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Preserving cognitive function with age or super-aging greatly contributes to successful aging. Super-aging nonagenarians born in Denmark in either year 1905 or 1915 were classified as Cognitively High-Performing Oldest Old individuals with a five item cognitive composite score, equivalent to or better than mean middle-aged subjects. Cognitively high-performers were more physically active and had a better physical performance on e.g., Activity of Daily Living (p-value < 0.01), gait speed (p-value < 0.01) and grip strength (p-value < 0.05) compared with age-matched peers. Cognitive high-performing was also linked to lower depression symptomatology. When comparing super-agers with semi super-agers classified by Mini Mental State Examination > 27, super-agers were still more physically active and had a better physical performance (p-value < 0.05). Results suggests that physical activity is a lifestyle factor strongly associated with both semi and full cognitive super-aging., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Cognitive function is a substantially heritable trait related to numerous important life outcomes. Several genome-wide association studies of cognitive function have in recent years led to the identification of thousands of significantly associated loci and genes. Individuals included in these studies have rarely been nonagenarians and centenarians, and since cognitive function is an important component of quality of life for this rapidly expanding demographic group, there is a need to explore genetic factors associated with individual differences in cognitive function at advanced ages. In this study, we pursued this by performing a genome-wide association study of cognitive function in 490 long-lived Danes (age range 90.1-100.8 years). While no genome-wide significant SNPs were identified, suggestively significant SNPs (P < 1 × 10 -5 ) were mapped to several interesting genes, including ZWINT, CELF2, and DNAH5, and the glutamate receptor genes GRID2 and GRM7. Additionally, results from a gene set over-representation analysis indicated potential roles of gene sets related to G protein-coupled receptor (GPCR) signaling, interaction between L1 and ankyrins, mitogen-activated protein kinase (MAPK) signaling, RNA degradation, and cell cycle. Larger studies are needed to shed further light on the possible importance of these suggestive genes and pathways in cognitive function in nonagenarians and centenarians., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Transient cognitive impairment is common in adult patients of all ages following anaesthesia and surgery. Apolipoprotein E (APOE) ε4 carriers may have a larger deterioration in short-term cognitive function after major surgery compared with APOE ε4 noncarriers., Objectives: The aim was to examine the effect of APOE ε4 on the association between exposure to surgery and anaesthesia, and subsequent cognitive functioning. A more pronounced deterioration in cognitive function in APOE ε4 carriers was hypothesised., Design: An observational cross-sectional and a 6 to 10 years longitudinal twin cohort design., Setting: Survey and register study of 2936 Danish twins aged 45 to 92 years., Main Outcome Measures: Cognitive function was assessed using five age-sensitive cognitive tests. In the cross-sectional study, we compared twins exposed to surgery with a reference group (unexposed). Linear regression models were used adjusting for sex and age and stratified by APOE ε4 carrier status. In the longitudinal cognitive follow-up study 1671 twins participated. Intrapair analyses were also performed using 70 same-sexed twin pairs concordant for APOE ε4 carrier status, but discordant for major surgery., Results: APOE ε4 carriers had lower cognitive scores compared with noncarriers, and this was statistically significant in elderly twins 70+ years of age (mean difference, -0.67; 95% CI, -1.14 to -0.17). There was no significant impact on cognitive function after surgery according to APOE ε4 carrier status in the cross-sectional study. Similarly, there was no APOE ε4 modification in the longitudinal study. Also, in the intrapair analyses no evidence was found of lower cognitive score after major surgery compared with the nonexposed cotwins among APOE ε4 carriers., Conclusion: No evidence was found of more pronounced long-term deterioration in cognitive function after surgery among APOE ε4 carriers, but elderly APOE ε4 carriers in general performed worse on the cognitive tests than noncarriers.

Neurobiology is regulated by miRNA. Here circulating plasma miRNAs were assayed on a 754 miRNA OpenArray platform using 90 monozygotic elderly twins (73-95 year of age) and associated with mini mental state examination (MMSE) and a five-component cognitive score (CCS) in an explorative study. Both ordinary individual and twin-pair analyses were performed with level of cognitive scores. Candidate miRNAs were further associated with cognitive decline over 10 years using up to six repeated assessments. A total of 278 miRNAs were expressed in plasma from at least ten participants and 23 miRNAs were nominally associated (i.e., at an uncorrected p < 0.05) with CCS or MMSE in the paired analyses. Generally, elderly individuals with poor cognitive function had increase miRNA expression compared with equivalent individuals who performed better on the cognitive scale. Three miRNAs, miR-151a-3p, miR-212-3p and miR-1274b were associated with CCS both in the paired and the individual analysis. Four miRNAs found to be associated with CCS in cross-sectional analysis were also found to show an association in longitudinal analysis such that increase miRNA expression was associated with steeper cognitive decline. We propose a shared biological path underlies dementia and normative cognitive aging.

Aim: To explore the genetic and environmental influences on cardiovascular risk factors (CVRF) and cognitive function in the world's largest and rapidly aging Chinese population., Methods: Cognitive function and CVRF, including body mass index, systolic blood pressure, diastolic blood pressure, pulse pressure, glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol were measured in 379 complete twin pairs. Univariate and bivariate twin models were fitted to estimate the genetic and environmental components in the variance and covariance of CVRF and cognition., Results: Mild-to-high heritability was estimated for CVRF and cognition (0.27-0.74). Unique environmental factors showed low-to-moderate contributions (0.23-0.56). Only HDLC presented significant common environmental contribution (0.50). Bivariate analysis showed significantly negative genetic correlations (r G ) between cognition and systolic blood pressure (r G = -0.56), diastolic blood pressure (r G = -0.42), pulse pressure (r G = -0.45), and positive genetic correlations between cognition and total cholesterol (r G = 0.33), triglyceride (r G = 0.23) and HDLC (r G = 0.41). HDLC and cognition presented a unique environmental correlation (r E = -0.13), but in the opposite direction., Conclusions: Cognitive function was genetically related to systolic blood pressure, diastolic blood pressure, pulse pressure, total cholesterol, triglyceride and HDLC with a negative or positive direction. Cognition and HDLC might share part of a similar unique environmental factor. Geriatr Gerontol Int 2018; 18: 352-359., (© 2017 Japan Geriatrics Society.)

Decline in cognitive abilities is a major concern in aging individuals. A potential important factor for functioning of the central nervous system in late-life stages is the KLOTHO (KL) gene. KL is expressed in various organs including the brain and is involved in multiple biological processes, for example, growth factor signaling. In the present study, 19 tagging gene variants in KL were studied in relation to 2 measures of cognitive function, a 5-item cognitive composite score and the Mini Mental State Examination, in 1,480 Danes 92-100 years of age. We found that heterozygotes for the previously reported KL-VS had poorer cognitive function than noncarriers. Two other variants positioned in the 5' end of the gene, rs398655 and rs562020, were associated with better cognitive function independently of KL-VS, and the common haplotype AG was associated with poorer cognition, consistently across two cognitive measures in two cohort strata. The haplotype effect was stronger than that of KL-VS. Two variants, rs2283368 and rs9526984, were the only variants significantly associated with cognitive decline over 7 years. We discuss an age-dependent effect of KL and the possibility that multiple gene variants in KL are important for cognitive function among the oldest old participants., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The CLU gene is one of the prime genetic candidates associated with Alzheimers disease. In the present study CLU genotypes and haplotypes were associated with baseline cognition and the rate of cognitive decline in two cohorts, the Danish 1905 birth cohort (93 years of age in 1998) and the Longitudinal Study of Aging Danish twins (LSADT) (73-83 year old twins in 1997). Both Mini Mental State Examination (MMSE) and a cognitive composite score was attained up to six times for up to 10 years and analysed using random effects models and vital status. The rs11136000 T allele was associated with better baseline cognitive performance both in the LSADT (effect on intercept: 0.41 95% CI [-0.04; 0.87]) and the 1905 birth cohort (effect on intercept: 0.28 95% CI [0.01; 0.55]), although it did not reach significance in the LSADT cohort. However, the rs11136000 T allele was significantly associated with a steeper decline (effect on slope: -0.06 95% CI [-0.11; -0.01]) in the LSADT cohort, but not in the 1905 birth cohort. Haplotype analyses revealed that carriers of the common rs11136000, rs1532278 and rs9331888 TTC haplotype (36%) in the CLU gene performed cognitively better than non-carriers in the 1905 birth cohort (effect on intercept: 0.50 95% CI [0.12; 0.91]) and carriers of a rare TCC haplotype (1%) performed worse on the cognitive composite score (effect on intercept: -1.51 95% CI [-2.92; -0.06]). The association between the TTC haplotype and better cognitive composite score was higher among those surviving past the age of 98 (p = 0.014), and among these the TTC haplotype was borderline associated with a steep decline (effect on slope: -0.13 95% CI [-0.27; 0.00]). In summery CLU genetic variants associate with cognition in two cohorts, but the genetic effect of CLU seems to regress toward the mean when aging.

A coding gene variant A673T (rs63750847) in the APP gene has recently been recognized as a protective variant of late-onset Alzheimer's Disease in a large Icelandic population and has been observed recurrently in populations from Nordic countries. The variant also was related to longevity in the Icelandic population. However, because of the extreme rarity of A673T in non-Nordic populations, the association with Alzheimer's disease has not yet been formally replicated. Because the variant has not been reported among the Danes, we aimed to study its frequency among healthy middle-age twins and oldest-old singletons and explore the possible effects on longevity and cognitive abilities. Surprisingly, only 1 of 3487 unrelated Danes carried the A673T variant, (0.014% [95% CI 0.000–0.080]), which was significantly lower than in the other Nordic countries averaging to 0.43% (95% CI 0.40–0.46). In conclusion, the A673T variant is rarer in Danes than other Nordic countries, thus precluding assessment of association with longevity or cognitive functioning. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association between exposure to surgery and 10-year change in cognitive functioning.Methods: Among 2351 middle-aged twins, a 10-year change in composite cognitive scores derived from five cognitive tests was compared between 903 (38%) twins exposed to surgery classified as major, minor, knee and hip replacement, and other, and a reference group of 1448 (62%) twins without surgery, using linear regression models adjusted for socioeconomic factors. Genetic and shared environmental confounding was addressed in intrapair analyses of 48 monozygotic and 74 dizygotic same-sexed twin pairs.Results: In individual-level analyses, twins with major surgery (mean difference, -0.37; 95% CI, -0.76 to 0.02) or knee and hip replacement surgery (mean difference, -0.54; 95% CI, -1.30 to 0.22) had a tendency of a negligibly higher rate of decline in cognitive score than the reference group. In the intrapair analyses, the surgery-exposed twin had a higher rate of cognitive decline than the co-twin in 55% (95% CI, 45% to 63%) of the pairs. The mean difference in cognitive decline within pairs was -0.21 (95% CI, -0.81 to 0.39).Conclusions: No significant associations were found between exposure to surgery and change in cognitive score either in individual-level or in intrapair analyses. [ABSTRACT FROM AUTHOR]