Genotypes and phenotypes for apolipoprotein E and Alzheimer disease in the Honolulu-Asia aging study

BACKGROUND: The utility of apolipoprotein E (ApoE) type as an indicator of genetic susceptibility to Alzheimer disease (AD) depends on the reliability of typing. Although ApoE protein isoform phenotyping is generally assumed equivalent to genotyping from DNA, phenotype-genotype differences have been reported. METHODS: ApoE genotype and phenotype results were examined for 3564 older (ages 71-93 years) Japanese-American male participants of the Honolulu-Asia Aging Study, an ongoing population-based study of aging and dementia. RESULTS: Both methods demonstrated similar associations of ApoE type with AD: a direct association with ApoE4 and a less dramatic inverse association ApoE2. Advanced age did not appear to influence the ApoE4-AD association. The association with AD among ApoE4 homozygotes [odds ratio (OR) = 14.7] was higher than expected based on an observed OR of 2.0 in heterozygotes. Phenotype-genotype nonconcordance was more frequent for ApoE2 than for ApoE4. The ApoE2 phenotype occurred at a frequency of 7.9% vs a genotype frequency of 4.9%, corresponding to a probability of 56% that an individual with ApoE2 phenotype had the same genotype. CONCLUSIONS: Whereas E4 and E2 phenotypes and genotypes were comparably associated with AD, neither method would be expected to substantially improve the efficiency of case finding in the context of population screening beyond prediction based on age and education. Nonconcordance of phenotype and genotype was substantial for E2 and modest for E4 in this population. The ApoE4-AD association was independent of age

NuRD and CAF-1-mediated silencing of the D4Z4 array is modulated by DUX4-induced MBD3L proteins

Functional Genomics of Muscle, Nerve and Brain Disorder

Continuity theorems for the M/M/1/nM/M/1/n queueing system

In this paper continuity theorems are established for the number of losses during a busy period of the $M/M/1/n$ queue. We consider an $M/GI/1/n$ queueing system where the service time probability distribution, slightly different in a certain sense from the exponential distribution, is approximated by that exponential distribution. Continuity theorems are obtained in the form of one or two-sided stochastic inequalities. The paper shows how the bounds of these inequalities are changed if further assumptions, associated with specific properties of the service time distribution (precisely described in the paper), are made. Specifically, some parametric families of service time distributions are discussed, and the paper establishes uniform estimates (given for all possible values of the parameter) and local estimates (where the parameter is fixed and takes only the given value). The analysis of the paper is based on the level crossing approach and some characterization properties of the exponential distribution.Comment: Final revision; will be published as i

Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models

Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD+/−/human APOE ɛ3 or ɛ4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits

Associations Between Air Pollution Exposure and Empirically Derived Profiles of Cognitive Performance in Older Women

Background:Elucidating associations between exposures to ambient air pollutants and profiles of cognitive performance may provide insight into neurotoxic effects on the aging brain. Objective:We examined associations between empirically derived profiles of cognitive performance and residential concentrations of particulate matter of aerodynamic diameter \u3c 2.5 (PM2.5) and nitrogen dioxide (NO2) in older women. Method:Women (N = 2,142) from the Women’s Health Initiative Study of Cognitive Aging completed a neuropsychological assessment measuring attention, visuospatial, language, and episodic memory abilities. Average yearly concentrations of PM2.5 and NO2 were estimated at the participant’s addresses for the 3 years prior to the assessment. Latent profile structural equation models identified subgroups of women exhibiting similar profiles across tests. Multinomial regressions examined associations between exposures and latent profile classification, controlling for covariates. Result:Five latent profiles were identified: low performance across multiple domains (poor multi-domain; n = 282;13%), relatively poor verbal episodic memory (poor memory; n = 216; 10%), average performance across all domains (average multi-domain; n = 974; 45%), superior memory (n = 381; 18%), and superior attention (n = 332; 15%). Using women with average cognitive ability as the referent, higher PM2.5 (per interquartile range [IQR] = 3.64μg/m3) was associated with greater odds of being classified in the poor memory (OR = 1.29; 95% Confidence Interval [CI] = 1.10–1.52) or superior attention (OR = 1.30; 95% CI = 1.10–1.53) profiles. NO2 (per IQR = 9.86 ppb) was associated with higher odds of being classified in the poor memory (OR = 1.38; 95% CI = 1.17–1.63) and lower odds of being classified with superior memory (OR = 0.81; 95% CI = 0.67–0.97). Conclusion:Exposure to PM2.5 and NO2 are associated with patterns of cognitive performance characterized by worse verbal episodic memory relative to performance in other domains

Dynamic Scaling and Two-Dimensional High-Tc Superconductors

There has been ongoing debate over the critical behavior of two-dimensional superconductors; in particular for high Tc superconductors. The conventional view is that a Kosterlitz-Thouless-Berezinskii transition occurs as long as finite size effects do not obscure the transition. However, there have been recent suggestions that a different transition actually occurs which incorporates aspects of both the dynamic scaling theory of Fisher, Fisher, and Huse and the Kosterlitz-Thouless-Berezinskii transition. Of general interest is that this modified transition apparently has a universal dynamic critical exponent. Some have countered that this apparent universal behavior is rooted in a newly proposed finite-size scaling theory; one that also incorporates scaling and conventional two-dimensional theory. To investigate these issues we study DC voltage versus current data of a 12 angstrom thick YBCO film. We find that the newly proposed scaling theories have intrinsic flexibility that is relevant to the analysis of the experiments. In particular, the data scale according to the modified transition for arbitrarily defined critical temperatures between 0 K and 19.5 K, and the temperature range of a successful scaling collapse is related directly to the sensitivity of the measurement. This implies that the apparent universal exponent is due to the intrinsic flexibility rather than some real physical property. To address this intrinsic flexibility, we propose a criterion which would give conclusive evidence for phase transitions in two-dimensional superconductors. We conclude by reviewing results to see if our criterion is satisfied.Comment: 14 page

Qualidade de Vida e Atitudes dos Idosos Face à Velhice

A problemática do envelhecimento tem assumido, nos últimos anos, uma crescente importância na consciência coletiva da população, tornando-se cada vez mais importante compreender a população idosa e a sua realidade. Posto isto, foi realizado um estudo quantitativo e correlacional, que teve como objectivo avaliar a qualidade de vida e atitudes face à velhice de idosos, bem como a relação entre estas e as variáveis sociodemográficas e familiares. Foram inquiridos 100 idosos, com mais de 65 anos e sem deficit cognitivo . Para a recolha de dados utilizou-se uma entrevista estruturada, constituída dados sóciodemográficos do idoso, WHOQOL-AGE (Caballero, Miret, Power, Chatterji, Tobiasz-Adamczyk, Koskinen, Leonardi, Olaya, Haro &Ayuso-Mateos, 2013) e o AAQ ( Laidlaw, Power, Schmidt and the WHOQOL-OLD Group, 2007). Dos resultados destacamos os seguintes: A amostra é constituída por 52% de idosos do sexo masculino tendo uma média de idades de 74,7 (DP=6,8). È no fator Perdas Psicossociais e no Desenvolvimento Psicológico que os idosos têm uma melhor atitude face ao envelhecimento. É no item “Tem dinheiro suficiente para satisfazer as suas necessidades?” que os idosos apresentam uma menor qualidade de vida. Não ter doença diagnosticada e ser do sexo masculino permitem ter melhores atitudes face ao envelhecimento. A Qualidade de Vida está relacionada com a idade, com o estado de saúde e com a intensidade de preocupação da família. Constatou-se que os idosos que não estão institucionalizados apresentam uma melhor qualidade de vida e uma melhor atitude face à velhice. Quem não precisa de ajudas técnicas para se movimentar apresenta uma melhor qualidade de vida. Diferenças nas atitudes face ao envelhecimento consoante a residência onde habita são significativas nas mudanças físicas e no desenvolvimento psicológico sendo que os idosos que não vivem em lares têm uma atitude mais positiva em ambos os fatores. / Over the past few years the issue of aging has played a growing importance in the population`s collective consciousness becoming increasingly important to understand the elderly population and this reality. Therefore a quantitative correlational study was performed to assess the quality of life of seniors and their attitudes towards old age, and the relationship between these and the socio-demographic and family factors. 100 seniors with more than 65 years and without cognitive deficit were surveyed. For data collection we used a structured interview consisting of sociodemographic data of the elderly, WHOQOL-AGE (Caballero Miret Power Chatterji Tobiasz-Adamczyk Koskinen Leonardi Olaya Ayuso-Mateos & Haro 2013) and AAQ (Laidlaw Power Schmidt and the WHOQOL-OLD Group 2007). We highlight: The sample is composed of 52% of males with a mean age of 74.7 (SD = 6.8). It is in the factor Psychosocial Losses and Psychological Development that elderly people have a better attitude towards aging. It is in the item "Do you have enough money to meet your needs?" that seniors show less quality of life. Not having illness and being male allows having better attitudes towards aging. Quality of Life is related to age, health condition and the intensity of family concerns. It was observed that the elderly who are not institutionalized have a better quality of life and a better attitude towards old age. Who does not need assistive devices to move around has a better quality of life. Differences in attitudes towards aging, according to residency, are significant in physical changes and psychological development, thus verifying that elderly who do not live in nursing homes have a more positive attitude in both factors

Ambient air pollution and long-term trajectories of episodic memory decline among older women in the whims-echo cohort

BACKGROUND: Episodic memory decline varies by age and underlying neuropathology. Whether ambient air pollution contributes to the heterogeneity of episodic memory decline in older populations remains unclear. OBJECTIVES: We estimated associations between air pollution exposures and episodic memory decline according to pollutant, exposure time window, age, and latent class subgroups defined by episodic memory trajectories. METHODS: Participants were from the Women’s Health Initiative Memory Study–Epidemiology of Cognitive Health Outcomes. Older women (n = 2,056; 74–92 years of age) completed annual (2008–2018) episodic memory assessments using the telephone-based California Verbal Learning Test (CVLT). We estimated 3-y average fine particulate matter [PM with an aerodynamic diameter of ≤2:5 lm (PM2:5)] and nitrogen dioxide (NO2 ) exposures at baseline and 10 y earlier (recent and remote exposures, respectively), using regionalized national universal kriging. Separate latent class mixed models were used to esti-mate associations between interquartile range increases in exposures and CVLT trajectories in women ≤80 and >80 years of age, adjusting for covariates. RESULTS: Two latent classes were identified for women ≤80 years of age (n = 828), “slow-decliners” {slope = − 0:12=y [95% confidence interval (CI): −0:23, −0:01] and “fast-decliners” [slope = − 1:79=y (95% CI: −2:08, −1:50)]}. In the slow-decliner class, but not the fast-decliner class, PM2:5 exposures were associated with a greater decline in CVLT scores over time, with a stronger association for recent vs. remote exposures [−0:16=y (95% CI: −2:08, −0:03) per 2:88 lg=m3 and −0:11=y (95% CI: −0:22, 0.01) per 3:27 lg=m3, respectively]. Among women ≥80 years of age (n = 1,128), the largest latent class comprised “steady-decliners” [slope = − 1:35=y (95% CI: −1:53, −1:17)], whereas the second class, “cognitively resilient”, had no decline in CVLT on average. PM2:5 was not associated with episodic memory decline in either class. A 6:25-ppb increase in recent NO2 was associated with nonsignificant acceleration of episodic memory decline in the ≤80-y-old fast-decliner class [−0:21=y (95% CI: −0:45, 0.04)], and in the >80-y-old cognitively resilient class [−0:10=y (95% CI: −0:24, 0.03)] and steady-decliner class [−0:11=y (95% CI: −0:27, 0.05)]. Associations with recent NO2 exposure in women >80 years of age were stronger and statistically significant when 267 women with incident probable dementia were excluded [e.g., −0:12=y (95% CI: −0:22, −0:02) for the cognitively resilient class]. In contrast with changes in CVLT over time, there were no associations between exposures and CVLT scores during follow-up in any subgroup. DISCUSSION: In a community-dwelling U.S. population of older women, associations between late-life exposure to ambient air pollution and episodic memory decline varied by age-related cognitive trajectories, exposure time windows, and pollutants