Genetically downregulated Interleukin-6 signalling is associated with a lower risk of frailty.

BACKGROUND: numerous studies point towards a critical role of Interleukin 6 (IL-6) pathway in frailty pathogenesis yet the causal relationship between the two remains elusive. METHODS: we selected genetic variants near the IL-6 receptor locus (IL-6R) associated with reduced C-reactive protein (CRP) levels, a downstream effector of IL-6 pathway, and we used them as genetic proxies of IL-6 signalling downregulation. We then performed a two-sample Mendelian randomisation (MR) to investigate the association with frailty status, as defined by the Frailty Index (FI) in 11,171 individuals from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD) study. MR analysis was repeated after excluding depression or cognition-related FI items as well as following age or sex stratification. Association with frailty was also examined using an alternative instrument, weighted on s-IL-6R levels. Replication was attempted in UK Biobank dataset. RESULTS: genetic predisposition to IL-6 signalling downregulation, weighted on CRP levels, was associated with lower risk of frailty, inserted either as categorical (odds ratio [95% confidence interval] = 0.15 [-3.39, -0.40], P = 0.013) or continuous variable (beta [se] = -0.09 [0.003], P = 0.0009). Sensitivity analyses revealed similar estimates across different MR methods with no evidence for horizontal pleiotropy or heterogeneity. Results remained robust after exclusion of depression or cognition-related FI items and following sex or age stratification. Genetically increased s-IL-6R levels were negatively correlated with frailty and this finding remained significant in a meta-analysis of UK Biobank and HELIAD cohorts. CONCLUSION: our results support a potential causal effect of IL-6 signalling on frailty and further suggest that downregulation of IL-6 levels may reduce frailty risk.

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.

Apolipoprotein ε4 allele is associated with frailty syndrome: results from the hellenic longitudinal investigation of ageing and diet study.

Apolipoprotein (APOE) ε4 allele has been associated with a number of age-related diseases but previous studies failed to identify any link with Frailty syndrome. The aim of the present study is to investigate the association between APOE ε4 allele and frailty syndrome. We operationalised Frailty according to the Fried definition, and we determined the APOE genotype in 1234 participants of the hellenic longitudinal investigation of ageing and diet study. Logistic regression analyses were performed to examine the association between APOE ε4 allele and frailty. Models were adjusted for age, education, sex, presence (or absence) of hypertension, diabetes, myocardial infraction, coronary disease, congestive heart failure, arrhythmia or other heart disease, family history of dementia and current smoking. The same models were performed after exclusion of patients with dementia and participants with APOE ε2/ε4 genotype. In the fully adjusted model, carriers of APOE ε4 allele had 2.753 higher odds of frailty relative to non-carriers. After trichotomization of APOE genotype, APOE ε4 heterozygotes had 2.675 higher risk of frailty compared to non-carriers while exclusion of patients with dementia or/and APOE ε2/ε4 genotype did not alter the association. The APOE ε4 allele may be a significant biomarker of frailty with diagnostic and prognostic capacity.

Associations between sleep and obesity indices in older adults: results from the HELIAD study.

BACKGROUND: Short sleep duration and low sleep quality are negatively associated with obesity in young adults, but in older people the results are inconsistent. AIMS: The aim of the present study was to examine the associations between sleep duration and quality with both body mass index (BMI) and waist circumference (WC) and to investigate sex- and age-specific associations in a population-representative cohort of older adults. METHODS: 1781 participants ≥ 65 years old from the HELIAD study were included. Sleep duration and quality were based on self-report, whereas BMΙ and WC were evaluated clinically. RESULTS: Sleep duration was inversely related to WC, only in women, even after adjustment for age, sex, years of education, total energy intake and level of physical activity. Furthermore, sleep quality was negatively related to both BMI and WC in women. In men, however, no significant relationships were observed between these variables. Associations between sleep and weight did not differ between those aged < 73 and ≥ 73 years old. DISCUSSION: To the best of our knowledge, this is the first study examining both sleep duration and quality with BMI and WC in older adults, performing by-sex analysis. Although additional studies are needed, improvements in sleep habits should be considered in weight management of older individuals. CONCLUSIONS: Our results suggest that poor sleep is associated to adverse weight effects in older women, but not men.

Mediterranean Lifestyle in Relation to Cognitive Health: Results from the HELIAD Study.

Many lifestyle factors have been linked to cognitive function but little is known about their combined effect. An overall lifestyle pattern for people living in the Mediterranean basin has been proposed, including diet, but also physical activity, sleep and daily living activities with social/intellectual aspects. We aimed to examine the associations between a combination of these lifestyle factors and detailed cognitive performance. A total of 1716 participants from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD), a population-based study of participants ≥65 years, were included in this analysis. Lifestyle factors were evaluated using standard, validated questionnaires and a Total Lifestyle Index (TLI) was constructed. Cognitive outcomes included mild cognitive impairment (MCI) diagnosis, a composite z-score (either continuous or with a threshold at the 25th percentile) and z-scores for five cognitive domains. A higher TLI was associated with 65% reduced odds for MCI in the non-demented individuals and 43% reduced odds for low global cognition when MCI participants were excluded, a risk reduction equivalent to 9 and 2.7 fewer years of ageing, respectively. Each lifestyle factor was differentially associated with domain-specific cognitive performance. Our results suggest that a TLI, more so than single lifestyle parameters, may be related to cognitive performance.

Associations between the mediterranean diet and sleep in older adults: Results from the hellenic longitudinal investigation of aging and diet study.

AIM: Although there is some evidence of the relationships between sleep duration/quality and nutrient and/or food intake, the associations between sleep and dietary patterns have been poorly explored. The aim of the present study was to evaluate sleep duration and quality in relation to adherence to the Mediterranean diet (MeDi), and to investigate the sex- and age-specific associations in a population-representative cohort of older adults. METHODS: Participants from the Hellenic Longitudinal Investigation of Aging and Diet were included. The sample consisted of 1639 adults aged ≥65 years. Sleep duration and quality were assessed through a self-report questionnaire, whereas adherence to the MeDi was evaluated by an a priori score. RESULTS: Sleep quality was positively associated with the MeDi in the unadjusted and the adjusted model (age, sex, depression, years of education, body mass index, level of physical activity and total energy intake were added as covariates). In contrast, sleep duration was not associated with MeDi adherence either in the unadjusted or the adjusted models. In relation to the age-related associations, sleep quality was positively associated with MeDi adherence in those aged ≤75 years, and not in those aged >75 years. Associations between sleep and MeDi did not differ between men and women. CONCLUSIONS: The present results suggest that sleep quality is associated with MeDi adherence in older adults; there are also age-specific associations between sleep quality and the MeDi. Although additional studies are required, improvements in diet quality should be considered in the context of sleep management interventions in older individuals. Geriatr Gerontol Int 2018; 18: 1543-1548.

Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease.

OBJECTIVE: To investigate the effects of completed pregnancy with childbirth and incomplete pregnancy without childbirth on the late-life cognition and the risk of Alzheimer disease (AD) in women. METHODS: Using the pooled data of 3,549 women provided by 2 population-based cohort studies, we conducted logistic regression analyses to examine retrospectively the associations of completed and incomplete pregnancy with the risks of mild cognitive impairment and AD. For women without dementia, we also conducted analyses of covariance to examine the associations of completed and incomplete pregnancy with Mini-Mental State Examination (MMSE) score. RESULTS: Grand multiparous women who experienced ≥5 completed pregnancies showed an ≈1.7-fold higher risk of AD than those who experienced 1 to 4 completed pregnancies (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.04-2.72), while those who had incomplete pregnancies showed half the level of AD risk compared with those who never experienced an incomplete pregnancy (OR 0.43, 95% CI 0.24-0.76 for 1 incomplete pregnancy; OR 0.56, 95% CI 0.34-0.92 for ≥2 incomplete pregnancies). In women without dementia, the grand multiparous had worse MMSE scores than those with 1 to 4 completed pregnancies (p < 0.001), while those who experienced ≥1 incomplete pregnancies had better MMSE scores than those who never experienced an incomplete pregnancy (p = 0.008). CONCLUSIONS: Grand multiparity was associated with high risk of AD, while incomplete pregnancy was associated with low risk of AD in late life.

Adherence to Mediterranean Diet and Frailty.

OBJECTIVE: Το investigate associations between adherence to the Mediterranean diet and frailty in a Greek population of older adults. DESIGN: Cross-sectional 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: Data from 1740 participants aged ≥65 years were included in the present analysis. Participants were selected through random sampling from the records of 2 Greek municipalities. MEASUREMENTS: Adherence to Mediterranean diet was evaluated through the MedDietScore, calculated from the information participants provided to a validated food frequency questionnaire. Frailty was assessed using 3 different definitions (the phenotypic approach proposed by Fried et al, the Frailty Index, and the Tilburg Frailty Indicator). Unadjusted and adjusted logistic and linear regression models were performed. RESULTS: Of our participants, 70 (4%), 325 (18.7%), and 442 (25.4%) were identified as frail according to the Fried et al definition, the Frailty Index, and the Tilburg Frailty Indicator, respectively. Adjusting for confounding factors, each additional unit in the MedDietScore was associated with a 5% (P = .09), 4% (P = .005), and 7% (P < .001) decrease in the odds for frailty according to the Fried definition, the Frailty Index, and the Tilburg Frailty Indicator, respectively. CONCLUSIONS: According to study results, a higher adherence to the Mediterranean diet was associated with lower odds of frailty, irrespective of the definition used. This finding may be of relevance in the setting of population-based prevention efforts as well as in clinical practice.

Mediterranean diet and cognitive health: Initial results from the Hellenic Longitudinal Investigation of Ageing and Diet.

BACKGROUND: The Mediterranean dietary pattern has been associated with a decreased risk of many degenerative diseases and cognitive function in particular; however, relevant information from Mediterranean regions, where the prototype Mediterranean diet is typically adhered to, have been very limited. Additionally, predefined Mediterranean diet (MeDi) scores with use of a priori cut-offs have been used very rarely, limiting comparisons between different populations and thus external validity of the associations. Finally, associations between individual components of MeDi (i.e., food groups, macronutrients) and particular aspects of cognitive performance have rarely been explored. We evaluated the association of adherence to an a priori defined Mediterranean dietary pattern and its components with dementia and specific aspects of cognitive function in a representative population cohort in Greece. METHODS: Participants from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD), an on-going population-based study, exploring potential associations between diet and cognitive performance in a representative sample from Greek regions, were included in this analysis. Diagnosis of dementia was made by a full clinical and neuropsychological evaluation, while cognitive performance was assessed according to five cognitive domains (memory, language, attention-speed, executive functioning, visuospatial perception) and a composite cognitive score. Adherence to MeDi was evaluated by an a priori score (range 0-55), derived from a detailed food frequency questionnaire. RESULTS: Among 1,865 individuals (mean age 73±6 years, 41% male), 90 were diagnosed with dementia and 223 with mild cognitive impairment. Each unit increase in the Mediterranean dietary score (MedDietScore) was associated with a 10% decrease in the odds for dementia. Adherence to the MeDi was also associated with better performance in memory, language, visuospatial perception and the composite cognitive score; the associations were strongest for memory. Fish consumption was negatively associated with dementia and cognitive performance positively associated with non-refined cereal consumption. CONCLUSIONS: Our results suggest that adherence to the MeDi is associated with better cognitive performance and lower dementia rates in Greek elders. Thus, the MeDi in its a priori constructed prototype form may have cognitive benefits in traditional Mediterranean populations.