Predictive capacity of the Integrated Care for Older People (ICOPE) screening tool for intrinsic capacity impairments: results from the INSPIRE-T cohort.

BACKGROUND: The Integrated Care for Older People (ICOPE) approach was developed by the World Health Organization (WHO) aiming to shift the traditional focus of care based on diseases to a function- and person-centered approach, focused on maintaining and monitoring intrinsic capacity (IC). This study aimed to investigate the ability of the ICOPE screening tool to identify older people with clinically meaningful impairments in IC domains. METHODS: This cross-sectional analysis included 603 older adults, participants (mean age 74.7 [SD 8.8] years, women 59.0%) of the INSPIRE Translational (INSPIRE-T) cohort. Responses at screening were compared to results of the subsequent in-depth assessment (i.e., Mini Mental State Examination, Mini Nutritional Assessment, Short Physical Performance Battery, Patient Health Questionnaire-9, and clinical investigation of vision problems) to determine its predictive capacity for impairments at the IC domains (i.e., cognition, psychological, sensory (vision), vitality, and locomotion). RESULTS: The ICOPE screening items provided very high sensitivity for identifying abnormality in vision (97.2%), and varied from 42.0% to 69.6% for the other domains. High specificity (>70%) was observed for all the IC domains, except for vision (2.7%). CONCLUSIONS: The ICOPE screening tool can be a useful instrument enabling the identification of older people with impairments in IC domains, but studies with different populations are needed. It should be considered as a low-cost and simple screening tool in clinical care.

TNFR-1 and GDF-15 Are Associated With Plasma Neurofilament Light Chain and Progranulin Among Community-Dwelling Older Adults: A Secondary Analysis of the MAPT Study.

There is growing evidence that cognitive decline can be affected by both nutritional aspects and inflammation. Plasma neurodegenerative biomarkers stand out as minimally invasive useful measures to monitor the potential risk of cognitive decline. This study aimed to investigate the associations between biomarkers of neurodegeneration, nutrition, and inflammation among community-dwelling older adults, and to verify if associations differed according to apolipoprotein E (APOE) ε4 status. This cross-sectional analysis included 475 participants ≥70 years old from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8 years (SD = 4.5), 59.4% women. Biomarkers of neurodegeneration (plasma amyloid-ß 42/40-Aß 42/40, neurofilament light chain-NfL, progranulin), nutrition (erythrocyte docosahexaenoic acid, eicosapentaenoic acid, omega-3 index; plasma homocysteine-Hcy, 25 hydroxyvitamin D), inflammation (plasma tumor necrosis factor receptor 1-TNFR-1, monocyte chemoattractant protein 1-MCP-1, interleukin 6-IL-6), and cellular stress (plasma growth differentiation factor 15-GDF-15) were assessed. Linear regression analyses were performed to investigate the associations between nutritional and inflammatory biomarkers (independent variables) and neurodegenerative biomarkers (dependent variables), with adjustments for age, sex, education, body mass index, physical activity, allocation to MAPT groups, and APOE ε4 status. After adjusting for confounders, Aß 42/40 was not associated with nutritional or inflammatory markers. NfL was positively associated with GDF-15, TNFR-1, IL-6, and Hcy. Progranulin was positively associated with GDF-15, TNFR-1, and MCP-1. Analyses restricted to APOE ε4 carriers (n = 116; 26.9%) or noncarriers were mostly similar. Our cross-sectional study with community-dwelling older adults corroborates previous evidence that inflammatory pathways are associated to plasma markers of neurodegeneration. Clinical Trials Registration Number: NCT00672685.

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

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.

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

We investigated combining a core AD neuropathology measure (plasma amyloid-beta [Aß] 42/40) with five plasma markers of inflammation, cellular stress, and neurodegeneration to predict cognitive decline. Among 401 participants free of dementia (median [IQR] age, 76 [73-80] years) from the Multidomain Alzheimer Preventive Trial (MAPT), 28 (7.0%) participants developed dementia, and 137 (34.2%) had worsening of clinical dementia rating (CDR) scale over 4 years. In the models utilizing plasma Aß alone, a tenfold increased risk of incident dementia (nonsignificant) and a fivefold increased risk of worsening CDR were observed as each nature log unit increased in plasma Aß levels. Models incorporating Aß plus multiple plasma biomarkers performed similarly to models included Aß alone in predicting dementia and CDR progression. However, improving Aß model performance for composite cognitive score (CCS) decline, a proxy of dementia, was observed after including plasma monocyte chemoattractant protein 1 (MCP1) and growth differentiation factor 15 (GDF15) as covariates. Participants with abnormal Aß, GDF15, and MCP1 presented higher CCS decline (worsening cognitive function) compared to their normal-biomarker counterparts (adjusted ß [95% CI], - 0.21 [- 0.35 to - 0.06], p = 0.005). In conclusion, our study found limited added values of multi-biomarkers beyond the basic Aß models for predicting clinically meaningful cognitive decline among non-demented older adults. However, a combined assessment of inflammatory and cellular stress status with Aß pathology through measuring plasma biomarkers may improve the evaluation of cognitive performance.

Interactions Between Weight Loss and Plasma Neurodegenerative Markers for Determining Cognitive Decline Among Community-Dwelling Older Adults.

This study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-ß 42/40 (Aß 42/40), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial, mean age 76.8 years (SD = 4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onward by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test; Digit Symbol Substitution Test; 10 MMSE orientation items (MMSEO) and free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL + lower Aß 42/40 (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p < .0001) and MMSEO (p = .021), compared with non-WL + higher Aß 42/40. WL + higher NfL (>94.55 pg/mL, highest quartile) or progranulin (>38.4 ng/mL, 3 higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO, and composite score (all p < .03), compared with non-WL + lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1-Q3 vs Q4) revealed higher cognitive decline among the WL + lower progranulin group compared with non-WL + lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aß 42/40 or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment. Clinical trial number: NCT00672685.

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

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.

Associations between markers of glucose metabolism and bone measures among diabetic and non-diabetic adults.

PURPOSE: To investigate the relationships between bone measures, vitamin D status and markers of glucose metabolism among diabetic and non-diabetic adults. METHODS: Cross sectional study with 298 adults (mean age 57.5 years, SD = 14.8; 44.3% male, 16.9% diabetic) participants of the Health Survey-São Paulo (ISA-Capital) 2014-2015. Blood samples were collected to assess serum glucose, insulin and 25 hydroxyvitamin D [25(OH)D] concentrations. Dual-energy x-ray absorptiometry (DXA) was performed to determine total body fat; total lean mass; full body bone mineral density (BMD); lumbar spine BMD and bone mineral content (BMC); and femur BMD and BMC. Fat mass index (FMI), lean mass index (LMI), quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and of ß-pancreatic cell function (HOMA-ß) were calculated. Linear regression analysis were performed. RESULTS: Multiple bone measures were associated with markers of glucose metabolism in analyses adjusted by age and sex. However, after additional adjustments by LMI, FMI and serum 25(OH)D, only associations of lumbar spine BMC with HOMA-IR (ß = 0.167; p = 0.035) and QUICKI (ß = -1.879; p = 0.027) persisted, in the subgroup of diabetic participants. Analysis restricted to diabetic subjects revealed stronger correlations between bone parameters and markers of glucose metabolism. CONCLUSIONS: Our study observed positive associations between BMD and markers of insulin resistance among a sample of adults. Correlations were stronger among diabetic subjects, and some associations between bone and glucose metabolism were independent of adiposity. Findings reinforce the need of further research for better understanding the bidirectional and multifactorial crosstalk between glucose homeostasis and bone metabolism.

Associations Between Nutritional Deficits and Physical Performance in Community-Dwelling Older Adults.

Background: Whether multiple nutritional deficiencies have a synergic effect on mobility loss remains unknown. This study aims to evaluate associations between multi-nutritional deficits and physical performance evolution among community-dwelling older adults. Methods: We included 386 participants from the Multidomain Alzheimer Preventive Trial (MAPT) (75.6 ± 4.5 years) not receiving omega-3 polyunsaturated fatty acid (PUFA) supplementation and who had available data on nutritional deficits. Baseline nutritional deficits were defined as plasma 25 hydroxyvitamin D <20 ng/ml, plasma homocysteine >14 µmol/L, or erythrocyte omega-3 PUFA index ≤ 4.87% (lower quartile). The Short Physical Performance Battery (SPPB), gait speed, and chair rise time were used to assess physical performance at baseline and after 6, 12, 24, 36, 48, and 60 months. We explored if nutrition-physical performance associations varied according to the presence of low-grade inflammation (LGI) and brain imaging indicators. Results: Within-group comparisons showed that physical function (decreased SPPB and gait speed, increased chair rise time) worsened over time, particularly in participants with ≥2 nutritional deficits; however, no between-group differences were observed when individuals without deficit and those with either 1 or ≥2 deficits were compared. Our exploratory analysis on nutritional deficit-LGI interactions showed that, among people with ≥2 deficits, chair rise time was increased over time in participants with LGI (adjusted mean difference: 3.47; 95% CI: 1.03, 5.91; p = 0.017), compared with individuals with no LGI. Conclusions: Accumulated deficits on vitamin D, homocysteine, and omega-3 PUFA were not associated with physical performance evolution in older adults, but they determined declined chair rise performance in subjects with low-grade inflammation. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT00672685], identifier [NCT00672685].

Associations of Omega-3 fatty acids with brain morphology and volume in cognitively healthy older adults: A narrative review.

INTRODUCTION: Human neurodevelopment is complete by the 4th decade of life at which point brain atrophy ensues with variable rate and regionality into old age. Literally all regions of the brain experience atrophy with older age, however the pattern and rate of atrophy can dictate the behavioral consequences (i.e., cognitive impairment, Alzheimer's disease). Substantial research has aimed to discover the reasons why some people experience greater morphologic changes that produce undesirable consequences with aging and how it may be prevented. One possible explanation is diet, particularly fish consumption and the intake of omega-3 polyunsaturated fatty acids (omega 3) concentrated in fish oil. This narrative review examines the available evidence on the association between omega-3 and brain volume in non-demented older adults. METHODS: A PubMed search of the literature was conducted in search of studies that investigated the associations of omega-3 on brain morphology and volume in cognitively intact older adults. Inclusion criteria were: populations of adults aged 45 years or over, who were cognitively intact, free of any central nervous system disease, and free of advanced structural brain atrophy. Study participants had to have DHA and EPA levels measured either by blood testing or scoring of dietary intake. There were no restrictions to dates of publication. Studies including demented participants, or participants with substantial white or grey matter atrophy visible on magnetic resonance imaging were excluded. RESULTS AND CONCLUSION: The search identified only 12 studies, 8 of which were cross-sectional observational studies, 3 longitudinal observational studies, and 1 randomized controlled trial published between 2007 and 2019. The largest amount of evidence indicated that the hippocampus was most frequently involved in this association, with a higher volume associated with higher omega-3 levels. Larger total grey matter, total brain volume, and lower white matter lesion volume were also associated with higher omega-3 among four of the reviewed studies. However, most studies reviewed provided mixed findings regarding the presence or absence of the association of interest, and the findings were observed to be brain region-dependent. Current evidence is still insufficient to formulate recommendations for omega-3 intake to support brain health specifically.

Five-Year Lower Extremity Function is Associated with White Matter Abnormality in Older Adults.

OBJECTIVE: To explore associations between changes of lower extremity function (LEF) parameters over a 5-year period and diffusion tensor imaging (DTI) parameters of white matter tracts among community-dwelling older adults. DESIGN: A secondary analysis on image and physical function data collected from the Multidomain Alzheimer's Preventive Trial (MAPT). PARTICIPANTS: 208 older adults (aged 75 ± 4 years, with spontaneous memory complaint or limited instrumental daily living activity or slow gait speed, 60% female) of the MAPT-magnetic resonance imaging (MRI) ancillary study. The time interval between a participant's enrolment and MRI scan was on average 110 ± 97 days. MEASUREMENTS: Forty-eight white matter tracts (WMTs) were measured. LEF parameters (measured after the MRI scan) were assessed as the short physical performance battery (SPPB) score, gait speed, and chair stands time over a 5-year period. Mixed-effects models were performed to explore the associations between baseline DTI values and the progression of LEF parameters. Bonferroni correction was applied for multiple comparison correction. RESULTS: The progression of LEF was associated with 35 baseline DTI parameters from 24 WMTs. Higher baseline DTI parameter values were related to more decreases in SPPB score and gait speed, and greater increases in chair stands time. Bilateral uncinate fasciculus was associated with all LEF parameters. Other WMTs in cingulum, cerebral and cerebellar peduncle, internal capsule, and corpus callosum also showed close connections with LEF changes. CONCLUSIONS: Our findings show that DTI parameters of some WMTs are associated with the 5-year decline in LEF, suggesting that alterations in WMT integrity (evaluated by DTI parameters) might be used to explore potential causes of impaired mobility in older adults when no clear explanations can be found.

Future avenues for Alzheimer's disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery.

When Alzheimer's disease (AD) disease-modifying therapies will be available, global healthcare systems will be challenged by a large-scale demand for clinical and biological screening. Validation and qualification of globally accessible, minimally-invasive, and time-, cost-saving blood-based biomarkers need to be advanced. Novel pathophysiological mechanisms (and related candidate biomarkers) - including neuroinflammation pathways (TREM2 and YKL-40), axonal degeneration (neurofilament light chain protein), synaptic dysfunction (neurogranin, synaptotagmin, α-synuclein, and SNAP-25) - may be integrated into an expanding pathophysiological and biomarker matrix and, ultimately, integrated into a comprehensive blood-based liquid biopsy, aligned with the evolving ATN + classification system and the precision medicine paradigm. Liquid biopsy-based diagnostic and therapeutic algorithms are increasingly employed in Oncology disease-modifying therapies and medical practice, showing an enormous potential for AD and other brain diseases as well. For AD and other neurodegenerative diseases, newly identified aberrant molecular pathways have been identified as suitable therapeutic targets and are currently investigated by academia/industry-led R&D programs, including the nerve-growth factor pathway in basal forebrain cholinergic neurons, the sigma1 receptor, and the GTPases of the Rho family. Evidence for a clinical long-term effect on cognitive function and brain health span of cholinergic compounds, drug candidates for repositioning programs, and non-pharmacological multidomain interventions (nutrition, cognitive training, and physical activity) is developing as well. Ultimately, novel pharmacological paradigms, such as quantitative systems pharmacology-based integrative/explorative approaches, are gaining momentum to optimize drug discovery and accomplish effective pathway-based strategies for precision medicine. This article is part of the special issue on 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.

Assessment of Plasma Amyloid-ß42/40 and Cognitive Decline Among Community-Dwelling Older Adults.

Importance: Plasma measurement of amyloid-ß (Aß) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce. Objective: To investigate the associations between plasma Aß42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns. Design, Setting, and Participants: This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in April 2016. Data analysis was conducted from April to October 2020. Exposure: Plasma Aß42 and Aß40 were measured at 12 months for 448 participants (92.8%) and at 24 months for the rest. The moment of Aß assessment was defined as the baseline for this study. Main Outcomes and Measures: Cognitive function was assessed at 12, 24, 36, 48, and 60 months by a composite cognitive score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum of boxes; and Alzheimer Disease Cooperative Study-Activities of Daily Living. Mixed-effect linear regressions were performed. Results: A total of 483 participants (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) were analyzed. Of them, 161 (33.3%) were classified as low plasma Aß42/40 (≤0.107). After adjusting for age, sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E ε4 genotype, and MAPT intervention groups, low plasma Aß42/40 was associated with more pronounced decline in composite cognitive score (adjusted between-group mean difference: -0.20, 95% CI, -0.34 to -0.07; P = .004) and decline in MMSE score (adjusted between-group mean difference: -0.59; 95% CI, -1.07 to -0.11; P = .02) during the follow-up period compared with the group with an Aß42/40 ratio greater than 0.107. Conclusions and Relevance: In this study, low plasma Aß42/40 was associated with more pronounced decline in cognitive function (measured by multiple outcomes) over time. Findings suggest that plasma Aß42/40 may be used to identify people at risk of cognitive decline, being an alternative to more complex and expensive measures, such as positron emission tomography imaging or cerebrospinal fluid measurement.

Cross-sectional and prospective associations between cerebral cortical thickness and frailty in older adults.

BACKGROUND: Several neurodegenerative markers measured by magnetic resonance imaging (MRI) have shown to be related with frailty. While most studies have focused on surrogates of cerebral vascular damage such as increased white matter lesions, the associations between cortical atrophy and frailty were less often investigated. OBJECTIVES: To investigate the cross-sectional and prospective associations between cortical thickness and frailty evolution in older adults. METHODS: We enrolled 484 community-dwelling adults aged ≥70 years, participants from the Multidomain Alzheimer Preventive Trial (MAPT), with data on cerebral cortical thickness and frailty. Cortical thickness was acquired by MRI for whole-brain and regional cortices. Two function-specific regions of interest, i.e., mobility-related regions and Alzheimer's disease (AD) signature, were selected on the basis of previous studies. Frailty status was assessed by the Fried frailty phenotype (i.e., weakness, slowness, involuntary weight loss, fatigue and low physical activity level) at baseline, after 6 months and every year until the end of the 5-year follow-up. RESULTS: Older adults with higher global cortical thickness were less likely to be pre-frail and frail at baseline (adjusted OR: 0.13, 95% CI: 0.03-0.65, p = 0.013). In addition, higher cortical thickness in mobility-related and AD-signature regions were associated with lower likelihood of being pre-frail and frail. Similar associations were observed for having weakness and slowness. However, neither global nor region-specific cortical thickness showed prospective associations with future frailty onset. CONCLUSIONS: The global and regional cortical thickness cross-sectionally associated with frailty in older adults, but no prospective associations with incident frailty were found. The longitudinal relationship between cortical thickness and frailty evolution requires further investigation.

Cognitive Restraint and History of Dieting Are Negatively Associated with Organic Food Consumption in a Large Population-Based Sample of Organic Food Consumers.

Organic food consumption has risen in many countries during the past decades, but individual motives leading to these choices remain unclear. This study aimed to evaluate the associations between cognitive restraint (CR), history of dieting and organic food intake. This cross-sectional analysis included 20,085 organic food consumers from the NutriNet-Santé cohort. CR (range score 1-4) was evaluated by the Three-Factor-Eating-Questionnaire and practice of dieting (never vs. past/current) was assessed by an ad hoc questionnaire. Frequencies of organic food intake overall and in 16 food groups were assessed by the Organic Food Frequency Questionnaire. Linear regression and analysis of covariance (ANCOVA) were performed to investigate the association between CR score, history of dieting and contribution of organic food intake to the total food intake. A lower overall contribution of organic options in the diet was observed in women with higher levels of CR (ß = -3.61%, 95% CI: -4.32; -2.91 for 1 point of CR, p < 0.001) and with a history of dieting (31.1 ± 0.4% in past/current vs. 32.6 ± 0.3% in never dieters; p = 0.001). Consistent associations were observed in men with a history of dieting (26.4 ± 0.8% in past/current vs. 28.7 ± 0.4% in never dieters; p = 0.012). Overall, individuals-in particular women-with higher CR scores or with a history of dieting selected fewer organic food options. Our findings illustrate the complexity of potentially concurrent motives to food choices, in a context of increasing interest in organic food consumption.

Associations of C-reactive protein and homocysteine concentrations with the impairment of intrinsic capacity domains over a 5-year follow-up among community-dwelling older adults at risk of cognitive decline (MAPT Study).

BACKGROUND: The World Health Organization (WHO) recently proposed an innovative model of care focusing on functional rather than disease-based perspectives, based on a construct of intrinsic capacity (IC). OBJECTIVE: This study aimed to analyze if low-grade inflammation (LGI) (chronically raised C-reactive protein - CRP) and hyperhomocysteinemia (HHcy) were associated with variation in IC domains (mobility, cognition, psychological and vitality) and in a combined IC Z-score over a 5-year follow-up among non-demented, community-dwelling older adults at risk of cognitive decline. DESIGN: This observational study included 1516 subjects ≥70 years (64.5% female, mean age 75.4 years, SD = 4.5), volunteers from the interventional study Multidomain Alzheimer Preventive Trial (MAPT). Plasma CRP (at baseline, 6 and 12 months) and homocysteine (at baseline) concentrations were measured. LGI was defined as having ≥2 consecutively CRP readings >3 to 10 mg/L between baseline and 12 months, and HHcy was defined as homocysteine >15 µM/L. IC domains were operationalized as follows: Psychological. Depressive symptoms evaluated by the Geriatric Depression Scale (GDS); Mobility. Assessed by the Short Physical Performance Battery (SPPB); Cognitive function. Examined by a Z-score combining four tests; Vitality. Based on hand grip strength. Outcomes were combined into a composite IC Z-score. RESULTS: IC Z-score decreased among groups with no inflammation and LGI after 5 years, but this decrease was more pronounced among the LGI group (unadjusted mean group difference: 0.09, 95%CI: 0.01 to 0.16; p = 0.032). Participants with HHcy also presented IC Z-score decreases over time. Combined conditions provided more pronounced declines, even after adjusting for potential confounders. CONCLUSION: LGI and HHcy were both related with impairment on the combined IC levels among older adults after a 5-year follow-up. Identifying biomarkers that strongly associate with IC may help to settle strategies aiming to prevent the incidence and slow down the evolution of age-related functional decline and care dependency.

Body Weight Variation Patterns as Predictors of Cognitive Decline over a 5 Year Follow-Up among Community-Dwelling Elderly (MAPT Study).

This study aimed to analyze associations between weight variation patterns and changes in cognitive function and hippocampal volume among non-demented, community-dwelling elderly. Sample was formed of 1394 adults >70 years (63.9% female), all volunteers from the Multidomain Alzheimer Preventive Trial (MAPT). Weight loss was defined as ≥5% of body weight decrease in the first year of follow-up; weight gain as ≥5% of weight increase; and stability if <5% weight variation. Cognition was examined by a Z-score combining four tests. Measures were assessed at baseline, 6, 12, 24, 36, 48, and 60 months of follow-up. Hippocampal volume was evaluated with magnetic resonance imaging in 349 subjects in the first year and at 36 months. Mixed models were performed. From the 1394 participants, 5.5% (n = 76) presented weight loss, and 9.0% (n = 125) presented weight gain. Cognitive Z-score decreased among all groups after 5 years, but decline was more pronounced among those who presented weight loss (adjusted between-group mean difference vs. stable: -0.24, 95%CI: -0.41 to -0.07; p = 0.006). After 3 years, hippocampal atrophy was observed among all groups, but no between-group differences were found. In conclusion, weight loss ≥5% in the first year predicted higher cognitive decline over a 5 year follow-up among community-dwelling elderly, independently of body mass index.

Association of 3-Year Multidomain Intervention and Omega-3 Supplementation with Frailty Incidence.

OBJECTIVES: To assess the associations of long-term lifestyle multidomain intervention (MI) and omega-3 supplementation with frailty level evolution and frailty incidence in community-dwelling older persons. DESIGN: Secondary analysis of the randomized controlled Multidomain Alzheimer Preventive Trial. SETTING: Thirteen memory centers in France and Monaco between 2008 and 2011. PARTICIPANTS: A total of 1588 community-dwelling persons aged 70 years or older with memory complaints (without dementia), slow gait speed, or limitation in one instrumental activity of daily living. INTERVENTION: A 3-year MI (43 group sessions including cognitive training, physical activity, and nutrition advice and three preventive consultations) plus daily omega-3 fatty acids, MI plus placebo, omega-3 alone, or placebo alone. MEASUREMENTS: The frailty phenotype (unintentional weight loss, exhaustion, low physical activity, slow gait, low handgrip strength: 0 to 5 score, higher is worse; a score of 3 or higher defines frailty) was assessed at baseline, 6, 12, 24, and 36 months. We used mixed-effect models for frailty level (0-5 score as an ordinal variable) and Cox models for frailty incidence. RESULTS: No differences were found between the intervention groups and placebo on the 3-year evolution of frailty level. Among 1394 non-frail participants at baseline, frailty incidence occurred in 134 (9.6%) persons: 26 (7.6%) in the MI plus omega-3 group, 34 (10%) in the omega-3 alone group, 31 (8.5%) in the MI plus placebo group, and 43 (12.3%) in the placebo-alone group). No differences regarding frailty incidence were found between intervention groups and placebo. After exclusion of 53 participants with incident frailty during the first year of follow-up, MI plus omega-3 was associated with a lower frailty incidence compared with placebo (hazard ratio = .43; 95% confidence interval = .22-.81). CONCLUSION: In community-dwelling older persons, the combination of a long-term lifestyle MI and omega-3 supplementation did not reduce frailty level or incidence. The reduction of frailty incidence associated with the combined intervention in a sensitivity analysis needs to be further confirmed. J Am Geriatr Soc 67:1700-1706, 2019.

Association between time perspective and organic food consumption in a large sample of adults.

BACKGROUND: Organic food intake has risen in many countries during the past decades. Even though motivations associated with such choice have been studied, psychological traits preceding these motivations have rarely been explored. Consideration of future consequences (CFC) represents the extent to which individuals consider future versus immediate consequences of their current behaviors. Consequently, a future oriented personality may be an important characteristic of organic food consumers. The objective was to analyze the association between CFC and organic food consumption in a large sample of the adult general population. METHODS: In 2014, a sample of 27,634 participants from the NutriNet-Santé cohort study completed the CFC questionnaire and an Organic-Food Frequency questionnaire. For each food group (17 groups), non-organic food consumers were compared to organic food consumers across quartiles of the CFC using multiple logistic regressions. Moreover, adjusted means of proportions of organic food intakes out of total food intakes were compared between quartiles of the CFC. Analyses were adjusted for socio-demographic, lifestyle and dietary characteristics. RESULTS: Participants with higher CFC were more likely to consume organic food (OR quartile 4 (Q4) vs. Q1 = 1.88, 95% CI: 1.62, 2.20). Overall, future oriented participants were more likely to consume 14 food groups. The strongest associations were observed for starchy refined foods (OR = 1.78, 95% CI: 1.63, 1.94), and fruits and vegetables (OR = 1.74, 95% CI: 1.58, 1.92). The contribution of organic food intake out of total food intake was 33% higher in the Q4 compared to Q1. More precisely, the contribution of organic food consumed was higher in the Q4 for 16 food groups. The highest relative differences between Q4 and Q1 were observed for starchy refined foods (22%) and non-alcoholic beverages (21%). Seafood was the only food group without a significant difference. CONCLUSIONS: This study provides information on the personality of organic food consumers in a large sample of adult participants. Consideration of future consequences could represent a significant psychological determinant of organic food consumption.

Comparison between body mass index and a body shape index with adiponectin/leptin ratio and markers of glucose metabolism among adolescents.

BACKGROUND: Besides body mass index (BMI), new parameters have been developed to classify individual body shape. AIM: To investigate the relationship between BMI, waist circumference (WC), a body shape index (ABSI) and ABSI-adolescents among adolescents and verify which would better predict lower adiponectin/leptin (A/L) ratio and disturbances on glucose metabolism. SUBJECTS AND METHODS: A cross-sectional study with 197 Brazilian adolescents of 14-18 years. Serum leptin, adiponectin, glucose and insulin were measured. A/L ratio, ABSI, ABSI-adolescents, BMI, homeostasis model assessment estimates of insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) and the quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: ABSI-adolescents positively correlated with WC (r = 0.83, p < 0.0001) and BMI (r = 0.66, p < 0.0001), but stronger correlations were observed between WC and BMI (r = 0.95, p < 0.0001). ABSI-adolescents, BMI and WC negatively correlated with A/L ratio (all p < 0.0001). The correlation between BMI and A/L ratio was the strongest (r = -0.63, p < 0.001). A/L ratio, BMI, WC and ABSI-adolescents correlated with markers of glucose metabolism (all p < 0.0001) and the strongest correlation was observed with BMI (QUICKI: r = -0.75; HOMA-IR: r = 0.76; HOMA-ß: r = 0.77; insulin: r = 0.79). Associations were confirmed by linear regression analysis, adjusted for sex and age. CONCLUSIONS: ABSI-adolescents, but not ABSI, was related to A/L ratio and to markers of glucose metabolism, but not more strongly than BMI and WC.

Crosstalk Between Bone and Fat Tissue: Associations Between Vitamin D, Osteocalcin, Adipokines, and Markers of Glucose Metabolism Among Adolescents.

OBJECTIVES: This study aimed to investigate the relationship between 25-hydroxyvitamin D (25(OH)D), osteocalcin, markers of glucose metabolism, and obesity-related parameters among adolescents. METHODS: This was a cross-sectional study with 198 adolescents age 14-18 years. Weight, height, and waist and hip circumferences were measured, as well as the following biochemical parameters: serum 25(OH)D, parathyroid hormone (PTH), total (tOC) and undercarboxylated (ucOC) osteocalcin, adiponectin, leptin, glucose, and insulin. The homeostasis model of assessment estimate of insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) and quantitative insulin sensitivity check index (QUICKI) were calculated. Student's t test, analysis of variance (ANOVA), Pearson's correlation, and linear regression models were performed. RESULTS: Overweight was observed in 42.6% of the sample. This group presented significantly higher PTH, leptin, insulin, HOMA-IR, and HOMA-ß and lower 25(OH)D, adiponectin, tOC, ucOC, and QUICKI than normal-weight subjects. 25(OH)D was positively correlated with ucOC and adiponectin and negatively associated with body mass index (BMI), weight, and waist circumference (p < 0.05 for all). The association between 25(OH)D and ucOC was also observed in the multiple regression analysis, adjusted for age, BMI, and season of the year (partial r2 = 0.071, p < 0.0001). 25(OH)D and ucOC were not associated with markers of glucose metabolism. However, leptin was strongly correlated with insulin, HOMA-IR, HOMA-ß, and QUICKI (p < 0.0001 for all). CONCLUSION: The present study demonstrated that undercarboxylated osteocalcin is related to 25(OH)D and adiponectin concentrations. Both ucOC and 25(OH)D were lower in overweight and obese adolescents, reinforcing the importance of fighting obesity. Although a relationship of ucOC and 25(OH)D with markers of glucose metabolism was not observed, leptin has shown to be the hormone most related to energy homeostasis.