APOE genotype and entorhinal cortex volume in non-demented community-dwelling adults in midlife and early old age

Copyright © 2012 IOS PressThis article has been made available through the Brunel Open Access Publishing Fund.The apolipoprotein E (APOE) ε4 allele is a risk factor for the neuropathological decline accompanying Alzheimer's disease (AD) while, conversely, the ε2 allele offers protection. One of the brain structures exhibiting the earliest changes associated with the disease is the entorhinal cortex. We therefore investigated the volumes of the entorhinal cortex and other structures in the medial temporal lobe including the parahippocampal gyrus, temporal pole, and inferior, middle, and superior temporal cortices, in relation to APOE genotype. Our main objectives were to determine if (a) volumes systematically varied according to allele in a stepwise fashion, ε2 > ε3 > ε4, and (b) associations varied according to age. We investigate this association in 627 non-demented community-dwelling adults in middle age (44 to 48 years; n = 314) and older age (64 to 68 years; n = 313) who underwent structural MRI scans. We found no evidence of APOE-related variation in brain volumes in the age groups examined. We conclude that if a ε2 > ε3 > ε4 pattern in brain volumes does emerge in non-demented adults living in the community in old age, it is not until after the age of 68 years.This study was funded by the UK Leverhulme Trust, the British Academy, the NHMRC Research Fellowship No. 471501, the NHMRC Research Fellowship No.#1002560, the National Health and Medical Research Council of Australia Unit Grant No. 973302, Program Grant No. 179805, Project grant No. 157125; Program grant no. 350833, and the National Computational Infrastructure. This article is made available through the Brunel Open Access Publishing Fund

Dietary patterns and depressive symptoms over time: examining the relationships with socioeconomic position, health behaviours and cardiovascular risk

Recent research suggests that diet quality influences depression risk; however, a lack of experimental evidence leaves open the possibility that residual confounding explains the observed relationships. The aim of this study was to document the cross-sectional and longitudinal associations between dietary patterns and symptoms of depression and to undertake a detailed examination of potential explanatory factors, particularly socioeconomic circumstances, in the diet-depression relationship

A longitudinal examination of the relationship between cannabis use and cognitive function in mid-life adults

Background: The relationship between cannabis use and cognitive function in mid-life has rarely been examined despite verbal learning deficits in young adults. Method: A longitudinal cohort study of 1,897 Australians recruited at 40–46 years of age and followed up 4 years (94%) and 8 years (87%) later. Random effects regression was used to assess within- and between-person associations between cannabis use and cognitive function across waves of data, and examine whether age-related changes in cognitive performance were modified by cannabis use. The first list of the California Verbal Learning Test (immediate and delayed recall), Symbol Digit Modality Test, Digit Backwards, simple and choice reaction time tasks, were administered at each wave. The Spot-the-Word test was used to assess premorbid verbal ability. Self-reported cannabis use in the past year (no use, < weekly use, ≥ weekly use) was assessed at each wave. Findings: Participants who used cannabis ≥ weekly had worse immediate recall (b = −0.68, p = 0.014) and showed a trend toward worse delayed recall (b = −0.55, p = 0.062) compared to non-users after adjusting for correlates of cannabis use and premorbid verbal ability. These effects were due to between-person differences. There were no significant within-person associations between cannabis use and recall, nor was there evidence of greater cognitive decline in cannabis users with age. Conclusions: Mid-life cannabis users had poorer verbal recall than non-users, but this was not related to their current level of cannabis use, and cannabis use was not associated with accelerated cognitive decline

A Scoping Review of Workplace Interventions to Promote Positive Attitudes Toward Older Workers and Reduce Age-Based Discrimination

Population aging trends have created a need for effective policies to extend adult working lives. Previous research has identified the prevalence of negative attitudes (age-related stereotypes, prejudice, and discriminatory behaviors) directed toward older workers in the workplace context.The current scoping review aimed to describe and assess the current evidence in support of different types of interventions aimed at promoting positive attitudes and reducing age-based discrimination in the workplace context. A search of peer-reviewed and grey literature databases identified 22 relevant studies, including data from 5,078 adult participants, across laboratory and field settings. From examination of these studies, we propose and describe four thematic categories of interventions, as a way of organizing this literature: “de-biasing interventions,” “brief attitudinal interventions,” “age diversity workshop interventions,” and “structural or contextual interventions.” At the current point in time, studies assessing age diversity workshop interventions appear to be the strongest, having a clear theoretical basis, having a focus on interventions that can be delivered in workplace settings, and providing evidence for positive effects on measures that are meaningful for organizations and older workers. While a number of promising interventions have been tested, most studies were only able to demonstrate improvements in explicit measurements of attitudes toward older adults, immediately following the intervention. Collaborative partnerships with organizations and further high-quality studies (particularly in field settings) are required to support the development, evaluation, and implementation of interventions to promote positive attitudes toward older adults in real-world workplace settings

The impact of mild cognitive impairment on decision-making under explicit risk conditions: Evidence from the Personality and Total Health (PATH) Through Life longitudinal study

Objective: Previous research has indicated that cognition and executive function are associated with decision-making, however the impact of mild cognitive impairment (MCI) on decision-making under explicit risk conditions is unclear. This cross-sectional study examined the impact of MCI, and MCI subtypes, on decision-making on the Game of Dice Task (GDT), among a cohort of older adults. Method: Data from 245 older adult participants (aged 72-78 years) from the fourth assessment of the Personality and Total Health Through Life study were analyzed. A diagnostic algorithm identified 103 participants with MCI, with subtypes of single-domain amnestic MCI (aMCI-single; n = 38), multi-domain amnestic MCI (aMCI-multi; n = 31), and non-amnestic MCI (n = 33), who were compared with an age-, sex-, education-, and income-matched sample of 142 cognitively unimpaired older adults. Decision-making scores on the GDT (net score, single number choices, and strategy changes) were compared between groups using nonparametric tests. Results: Participants with MCI showed impaired performance on the GDT, with higher frequencies of single number choices and strategy changes. Analyses comparing MCI subtypes indicated that the aMCI-multi subtype showed increased frequency of single number choices compared to cognitively unimpaired participants. Across the sample of participants, decision-making scores were associated with measures of executive function (cognitive flexibility and set shifting). Conclusion: MCI is associated with impaired decision-making performance under explicit risk conditions. Participants with impairments in multiple domains of cognition showed the clearest impairments. The GDT may have utility in discriminating between MCI subtypes

Modelling a Hot Horizon in Global 21 cm Experimental Foregrounds

The 21 cm signal from cosmic hydrogen is one of the most propitious probes of the early Universe. The detection of this signal would reveal key information about the first stars, the nature of dark matter, and early structure formation. We explore the impact of an emissive and reflective, or `hot', horizon on the recovery of this signal for global 21 cm experiments. It is demonstrated that using physically motivated foreground models to recover the sky-averaged 21 cm signal one must accurately describe the horizon around the radiometer. We show that not accounting for the horizon will lead to a signal recovery with residuals an order of magnitude larger than the injected signal, with a log Bayesian evidence of almost 1600 lower than when one does account for the horizon. It is shown that signal recovery is sensitive to incorrect values of soil temperature and reflection coefficient in describing the horizon, with even a 10% error in reflectance causing twofold increases in the RMSE of a given fit. We also show these parameters may be fitted using Bayesian inference to mitigate for these issues without overfitting and mischaracterising a non-detection. We further demonstrate that signal recovery is sensitive to errors in measurements of the horizon projection onto the sky, but fitting for soil temperature and reflection coefficients with priors that extend beyond physical expectation can resolve these problems. We show that using an expanded prior range can reliably recover the signal even when the height of the horizon is mismeasured by up to 20%, decreasing the RMSE from the model that does not perform this fitting by a factor of 9.Comment: 12 pages, 11 figures, 5 table

The feasibility of a multidomain dementia risk reduction randomised controlled trial for people experiencing cognitive decline: the Body, Brain, Life for Cognitive Decline (BBL-CD)

Objectives: To evaluate the feasibility of a proof-of-concept multidomain dementia risk reduction intervention. Method: An 8-week, parallel-group RCT, focused on increasing adherence to lifestyle domains of Mediterranean diet (MeDi), Physical Activity (PA), and Cognitive Engagement (CE). Feasibility was evaluated against the Bowen Feasibility Framework objectives of: Acceptability of the intervention, compliance with the protocol, and efficacy of the intervention to change behaviour in the three domains of interest. Results: High acceptability of the intervention was demonstrated through a participant retention rate of 80.7% (Intervention: 84.2%; Control: 77.4%). Compliance to the protocol was strong with 100% of participants completing all educational modules and all MeDi and PA components, with 20% compliance for CE. Linear mixed models demonstrated efficacy to change behaviour through significant effects of adherence to MeDi (χ2 = 16.75, df = 3, p <.001) and CE (χ2 = 9.83, df = 3, p =.020), but not PA (χ2 = 4.48, df = 3, p =.211). Conclusion: Overall the intervention was shown to be feasible. Recommendations for future trials in this area are: The implementation of practical, one-on-one sessions as they are more effective than passive education at eliciting behaviour change; use of booster sessions to increase likelihood of lifestyle changes being sustained; and collection of qualitative data to identify barriers to change

Western diet is associated with a smaller hippocampus: a longitudinal investigation

Background: Recent meta-analyses confirm a relationship between diet quality and both depression and cognitive health in adults. While the biological pathways that underpin these relationships are likely multitudinous, extensive evidence from animal studies points to the involvement of the hippocampus. The aim of this study was to examine the association between dietary patterns and hippocampal volume in humans, and to assess whether diet was associated with differential rates of hippocampal atrophy over time. Methods: Data were drawn from the Personality and Total Health Through Life Study and focused on a subsample of the cohort (n = 255) who were aged 60-64 years at baseline in 2001, completed a food frequency questionnaire, and underwent two magnetic resonance imaging scans approximately 4 years apart. Longitudinal generalized estimating equation linear regression models were used to assess the association between dietary factors and left and right hippocampal volumes over time. Results: Every one standard deviation increase in healthy &quot;prudent&quot; dietary pattern was associated with a 45.7 mm3 (standard error 22.9 mm3) larger left hippocampal volume, while higher consumption of an unhealthy &quot;Western&quot; dietary pattern was (independently) associated with a 52.6 mm3 (SE 26.6 mm3) smaller left hippocampal volume. These relationships were independent of covariates including age, gender, education, labour-force status, depressive symptoms and medication, physical activity, smoking, hypertension and diabetes. While hippocampal volume declined over time, there was no evidence that dietary patterns influenced this decline. No relationships were observed between dietary patterns and right hippocampal volume. Conclusions: Lower intakes of nutrient-dense foods and higher intakes of unhealthy foods are each independently associated with smaller left hippocampal volume. To our knowledge, this is the first human study to demonstrate associations between diet and hippocampal volume concordant with data previously observed in animal models

Gender specific factors contributing to cognitive resilience in APOE ɛ4 positive older adults in a population-based sample

Although APOE ɛ4 has been identified as the strongest genetic risk factor for Alzheimer’s Disease, there are some APOE ɛ4 carriers who do not go on to develop Alzheimer’s disease or cognitive impairment. This study aims to investigate factors contributing to this “resilience” separately by gender. Data were drawn from APOE ɛ4 positive participants who were aged 60 + at baseline in the Personality and Total Health Through Life (PATH) Study (N = 341, Women = 46.3%). Participants were categorised into “resilient” and “non-resilient” groups using Latent Class Analysis based on their cognitive impairment status and cognitive trajectory across 12 years. Logistic regression was used to identify the risk and protective factors that contributed to resilience stratified by gender. For APOE ɛ4 carriers who have not had a stroke, predictors of resilience were increased frequency of mild physical activity and being employed at baseline for men, and increased number of mental activities engaged in at baseline for women. The results provide insights into a novel way of classifying resilience among APOE ɛ4 carriers and risk and protective factors contributing to resilience separately for men and women

Diastolic Blood Pressure Variability in Later Life May Be a Key Risk Marker for Cognitive Decline

BACKGROUND: There is an increasing awareness of the need to understand the interaction between long-term blood pressure patterns and their impact on the brain and cognition. METHODS: Our aim was to investigate the relationship between repeated blood pressure measures and change in cognitive performance over 12 years and imaging data at 12 years using a longitudinal population study. The data consisted of 2 cohorts, one midlife and one later life. Using linear regression, we examined the relationship between blood pressure (systolic, diastolic, change in blood pressure between visits, and visit-to-visit variability), change in cognitive performance and imaging at 12 years. RESULTS: Data on cognitive change were available in 1054 at midlife, baseline age 42.7 (SD 1.5) and 1233 in later life, 62.5 (1.5) years. Imaging data were available in 168 and 233, respectively. After adjustment for multiple comparisons greater diastolic blood pressure variability in later life was associated with a −1.95 point decline (95% CI, −2.89 to −1.01) on an attention-based task and a −0.42 point (95% CI, −0.68 to −0.15) decline in performance on a psychomotor task. A higher SD in diastolic pressure across follow-up was associated with greater white matter hyperintensity volume (%increase per 10 mmHg increase in the SD [1.50 (95% CI, 1.16–1.94]). CONCLUSIONS: In a largely normotensive/mildly hypertensive population, our analyses reported no relationships between blood pressure and cognition in midlife but a potential role for diastolic blood pressure variability in later life as a risk marker for cognitive decline. This may indicate an at-risk period or a means to identify an at-risk population at the age where diastolic pressure is starting to decline