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

International audiencePhysical activity (PA) demonstrated benefits on brain health, but its relationship with blood biomarkers of neurodegeneration remains poorly investigated. We explored the cross-sectional associations of PA with blood concentrations of neurofilament light chain (NFL) and beta amyloid (Aβ)42/40. We further examined whether the interaction between PA and these biomarkers was longitudinally related to cognition. Four-hundred and sixty-five nondemented older adults engaged in an interventional study and who had a concomitant assessment of PA levels and blood measurements of NFL (pg/mL) and Aβ 42/40 were analyzed. A composite Z-score combining 4 cognitive tests was used for cognitive assessment up to a 4-year follow-up. Multiple linear regressions demonstrated that people achieving 500–999 and 2000+ MET-min/week of PA had lower (ln)NFL concentrations than their inactive peers. Logistic regressions revealed that achieving at least 90 MET-min/week of PA was associated with a lower probability of having high NFL concentrations (ie, ≥91.961 pg/mL [third quartile]). PA was not associated with (Aβ)42/40. Mixed-model linear regressions demonstrated that the reverse relationship between PA and cognitive decline tended to be more pronounced as Aβ 42/40 increased, while it was dampened with increasing levels of (ln)NFL concentrations. This study demonstrates that PA is associated with blood NFL but not with Aβ 42/40. Furthermore, it suggests that PA may attenuate the negative association between amyloid load and cognition, while having high NFL levels mitigates the favorable relationship between PA and cognition. More investigations on non demented older adults are required for further validation of the present findings

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

International audienceNeurofilament 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

Biological and Neuroimaging Markers as Predictors of 5-Year Incident Frailty in Older Adults: A Secondary Analysis of the MAPT Study

International audienceBackground This study aims to investigate the predictive value of biological and neuroimaging markers to determine incident frailty among older people for a period of 5 years. Methods We included 1394 adults aged 70 years and older from the Multidomain Alzheimer Preventive Trial, who were not frail at baseline (according to Fried’s criteria) and who had at least 1 post-baseline measurement of frailty. Participants who progressed to frailty during the 5-year follow-up were categorized as “incident frailty” and those who remained non-frail were categorized as “without frailty.” The differences of baseline biochemical factors (25-hydroxyvitamin D, homocysteine, omega-3 index, C-reactive protein), other biological markers (Apolipoprotein E genotypes, amyloid-β deposits), and neuroimaging data (gray matter volume, hippocampal volume, white matter hyperintensities) were compared between groups. Cox proportional hazard model was used to evaluate the associations between biomarkers and incident frailty. Results A total of 195 participants (14.0%) became frail over 5 years. Although 25-hydroxyvitamin D deficiency, homocysteine levels, low-grade inflammation (persistently increased C-reactive protein 3–10 mg/L), gray matter, and hippocampal volume were significantly associated with incident frailty in unadjusted models, these associations disappeared after adjustment for age, sex, and other confounders. Omega-3 index was the sole marker that presented a trend of association with incident frailty (hazard ratio: 0.92; 95% confidence interval: 0.83–1.01; p = .082). Conclusions This study failed to identify biomarkers able to predict frailty incidence in community-dwelling older adults for a period of 5 years. Further longitudinal research with multiple measurements of biomarkers and frailty is needed to evaluate the long-term relationships between changes in biomarkers levels and frailty evolution

Redox Systems, Antioxidants and Sarcopenia

International audienc

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

International audienceBACKGROUND:No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline.METHODS:The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685).FINDINGS:1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events.INTERPRETATION:The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings

Adherence to multidomain interventions for dementia prevention: Data from the FINGER and MAPT trials

Introduction: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable. Methods: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo. Results: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms. Discussion: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials