Optimism and Longevity Among Japanese Older Adults.

Background: Optimism has been linked to better physical health across various outcomes, including greater longevity. However, most evidence is from Western populations, leaving it unclear whether these relationships may generalize to other cultural backgrounds. Using secondary data analysis, we evaluated the associations of optimism among older Japanese adults. Methods: Data were from a nationwide cohort study of Japanese older adults aged ≥65 years (Japan Gerontological Evaluation Study; n = 10,472). In 2010, optimism and relevant covariates (i.e., sociodemographic factors, physical health conditions, depressive symptoms, and health behaviors) were self-reported. Optimism was measured using the Japanese version of the Life Orientation Test-Revised (LOT-R). Lifespan was determined using mortality information from the public long-term care insurance database through 2017 (7-year follow-up). Accelerated failure time models examined optimism (quintiles or standardized continuous scores) in relation to percent differences in lifespan. Potential effect modification by gender, income, and education was also investigated. Results: Overall, 733 individuals (7%) died during the follow-up period. Neither continuous nor categorical levels of optimism were associated with lifespan after progressive adjustment for covariates (e.g., in fully-adjusted models: percent differences in lifespan per 1-SD increase in continuous optimism scores= -1.2%, 95%CI: -3.4, 1.1 higher versus lower optimism quintiles= -4.1%, 95%CI: -11.2, 3.6). The association between optimism and lifespan was null across all sociodemographic strata as well. Conclusion: Contrary to the existing evidence from Western populations, optimism was unrelated to longevity among Japanese older adults. The association between optimism, as evaluated by the LOT-R, and longevity may differ across cultural contexts.

Posttraumatic stress disorder symptoms and cognitive function in a large cohort of middle-aged women.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been linked to cognitive decline, but research in women is generally lacking. We examined whether trauma and elevated PTSD symptoms were associated with worse cognitive function in middle-aged civilian women. A secondary objective was to investigate the possible role of depression in the relation of PTSD symptoms to cognitive function. METHODS: The sample comprised 14,029 middle-aged women in the Nurses' Health Study II. Lifetime trauma exposure, lifetime PTSD symptoms, and past-week depressive symptoms were measured in 2008. Cognitive function was measured in 2014-2016 using the Cogstate Brief Battery, a self-administered online cognitive battery that assesses psychomotor speed, attention, learning, and working memory. We used linear regression models to estimate mean differences in cognition across PTSD symptom levels. RESULTS: Compared to no trauma, elevated PTSD symptoms consistent with probable PTSD (i.e., 4+ symptoms on a screening questionnaire) were associated with worse performance on psychomotor speed/attention (b = -0.08 standard units, p = .001) and learning/working memory (b = -0.09, p < .001) composites, after adjusting for sociodemographics. Although attenuated, associations remained significant when adjusted for depressive symptoms and other cognitive risk factors. We found the strongest associations among women with comorbid probable PTSD and depression. CONCLUSIONS: PTSD symptoms were negatively related to measures of psychomotor speed/attention and learning/working memory in middle-aged women. Our study adds to a growing literature that suggests that mental disorders are associated with worse cognitive function over the life course.

The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project--design, population and data harmonization of a large-scale, international study.

There is a public health demand to prevent health conditions which lead to increased morbidity and mortality among the rapidly-increasing elderly population. Data for the incidence of such conditions exist in cohort studies worldwide, which, however, differ in various aspects. The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project aims at harmonizing data from existing major longitudinal studies for the elderly whilst focussing on cardiovascular diseases, diabetes mellitus, cancer, fractures and cognitive impairment in order to estimate their prevalence, incidence and cause-specific mortality, and identify lifestyle, socioeconomic, and genetic determinants and biomarkers for the incidence of and mortality from these conditions. A survey instrument assessing ageing-related conditions of the elderly will be also developed. Fourteen cohort studies participate in CHANCES with 683,228 elderly (and 150,210 deaths), from 23 European and three non-European countries. So far, 287 variables on health conditions and a variety of exposures, including biomarkers and genetic data have been harmonized. Different research hypotheses are investigated with meta-analyses. The results which will be produced can help international organizations, governments and policy-makers to better understand the broader implications and consequences of ageing and thus make informed decisions.

Estrogen Receptor Genes, Cognitive Decline, and Alzheimer Disease.

BACKGROUND AND OBJECTIVES: Lifetime risk of Alzheimer disease (AD) dementia is twofold higher in women compared with men, and low estrogen levels in postmenopause have been suggested as a possible contributor. We examined 3 ER (GPER1, ER2, and ER1) variants in association with AD traits as an indirect method to test the association between estrogen and AD in women. Although the study focus was on women, in a comparison, we separately examined ER molecular variants in men. METHODS: Participants were followed for an average of 10 years in one of the 2 longitudinal clinical pathologic studies of aging. Global cognition was assessed using a composite score derived from 19 neuropsychological tests' scores. Postmortem pathologic assessment included examination of 3 AD (amyloid-ß and tau tangles determined by immunohistochemistry, and a global AD pathology score derived from diffuse and neurotic plaques and neurofibrillary tangle count) and 8 non-AD pathology indices. ER molecular genomic variants included genotyping and examining ER DNA methylation and RNA expression in brain regions including the dorsolateral prefrontal cortex (DLPFC) that are major players in cognition and often have AD pathology. RESULTS: The mean age of women (N = 1711) at baseline was 78.0 (SD = 7.7) years. In women, GPER1 molecular variants had the most consistent associations with AD traits. GPER1 DNA methylation was associated with cognitive decline, tau tangle density, and global AD pathology score. GPER1 RNA expression in DLPFC was related to cognitive decline and tau tangle density. Other associations included associations of ER2 and ER1 sequence variants and DNA methylation with cognition. RNA expressions in DLPFC of genes involved in signaling mechanisms of activated ERs were also associated with cognitive decline and tau tangle density in women. In men (N = 651, average age at baseline: 77.4 [SD = 7.3]), there were less robust associations between ER molecular genomic variants and AD cognitive and pathologic traits. No consistent association was seen between ER molecular genomic variations and non-AD pathologies in either of the sexes. DISCUSSION: ER DNA methylation and RNA expression, and to some extent ER polymorphisms, were associated with AD cognitive and pathologic traits in women, and to a lesser extent in men.

Novel Epigenetic Clock Biomarkers of Age-Related Macular Degeneration.

Age-Related Macular Degeneration (AMD) is a bilateral ocular condition resulting in irreversible vision impairment caused by the progressive loss of photoreceptors in the macula, a region at the center of the retina. The progressive loss of photoreceptor is a key feature of dry AMD but not always wet AMD, though both forms of AMD can lead to loss of vision. Regression-based biological age clocks are one of the most promising biomarkers of aging but have not yet been used in AMD. Here we conducted analyses to identify regression-based biological age clocks for the retina and explored their use in AMD using transcriptomic data consisting of a total of 453 retina samples including 105 Minnesota Grading System (MGS) level 1 samples, 175 MGS level 2, 112 MGS level 3 and 61 MGS level 4 samples, as well as 167 fibroblast samples. The clocks yielded good separation among AMD samples with increasing severity score viz., MGS1-4, regardless of whether clocks were trained in retina tissue, dermal fibroblasts, or in combined datasets. Clock application to cultured fibroblasts, embryonic stem cells, and induced Pluripotent Stem Cells (iPSCs) were consistent with age reprograming in iPSCs. Moreover, clock application to in vitro neuronal differentiation suggests broader applications. Interesting, many of the age clock genes identified include known targets mechanistically linked to AMD and aging, such as GDF11, C16ORF72, and FBN2. This study provides new observations for retina age clocks and suggests new applications for monitoring in vitro neuronal differentiation. These clocks could provide useful markers for AMD monitoring and possible intervention, as well as potential targets for in vitro screens.

The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals.

Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This "disease signature" approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases.

Associations between red meat intake and biomarkers of inflammation and glucose metabolism in women.

BACKGROUND: Greater red meat intake is associated with an increased type 2 diabetes and cardiovascular disease risk. However, the relation of red meat intake to biomarkers of inflammation and glucose metabolism has not been investigated thoroughly. OBJECTIVE: We hypothesized that greater red meat intake would be associated with biomarkers of inflammation and glucose metabolism, which would be partly explained by body mass index (BMI). DESIGN: We analyzed cross-sectional data from diabetes-free female participants in the Nurses' Health Study (n = 3690). Multiple linear regression was conducted to assess the associations of total, unprocessed, and processed red meat intakes (quartile categories) with plasma C-reactive protein (CRP), ferritin, adiponectin, fasting insulin, and hemoglobin A1c (Hb A1c). RESULTS: Greater total, unprocessed, and processed red meat intakes were associated with higher plasma CRP, ferritin, fasting insulin, and Hb A1c and lower adiponectin after adjustment for demographic information (P-trend ≤ 0.03 for all). Adiponectin was not associated with any type of red meat intake when further adjusted for medical and lifestyle factors. After adjustment for BMI, most of these associations with inflammatory and glucose metabolic biomarkers were substantially attenuated and no longer significant. BMI accounted for a statistically significant proportion of associations with CRP, Hb A1c, and fasting insulin (P-contribution ≤ 0.02 for all) but not with ferritin. Substituting a serving of total red meat intake with alternative protein food in a combination of poultry, fish, legumes, and nuts was associated with significantly lower CRP (ß ± SE: -0.106 ± 0.043), ferritin (-0.212 ± 0.075), Hb A1c (-0.052 ± 0.015), and fasting insulin (-0.119 ± 0.036) (all P ≤ 0.02 for comparison of extreme quartiles for all). CONCLUSIONS: Greater red meat intake is associated with unfavorable plasma concentrations of inflammatory and glucose metabolic biomarkers in diabetes-free women. BMI accounts for a significant proportion of the associations with these biomarkers, except for ferritin. Substituting red meat with another protein food is associated with a healthier biomarker profile of inflammatory and glucose metabolism.

Migraine and cognitive decline among women: prospective cohort study.

OBJECTIVE: To evaluate the association between migraine and cognitive decline among women. DESIGN: Prospective cohort study. SETTING: Women's Health Study, United States. PARTICIPANTS: 6349 women aged 65 or older enrolled in the Women's Health Study who provided information about migraine status at baseline and participated in cognitive testing during follow-up. Participants were classified into four groups: no history of migraine, migraine with aura, migraine without aura, and past history of migraine (reports of migraine history but no migraine in the year prior to baseline). MAIN OUTCOME MEASURES: Cognitive testing was carried out at two year intervals up to three times using the telephone interview for cognitive status, immediate and delayed recall trials of the east Boston memory test, delayed recall trial of the telephone interview for cognitive status 10 word list, and a category fluency test. All tests were combined into a global cognitive score, and tests assessing verbal memory were combined to create a verbal memory score. RESULTS: Of the 6349 women, 853 (13.4%) reported any migraine; of these, 195 (22.9%) reported migraine with aura, 248 (29.1%) migraine without aura, and 410 (48.1%) a past history of migraine. Compared with women with no history of migraine, those who experienced migraine with or without aura or had a past history of migraine did not have significantly different rates of cognitive decline in any of the cognitive scores: values for the rate of change of the global cognitive score between baseline and the last observation ranged from -0.01 (SE 0.04) for past history of migraine to 0.08 (SE 0.04) for migraine with aura when compared with women without any history of migraine. Women who experienced migraine were also not at increased risk of substantial cognitive decline (worst 10% of the distribution of decline). When compared with women without a history of migraine, the relative risks for the global score ranged from 0.77 (95% confidence interval 0.46 to 1.28) for women with migraine without aura to 1.17 (0.84 to 1.63) for women with a past history of migraine. CONCLUSION: In this prospective cohort of women, migraine status was not associated with faster rates of cognitive decline.