Trajectories of frailty with aging:Coordinated analysis of five longitudinal studies

BACKGROUND AND OBJECTIVES: There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS: We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS: Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS: Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions

Dietary habits, frailty and cognitive impairment in older people

Frailty is a geriatric condition, characterized by the inability to preserve homeostasis in response to even minor stressors. The aim of the current study was a) to estimate the prevalence of frailty using five different instruments in a cohort of Greek older adults and explore the association between frailty and various risk factors and b) to investigate the relationship between nutrition factors and frailty. Data were drawn from the Hellenic longitudinal Investigation of Aging and Diet (HELIAD) and in total 1943 people aged 65 years and above had participated. The prevalence of frailty varied depending on the frailty definition used (Fried definition: 4.1%, FRAIL Scale: 1.5%, FI: 19.7%, TFI: 24.5%, and GFI: 30.2%). As far as the dietary factors are concerned, high consumption of vegetables and high adherence to the Mediterranean Diet were associated with lower odds of frailty. More specifically, adjusting for confounding factors, each additional unit in the MedDietScore was associated with an 11% (p=0.09), 4% (p=0.005), and 7% (p <0.001) decrease in the odds for frailty according to the Fried definition, the Frailty Index, and the Tilburg Frailty Indicator, respectively. In the present study, the prevalence of frailty in Greece was found lower to that reported in other population studies. The fact that adherence to the Mediterranean diet was consistently associated with frailty irrespective of the definition used increases the robustness of our results.Η ευπάθεια είναι ένα γηριατρικό σύνδρομο το οποίο χαρακτηρίζεται από μειωμένη δύναμη και αντοχή και από ελλειμματική λειτουργία των συστημάτων του οργανισμού. Στόχος της παρούσας διδακτορικής διατριβής ήταν α) η καταγραφή του επιπολασμού της ευπάθειας, χρησιμοποιώντας πέντε διαφορετικά εργαλεία αξιολόγησής της και β) η διερεύνηση του ρόλου διατροφικών παραμέτρων στην εμφάνιση του συνδρόμου της ευπάθειας. Το δείγμα της παρούσας μελέτης (1943 άτομα άνω των 65 ετών) προήλθε από την μελέτη Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Το μικρότερο ποσοστό επιπολασμού εντοπίστηκε με την κλίμακα FRAIL (1,5%) και το μεγαλύτερο με το εργαλείο GFI (30,2%). Ως προς τους διατροφικούς παράγοντες, η υψηλή κατανάλωση λαχανικών και ο υψηλός βαθμός υιοθέτησης της Μεσογειακής Δίαιτας σχετίστηκαν σημαντικά με μειωμένο επιπολασμό ευπάθειας. Συγκεκριμένα, κάθε επιπλέον μονάδα αύξησης του δείκτη MedDietScore σχετίστηκε με 11% (p=0,09), 4% (p=0,005) και 7% (p<0.001) λιγότερες πιθανότητες εμφάνισης της ευπάθειας, όπως αυτή μετρήθηκε με το εργαλείο της Fried, το εργαλείο Frailty Index και το εργαλείο Tilburg Frailty Indicator, αντίστοιχα. Στον ελληνικό πληθυσμό, ανεξάρτητα από τον ορισμό της ευπάθειας που χρησιμοποιείται, η συχνότητά της βρέθηκε χαμηλότερη από αυτήν που έχει αναφερθεί σε αντίστοιχες μελέτες που έχουν πραγματοποιηθεί σε ανεπτυγμένες χώρες. Το γεγονός ότι, ανεξάρτητα από το εργαλείο αξιολόγησης του συνδρόμου της ευπάθειας, βρέθηκε σημαντική συσχέτιση ανάμεσα στο βαθμό υιοθέτησης της Μεσογειακής Δίαιτας και της ευπάθειας αποτελεί το βασικό εύρημα αυτής της μελέτης, η οποία ανέδειξε την προστατευτική δράση της Μεσογειακής Δίαιτας απέναντι στο σύνδρομο της ευπάθειας

Objective Physical Function in the Alzheimer’s Disease Continuum: Association with Cerebrospinal Fluid Biomarkers in the ALBION Study

Cognitive and physical decline, both indicators of aging, seem to be associated with each other. The aim of the present study was to investigate whether physical function parameters (walking time and handgrip strength) are related to cerebrospinal fluid (CSF) biomarkers (amyloid-beta Aβ42, Tau, PhTau) in individuals in the Alzheimer’s disease (AD) continuum. The sample was drawn from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study, comprising 163 individuals aged 40–75 years: 112 cognitively normal (CN) and 51 with mild cognitive impairment (MCI). Physical function parameters were measured at baseline, a lumbar puncture was performed the same day and CSF biomarkers were analyzed using automated methods. The association between walking time, handgrip strength and CSF biomarkers was evaluated by linear correlation, followed by multivariate linear regression models adjusted for age, sex, education and APOEe4 genotype. Walking time was inversely related to CSF Aβ42 (lower CSF values correspond to increased brain deposition) in all participants (p < 0.05). Subgroup analysis showed that this association was stronger in individuals with MCI and participants older than 60 years old, a result which remained statistically significant after adjustment for the aforementioned confounding factors. These findings may open new perspectives regarding the role of mobility in the AD continuum

The Association of Adherence to the Mediterranean Diet with Depression in Older Adults Longitudinally Taking into Account Cognitive Status: Results from the HELIAD Study

Although research has generally shown a negative association between depression and adherence to the Mediterranean diet (MeDi), the literature related to older adults is controversial, perhaps partially due to the fact that cognitive status has not been considered. The aim of the current work was to investigate the association between MeDi and incident depression in a representative cohort of people, taking into account their cognitive status in multiple ways. The sample was drawn from the HELIAD study, a longitudinal study including a follow-up of 3 years after the baseline assessment. In total, 879 participants without depression at baseline were included (55.4% women, mean age ± Standard Deviation: 73.3 ± 5.0 years). Depression was determined as a score in the Geriatric depression scale ≥6 and/or antidepressant medication and/or clinical diagnosis of depression. Cox proportional hazard models adjusted for age, sex and education were employed. In the basic model, adherence to the MeDi was negatively associated with depression. In the most conservative model, excluding participants with dementia and Mild Cognitive Impairment, and after controlling for the baseline Cognitive Status, each unit (range 0–55) increase in MeDi was associated with a 6.2% decrease in the risk for depression (p < 0.001). These findings indicate that MeDi is negatively associated with depression longitudinally in older adults, above and beyond cognitive status

Daily Energy Intake Distribution and Cognitive Performance in Non-Demented Individuals

Cognitive disorders have become important public health issues around the world. Studies evaluating the association between cognitive decline and food timing are lacking. The objective of this study was to examine the potential association between energy intake distribution during the day and cognitive performance in cognitively healthy and mildly cognitive impaired individuals. Data were derived from the ongoing Albion study which includes people aged 40 years or older who have a positive family history of cognitive disorder or concern about their cognitive status. A thorough dietary and cognitive assessment was performed. Participants consuming low energy intake at the beginning of the day or high energy at the end of the day had higher cognitive function compared to participants characterized by the opposite pattern. This trend remained statistically significant even after adjustment for potential confounders (p = 0.043). This study suggests that individuals with worse cognitive function may choose to eat earlier during the day, when cognitive performance is better, and it might be hypothesized that a meal pattern characterized by high energy consumption at the beginning of the day or low energy at the end of the day could be a marker of cognitive impairment

Longitudinal Examination of Body Mass Index and Cognitive Function in Older Adults: The HELIAD Study

Given the increase in the aging population and thus in the prevalence of dementia, the identification of protective factors against cognitive decline is necessary. In a cohort of 1076 non-demented adults ≥ 65 years old (59.7% women) from the HELIAD study, we assessed whether changes in body mass index (BMI) were associated with changes in cognition over a 3-year follow-up period separately for those ≤ 75 and >75 years old. We identified six BMI trajectory groups based on participants’ BMI status at baseline and at the first follow-up visit; normal to normal BMI was the reference group. Major cognitive domains were evaluated, and a composite index reflecting global cognition was calculated. In participants aged ≤75 years, weight loss—moving from obesity to overweight or normal BMI—was associated with less decline in the memory composite score over time (β = 0.141; p = 0.035), while 3-year maintenance of a BMI ≥ 25 kg/m2 was related to greater reduction in the visuospatial composite score over time (β = −0.093; p = 0.020). Regarding participants aged >75 years, 3-year maintenance of a BMI ≥ 30 kg/m2 contributed to a slower rate of decline in the memory composite score over time (β = 0.102; p = 0.042), whereas weight loss—from overweight to normal BMI—was associated with a decreased attention/processing speed composite score longitudinally (β = −0.275; p = 0.043). Our findings indicated that the association between changes in BMI and cognitive functioning was modified by age. Weight management may have the potential to delay cognitive decline in older adults

Initial Data and a Clinical Diagnosis Transition for the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) Study

Background and Objectives: This article presents data from the ongoing Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study (ALBION) regarding baseline clinical characterizations and CSF biomarker profiles, as well as preliminary longitudinal data on clinical progression. Materials and Methods: As of March 2022, 138 participants who either were cognitively normal (CN, n = 99) or had a diagnosis of mild cognitive impairment (MCI, n = 39) had been recruited at the specialist cognitive disorders outpatient clinic at Aiginition Hospital. Clinical characteristics at baseline were provided. These patients were followed annually to determine progression from CN to MCI or even dementia. CSF biomarker data (amyloid &beta;1-42, phosphorylated tau at threonine 181, and total tau) collected using automated Elecsys&reg; assays (Roche Diagnostics) were available for 74 patients. These patients were further sorted based on the AT(N) classification model, as determined by CSF A&beta;42 (A), CSF pTau (T), and CSF tTau (N). Results: Of the 49 CN patients with CSF biomarker data, 21 (43%) were classified as exhibiting &ldquo;Alzheimer&rsquo;s pathologic change&rdquo; (A+&Tau;&ndash; (&Nu;)&minus;) and 6 (12%) as having &ldquo;Alzheimer&rsquo;s disease&rdquo; (A+T&ndash;(N)+, A+T+(N)&ndash;, or A+T+(N)+). Of the 25 MCI patients, 8 (32%) displayed &ldquo;Alzheimer&rsquo;s pathologic change&rdquo;, and 6 (24%) had &ldquo;Alzheimer&rsquo;s disease&rdquo;. A total of 66 individuals had a mean follow-up of 2.1 years (SD = 0.9, min = 0.8, max = 3.9), and 15 of those individuals (22%) showed a clinical progression (defined as a worsening clinical classification, i.e., from CN to MCI or dementia or from MCI to dementia). Overall, participants with the &ldquo;AD continuum&rdquo; AT(N) biomarker profile (i.e., A+T&ndash;(N)&ndash;, A+T&ndash;(N)+, A+T+(N)&ndash;, and A+T+(N)+) were more likely to clinically progress (p = 0.04).&nbsp;Conclusions: A CSF &ldquo;AD continuum&rdquo; AT(N) biomarker profile&nbsp;is associated with an increased risk of future clinical decline in CN or MCI subjects

Dementia Prevalence in Greece: The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)

Introduction:Study of the epidemiology of dementia to gain insight into putative predisposing and prophylactic factors is the first step toward establishing effective preventive and therapeutic strategies for this ever-growing public health problem. Relevant data in Greece are scattered and outdated.Methods:We investigated dementia prevalence as part of a population-representative epidemiological study [Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)] in 2 Greek regions.Results:Our sample comprised 1792 adults 65 years of age or older, who received a full neurological and neuropsychological evaluation that led to a consensus diagnosis. The overall prevalence of dementia was 5.0%, with 75.3% of the cases attributed to Alzheimer disease. Dementia odds were 15.8% higher for every year of advancing age and 9.4% lower for every additional year of education. Carrying at least 1 APOE-epsilon 4 allele doubled the risk of dementia, whereas sex did not exert a statistically significant effect.Conclusions:Our results are consistent with previous research in Southern European countries; dementia prevalence in Greece is in the lower range of what has been reported globally

Sleep Polygenic Risk Score Is Associated with Cognitive Changes over Time

Sleep problems have been associated with cognition, both cross-sectionally and longitudinally. Specific genes have been also associated with both sleep regulation and cognition. In a large group of older non-demented adults, we aimed to (a) validate the association between Sleep Polygenic Risk Score (Sleep PRS) and self-reported sleep duration, and (b) examine the association between Sleep PRS and cognitive changes in a three-year follow-up. Participants were drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A structured, in-person interview, consisting of a medical history report and physical examination, was conducted for each participant during each of the visits (baseline and first follow-up). In total, 1376 participants were included, having all demographic, genetic, and cognitive data, out of which, 688 had at least one follow-up visit. In addition, an extensive neuropsychological assessment examining five cognitive domains (memory, visuo-spatial ability, attention/speed of processing, executive function, and language) was administered. A PRS for sleep duration was created based on previously published, genome-wide association study meta-analysis results. In order to assess the relationship between the Sleep PRS and the rate of cognitive change, we used generalized estimating equations analyses. Age, sex, education, ApolipoproteinE-ε4 genotype status, and specific principal components were used as covariates. On a further analysis, sleep medication was used as a further covariate. Results validated the association between Sleep PRS and self-reported sleep duration (B = 1.173, E-6, p = 0.001). Further, in the longitudinal analyses, significant associations were indicated between increased Sleep PRS and decreased visuo-spatial ability trajectories, in both the unadjusted (B = −1305.220, p = 0.018) and the adjusted for the covariates model (B = −1273.59, p = 0.031). Similarly, after adding sleep medication as a covariate (B = −1372.46, p = 0.019), none of the associations between Sleep PRS and the remaining cognitive domains were significant. PRS indicating longer sleep duration was associated with differential rates of cognitive decline over time in a group of non-demented older adults. Common genetic variants may influence the association between sleep duration and healthy aging/cognitive health