Subjective Cognitive Decline as a predictor of Frailty in older adults: Hellenic Longitudinal Investigation of Aging and Diet study (HELIAD).

BACKGROUND: Subjective cognitive decline (SCD) is a self-evaluation of cognitive impairment, in the absence of observed objective cognitive deficits on a neuropsychological assessment. Frailty refers to a multidimensional syndrome where the individual has poor health including falls, disabilities, hospitalization, and vulnerability. Both terms are associated with cognitive decline and increased incidence of dementia. The present longitudinal study explored whether the detection of SCD can predict the development of frailty over time. METHODS: The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) is an epidemiological, population-based study. From the original testing sample of 1,984 older Greek individuals (≥65 years old), 1,121 remained in the longitudinal analysis. Participants diagnosed with frailty, Mild Cognitive Impairment (MCI), dementia, severe depression, and anxiety, in the baseline assessment were excluded from the analysis (n=146), resulting in a total sample of 975 participants. The average follow-up interval was 3.1 years (SD=0.84 years). SCD was assessed in the baseline assessment with a series of eighteen questions. The questions regarding SCD were categorized according to cognitive domains. Frailty was assessed according to a phenotypic-physiologic (Fried's definition) and a multidomain approach (Frailty Index). Univariate and multivariate Cox regression analyses were used for exploring the role of SCD in developing frailty. RESULTS: The proportion of individuals with frailty according to Fried's definition was greater compared to the Frailty Index. At follow-up according to Fried's definition, a greater proportion of cases with frailty was found in those who reported SCD complaints regarding orientation (OD) (HR=3.12 95% CI:1.45-6.73 p<0.004) or in those who reported at least three SCD complaints regarding their memory performance (SMC3) (HR=1.92 95% CI:1.05-3.52 p<0.035) at the baseline assessment. Subjective complaints regarding orientation were predictive of a greater hazard of frailty as defined by the Fried scale (HR=3.12 95% CI:1.45-6.73 p<0.004) and the Frailty Index (HR=3.59 95% CI:1.77-7.25 p<0.001). CONCLUSION: Our findings demonstrate that healthy older adults who report SCD complaints regarding orientation or state that they have at least three memory complaints have a higher risk of developing frailty. Additionally, the number of participants with a clinical diagnosis of MCI or dementia, compared to individuals with normal aging, at follow-up was found to be significantly greater in cases with frailty according to both frailty definitions applied (p<0.001). Consequently, it is advisable to use screening questionnaires for SCD covering multiple cognitive domains in clinical practice for identifying and managing frailty, thus, implementing effective interventions to promote healthy aging.

Sex Differences in Frailty Incidence in Greek Community-Dwelling Older People: The HELIAD Study.

BACKGROUND: Previous frailty studies found higher prevalence of frailty in female than in male participants. This was mainly attributed to the fact that compared to men, women show increased longevity. Recent studies have reported that the observed difference between sexes applies irrespectively of the age of older people. OBJECTIVES: To provide data on sex differences in incident frailty by applying both phenotypic and multi-domain frailty measures in the same population of Greek community-dwelling older people. DESIGN: Longitudinal study. SETTING: Data were drawn from the Hellenic longitudinal Investigation of Aging and Diet (HELIAD), a population-based, multidisciplinary study designed to estimate the prevalence and incidence of dementia in the Greek population. PARTICIPANTS: 1104 participants aged 65 year and above were included in this longitudinal study. This incidence cohort was re-evaluated after a mean follow-up period of 3.04±0.90 years. MEASUREMENTS: Frailty was operationalized using 5 different definitions in the same population: the Fried Frailty Phenotype (FFP) definition, the FRAIL Scale, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI) and the Groningen Frailty Index (GFI). Frailty incidence was calculated a) for the whole sample, b) separately for men and women and c) after both age and sex stratification. RESULTS: Age and sex stratification revealed that irrespective of age and frailty measurement, women showed higher incidence rates of frailty than men. Specifically, frailty seems to be a condition concerning women >65 years old, but when it comes to men, it is more frequent in those aged more than 75 years old. Finally, in relation to overall frailty incidence and comparing our results to previous studies, we detected a lower frailty incidence in the Greek population. CONCLUSIONS: Differences between the two sexes indicate that when exploring the factors that are related to frailty, studies should provide data disaggregated for men and women.

Adherence to the Mediterranean diet and incident frailty: Results from a longitudinal study.

OBJECTIVES: The aim of the current prospective study was to examine the relationship between adherence to the Mediterranean diet and incident frailty. STUDY DESIGN: 1075 Greek community-dwelling older adults from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present longitudinal analysis. MAIN OUTCOME MEASURES: Adherence to the Mediterranean diet was evaluated through the MedDietScore, calculated from the information participants provided on a validated food frequency questionnaire. Frailty was assessed using two multidomain tools: the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI). Analysis of the incidence of frailty as a function of the baseline MedDietScore was performed using Cox proportional hazards models. Additionally, Generalized Estimating Equations (GEE) models were used to explore whether the baseline MedDietScore was associated with the change in the total number of frailty criteria met by participants over time. In testing for a dose-response association between Mediterranean diet and frailty, the MedDietScore was treated either as a continuous variable or as tertiles of low, medium and high adherence to MeDi. RESULTS: 176 and 131 participants developed incident frailty, as measured with the FI and TFI respectively. Each unit of MedDietScore was associated with a 5% (ΗR 0.95, 95% CI 0.91-0.99, p = 0.012) and 10% (ΗR 0.90, 95% CI 0.86-0.95, p ≤ 0.001) decrease in the risk of incident frailty when measured with the FI and TFI respectively. Compared with participants reporting low adherence to the Mediterranean diet (lowest tertile), those with high adherence (highest tertile) had a 41% (ΗR 0.59, 95% CI 0.38-0.91, p = 0.017) and a 57% (ΗR 0.43, 95% CI 0.27-0.70, p ≤ 0.001) lower risk of incident frailty as measured with the FI and TFI respectively. After excluding from the analyses participants diagnosed with dementia at baseline or follow-up, the same results were obtained: each unit of MedDietScore was associated with a 5% (HR 0.95 CI 0.91-0.99, p = 0.023) and a 10% (HR 0.90 CI 0.86-0.94, p ≤ 0.001) decrease in the risk of incident frailty as measured with the FI and TFI respectively. CONCLUSIONS: The present longitudinal study showed that non-frail community-dwelling older adults with high adherence to the Mediterranean dietary pattern had a significantly lower incidence of frailty.

Association between 9p21-23 Locus and Frailty in a Community-Dwelling Greek Population: Results from the Hellenic Longitudinal Investigation of Ageing and Diet.

BACKGROUND: Frailty is a complex geriatric syndrome arising from a combination of genetic and environmental factors and is associated with adverse health outcomes and mortality. A recent study reported an association between variants of the 9p21-23 locus, associated with a number of age-related disorders, including Alzheimer's disease (AD), and frailty. Frailty has been associated with increased risk of developing AD and it has been proposed that frailty burden may modify AD clinical presentation. In view of the overlapping genetic architecture between the two disorders, it is noteworthy to conduct studies to uncover risk variants that contribute to both AD and frailty. The purpose of this study is to test the reproducibility of the association of 9p21-23 locus with frailty in a population that is ethnically different from previous work and in the context of multidimensional definitions of frailty that will allow us to examine the potential impact to domains pertaining to AD pathology. METHODS: We operationalized frailty according two definitions and the corresponding instruments, the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI) and we determined genotypes of eight alleles previously identified as risk increasing for frailty in 1172 community-dwelling older participants (57% females) from the HELIAD study with a mean age of 74 years old. We cross-sectionally investigated the association between risk alleles and frailty, as well as with specific components of each definition using linear regression analyses adjusted for age, sex and years of education. RESULTS: Compared to non-carriers, carriers of rs7038172 C risk allele, were associated with a higher FI Score (ß=0.089, p=0.002). Similarly, we found a positive association between the presence of at least one rs7038172 C variant and TFI score (ß=0.053, p=0.04). Moreover, the rs7038172 variant was associated, irrespectively of dementia status, with the memory and psychological domain of FI and TFI, respectively. CONCLUSION: Our study confirms the association of the rs7038172 C allele with the frailty syndrome in a Greek population and in the context of multidimensional definitions of frailty. Furthermore, we report novel associations between this allele and the memory domain of FI and the psychological domain of TFI, that includes memory problems on its components. Given that frailty burden has been shown to modify the AD clinical presentation, it is likely that rs7038172 C allele may accelerate the transition of AD or frailty to dementia Overall, our study corroborates the role of the 9p21-23 region in frailty development and draw potential links with AD pathology.

Plasma GSH levels and Alzheimer's disease. A prospective approach.: Results from the HELIAD study.

BACKGROUND: Potential links between oxidative stress and the pathophysiology of Alzheimer's disease (AD) have been reported in the existing literature. Biological markers of oxidative stress, such as the reduced form of glutathione (GSH), may have a potential role as predictive biomarkers for AD development. The aim of the present study was to explore the longitudinal associations between plasma GSH and the risk of developing AD or cognitive decline, in a sample of community-dwelling, non-demented older adults. METHODS: Participants from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present prospective study. The sample used in the analyses consisted of 391 non-demented individuals over the age of 64 (mean age = 73.85 years; SD = 5.06), with available baseline GSH measurements and longitudinal follow-up. Plasma GSH was treated both as a continuous variable and as tertiles in our analyses. Cox proportional hazards models were used to evaluate the hazard ratio (HR) for AD incidence as a function of baseline plasma GSH. Generalized estimating equations (GEE) models were deployed to explore the associations between baseline plasma GSH and the rate of change of performance scores on individual cognitive domains over time. Models were adjusted for age, years of education and sex. Supplementary exploratory models were also adjusted for mild cognitive impairment (MCI) at baseline, risk for malnutrition, physical activity and adherence to the Mediterranean dietary pattern. RESULTS: A total of 24 incident AD cases occurred during a mean (SD) of 2.99 (0.92) years of follow-up. Individuals in the highest GSH tertile group (highest baseline plasma GSH values) had a 70.1% lower risk for development of AD, compared to those in the lowest one [HR = 0.299 (0.093-0.959); p = 0.042], and also demonstrated a slower rate of decline of their executive functioning over time (5.2% of a standard deviation less decline in the executive composite score for each additional year of follow-up; p = 0.028). The test for trend was also significant suggesting a potential dose-response relationship. CONCLUSION: In the present study, higher baseline plasma GSH levels were associated with a decreased risk of developing AD and with a better preservation of executive functioning longitudinally.

Prevalence and Risk Factors of Frailty in a Community-Dwelling Population: The HELIAD Study.

Objective: To estimate the prevalence of frailty using five different instruments in a cohort of older adults and explore the association between frailty and various risk factors. Method: 1,867 participants aged 65 years and above were included in the current retrospective cross-sectional study. Frailty was operationalized according to the Fried definition, the FRAIL Scale, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI), and the Groningen Frailty Index (GFI). We explored the role of various frailty risk factors using logistic regression analyses. Results: The prevalence of frailty varied depending on the definition used (Fried definition = 4.1%, FRAIL Scale = 1.5%, FI = 19.7%, TFI = 24.5%, and GFI = 30.2%). The only risk factors consistently associated with frailty irrespectively of definition were education and age. Conclusion: The frailty prevalence reported in our study is similar or lower to that reported in other population studies. Qualitative differences between frailty definitions were observed.

Assessing functional status using the IADL-extended scale: results from the HELIAD study.

OBJECTIVES: Instrumental activities of daily living (IADL) have been operationalized as exhibiting a greater level of complexity than basic ADL. In the same way, incorporating more advanced ADLs may increase the sensitivity of functional measures to identify cognitive changes that may precede IADL impairment. Towards this direction, the IADL-extended scale (IADL-x) consists of four IADL tasks and five advanced ADLs (leisure time activities). DESIGN: Retrospective, cross-sectional study. SETTING: Athens and Larissa, Greece. PARTICIPANTS: 1,864 community-dwelling men and women aged over 64. MEASUREMENTS: We employed both the IADL-x and IADL scales to assess functional status among all the participants. Diagnoses were assigned dividing the population of our study into three groups: cognitively normal (CN), mild cognitive impairment (MCI) and dementia patients. Neuropsychological evaluation was stratified in five cognitive domains: memory, language, attention-speed, executive functioning and visuospatial perception. Z scores for each cognitive domain as well as a composite z score were constructed. Models were controlled for age, sex, education and depression. RESULTS: In both IADL-x and IADL scales dementia patients reported the most functional difficulties and CN participants the fewest, with MCI placed in between. When we restricted the analyses to the CN population, lower IADL-x score was associated with worse cognitive performance. This association was not observed when using the original IADL scale. CONCLUSION: There is strong evidence that the endorsement of more advanced IADLs in functional scales may be useful in detecting cognitive differences within the normal spectrum.

Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION): study design, cohort description, and preliminary data.

Objectives: Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) is a longitudinal ongoing study initiated in 2018 that takes place in the Cognitive Disorders Clinic of Aiginition Hospital of the National and Kapodistrian University of Athens. Its aim is to address several research questions concerning the preclinical and prodromal stage of Alzheimer's disease and explore potential markers for early detection, prediction, and primary prevention of dementia. Methods: We here present the design and the preliminary baseline characteristics of ALBION. The sample of our study consists of people aged over 50 who are concerned about their memory but are cognitively normal (CN) or have mild cognitive deficits. Each participant undergoes an extensive assessment including several demographic, medical, social, environmental, clinical, nutritional, neuropsychological determinants and lifestyle activities. Furthermore, we are collecting data from portable devices, neuroimaging techniques and biological samples (blood, stools, CSF). All participants are assessed annually for a period of 10 years. Results: In total, 47 participants have completed the initial evaluation up to date and are divided in two groups, CN individuals (N = 26) and MCI patients (N = 21), based on their cognitive status. The participants are, on average, 64 years old, 46.3% of the sample is male with an average of 12.73 years of education. MCI patients report more comorbidities and have a lower score in the MMSE test. Regarding APOE status, 2 participants are ε4 homozygotes and 10 ε4 heterozygotes. CSF analyses (Aß42, Τ-tau, P-tau) revealed no differences between the two groups. Conclusion: The ALBION study offers an opportunity to explore preclinical dementia and identify new and tailored markers, particularly relating to lifestyle. Further investigation of these populations may provide a wider profile of the changes taking place in the preclinical phase of dementia, leading to potentially effective therapeutic and preventive strategies.

History of induced abortions and frailty in older Greek women: results from the HELIAD study.

PURPOSE: Women are almost twice as likely as men to develop frailty and early-traumatic experiences related to reproduction may have a role to play. The purpose of this study was to investigate the association between a history of induced abortions and risk of frailty. METHODS: 1062 women aged ≥ 65 years from the HELIAD study were included in the present cross-sectional study. Frailty was assessed by frailty index and Fried definitions. The history of abortion and of other reproductive experiences (age onset of menstruation, age of menopause, number of offspring, and number of miscarriages) was obtained by all participants. Logistic and linear regression analyses were performed to examine whether the number of abortions was related to frailty. RESULTS: When frailty was defined with frailty index, women with 1 or 2 abortions had 1.7 higher risk of frailty compared to women with no history of abortions, while those with more than 3 abortions had more than a twofold higher risk of frailty. Two supplementary analyses excluding women with surgical operations' history and women with dementia revealed similar results. When frailty was defined with Fried definition, the analysis was marginally significant when abortion was inserted as a categorical variable. Women with more than 3 abortions showed 2.4 higher risk of frailty compared to women with no history of abortion. CONCLUSION: The number of induced abortions was associated with moderate higher odds of frailty, when frailty was defined according to frailty index. A similar trend was revealed in the model with Fried definition after trichotomization of abortions.