults with obesity compared to those without obesity regarding the relationships between PA and PGRN levels. Longitudinal and experimental investigations are required to understand the mechanisms that underlie the present findings. Clinical Trials Registration Number: NCT00672685

Type of Medium: Online Resource

ISSN: 1079-5006 , 1758-535X

URL: Article

DOI: 10.1093/gerona/glac018

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2043927-1

SSG: 12

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3

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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 ; de Souto Barreto, Philipe ; Aggarwal, Geetika ; [et al.]

Springer Science and Business Media LLC ; 2020

In: Alzheimer's Research & Therapy Vol. 12, No. 1 ( 2020-12)

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In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2020-12)

Abstract: 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 Aβ 42 /Aβ 40 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 Aβ 42 /Aβ 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 ].

Type of Medium: Online Resource

ISSN: 1758-9193

URL: Article

DOI: 10.1186/s13195-020-00697-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

detail.hit.zdb_id: 2506521-X

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4

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Low circulating adropin concentrations predict increased risk of cognitive decline in community-dwelling older adults

Aggarwal, Geetika ; Morley, John E. ; Vellas, Bruno ; [et al.]

Springer Science and Business Media LLC ; 2023

In: GeroScience

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In: GeroScience, Springer Science and Business Media LLC

Abstract: The secreted peptide adropin is highly expressed in human brain tissues and correlates with RNA and proteomic risk indicators for dementia. Here we report that plasma adropin concentrations predict risk for cognitive decline in the Multidomain Alzheimer Preventive Trial (ClinicalTrials.gov Identifier, NCT00672685; mean age 75.8y, SD = 4.5 years, 60.2% female, n = 452). Cognitive ability was evaluated using a composite cognitive score (CCS) that assessed four domains: memory, language, executive function, and orientation. Relationships between plasma adropin concentrations and changes in CCS (∆CCS) were examined using Cox Proportional Hazards Regression, or by grouping into tertiles ranked low to high by adropin values and controlling for age, time between baseline and final visits, baseline CCS, and other risk factors (e.g., education, medication, APOE4 status). Risk of cognitive decline (defined as a ∆CCS of − 0.3 or more) decreased with increasing plasma adropin concentrations (hazard ratio = 0.873, 95% CI 0.780–0.977, P = 0.018). Between adropin tertiles, ∆CCS was significantly different ( P = 0.01; estimated marginal mean ± SE for the 1st to 3rd tertile, − 0.317 ± 0.064; − 0.275 ± 0.063; − 0.042 ± 0.071; n = 133,146, and 130, respectively; P 〈 0.05 for 1st vs. 2nd and 3rd adropin tertiles). Normalized plasma Aß 42/40 ratio and plasma neurofilament light chain, indicators of neurodegeneration, were significantly different between adropin tertile. These differences were consistent with reduced risk of cognitive decline with higher plasma adropin levels. Overall, these results suggest cognitive decline is reduced in community-dwelling older adults with higher circulating adropin levels. Further studies are needed to determine the underlying causes of the relationship and whether increasing adropin levels can delay cognitive decline.

Type of Medium: Online Resource

ISSN: 2509-2723

URL: Article

DOI: 10.1007/s11357-023-00824-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2886418-9

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5

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Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial

Andrieu, Sandrine ; Guyonnet, Sophie ; Coley, Nicola ; [et al.]

Elsevier BV ; 2017

In: The Lancet Neurology Vol. 16, No. 5 ( 2017-05), p. 377-389

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In: The Lancet Neurology, Elsevier BV, Vol. 16, No. 5 ( 2017-05), p. 377-389

Type of Medium: Online Resource

ISSN: 1474-4422

URL: Article

DOI: 10.1016/S1474-4422(17)30040-6

Language: English

Publisher: Elsevier BV

Publication Date: 2017

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6

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Association between urate-lowering therapies and cognitive decline in community-dwelling older adults

Molet-Benhamou, Luc ; Giudici, Kelly Virecoulon ; de Souto Barreto, Philipe ; [et al.]

Springer Science and Business Media LLC ; 2022

In: Scientific Reports Vol. 12, No. 1 ( 2022-09-12)

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In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-09-12)

Abstract: Long-term use of urate-lowering therapies (ULT) may reduce inflammaging and thus prevent cognitive decline during aging. This article examined the association between long-term use of ULT and cognitive decline among community-dwelling older adults with spontaneous memory complaints. We performed a secondary observational analysis using data of 1673 participants ≥ 70 years old from the Multidomain Alzheimer Preventive Trial (MAPT Study), a randomized controlled trial assessing the effect of a multidomain intervention, the administration of polyunsaturated fatty acids (PUFA), both, or placebo on cognitive decline. We compared cognitive decline during the 5-year follow-up between three groups according to ULT (i.e. allopurinol and febuxostat) use: participants treated with ULT during at least 75% of the study period (PT ≥ 75; n = 51), less than 75% (PT 〈 75; n = 31), and non-treated participants (PNT; n = 1591). Cognitive function (measured by a composite score) was assessed at baseline, 6 months and every year for 5 years. Linear mixed models were performed and results were adjusted for age, sex, body mass index (BMI), diagnosis of arterial hypertension or diabetes, baseline composite cognitive score, and MAPT intervention groups. After the 5-year follow-up, only non-treated participants presented a significant decline in the cognitive composite score (mean change − 0.173, 95%CI − 0.212 to − 0.135; p 〈 0.0001). However, there were no differences in change of the composite cognitive score between groups (adjusted between-group difference for PT ≥ 75 vs. PNT: 0.144, 95%CI − 0.075 to 0.363, p = 0.196; PT 〈 75 vs. PNT: 0.103, 95%CI − 0.148 to 0.353, p = 0.421). Use of ULT was not associated with reduced cognitive decline over a 5-year follow-up among community-dwelling older adults at risk of dementia.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-022-17808-6

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

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7

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Biomarkers of mitochondrial dysfunction and inflammaging in older adults and blood pressure variability

Bencivenga, Leonardo ; Strumia, Mathilde ; Rolland, Yves ; [et al.]

Springer Science and Business Media LLC ; 2023

In: GeroScience Vol. 45, No. 2 ( 2023-04), p. 797-809

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In: GeroScience, Springer Science and Business Media LLC, Vol. 45, No. 2 ( 2023-04), p. 797-809

Type of Medium: Online Resource

ISSN: 2509-2715 , 2509-2723

URL: Article

DOI: 10.1007/s11357-022-00697-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2886418-9

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8

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Investigating the combination of plasma amyloid-beta and geroscience biomarkers on the incidence of clinically meaningful cognitive decline in older adults

Lu, Wan-Hsuan ; Giudici, Kelly Virecoulon ; Morley, John E. ; [et al.]

Springer Science and Business Media LLC ; 2022

In: GeroScience Vol. 44, No. 3 ( 2022-06), p. 1489-1503

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In: GeroScience, Springer Science and Business Media LLC, Vol. 44, No. 3 ( 2022-06), p. 1489-1503

Type of Medium: Online Resource

ISSN: 2509-2715 , 2509-2723

URL: Article

DOI: 10.1007/s11357-022-00554-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2886418-9

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9

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Soriano, Gaëlle ; De Souto Barreto, Philippe ; Virecoulon Giudici, Kelly ; [et al.]

Elsevier BV ; 2020

In: Clinical Nutrition Vol. 39, No. 11 ( 2020-11), p. 3483-3488

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In: Clinical Nutrition, Elsevier BV, Vol. 39, No. 11 ( 2020-11), p. 3483-3488

Type of Medium: Online Resource

ISSN: 0261-5614

URL: Article

DOI: 10.1016/j.clnu.2020.03.011

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2009052-3

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10

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Plasma MCP-1 and changes on cognitive function in community-dwelling older adults

Sanchez-Sanchez, Juan Luis ; Giudici, Kelly V. ; Guyonnet, Sophie ; [et al.]

Springer Science and Business Media LLC ; 2022

In: Alzheimer's Research & Therapy Vol. 14, No. 1 ( 2022-01-07)

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In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2022-01-07)

Abstract: Monocyte Chemoattractant Protein-1 (MCP-1), a glial-derived chemokine, mediates neuroinflammation and may regulate memory outcomes among older adults. We aimed to explore the associations of plasma MCP-1 levels (alone and in combination with β-amyloid deposition—Aβ 42/40 ) with overall and domain-specific cognitive evolution among older adults. Methods Secondary analyses including 1097 subjects (mean age = 75.3 years ± 4.4; 63.8% women) from the Multidomain Alzheimer Preventive Trial (MAPT). MCP-1 (higher is worse) and Aβ 42/40 (lower is worse) were measured in plasma collected at year 1. MCP-1 in continuous and as a dichotomy (values in the highest quartile (MCP-1 + )) were used, as well as a dichotomy of Aβ 42/40 . Outcomes were measured annually over 4 years and included the following: cognitive composite z -score (CCS), the Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) sum of boxes (overall cognitive function); composite executive function z -score, composite attention z -score, Free and Cued Selective Reminding Test (FCSRT - memory). Results Plasma MCP-1 as a continuous variable was associated with the worsening of episodic memory over 4 years of follow-up, specifically in measures of free and cued delayed recall. MCP-1 + was associated with worse evolution in the CCS (4-year between-group difference: β = −0.14, 95%CI = −0.26, −0.02) and the CDR sum of boxes (2-year: β = 0.19, 95%CI = 0.06, 0.32). In domain-specific analyses, MCP-1 + was associated with declines in the FCSRT delayed recall sub-domains. In the presence of low Aβ 42/40 , MCP-1 + was not associated with greater declines in cognitive functions. The interaction with continuous biomarker values Aβ 42/40 × MCP-1 × time was significant in models with CDR sum of boxes and FCSRT DTR as dependent variables. Conclusions Baseline plasma MCP-1 levels were associated with longitudinal declines in overall cognitive and episodic memory performance in older adults over a 4-year follow-up. How plasma MCP-1 interacts with Aβ 42/40 to determine cognitive decline at different stages of cognitive decline/dementia should be clarified by further research. The MCP-1 association on cognitive decline was strongest in those with amyloid plaques, as measured by blood plasma Aβ 42/40.

Type of Medium: Online Resource

ISSN: 1758-9193

URL: Article

DOI: 10.1186/s13195-021-00940-2

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2506521-X

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