Phenotyping Superagers Using Resting-State fMRI.

BACKGROUND AND PURPOSE: Superagers are defined as older adults with episodic memory performance similar or superior to that in middle-aged adults. This study aimed to investigate the key differences in discriminative networks and their main nodes between superagers and cognitively average elderly controls. In addition, we sought to explore differences in sensitivity in detecting these functional activities across the networks at 3T and 7T MR imaging fields. MATERIALS AND METHODS: Fifty-five subjects 80 years of age or older were screened using a detailed neuropsychological protocol, and 31 participants, comprising 14 superagers and 17 cognitively average elderly controls, were included for analysis. Participants underwent resting-state-fMRI at 3T and 7T MR imaging. A prediction classification algorithm using a penalized regression model on the measurements of the network was used to calculate the probabilities of a healthy older adult being a superager. Additionally, ORs quantified the influence of each node across preselected networks. RESULTS: The key networks that differentiated superagers and elderly controls were the default mode, salience, and language networks. The most discriminative nodes (ORs > 1) in superagers encompassed areas in the precuneus posterior cingulate cortex, prefrontal cortex, temporoparietal junction, temporal pole, extrastriate superior cortex, and insula. The prediction classification model for being a superager showed better performance using the 7T compared with 3T resting-state-fMRI data set. CONCLUSIONS: Our findings suggest that the functional connectivity in the default mode, salience, and language networks can provide potential imaging biomarkers for predicting superagers. The 7T field holds promise for the most appropriate study setting to accurately detect the functional connectivity patterns in superagers.

The Brain Metabolic Signature in Superagers Using In Vivo 1H-MRS: A Pilot Study.

BACKGROUND AND PURPOSE: Youthful memory performance in older adults may reflect an underlying resilience to the conventional pathways of aging. Subjects having this unusual characteristic have been recently termed "superagers." This study aimed to explore the significance of imaging biomarkers acquired by 1H-MRS to characterize superagers and to differentiate them from their normal-aging peers. MATERIALS AND METHODS: Fifty-five patients older than 80 years of age were screened using a detailed neuropsychological protocol, and 25 participants, comprising 12 superagers and 13 age-matched controls, were statistically analyzed. We used state-of-the-art 3T 1H-MR spectroscopy to quantify 18 neurochemicals in the posterior cingulate cortex of our subjects. All 1H-MR spectroscopy data were analyzed using LCModel. Results were further processed using 2 approaches to investigate the technique accuracy: 1) comparison of the average concentration of metabolites estimated with Cramer-Rao lower bounds <20%; and 2) calculation and comparison of the weighted means of metabolites' concentrations. RESULTS: The main finding observed was a higher total N-acetyl aspartate concentration in superagers than in age-matched controls using both approaches (P = .02 and P = .03 for the weighted means), reflecting a positive association of total N-acetyl aspartate with higher cognitive performance. CONCLUSIONS: 1H-MR spectroscopy emerges as a promising technique to unravel neurochemical mechanisms related to cognitive aging in vivo and providing a brain metabolic signature in superagers. This may contribute to monitoring future interventional therapies to avoid or postpone the pathologic processes of aging.

Prevalence of Frailty in Brazilian Older Adults: A Systematic Review and Meta-analysis.

OBJECTIVES: Frailty is characterized by a functioning decline in multiple systems accompanied by an increase in individual's vulnerability to stressors. It appears to be higher in low and middle-income countries compared with high-income ones. This study aimed to evaluate the prevalence of frailty in non-institutionalized Brazilian older adults. DESIGN: a systematic review and meta-analysis study. SETTING: Cross-sectional and prospective data from Brazil. PARTICIPANTS: non-institutionalized adults aged 60 and older. METHODS: Electronic searches were performed in PubMed/MEDLINE, LILACS, SCOPUS and Web of Science, considering the studies published between March 2001 and July 2018, using a combination of the following terms and correlates: "elder" AND "frail" AND "prevalence" AND "Brazil". Two independent reviewers selected studies according to the inclusion criteria. Disagreements were resolved by a third reviewer (title/abstract) and by consensus. Studies with samples ≥221 subjects were considered for meta-analysis. RESULTS: 28 studies were included, while 18 had the data meta-analyzed. The majority of studies (61%) included older adults only from the Southeastern region. The number of subjects ranged from 53 to 5,532 individuals (N = 17,604) and the average age ranged from 65.6 to 85.5 years. The overall prevalence of frailty was 24%. When considering the different assessment methods, the prevalence was lower for frailty phenotype (16%) compared with other criteria (40%). Regarding sex, the prevalence of frailty was similar for women (28%) and men (25%). The prevalence of frailty was higher in older adults recruited from health care services (30%) compared to community ones (22%). CONCLUSION: In Brazil, the overall prevalence of frailty in non-institutionalized older adults is higher than observed from more developed countries. However, it may vary according to the assessment methods and settings.

Multimorbidity, frailty and functional disability in octogenarians: A structural equation analysis of relationship.

Path analysis allows for an understanding of the complex interrelationships between multiple variables and interactions in the octogenarians. The aim of this study was to estimate the isolated and combined prevalence of multimorbidity, frailty and functional disability and the direct and indirect association of these conditions in octogenarians. A cross-sectional study was conducted with 166 community-dwelling individuals aged 80 years or older participating in the FIBRA80+ epidemiological study. Multimorbidity was defined by three or more chronic diseases, frailty according to 3 or more components of physical frailty phenotype and functional disability as aid needed to perform one or more activities of daily living (ADLs). Associations were tested by Pearson's chi-square test; the relationship between the variables of interest and the mediating variables was tested with structural equation (path) analysis. We observed a higher prevalence of seniors with disability and multimordibity/disability. In path analysis, number of chronic diseases mediated the relation between sex and number of frailty components (p = 0.031), and these mediated the relation between number of diseases and disability (p = 0.008). The study points out the relationship between the simultaneous presence and interaction between multimorbidity, functional disability and frailty. Through path analysis, our findings provide characteristics in relation to the health-disease process, mainly mediation and interaction among octogenarians.

Frailty criteria and cognitive performance are related: data from the FIBRA study in Ermelino Matarazzo, São Paulo, Brazil.

OBJECTIVES: To assess the relationship between the CHS frailty criteria (Fried et al., 2001) and cognitive performance. DESIGN: Cross sectional and population-based. SETTING: Ermelino Matarazzo, a poor sub district of the city of São Paulo, Brazil. PARTICIPANTS: 384 community dwelling older adults, 65 and older. MEASUREMENTS: Assessment of the CHS frailty criteria, the Brief Cognitive Screening Battery (memorization of 10 black and white pictures, verbal fluency animal category, and the Clock Drawing Test) and the Mini-Mental State Examination (MMSE). RESULTS: Frail older adults performed significantly lower than non-frail and pre frail elderly in most cognitive variables. Grip strength and age were associated to MMSE performance, age was associated to delayed memory recall, gait speed was associated to verbal fluency and CDT performance, and education was associated to CDT performance. CONCLUSION: Being frail may be associated with cognitive decline, thus, gerontological assessments and interventions should consider that these forms of vulnerability may occur simultaneously.

Executive dysfunction correlates with impaired functional status in older adults with varying degrees of cognitive impairment.

BACKGROUND: Previous studies have reported an association between executive dysfunction and the ability to perform activities of daily living (ADL)s among older adults. This study aims to examine the association between executive functions and functional status in a cross-section of older adults with varying degrees of cognitive impairment. METHODS: 89 individuals (mean age 73.8 years) were recruited at a memory clinic in São Paulo, Brazil. Subjects underwent evaluation, and were allocated into three diagnostic groups according to cognitive status: normal controls (NC, n = 32), mild cognitive impairment (MCI, n = 31) and mild Alzheimer's disease (AD, n = 26). Executive functions were assessed with the 25-item Executive Interview (EXIT25), and functional status was measured with the Direct Assessment of Functional Status test (DAFS-R). RESULTS: Significantly different total DAFS-R scores were observed across the three diagnostic groups. Patients with AD performed significantly worse in EXIT25 compared with subjects without dementia, and no significant differences were detected between NC and MCI patients. We found a robust negative correlation between the DAFS-R and the EXIT25 scores (r =-0.872, p < 0.001). Linear regression analyses suggested a significant influence of the EXIT-25 and the CAMCOG on the DAFS-R scores. CONCLUSION: Executive dysfunction and decline in general measures of cognitive functioning are associated with a lower ability to undertake instrumental ADLs. MCI patients showed worse functional status than NC subjects. MCI patients may show subtle changes in functional status that may only be captured by objective measures of ADLs.