Associations Between Physical Activity, Blood-Based Biomarkers of Neurodegeneration, and Cognition in Healthy Older Adults: The MAPT Study

Raffin, Jérémy; Rolland, Yves; Aggarwal, Geetika; Nguyen, Andrew; Morley, John E.; Li, Yan; Bateman, Randall J.; Vellas, Bruno; Barreto, Philipe de Souto; Mapt,; Guyonnet, Sophie; Carrié, Isabelle; Brigitte, Lauréane; Faisant, C.; Lala, Françoise; Delrieu, Julien; Villars, H.; Combrouze, Emeline; Badufle, Carole; Zueras, Audrey; Andrieu, Sandrine; Cantet, Christelle; Morin, Christophe; Kan, Gabor Abellán van; Dupuy, Charlotte; Caillaud, Céline; Ousset, Pierre‐Jean; Gilbert, Brigitte; Fontaine, Francine; Dartigues, Jean‐François; Marcet, Isabelle; Delva, Fleur; Foubert, Alexandra; Cerda, Sandrine; Costes, Corinne; Rouaud, Olivier; Manckoundia, Patrick; Quipourt, Valérie; Marilier, Sophie; Franon, Evelyne; Bories, Lawrence; Pader, Marie‐Laure; Basset, Marie‐France; Lapoujade, Bruno; Faure, Valérie; Tong, Michael Li Yung; Malick‐Loiseau, Christine; Cazaban‐Campistron, Evelyne; Desclaux, Françoise; Blatge, Colette; Dantoine, Thierry; Laubarie‐Mouret, Cécile; Saulnier, Isabelle; Clément, Jean‐Pierre; Picat, Marie‐Agnès; Bernard‐Bourzeix, Laurence; Willebois, Stéphanie; Desormais, Iléana; Cardinaud, Noëlle; Bonnefoy, Marc; Livet, Pierre; Rebaudet, Pascale; Gédéon, Claire; Burdet, Catherine; Terracol, Flavien; Pesce, A.; Roth, Stéphanie; Chaillou, Sylvie; Louchart, Sandrine; Sudres, Kristel; Lebrun, Nicolas; Barro‐Belaygues, Nadège; Touchon, Jacques; Bennys, Karim; Gabelle, Audrey; Romano, A.; Touati, Lynda; Marelli, Cécilia; Pays, Cécile; Robert, Philippe; Duff, Franck Le; Gervais, Claire; Gonfrier, Sébastien; Gasnier, Yannick; Bordes, Serge; Begorre, Danièle; Carpuat, Christian; Khales, Khaled; Lefebvre, Jean‐François; Idrissi, Samira Misbah El; Skolil, Pierre; Salles, Jean‐Pierre; Dufouil, Carole; Lehericy, Stéphane; Chupin, Marie; Mangin, Jean‐François; Bouhayia, Ali; Allard, Michèle; Ricolfi, F.; Dubois, Dominique; Martel, Marie; Cotton, François; Bonafé, Alain; Chanalet, S.; Hugon, Françoise; Bonneville, Fabrice; Cognard, Christophe; Chollet, François; Payoux, Pierre; Voisin, Thierry; Peiffer, Sophie; Hitzel, Anne; Zanca, Michel; Monteil, Jacques; Darcourt, Jacques; Molinier, Laurent; Derumeaux, Hélène; Costa, Nadège; Perret, Bertrand; Vinel, Claire; Caspar-Bauguil, Sylvie; Olivier‐Abbal, Pascale; Coley, Nicola

doi:10.1093/gerona/glab094

Cited by 24 publications

(19 citation statements)

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“… 3 Examining the associations between AD biomarkers and health behaviors such as physical activity is a new area of research. 25 We found only 1 study, the Multidomain Alzheimer Preventive Trial (MAPT), 26 that evaluated associations between NfL concentrations in blood and physical activity over 4 years. In that study, high NfL concentrations were associated with reductions in the benefits of physical activity on cognitive function.…”

Section: Discussionmentioning

confidence: 99%

“…In that study, high NfL concentrations were associated with reductions in the benefits of physical activity on cognitive function. Investigators have called for the need to validate results and to examine the associations between physical activity and NfL concentrations in a sample that has not received intervention . The present study leveraged the longitudinal cohort design and population-based sample of CHAP to address this need.…”

Section: Discussionmentioning

confidence: 99%

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Examination of Neurofilament Light Chain Serum Concentrations, Physical Activity, and Cognitive Decline in Older Adults

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Examination of Neurofilament Light Chain Serum Concentrations, Physical Activity, and Cognitive Decline in Older Adults

et al. 2022

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“…Indeed, higher CSF NfL levels have been associated with slower gait speed, 20 but similar associations did not replicate by using plasma NfL levels in another secondary analysis of the MAPT Study 6 . While Raffin et al demonstrated a cross‐sectional association between physical inactivity and higher NfL levels in blood among MAPT participants, 21 Jensen et al found no effect of exercise training on the change of CSF NfL concentrations in AD patients 22 . Noteworthy, our sensitivity analysis found that individuals with high plasma NfL levels were more likely to experience exhaustion at baseline; a similar association was observed for plasma PGRN using categorical measures.…”

Section: Discussionmentioning

confidence: 99%

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

Giudici

Guyonnet

et al. 2021

J American Geriatrics Society

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Background: In previous studies, plasma neurofilament light chain (NfL) and progranulin (PGRN) levels are associated with cognitive and physical impairment in older individuals. However, evidence of their relationships with frailty is lacking. This study aims to explore the associations of plasma NfL and PGRN levels with frailty in community-dwelling older adults. Methods: We included 507 older adults (mean [standard deviation] age, 76.7 [4.5] years) with plasma NfL and PGRN measurements from the Multidomain Alzheimer Preventive Trial (MAPT). The timepoint of biomarker measurements, either 12 or 24 months after study enrollment, was defined as the baseline for each participant. Frailty phenotype (robust, pre-frail, and frail) was assessed at 12, 24, 36, 48, and 60 months by Fried's frailty criteria. The cross-sectional associations between plasma neurodegenerative biomarkers and frailty severity were examined using logistic regressions. We further used Cox proportional hazard models to evaluate the associations between plasma biomarkers and incident frailty among robust or pre-frail participants at baseline (n = 403).Results: At baseline, participants with high plasma NfL levels (>93.11 pg/ml [the upper quartile]) had a higher likelihood of pre-frailty or frailty compared to their normal NfL counterparts (odds ratio = 1.68; 95% confidence interval = 1.10-2.57); however, this association did not remain significant after controlling for covariates. Neither NfL nor PGRN levels showed prospective associations with incident frailty over 4 years. Conclusions: This study failed to find associations of circulating NfL and PGRN levels with frailty among community-dwelling older adults in adjusted analyses. Whether plasma neurodegenerative markers serve as potential biomarkers of frailty requires further investigation. K E Y W O R D S biomarker, frailty, neurofilament light chain, older adults, progranulin Members of the MAPT/DSA Group are listed in Acknowledgments section.

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“…To take into account potential confounding factors, the following variables were considered: age, sex, body mass index (BMI = weight (kg)/height (m) 2 ), diagnosis of arterial hypertension or diabetes, physical activity (minutes per week) and allocation to MAPT intervention groups. History of smoking and alcohol intake was not included in the analysis because data were available for less than half of the participants 22 .…”

Section: Methodsmentioning

confidence: 99%

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

Molet-Benhamou

Giudici²,

Barreto³

et al. 2022

Sci Rep

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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.

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Associations Between Physical Activity, Blood-Based Biomarkers of Neurodegeneration, and Cognition in Healthy Older Adults: The MAPT Study

Cited by 24 publications

References 57 publications

Examination of Neurofilament Light Chain Serum Concentrations, Physical Activity, and Cognitive Decline in Older Adults

Examination of Neurofilament Light Chain Serum Concentrations, Physical Activity, and Cognitive Decline in Older Adults

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

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

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