The APOE paradox: how do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Possession of an APOE e4 allele is an established risk factor for Alzheimer’s disease, while the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. 66 volunteers, aged 45-55 years, completed three tasks that provided complementary measures of attentional control: prospective memory, sustained attention and inhibition. Performance was compared between e2 carriers, e4 carriers and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared to the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes

Exploring psychological well-being in working family carers

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Depression in HIV and HCV co-infected patients: a systematic review and meta-analysis

The aim of this study was to carry out a systematic review and meta-analysis of the differences in the prevalence of depression and presence of depressive symptoms between HIV/HCV co-infection, HIV mono-infection, and hepatitis C virus (HCV) mono-infection. A systematic electronic search of bibliographic databases was performed to locate articles published from the earliest available online until December 2014. Outcomes of depression were based on clinical interviews and validated self-reported measures of depression/depressive symptoms. Of the 188 records initially screened, 29 articles were included in the descriptive systematic review and six were included in the meta-analysis. The meta-analytic results indicated that, as measured by self-reported measures of depression, HIV/HCV co-infected patients were significantly more likely to report depressive symptoms than either HIV (SMD = .24, 95% CI: .03-.46, p = .02) or HCV mono-infected (SMD = .55, 95% CI: .17-.94, p = .005) patients. The variability of the results of the reviewed studies, largely dependent on the samples' characteristics and the methods of assessment of depression, suggests that a clear interpretation of how depression outcomes are affected by the presence of HIV/HCV co-infection is still needed. Failing to diagnose depression or to early screen depressive symptoms may have a significant impact on patients' overall functioning and compromise treatments' outcomes

Cognitive impairment in HIV and HCV co-infected patients: a systematic review and meta-analysis

Cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections. However, in the context of HIV/HCV co-infection the research is more limited. The aim of this systematic review was to describe the characteristics of cognitive impairment in HIV/HCV co-infection and to examine the differences in cognitive performance between HIV/HCV and HIV and HCV mono-infected patients. Of the 437 records initially screened, 24 papers met the inclusion criteria and were included in the systematic review. Four studies were included in the meta-analysis. Most studies indicated that HIV/HCV co-infected patients had a higher level of cognitive impairment than HIV mono-infected patients. Meta-analysis also indicated that HIV mono-infected patients had a significantly lower global deficit score than co-infected patients. The results also indicated that co-infected patients were more likely to be impaired in information processing speed than HIV mono-infected patients. These findings can be challenged by biasing factors such as the small number of included studies, heterogeneity of the samples and a large diversity of methodological procedures. Future research with consistent and comprehensive neuropsychological batteries and covering a greater diversity of risk factors is needed, in order to clarify the effects of both viruses on cognitive function and the mechanisms that underlie these effects. Because cognitive impairments may pose significant challenges to medication adherence, quality of life and overall functioning, such knowledge may have important implications to the planning and implementation of effective interventions aimed at optimising the clinical management of these infections

Longitudinal associations of affective symptoms with midlife cognitive function: evidence from a British birth cohort

Background: Affective disorders are associated with poorer cognition in older adults; however, whether this association can already be observed in midlife remains unclear. Aims: This study investigated effects of affective symptoms over a period of 30 years on midlife cognitive function. First, we explored whether timing (sensitive period) or persistence (accumulation) of affective symptoms predicted cognitive function. Second, we tested how different longitudinal trajectories of affective symptoms were associated with cognitive function. Method: The study used data from the National Child Development Study. Memory, verbal fluency, information processing speed and accuracy were measured at age 50. Affective symptoms were measured at ages 23, 33, 42, and 50 and used to derive longitudinal trajectories. A structured modelling approach compared a set of nested models to test accumulation versus sensitive period hypotheses. Linear regressions and structural equation modelling were used to test for longitudinal associations of affective symptoms with cognitive function. Results: Accumulation of affective symptoms was found to be the best fit for the data, with persistent affective symptoms being associated with poorer immediate memory (B=-0.07, SE=0.03, P=.01), delayed memory (B=-0.13, SE=0.04, P<.001), and information processing accuracy (B=0.18, SE=0.08, P=.03), but not with information processing speed (B=3.15, SE=1.89, P=.10). Longitudinal trajectories of repeated affective symptoms were associated with poorer memory, verbal fluency, and information processing accuracy. Conclusions: Persistent affective symptoms can affect cognitive function in midlife. Effective management of affective disorders to prevent recurrence may reduce risk of poor cognitive outcomes and promote healthy cognitive ageing

Long-term high-effort endurance exercise in older adults: diminishing returns for cognitive and brain aging

While there is evidence that age-related changes in cognitive performance and brain structure can be offset by increased exercise, little is known about the impact on these of long-term high-effort endurance exercise. In a cross-sectional design with 12-month follow-up, we recruited older adults engaging in high-effort endurance exercise over at least twenty years, and compared their cognitive performance and brain structure with a non-sedentary control group similar in age, sex, education, IQ, and lifestyle factors. Our findings showed no differences on measures of speed of processing, executive function, incidental memory, episodic memory, working memory, or visual search for older adults participating in long-term high-effort endurance exercise, when compared without confounds to non-sedentary peers. On tasks that engaged significant attentional control, subtle differences emerged. On indices of brain structure, long-term exercisers displayed higher white matter axial diffusivity than their age-matched peers, but this did not correlate with indices of cognitive performance

A longitudinal study assessing depression in hepatitis C: does gender play a role in the new onset depression during interferon-alpha treatment?

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Accumulation of affective symptoms and midlife cognitive function: the role of inflammation

Background: The aim of the present study was to test whether C-Reactive Protein (CRP), a proxy measure of inflammation, is elevated in people with higher child and adulthood affective symptoms and whether elevated CRP predicts midlife cognitive function. Methods: Data were used from the National Child Development Study (n = 6276). Measures of memory, verbal fluency, information processing speed and accuracy were available in midlife (age 50). Affective symptoms were assessed in childhood (ages 7, 11, 16) and in adulthood (ages 23, 33, 42, 50). The level of plasma CRP was measured at age 44. Pathway models, unadjusted and fully adjusted for sex, education, childhood socioeconomic position, childhood cognitive ability and affective symptoms at age 50, were fitted to test direct associations between affective symptoms and midlife cognitive function, and indirect associations via the inflammatory pathway (CRP level). Results: In a fully adjusted model, there were significant indirect associations between adult affective symptoms and immediate memory (β=-0.01, SE=0.003, p=.03) and delayed memory (β=-0.01, SE=0.004, p=.03) via CRP. In addition, there were significant indirect associations between affective symptoms in childhood and immediate memory (β=-0.001, SE=0.00, p=.03) and delayed memory (β=-0.001, SE=0.001, p=.03), via adult affective symptoms and associated CRP. Independent of CRP, there was a significant direct association between adult affective symptoms and information processing errors (β=0.47, SE=0.21, p=.02). There were no direct or indirect associations between affective symptoms and verbal fluency or information processing speed. Conclusions: CRP at age 44 is elevated in people with higher affective symptoms from age 7 to 42, and elevated CRP is associated with poorer immediate and delayed memory at age 50

Using event-related fMRI to examine sustained attention processes and effects of APOE ε4 in young adults

In this study we investigated effects of the APOE ε4 allele (which confers an enhanced risk of poorer cognitive ageing, and Alzheimer’s Disease) on sustained attention (vigilance) performance in young adults using the Rapid Visual Information Processing (RVIP) task and event-related fMRI. Previous fMRI work with this task has used block designs: this study is the first to image an extended (6-minute) RVIP task. Participants were 26 carriers of the APOE ε4 allele, and 26 non carriers (aged 18–28). Pupil diameter was measured throughout, as an index of cognitive effort. We compared activity to RVIP task hits to hits on a control task (with similar visual parameters and response requirements but no working memory load): this contrast showed activity in medial frontal, inferior and superior parietal, temporal and visual cortices, consistent with previous work, demonstrating that meaningful neural data can be extracted from the RVIP task over an extended interval and using an event-related design. Behavioural performance was not affected by genotype; however, a genotype by condition (experimental task/control task) interaction on pupil diameter suggested that ε4 carriers deployed more effort to the experimental compared to the control task. fMRI results showed a condition by genotype interaction in the right hippocampal formation: only ε4 carriers showed downregulation of this region to experimental task hits versus control task hits. Experimental task beta values were correlated against hit rate: parietal correlations were seen in ε4 carriers only, frontal correlations in non-carriers only. The data indicate that, in the absence of behavioural differences, young adult ε4 carriers already show a different linkage between functional brain activity and behaviour, as well as aberrant hippocampal recruitment patterns. This may have relevance for genotype differences in cognitive ageing trajectories