Carriers of the APOE E4 allele have an increased risk of developing Alzheimer's disease. However, it is less clear whether APOE E4 status may also be involved in non-pathological cognitive ageing. ...The present study investigated the associations between APOE genotypes and cognitive change over 8 years in older community-dwelling individuals. APOE genotype was determined in 501 participants of the Lothian Birth Cohort 1921, whose intelligence had been measured in childhood in the Scottish Mental Survey 1932. A polymorphic variant of TOMM40 (rs10524523) was included to differentiate between the effects of the APOE E3 and E4 allelic variants. Cognitive performance on the domains of verbal memory, abstract reasoning and verbal fluency was assessed at mean age 79 years (n=501), and again at mean ages of 83 (n=284) and 87 (n=187). Using linear mixed models adjusted for demographic variables, vascular risk factors and IQ at age 11 years, possession of the APOE E4 allele was associated with a higher relative rate of cognitive decline over the subsequent 8 years for verbal memory and abstract reasoning. Individuals with the long allelic variant of TOMM40, which is linked to APOE E4, showed similar results. Verbal fluency was not affected by APOE E4 status. APOE E2 status was not associated with change in cognitive performance over 8 years. In non-demented older individuals, possession of the APOE E4 allele predicted a higher rate of cognitive decline on tests of verbal memory and abstract reasoning between 79 and 87 years. Thus, possession of the APOE E4 allele may not only predispose to Alzheimer's disease, but also appears to be a risk factor for non-pathological decline in verbal memory and abstract reasoning in the ninth decade of life.
ABSTRACT We present the results of a high angular resolution (1.1 arcsec) and sensitivity (maximum of ∼0.1 mJy) radio survey at 1–2 GHz in the Galactic Bulge. This complements the X-ray Chandra ...Galactic Bulge Survey, and investigates the full radio source population in this dense Galactic region. Radio counterparts to sources at other wavelengths can aid in classification, as there are relatively few types of objects that are reasonably detectable in radio at kiloparsec distances, and even fewer that are detected in both X-rays and radio. This survey covers about 3 sq deg of the Galactic Bulge Survey area (spanning the Galactic coordinate range of −3° < l < +3° and +1.6° < b < +2.1°) as a first look into this region of the Galaxy with this combination of frequency, resolution, and sensitivity. Spectral indices within the observed band of 1–2 GHz were calculated for each source to assist in determining its emission mechanism. We find 1617 unique sources in the survey, 25 of which are radio counterparts to X-ray sources, and about 100 of which are steep-spectrum (α ≲ −1.4) point sources that are viable pulsar candidates. Four radio sources are of particular interest: a compact binary; an infrared transient with an inverted radio spectrum; a potential transitional millisecond pulsar candidate; and a very steep spectrum radio source with an X-ray and bright infrared counterpart. We discuss other notable sources, including possible radio transients, potential new planetary nebulae, and active galactic nuclei.
The observation of neutrons turning into antineutrons would constitute a discovery of fundamental importance for particle physics and cosmology. Observing the n–n̄ transition would show that baryon ...number (B) is violated by two units and that matter containing neutrons is unstable. It would provide a clue to how the matter in our universe might have evolved from the B=0 early universe. If seen at rates observable in foreseeable next-generation experiments, it might well help us understand the observed baryon asymmetry of the universe. A demonstration of the violation of B–L by 2 units would have a profound impact on our understanding of phenomena beyond the Standard Model of particle physics.
Slow neutrons have kinetic energies of a few meV. By exploiting new slow neutron sources and optics technology developed for materials research, an optimized search for oscillations using free neutrons from a slow neutron moderator could improve existing limits on the free oscillation probability by at least three orders of magnitude. Such an experiment would deliver a slow neutron beam through a magnetically-shielded vacuum chamber to a thin annihilation target surrounded by a low-background antineutron annihilation detector. Antineutron annihilation in a target downstream of a free neutron beam is such a spectacular experimental signature that an essentially background-free search is possible. An authentic positive signal can be extinguished by a very small change in the ambient magnetic field in such an experiment. It is also possible to improve the sensitivity of neutron oscillation searches in nuclei using large underground detectors built mainly to search for proton decay and detect neutrinos.
This paper summarizes the relevant theoretical developments, outlines some ideas to improve experimental searches for free neutron oscillations, and suggests avenues both for theoretical investigation and for future improvement in the experimental sensitivity.
The precise value of the mean neutron lifetime, τ
, plays an important role in nuclear and particle physics and cosmology. It is used to predict the ratio of protons to helium atoms in the primordial ...universe and to search for physics beyond the Standard Model of particle physics. We eliminated loss mechanisms present in previous trap experiments by levitating polarized ultracold neutrons above the surface of an asymmetric storage trap using a repulsive magnetic field gradient so that the stored neutrons do not interact with material trap walls. As a result of this approach and the use of an in situ neutron detector, the lifetime reported here 877.7 ± 0.7 (stat) +0.4/-0.2 (sys) seconds does not require corrections larger than the quoted uncertainties.
Objectives.
Grip strength and reasoning are associated in old age. This is one of the few longitudinal studies addressing whether aging of one causes decline in the other or whether they share causal ...influences.
Methods.
The Lothian Birth Cohort 1921 were assessed for grip strength and nonverbal reasoning at ages M = 79 (N = 550), M = 83 (N = 321), and M = 87 (N = 207). Associations among intercepts and slopes for grip strength and reasoning and covariates were examined by fitting a bivariate growth curve structural equation model.
Results.
Grip strength and reasoning declined with age. They were each significantly correlated on each occasion. Their intercepts were significantly correlated (.20) but not their slopes. Neither intercept was significantly associated with its own or the other's slope. Better reasoning was associated with higher childhood intelligence, more professional occupations, male sex, and being taller. There were no significant reasoning slope associations. Stronger grip strength was associated with male sex, being taller, and drinking less alcohol. Women showed less age-related decline in grip strength.
Discussion.
Physical and mental "grips" declined in the ninth decade of life. Their levels were significantly correlated; their slopes were not. There was no evidence for reciprocal dynamic influences nor for shared associations.
Low blood levels of B vitamins have been implicated in age‐associated cognitive impairment. The present study investigated the association between genetic variation in folate metabolism and ...age‐related cognitive decline in the ninth decade of life. Both the 677C>T (rs1801133) polymorphism and the scarcely studied 1298A>C (rs1801131) polymorphism of the MTHFR gene were assessed in relation to cognitive change over 8 years in older community‐dwelling individuals. MTHFR genotype was determined in 476 participants of the Lothian Birth Cohort 1921, whose intelligence was measured in childhood in the Scottish Mental Survey of 1932. Cognitive performance on the domains of verbal memory, reasoning and verbal fluency was assessed at mean age of 79 (n = 476) and again at mean ages of 83 (n = 275) and 87 (n = 180). Using linear mixed models, the MTHFR 677C>T and 1298A>C variants were not associated with the rate of cognitive change between 79 and 87 years, neither in the total sample, nor in a subsample of individuals with erythrocyte folate levels below the median. APOE E4 allele carrier status did not interact with MTHFR genotype in affecting change in cognitive performance over 8 years. No significant combined effect of the two polymorphisms was found. In conclusion, MTHFR 677C>T and 1298A>C polymorphisms were not associated with individual change in cognitive functioning in the ninth decade of life. Although polymorphisms in the MTHFR gene may cause disturbances in folate metabolism, they do not appear to be accompanied by changes in cognitive functioning in old age.
Brain age predicts mortality Cole, J H; Ritchie, S J; Bastin, M E ...
Molecular psychiatry,
05/2018, Letnik:
23, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed ...to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, 'brain-predicted age', derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.
Amyloid-beta (Abeta) is cleared from the brain by both proteolytic digestion and transport across the blood-brain-barrier into the peripheral circulatory system. To investigate the role peripheral ...Abeta levels play in regulating Abeta brain clearance, we measured the clearance of 125I-Abeta(1-40) injected into the brains of liver-ligated rats that allowed peripheral Abeta levels to be maintained at elevated levels for approximately one hour with/without a single peripheral bolus of unlabeled Abeta(1-40). We found that elevating peripheral Abetalevels significantly decreased 125I-Abeta(1-40) brain clearance, thus supporting the hypothesis that peripheral Abeta levels regulate Abeta clearance from the central nervous system.
DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures ...aspects of biological age.
Here we test whether differences between people's chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43.
DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.
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