Polygenic indices for cognition in healthy aging; the role of brain measures.

Background: Genome-wide association studies (GWAS) have identified large numbers of genetic variants associated with cognition. However, little is known about how these genetic discoveries impact cognitive aging. Methods: We conducted polygenic-index (PGI) analysis of cognitive performance in n = 168 European-ancestry adults aged 20-80. We computed PGIs based on GWAS of cognitive performance in young/middle-aged and older adults. We tested associations of the PGI with cognitive performance, as measured through neuropsychological evaluation. We explored whether these associations were accounted for by magnetic resonance imaging (MRI) measures of brain-aging phenotypes: total gray matter volume (GM), cortical thickness (CT), and white matter hyperintensities burden (WMH). Results: Participants with higher PGI values performed better on cognitive tests (B = 0.627, SE = 0.196, p = 0.002) (age, sex, and principal components as covariates). Associations remained significant with inclusion of covariates for MRI measures of brain aging; B = 0.439, SE: 0.198, p = 0.028). PGI associations were stronger in young and middle-aged (age<65) as compared to older adults. For further validation, linear regression for Cog PGI and cognition in the fully adjusted model and adding the interaction between age group and Cog PGI, showed significant results (B = 0.892, SE: 0.325, p = 0.007) driven by young and middle-aged adults (B = -0.403, SE: 0.193, p = 0.039). In ancillary analysis, the Cognitive PGI was not associated with any of the brain measures. Conclusions: Genetics discovered in GWAS of cognition are associated with cognitive performance in healthy adults across age, but most strongly in young and middle-aged adults. Associations were not explained by brain-structural markers of brain aging. Genetics uncovered in GWAS of cognitive performance may contribute to individual differences established relatively early in life and may not reflect genetic mechanisms of cognitive aging.

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.

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.

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.