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

White matter hyperintensities and within-person variability in community-dwelling adults aged 60–64 years

Estimates of white matter hyperintensities (WMH) derived from T2-weighted MRI were investigated in relation to cognitive performance in 469 healthy community-dwelling adults aged 60–64 years. Frontal lobe WMH but not WMH from other brain regions (temporal, parietal, and occipital lobes, anterior and posterior horn, periventricular body) were associated with elevated within-person reaction time (RT) variability (trial to trial fluctuations in RT performance) but not performance on several other cognitive tasks including psychomotor speed, memory, and global cognition. The findings are consistent with the view that elevated within-person variability is related to neurobiological disturbance, and that attentional mechanisms supported by the frontal cortex play a key role in this type of variability

Invalid party wall awards and how to avoid them

Considers the reasons for the invalidity of party wall awards. Examines decided cases under earlier party wall legislation in the context of the Party Wall etc. Act 1996. Explains invalidity on the basis of an excess of the surveyors’ statutory authority. Defines this authority in terms of jurisdiction and power. Demonstrates the limits of the surveyors’ authority and emphasises the importance of strict compliance with statutory procedures. Concludes that surveyors should adopt an inquisitive and analytical approach to the scope of their authority to avoid the possibility of invalid awards. Echoes John Anstey’s earlier warning that surveyors should avoid a broad-brush approach to their duties which will only leave them “covered in soot”

High Morbidity during Treatment and Residual Pulmonary Disability in Pulmonary Tuberculosis: Under-Recognised Phenomena

BACKGROUND In pulmonary tuberculosis (PTB), morbidity during treatment and residual pulmonary disability can be under-estimated. METHODS Among adults with smear-positive PTB at an outpatient clinic in Papua, Indonesia, we assessed morbidity at baseline and during treatment, and 6-month residual disability, by measuring functional capacity (six-minute walk test [6MWT] and pulmonary function), quality of life (St George's Respiratory Questionnaire [SGRQ]) and Adverse Events ([AE]: new symptoms not present at outset). Results were compared with findings in locally-recruited volunteers. RESULTS 200 PTB patients and 40 volunteers were enrolled. 6WMT was 497m (interquartile range 460-529) in controls versus 408m (IQR 346-450) in PTB patients at baseline (p<0.0001) and 470m (IQR 418-515) in PTB patients after 6 months (p=0.02 versus controls). SGRQ total score was 0 units (IQR 0-2.9) in controls, versus 36.9 (27.4-52.8) in PTB patients at baseline (p<0.0001) and 4.3 (1.7-8.8) by 6 months (p<0.0001). Mean percentage of predicted FEV1 was 92% (standard deviation 19.9) in controls, versus 63% (19.4) in PTB patients at baseline (p<0.0001) and 71% (17.5) by 6 months (p<0.0001). After 6 months, 27% of TB patients still had at least moderate-severe pulmonary function impairment, and 57% still had respiratory symptoms, despite most achieving 'successful' treatment outcomes, and reporting good quality of life. More-advanced disease at baseline (longer illness duration, worse baseline X-ray) and HIV positivity predicted residual disability. AE at any time during treatment were common: itch 59%, arthralgia 58%, headache 40%, nausea 33%, vomiting 16%. CONCLUSION We found high 6-month residual pulmonary disability and high AE rates. Although PTB treatment is highly successful, the extent of morbidity during treatment and residual impairment could be overlooked if not specifically sought. Calculations of PTB-related burden of disease should acknowledge that TB-related morbidity does not stop at 6 months. Early case detection and treatment are key in minimising residual impairment.The study received funding from the Australian Respiratory Council, Royal Australasian College of Physicians (Covance Award to APR), National Health and Medical Research Council (NHMRC) of Australia (Grants 605806 and 496600, a scholarship to APR, and fellowships to APR, TWY, PMK, NMA). Graeme Maguire is supported by an NHMRC Practitioner Fellowship and the Margaret Ross Chair in Indigenous Health. Views expressed in this publication are those of the authors and do not reflect the views of NHMRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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

The protective effects of wellbeing and flourishing on long-term mental health risk

Objective: Personal wellbeing reflects individuals’ experiences of positive mental health and those with high wellbeing can be described as flourishing. Increasingly, wellbeing and flourishing are informing public health policy and clinical practice. However, the long-term benefit of wellbeing and flourishing on negative mental health outcomes over the life course is not widely explored. Method: Data were from the Personality and Total Health Through Life study, based in Canberra, Australia. Participants were recruited to three age cohorts (Early Adulthood n ​= ​991; Middle Adulthood n ​= ​1,510; Later Adulthood n ​= ​1,432). Wellbeing was operationalised by positive and negative affect, life satisfaction, morale, resilience and social support. Flourishing status was defined by those reporting the highest levels of wellbeing. Mental Health was operationalised by depression and anxiety symptoms, and any depressive disorder. A sub-set of early (n ​= ​439) and middle adulthood (n ​= ​1,275) participants completed the Composite International Diagnostic Interview (CIDI). Results: Associations between individual wellbeing indicators with mental health were mostly attenuated or of small magnitude in multivariate analyses, except for negative affect and low mastery which consistently reported substantial 4-year risk for all age cohorts. In contrast flourishing status reported consistently strong protection against poor mental health outcomes. Conclusion: Individual wellbeing indicators are not as strongly related to mental health outcomes as a higher-order latent wellbeing factor reflecting flourishing. However, multiple measures of wellbeing are needed to capture the gamut of wellbeing experiences and are related to improved mental health outcomes over the long-term and are generally consistent across adulthood

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

The influence of smoking, sedentary lifestyle and obesity on cognitive impairment-free life expectancy

BACKGROUND Smoking, sedentary lifestyle and obesity are risk factors for mortality and dementia. However, their impact on cognitive impairment-free life expectancy (CIFLE)has not previously been estimated. METHODS Data were drawn from the DYNOPTA dataset which was derived by harmonizing and pooling common measures from five longitudinal ageing studies. Participants for whom the Mini-Mental State Examination was available were included (N¼8111,48.6% men). Data on education, sex, body mass index, smoking and sedentary lifestyle were collected and mortality data were obtained from Government Records via data linkage.Total life expectancy (LE), CIFLE and years spent with cognitive impairment (CILE)were estimated for each risk factor and total burden of risk factors. RESULTS CILE was approximately 2 years for men and 3 years for women, regardless of age. For men and women respectively, reduced LE associated with smoking was 3.82and 5.88 years, associated with obesity was 0.62 and 1.72 years and associated with being sedentary was 2.50 and 2.89 years. Absence of each risk factor was associated with longer LE and CIFLE, but also longer CILE for smoking in women and being sedentary in both sexes. Compared with participants with no risk factors, those with 2þ had shorter CIFLE of up to 3.5 years depending on gender and education level. CONCLUSIONS Population level reductions in smoking, sedentary lifestyle and obesity increase longevity and number of years lived without cognitive impairment. Years lived with cognitive impairment may also increase.This work was supported by a National Health and Medical Research Council grant # 410215 and by the Australian Research Council Centre of Excellence in Population Ageing Research (CE110001029). K.J.A is funded by NHMRC Fellowship #1002560. C.J. is funded by the AXA Research Fund