Risk of Mild Behavioral Impairment: the role of gender and APOE allele carrier status

Background Gender differences in dementia and dementia‐related neuropsychiatric symptoms are well described. Similarly, the Apolipoprotein E (APOE) ε4 allele is a well‐known predictor of Alzheimer’s disease. However, their impact on the clinical manifestation of Mild Behavioral Impairment (MBI) remains unclear. Using data from the Australian population‐based PATH Through Life Study we explored the associations between gender and APOE ε4 carrier status with MBI. We hypothesized that MBI likelihood would be greater in males and ε4 carriers. Method 1316 dementia‐free participants (48% female; aged 72‐79) were included. Gender was self‐reported (female/male). Participants were classified as APOE ε4+ if they carried at least one ε4 allele (APOE ε4/ε4, ε2/ε4, ε3/ε4). MBI was approximated using a previously published transformation algorithm, which utilizes items from the Neuropsychiatric Inventory assessed at a single study visit. Binomial logistic regression was used to examine the role of gender and APOE ε4 carrier status, and their interaction, on predicting MBI status, while controlling for self‐reported years of education. Result Of the 1316 participants, 339 (25.8%) were APOE ε4+ and 445 (34%) had MBI symptoms. A higher proportion of APOE ε4+ carriers (χ2 (1) = 5.99, p = .014) and men (χ2 (1) = 4.59, p = .032) were in the MBI group compared to the non‐MBI group. Binomial logistic regression showed APOE ε4 carrier status (OR = 1.58, 95% CI: 1.063‐2.344) and male gender (OR = 1.45, 95% CI: 1.093‐1.925) were associated with a greater likelihood of MBI. Male gender was also associated with a 2‐fold greater likelihood of having symptoms of the Decreased Motivation (OR = 2.08, 95% CI: 1.13‐3.86) and Impulse Dyscontrol (OR = 2.16, 95% CI: 1.54‐3.03) domains. No interaction effects were found between gender and APOE ε4 carrier status for MBI or any of its domains. Conclusion The current study found that in dementia‐free older adults both male gender and APOE ε4+ status increased the risk of having MBI. However, no cumulative/interaction effect between gender and APOE ε4 carrier status was found, suggesting that being both male and APOE ε4+ does not further increase the risk of MBI. These results provide novel and valuable insight into the connection between gender, APOE ε4 carrier status and MBI

Association of cognitive function with glucose tolerance and trajectories of glucose tolerance over 12 years in the AusDiab study

INTRODUCTION: We investigated the association between glucose tolerance status and trajectories of change in blood glucose, and cognitive function in adults aged 25 to 85. METHODS: The sample (n = 4547) was drawn from a national, population-based cohort study in Australia (AusDiab). Fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and general health were assessed at 0, 5 and 12 years. Covariates included age, education, body mass index, blood pressure and physical activity. At 12 years, participants completed assessments of memory, processing speed and verbal ability. RESULTS: Known diabetes at baseline was associated with slower processing speed at 12 years in both younger (25–59 years) and older (>60 years) age-groups. After 12 years of follow-up, adults aged < 60 with diabetes at baseline had a mean speed score of 49.17 (SE = 1.09) compared with 52.39 (SE = 0.20) in normals. Among younger males without diagnosed diabetes, reduced memory at 12 years was associated with higher HbA1c at 5 years (β = −0.91, SE = 0.26, p < 0.001). No effects were apparent for females or older males. Adjusting for insulin sensitivity (HOMA-%S) and hs-C reactive protein attenuated these associations, but depression and CVD risk did not. Latent class analysis was used to analyse the associations between trajectories of HbA1C and glucose over 12 years, and cognition. Identified classes were described as 1) normal and stable blood glucose over time (reference), 2) high intercept but stable blood glucose over time, and 3) increasing blood glucose over time. In both young males and females, high stable glucose measures were associated with poorer cognitive function after 12 years. CONCLUSIONS: Those with type 2 diabetes, younger males with high non-diabetic HbA1c, and adults with high stable blood glucose are at increased risk of poorer cognition. The findings reinforce the need for management of diabetes risk factors in midlife.For funding or logistical support, the authors are grateful to the National Health and Medical Research Council (NHMRC grants 233200 and 1007544), the Australian Government Department of Health and Ageing, Abbott Australasia Pty Ltd, Alphapharm Pty Ltd, Amgen Australia, AstraZeneca, Bristol-Myers Squibb, City Health Centre—Diabetes Service—Canberra, Department of Health and Community Services—Northern Territory, Department of Health and Human Services—Tasmania, Department of Health—New South Wales, Department of Health—Western Australia, Department of Health—South Australia, Department of Human Services— Victoria, Diabetes Australia, Diabetes Australia Northern Territory, Eli Lilly Australia, Estate of the Late Edward Wilson, GlaxoSmithKline, Jack Brockhoff Foundation, Janssen-Cilag, Kidney Health Australia, Marian & FH Flack Trust, Menzies Research Institute, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Pfizer Pty Ltd, Pratt Foundation, Queensland Health, Roche Diagnostics Australia, Royal Prince Alfred Hospital, Sydney, Sanofi Aventis, sanofi-synthelabo, and the Victorian Government’s OIS Program. KJA is funded by NHMRC Research Fellowship No. 1002560. JES is funded by NHMRC Research Fellowship No. 586623

Using sulcal and gyral measures of brain structure to investigate benefits of an active lifestyle

Background: Physical activity is associated with brain and cognitive health in ageing. Higher levels of physical activity are linked to larger cerebral volumes, lower rates of atrophy, better cognitive function and lesser risk of cognitive decline and dementia. Neuroimaging studies have traditionally focused on volumetric brain tissue 17 measures to test associations between factors of interest (e.g. physical activity) and brain structure. However, cortical sulci may provide additional information to these more standard measures. Method: Associations between physical activity, brain structure, and cognition were investigated in a large, community-based sample of cognitively healthy individuals (N = 317) using both sulcal and volumetric measures. Results: Physical activity was associated with narrower width of the Left Superior Frontal Sulcus and the Right Central Sulcus,while volumetric measures showed no association with physical activity. In addition, Left Superior Frontal Sulcal width was associated with processing speed and executive function. Discussion: These findings suggest sulcalmeasuresmay be a sensitive index of physical activity related to cerebral health and cognitive function in healthy older individuals. Further research is required to confirm these findings and to examine how sulcal measures may be most effectively used in neuroimaging

Machine Learning for Prediction of Cognitive Health in Adults Using Sociodemographic, Neighbourhood Environmental, and Lifestyle Factors

The environment we live in, and our lifestyle within this environment, can shape our cognitive health. We investigated whether sociodemographic, neighbourhood environment, and lifestyle variables can be used to predict cognitive health status in adults. Cross-sectional data from the AusDiab3 study, an Australian cohort study of adults (34–97 years) (n = 4141) was used. Cognitive function was measured using processing speed and memory tests, which were categorized into distinct classes using latent profile analysis. Sociodemographic variables, measures of the built and natural environment estimated using geographic information system data, and physical activity and sedentary behaviours were used as predictors. Machine learning was performed using gradient boosting machine, support vector machine, artificial neural network, and linear models. Sociodemographic variables predicted processing speed (r2 = 0.43) and memory (r2 = 0.20) with good accuracy. Lifestyle factors also accurately predicted processing speed (r2 = 0.29) but weakly predicted memory (r2 = 0.10). Neighbourhood and built environment factors were weak predictors of cognitive function. Sociodemographic (AUC = 0.84) and lifestyle (AUC = 0.78) factors also accurately classified cognitive classes. Sociodemographic and lifestyle variables can predict cognitive function in adults. Machine learning tools are useful for population-level assessment of cognitive health status via readily available and easy-to-collect data

Exploring perceptions of Advanced Driver Assistance Systems (ADAS) in older drivers with age-related declines

Perceptions of Advanced Driver Assistance Systems (ADAS) were explored in two semi-structured face-to-face focus group studies of 42 older drivers (aged 65 years and older) with and without age-related declines. Study 1 explored perceptions regarding ADAS, focusing on visual, auditory, physical, and cognitive factors. Study 2 extended this by additionally exploring perceptions following exposure to videos and stationary vehicle demonstrations of an ADAS. Participants had a range of visual, hearing, memory, and health characteristics which impacted on their daily life. In both studies, some participants had insights regarding various ADAS technologies prior to the study, but many were unfamiliar with these systems. Nevertheless, overall, participants reported that ADAS would assist them to drive as they age and increase their mobility and independence. There were comments regarding the benefits of warning alerts, although the potential for them to be distracting was also highlighted. Participants with vision impairment preferred audio alerts and participants with hearing impairment preferred visual display alerts. Findings highlighted the potential for ADAS to assist those with age-related declines and the need to increase the flexibility of warning system alerts to suit the varying requirements of older drivers, as well as to reduce the complexity of vehicle interfaces. Collectively, these strategies would maximize the benefits of these vehicles to increase the mobility, independence, and quality of life of older drivers with and without age-related declines

Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

BackgroundIn areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. MethodsThis prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy performed by an experienced research microscopist, for the diagnosis of PCR-confirmed Plasmodium falciparum, P. knowlesi, and Plasmodium vivax malaria. ResultsA total of 304 patients with PCR-confirmed Plasmodium infection were enrolled, including 130 with P. knowlesi, 122 with P. falciparum, 43 with P. vivax, one with Plasmodium malariae and eight with mixed species infections. Among patients with P. knowlesi mono-infection, routine and cross-check microscopy both identified 94 (72%) patients as &ldquo;P. malariae/P. knowlesi&rdquo;; 17 (13%) and 28 (22%) respectively were identified as P. falciparum, and 13 (10%) and two (1.5%) as P. vivax. Among patients with PCR-confirmed P. falciparum, routine and cross-check microscopy identified 110/122 (90%) and 112/118 (95%) patients respectively as P. falciparum, and 8/122 (6.6%) and 5/118 (4.2%) as &ldquo;P. malariae/P. knowlesi&rdquo;. Among those with P. vivax, 23/43 (53%) and 34/40 (85%) were correctly diagnosed by routine and cross-check microscopy respectively, while 13/43 (30%) and 3/40 (7.5%) patients were diagnosed as &ldquo;P. malariae/P. knowlesi&rdquo;. Four of 13 patients with PCR-confirmed P. vivax and misdiagnosed by routine microscopy as &ldquo;P. malariae/P. knowlesi&rdquo; were subsequently re-admitted with P. vivax malaria. ConclusionsMicroscopy does not reliably distinguish between P. falciparum, P. vivax and P. knowlesi in a region where all three species frequently occur. Misdiagnosis of P. knowlesi as both P. vivax and P. falciparum, and vice versa, is common, potentially leading to inappropriate treatment, including chloroquine therapy for P. falciparum and a lack of anti-relapse therapy for P. vivax. The limitations of microscopy in P. knowlesi-endemic areas supports the use of unified blood-stage treatment strategies for all Plasmodium species, the development of accurate rapid diagnostic tests suitable for all species, and the use of PCR-confirmation for accurate surveillance

Associations between corpus callosum size and ADHD symptoms in older adults: The PATH through life study

Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed deviations of the corpus callosum in children and adolescents. However, little is known about the link between callosal morphology and symptoms of inattention or hyperactivity in adulthood, especially later in life. Here, we investigated in a large population-based sample of 280 adults (150 males, 130 females) in their late sixties and early seventies whether ADHD symptoms correlate with callosal thickness. In addition, we tested for significant sex interactions, which were followed by correlation analyses stratified by sex. Within males, there were significant negative correlations with respect to inattention and hyperactivity in various callosal regions, including the anterior third, anterior and posterior midbody, isthmus, and splenium. A thinner corpus callosum may be associated with fewer fibers or less myelination of fibers. Thus, the observed negative correlations suggest impaired inter-hemispheric communication channels necessary to sustain motor control and attention, which may contribute to symptoms of hyperactivity, impulsivity and/or inattention. Interestingly, within females, callosal thickness was positively related to hyperactivity in a small area within the rostral body, suggesting a sexually dimorphic neurobiology of ADHD symptoms. Altogether, the present results may reflect a lasting relationship between callosal morphology and ADHD symptoms throughout life.The study was supported by NHMRC Grants 973302, 179805, 157125, 1063907 and ARC Grant 130101705. Nicolas Cherbuin is funded by ARC research fellowship 12010022, Kaarin Anstey by NHMRC research fellowships 1002560, and Debjani Das by NHMRC research fellowship 410215. This research was partly undertaken on the National Computational Infrastructure (NCI) facility in Canberra, Australia, which is supported by the Australian Commonwealth Government