A 1-year randomized controlled trial of a nutritional blend to improve nutritional biomarkers and prevent cognitive decline among community-dwelling older adults: The Nolan Study.

Introduction: This study aimed to test the efficacy of a nutritional blend (NB) in improving nutritional biomarkers and preventing cognitive decline among older adults. Methods: A 1-year randomized, double-blind, multicenter, placebo-controlled trial with 362 adults (58.6% female, mean 78.3 years, SD = 4.8) receiving an NB or placebo. Erythrocyte ω-3 index and homocysteine concentrations were primary outcomes. Other outcomes included Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognition-Abilities, composite cognitive score (CCS), Cognitive Function Instrument (CFI) self-assessment and study partner, hippocampal volume (HV), and Alzheimer's disease signature cortical thickness (CT). Results: A total of 305 subjects completed the follow-up. Supplementation increased ω-3 index and decreased homocysteine, but did not affect CCS, CFI self-assessment, HV, and CT. Placebo improved and treatment did not change PROMIS at 1 month. Intervention showed a positive effect on CFI study partner. Discussion: Although improving nutritional biomarkers, this 1-year trial with a multi-nutrient novel approach was not able to show effects on cognitive outcomes among older adults.

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

BACKGROUND: 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 ß-amyloid deposition-Aß42/40) 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 Aß42/40 (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 Aß42/40. 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: ß = -0.14, 95%CI = -0.26, -0.02) and the CDR sum of boxes (2-year: ß = 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 Aß42/40, MCP-1+ was not associated with greater declines in cognitive functions. The interaction with continuous biomarker values Aß42/40× 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 Aß42/40 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 Aß42/40.

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

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.

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

BACKGROUND: 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-ß 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.

Cross-Sectional and Longitudinal Associations Between Plasma Neurodegenerative Biomarkers and Physical Performance Among Community-Dwelling Older Adults.

BACKGROUND: Plasma amyloid-beta (Aß), neurofilament light chain (NfL), and progranulin (PGRN) have been related to multiple neurodegenerative conditions that might affect physical performance. The aim of this study was to explore the relationship between these plasma neurodegenerative markers and physical performance among community-dwelling older adults. METHODS: Five hundred and seven older adults (aged 76 ± 5 years) previously recruited in the Multidomain Alzheimer's Preventive Trial, and had received blood and physical performance tests, were included in this study. Plasma Aß (Aß 42/Aß 40 ratio), NfL, and PGRN levels were measured. Physical performance was assessed by handgrip strength and the Short Physical Performance Battery (combining gait speed, chair stands, and balance tests). Physical performance measured at the same time point and after the blood tests were used. Mixed-effect linear models were performed with age, sex, allocation to Multidomain Alzheimer's Preventive Trial group, body mass index, and Mini-Mental State Examination score as covariates. RESULTS: The mean values of Aß 42/Aß 40 ratio, NfL, and PGRN were 0.11, 84.06 pg/mL, and 45.43 ng/mL, respectively. At the cross-sectional level, higher plasma NfL was associated with a lower Short Physical Performance Battery score (ß = -0.004, 95% CI [-0.007, -0.001]). At the longitudinal level, higher PGRN levels were associated with decreasing handgrip strength over time (ß = -0.02, 95% CI [-0.04, -0.007]). All the other associations were statistically nonsignificant. CONCLUSION: Our findings suggest the possibility of using plasma NfL and PGRN as markers of physical performance in older adults.

Correlations among vitamin K intake, body fat, lipid profile and glucose homeostasis in adults and the elderly.

Objective Recent research has investigated the possible inverse relationship between vitamin K intake and body fat. In addition, an increasing number of studies are supporting a key role for this vitamin in improving lipid profile and insulin sensitivity and reducing the risk of type 2 diabetes mellitus, but little is known about what mechanisms would be involved. Thus, the objective of this study was to investigate the relationship between vitamin K intake (in the form of phylloquinone - PK), body fat, lipid profile and markers of glucose homeostasis in adults and the elderly. Subjects and methods A cross-sectional study with 298 participants (46% men) in the São Paulo Health Survey 2014-2015. Spearman correlations were performed to evaluate the associations between vitamin K intake and the biochemical and body composition measures. Results Among normal-weight male adults (n = 15), PK intake presented a positive correlation with the quantitative insulin sensitivity check index (QUICKI) (r = 0.525; p = 0.045). Among men with high fat mass index (FMI) (n = 101), PK intake had a negative correlation with homeostasis model assessment estimate for ß-cell function (HOMA-ß) (r = -0.227; p = 0.022). In women with high FMI (n = 122), PK intake had a negative correlation with HOMA-ß (r = -0.199, p = 0.032) and insulin (r = -0.207, p = 0.026). No correlations were found between PK intake and lipid profile. Conclusions Our findings support a potential relationship among PK intake, body fat and markers of glucose homeostasis in adults and the elderly.

Relationships between n-3 polyunsaturated fatty acid intake, serum 25 hydroxyvitamin D, food consumption, and nutritional status among adolescents.

We have hypothesized that higher n-3 polyunsaturated fatty acid (PUFA) intake is associated with better lipid profile, higher 25 hydroxyvitamin D (25(OH)D) serum concentrations, and healthy food consumption and nutritional status. Thus, this study aimed to evaluate the relationships between n-3 PUFA intake, serum 25(OH)D, lipid profile, nutritional status, and food consumption among adolescents. A total of 198 Brazilian adolescents (51% male), with mean age of 16.3 ± 1.4 years, were enrolled in this cross-sectional study. Blood was collected for 25(OH)D and lipid profile serum measurement. Weight and height were measured, and food consumption was accessed by a 24-hour food record (n = 69). Analysis of variance, the Student t test, and Pearson correlation were performed using SPSS software (SPSS, Chicago, IL, USA). The prevalence of vitamin D inadequacy (25(OH)D, <30 ng/mL) was 71.7%. Serum 25(OH)D negatively correlated with body mass index (r = -0.294; P < .0001) and positively correlated with high-density lipoprotein cholesterol (r = 0.323; P < .0001). N-3 PUFA intake negatively correlated with body mass index (r = -0.286; P = .017), total cholesterol (r = -0.292; P = .015), and low-density lipoprotein cholesterol (r = -0.333; P = .005) and positively correlated with the intake of fat meats and eggs (r = 0.391; P = .006), vegetable proteins (r = 0.297; P = .048), fats/oils (r = 0.574; P < .001), and refined cereals (r = 0.351; P = .006). Vitamin D status and n-3 PUFA intake were related with better nutritional status and favorable lipid profile. Food groups usually found in Brazilian traditional meals (characterized by rice, beans, meat, and vegetables) were associated with higher n-3 PUFA intake, which may contribute to prevent the development of noncommunicable diseases in adolescence and adulthood.