Longitudinal Changes in Fat Mass and the Hippocampus

OBJECTIVE: This study aimed to investigate cross-sectional and longitudinal associations between fat mass (i.e., body mass index [BMI], waist circumference [WC], and waist to hip ratio [WTHR]) and hippocampal volumes. METHODS: UK Biobank participants (N = 20,395) aged 40 to 70 years (mean follow-up = 7.66 years), were included and categorized into one of four groups, which represented their baseline fat mass status and trajectory of change by follow-up assessment: normal weight to overweight/obesity, overweight/obesity to normal weight (ON), normal weight stable (NS), or overweight/obesity stable (OS). Regression models used NS (WC < 80 cm in women and < 94 cm in men; WTHR < 0.85 in women and < 0.90 in men; BMI < 25 kg/m2 in women and men) as the reference group. Hippocampal volumes were automatically segmented using the FMRIB Software Library. RESULTS: Compared with NS, OS (BMI: B = -62.23 [SE = 16.76]; WC: B = -145.56 [SE = 16.97]; WTHR: B = -101.26 [SE = 19.54]) and ON (BMI: B = -61.1 [SE = 30.3]; WC: B = -93.77 [SE = 24.96]; WTHR: B = -69.92 [SE = 26.22]) had significantly lower hippocampal volumes. CONCLUSIONS: The detrimental effects of overweight/obesity may extend beyond the duration of overweight/obesity itself

Investigating the synergistic effects of hormone replacement therapy, apolipoprotein E and age on brain health in the UK Biobank

Global prevalence of Alzheimer's Disease has a strong sex bias, with women representing approximately two-thirds of the patients. Yet, the role of sex-specific risk factors during midlife, including hormone replacement therapy (HRT) and their interaction with other major risk factors for Alzheimer's Disease, such as apolipoprotein E (APOE)-e4 genotype and age, on brain health remains unclear. We investigated the relationship between HRT (i.e., use, age of initiation and duration of use) and brain health (i.e., cognition and regional brain volumes). We then consider the multiplicative effects of HRT and APOE status (i.e., e2/e2, e2/e3, e3/e3, e3/e4 and e4/e4) via a two-way interaction and subsequently age of participants via a three-way interaction. Women from the UK Biobank with no self-reported neurological conditions were included (N = 207,595 women, mean age = 56.25 years, standard deviation = 8.01 years). Generalised linear regression models were computed to quantify the cross-sectional association between HRT and brain health, while controlling for APOE status, age, time since attending centre for completing brain health measure, surgical menopause status, smoking history, body mass index, education, physical activity, alcohol use, ethnicity, socioeconomic status, vascular/heart problems and diabetes diagnosed by doctor. Analyses of structural brain regions further controlled for scanner site. All brain volumes were normalised for head size. Two-way interactions between HRT and APOE status were modelled, in addition to three-way interactions including age. Results showed that women with the e4/e4 genotype who have used HRT had 1.82% lower hippocampal, 2.4% lower parahippocampal and 1.24% lower thalamus volumes than those with the e3/e3 genotype who had never used HRT. However, this interaction was not detected for measures of cognition. No clinically meaningful three-way interaction between APOE, HRT and age was detected when interpreted relative to the scales of the cognitive measures used and normative models of ageing for brain volumes in this sample. Differences in hippocampal volume between women with the e4/e4 genotype who have used HRT and those with the e3/e3 genotype who had never used HRT are equivalent to approximately 1–2 years of hippocampal atrophy observed in typical health ageing trajectories in midlife (i.e., 0.98%–1.41% per year). Effect sizes were consistent within APOE e4/e4 group post hoc sensitivity analyses, suggesting observed effects were not solely driven by APOE status and may, in part, be attributed to HRT use. Although, the design of this study means we cannot exclude the possibility that women who have used HRT may have a predisposition for poorer brain health

Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later

Introduction: The menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology. Methods: In this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40–70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline. Results: Postmenopausal females showed higher levels of baseline blood lipids (HDL β = 0.14, p  Discussion: Our findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years

Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later

Introduction: The menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology. Methods: In this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40–70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline. Results: Postmenopausal females showed higher levels of baseline blood lipids (HDL (Formula presented.) = 0.14, p &lt; 0.001, LDL (Formula presented.) = 0.20, p &lt; 0.001, triglycerides (Formula presented.) = 0.12, p &lt; 0.001) and HbA1c ((Formula presented.) = 0.24, p &lt; 0.001) compared to premenopausal women, beyond the effects of age. Over time, BMI increased more in the premenopausal compared to the postmenopausal group ((Formula presented.) = −0.08, p &lt; 0.001), while WHR increased to a similar extent in both groups ((Formula presented.) = −0.03, p = 0.102). The change in WHR was however driven by increased waist circumference only in the premenopausal group. While the group level changes in BMI and WHR were in general small, these findings point to distinct anthropometric changes in pre- and postmenopausal females over time. Higher baseline measures of BMI, WHR, triglycerides, blood pressure, and HbA1c, as well as longitudinal increases in BMI and WHR, were associated with larger WMH volumes ((Formula presented.) range = 0.03–0.13, p ≤ 0.002). HDL showed a significant inverse relationship with WMH volume ((Formula presented.) = −0.27, p &lt; 0.001). Discussion: Our findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years.</p

Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later

IntroductionThe menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology.MethodsIn this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40–70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline.ResultsPostmenopausal females showed higher levels of baseline blood lipids (HDL β = 0.14, p &lt; 0.001, LDL β = 0.20, p &lt; 0.001, triglycerides β = 0.12, p &lt; 0.001) and HbA1c (β = 0.24, p &lt; 0.001) compared to premenopausal women, beyond the effects of age. Over time, BMI increased more in the premenopausal compared to the postmenopausal group (β = −0.08, p &lt; 0.001), while WHR increased to a similar extent in both groups (β = −0.03, p = 0.102). The change in WHR was however driven by increased waist circumference only in the premenopausal group. While the group level changes in BMI and WHR were in general small, these findings point to distinct anthropometric changes in pre- and postmenopausal females over time. Higher baseline measures of BMI, WHR, triglycerides, blood pressure, and HbA1c, as well as longitudinal increases in BMI and WHR, were associated with larger WMH volumes (β range = 0.03–0.13, p ≤ 0.002). HDL showed a significant inverse relationship with WMH volume (β = −0.27, p &lt; 0.001).DiscussionOur findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years

Women's brain health: disentangling the role of menopause and ageing

Maintaining a healthy brain has been recognised as an important health challenge facing women, given global estimates indicate almost twice as many women die of dementia than men. In part, this is due to their increased longevity, however, this does not explain all of the difference. Other contributors include different exposure to risk factors as well as sex-related physiological differences. This thesis focused on the latter, specifically in relation to possible impacts of menopause, as this stage of life has been suggested to involve particular risks to brain health. To address this question, five studies were conducted to precisely characterise and quantify (1) changes in fat mass during menopause; (2) lipid profile differences during menopause; (3) heterogeneity of menopause nomenclature used in peer-reviewed literature; (4) changes in fat mass and the brain; and (5) menstruation history (including menopausal status and age at menopause) and the brain. Moreover, an important conceptual and theoretical question embedded throughout this thesis has been to determine how much of the observed effects were attributable to ageing, rather than a possible effect of menopause. This has been a significant challenge, given menopause and ageing co-occur. The first two studies revealed that fat mass was higher in postmenopausal compared to premenopausal women across most measures, with the exception of leg fat which decreased, indicative of a potential change in fat mass distribution after menopause. However, the change in fat mass quantity was predominantly attributable to increasing age with menopause having no detectable additional influence. Furthermore, lipoproteins were significantly higher in postmenopausal women than premenopausal women, with the exception of high-density lipoprotein, which was not significantly different between groups. Measures of ageing explained some, but not all of the differences in lipid levels. The third study found a significant amount of heterogeneity associated with the definition of "premenopause", compared with "postmenopause". The fourth study demonstrated that those who suffered from overweight or obesity had smaller hippocampal volumes than those who maintained a normal weight. Furthermore, those who suffered from overweight or obesity in the past, but currently had a normal level of fat mass also had a smaller hippocampus than those who had always maintained a normal weight. The fifth study revealed an association between menopause and the brain, beyond typical ageing effects. Notably, postmenopausal women had larger brain volumes than premenopausal women but also experience greater decreases in total brain volume, but not hippocampal volume, over time. In addition, delayed age of menopause was negatively associated with brain volume. The findings from this thesis have demonstrated an association between menopause and the brain, which cannot be uniquely explained by ageing. Specifically, although menopause alone was not found to be negatively associated brain health, it was associated with somewhat poorer brain health when considered concurrently with other changes around menopause. Moreover, when considering that women tend to gain abdominal fat around menopause, as well as develop an unfavourable lipid profile, and given extensive evidence in the literature that higher abdominal fat and lipid levels are associated with a greater risk of cerebro-vascular disease and dementia, hypothesising a link between menopause and poorer brain health seems warranted but will require further confirmation in future research. As a whole, the findings from this thesis paint an optimistic picture for women's health, since the risk factors identified and linked with deleterious brain health outcomes are modifiable. If adequate support is available at a health policy, clinical and community level, these specific risks to brain health may be reduced or prevented

The impact of improving feelings of relatedness on motivation and engagement for tertiary students

First-year undergraduates may be particularly prone to experiencing difficulties with facilitating feelings of relatedness, due to the recent shift in educational environments (i.e. from high school to university), which may be unfamiliar. Therefore, the current study aimed to determine whether the implementation of a single pedagogical strategy, centred within the self-determination theory framework, could effectively address students’ innate need for relatedness. Specifically, informal verbal feedback was utilized to enhance teacher–student communication, where the teacher spoke with each undergraduate student individually at the start of every lesson for 1–2 minutes. A total of 243 Advanced Science undergraduates enrolled in the first-year course at the University of New South Wales, Sydney, were included in the study. Seventy-one undergraduates were enrolled in 2016, whereas 172 undergraduates were enrolled in 2017. A mixed research methodology was employed to best leverage the utility of both qualitative and quantitative data. Interestingly, the use of informal verbal feedback as a pedagogical strategy significantly improved the student’ perceptions of receiving helpful feedback to aid their learning. These findings are important as they emphasize the utility and effectiveness of implementing one new pedagogical strategy to facilitate student’ motivation, by enhancing feelings of relatedness

E-Examinations and the Student Experience Regarding Appropriateness of Assessment and Course Quality in Science and Medical Science

The interest in, and use of, computers and software for assessment is reported to be increasingly popular via electronic examinations (e-exams). We deepen our understanding of the design, reception, and effectiveness of e-exams for history and philosophy of science modules, undertaken by first-year advanced science and medical science students at university. We employ a quasi-experimental research design approach to examine our implementation of e-exams on reported student satisfaction regarding the suitability of the information provided about the assessment requirements, appropriateness of the assessment methods, and overall quality of the associated courses. We report statistically significant increases in student satisfaction regarding the suitability and appropriateness of the assessment methods or requirements. The outcomes of this research highlight new avenues for educators to explore including (a) the innovative use of associated software (Maple TA™) for e-exams and (b) the implications that e-exams can have on the student experience in the context of medium-stakes testing.This work was partially funded by a grant from the university

Poorer sleep impairs brain health at midlife

Sleep is an emerging risk factor for dementia but its association with brain health remains unclear. This study included UK Biobank (n = 29,545; mean age = 54.65) participants at imaging visit with sleep measures and brain scans, and a subset (n = 14,206) with cognitive measures. Multiple linear regression analyses were conducted to study the associations between sleep and brain health. Every additional hour of sleep above 7 h/day was associated with 0.10–0.25% lower brain volumes. In contrast, a negative non-linear association was observed between sleep duration, grey matter, and hippocampal volume. Both longer (> 9 h/day) and shorter sleep ( 9 h/day, daytime dozing) at midlife was associated with lower brain health. Sleep may be an important target to improve brain health into old age and delay the onset of dementia

Poorer sleep impairs brain health at midlife

Abstract Sleep is an emerging risk factor for dementia but its association with brain health remains unclear. This study included UK Biobank (n = 29,545; mean age = 54.65) participants at imaging visit with sleep measures and brain scans, and a subset (n = 14,206) with cognitive measures. Multiple linear regression analyses were conducted to study the associations between sleep and brain health. Every additional hour of sleep above 7 h/day was associated with 0.10–0.25% lower brain volumes. In contrast, a negative non-linear association was observed between sleep duration, grey matter, and hippocampal volume. Both longer (> 9 h/day) and shorter sleep ( 9 h/day, daytime dozing) at midlife was associated with lower brain health. Sleep may be an important target to improve brain health into old age and delay the onset of dementia