Sex-specific effects of central adiposity and inflammatory markers on limbic microstructure

Metzler‐Baddeley, Claudia; Mole, Jilu P.; Leonavičiūtė, Erika; Sims, Rebecca; Kidd, Emma Jane; Ertefai, Benyamin; Kelso-Mitchell, Aurora; Gidney, Florence; Fasano, Fabrizio; Evans, John; Jones, Derek K.; Baddeley, Roland

doi:10.1016/j.neuroimage.2019.02.007

Cited by 24 publications

(65 citation statements)

References 91 publications

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“…Similarly, women relative to men showed lower kf, ISOSF and ODI in WBWM and the fornix as well as larger MPF in the fornix but no differences in PHC. Previously, we reported negative correlations between central obesity measures, including estimates of abdominal visceral fat, and qMT indices (MPF, kf), that were particularly prominent in the fornix tract without any effects of family history or APOE 60 . Thus, while interaction effects between family history, APOE and WHR were observed for MPF (and ICSF) and were most prominent in the PHC, they were absent in the fornix.…”

Section: Discussionmentioning

confidence: 90%

“…We therefore investigated the interaction effects between APOE, family history of dementia, and Waist-Hip-Ratio, a measure of central obesity, in 166 asymptomatic individuals (38 -71 years) from the Cardiff Ageing and Risk of Dementia Study (CARDS) 59,60 with a focus on white matter microstructure and cognition (Table 1). Based on the myelin model, we hypothesized that risk-related effects would be particularly apparent in myelinsensitive MRI metrics in temporal lobe pathways known to be susceptible to LOAD, i.e.…”

Section: Insert Table 1 and Figure 1 Herementioning

confidence: 99%

“…Participants between the age of 35 and 75 years were recruited for the Cardiff Ageing and Risk of Dementia Study (CARDS) 59,60 via Cardiff University community panels and notice boards as well as via internet and local poster advertisements. Participants had a good command of the English language and were without a history of neurological and/or psychiatric disease, head injury with loss of consciousness, drug or alcohol dependency, high risk cardio-embolic source or known significant large-vessel disease.…”

Section: Participantsmentioning

confidence: 99%

“…N = 166 CARDS volunteers that fulfilled MRI screening criteria underwent scanning at the Cardiff University Brain Research Imaging Centre (CUBRIC). Table 1 summarises information about demographics, cognition, and genetic and lifestyle dementia risk for these 166 participants (as described in 59,60 ). Participants' intellectual function was assessed with the National Adult Reading Test (NART) 109 , cognitive impairment was screened for with the Mini Mental State Exam (MMSE) 110 and depression with the PHQ-9 111 .…”

Section: Participantsmentioning

confidence: 99%

“…A detailed description of the microstructural data processing was provided in Metzler-Baddeley et al 59,60 . The dual-shell HARDI data were split and b = 1200 and 2400 s/mm 2 data were corrected separately for distortions induced by the diffusion-weighted gradients 20 and motion artifacts with appropriate reorientation of the encoding vectors 118 in ExploreDTI (Version 4.8.3) 119 .…”

Section: Hardi and Qmt Data Processingmentioning

confidence: 99%

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Genetic risk of dementia modifies the impact of obesity on limbic white matter and spatial navigation behavior in cognitively healthy adults

Mole

Fasano

Evans

et al. 2019

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A family history (FH) of dementia, APOE-e4 genotype, and obesity are major risk factors for developing Alzheimer's disease but their combined effects on the brain and cognition remain elusive. We tested the hypothesis that these risk factors affect apparent white matter (WM) myelin and cognition including spatial navigation and processing speed in 166 asymptomatic individuals (38-71 years). Microstructure in temporal [fornix, parahippocampal cingulum, uncinate fasciculus], motor and whole-brain WM was assessed with myelin-sensitive indices from quantitative magnetization transfer [macromolecular proton fraction (MPF)] and axon density from diffusion imaging. Individuals with the highest genetic risk compared to those with FH+ alone showed obesity-related reductions in MPF and axon density in the right parahippocampal cingulum. No effects were present for those without FH.Furthermore, FH modulated obesity-related effects on spatial navigation behaviour. In summary, an individual's genetic dementia risk influenced the impact of obesity on WM myelin and cognition. quantitative magnetization transfer, NODDI, white matter, myelin, parahippocampal cingulum 7 ResultsInsert Table 2 and Figures 2 and 3 here 2.1 Multivariate covariance analysis (MANCOVA) of white matter microstructural indices MANCOVA tested for the effects of APOE genotype (e4+, e4-), family history (FH+, FH-) and central obesity (WHR+, WHR-) on all microstructural indices (MPF, kf, R1, ISOSF, ICSF, ODI) in all white matter pathways (left PHC, right PHC, left UF, right UF, left CST, right CST and fornix) and WBWM regions whilst controlling for age, sex, and years of education. Omnibus effects: Main effects were observed for age [F(48,60) = 2.64, p < 0.001, hp 2 = 0.68] and sex [F(48,60) = 2.61, p < 0.001, hp 2 = 0.67]. Interaction effects were present between APOE and WHR [F(48,60) = 1.6, p = 0.04, hp 2 = 0.56] and between APOE, FH and WHR [F(48,60) = 1.7, p = 0.02, hp 2 = 0.58].Post-hoc effects: Ageing was associated with reductions in MPF, kf, and R1 in WBWM, fornix and right UF (Table 2). MPF and kf reductions were also present in the left UF and bilateral CST respectively. In addition, age-related increases in ISOSF were observed in WBWM and fornix and increases in ODI in the fornix (Table 2, Figure 2A).Women relative to men showed lower kf, ISOSF and ODI in WBWM and the fornix and larger fornix MPF (Table 2, Figure 2B). Two-way interaction effects between APOE and WHR were present for right PHC ( Figure 3A) and bilateral CST but additional post-hoc group comparisons to assess the directions of these effects were non-significant. Three-way interaction effects between FH, APOE and WHR were observed for MPF in WBWM, bilateral CST, bilateral UF and right PHC ( Figure 3B). For right PHC there was also an effect on ICSF. These three-way interaction effects were followed up by testing for APOE and WHR interactions in FH+ and FH-individuals separately ( Figure 3C). FH-individuals did not show any interaction effects B from the Alzheimer's Society and the BR...

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Section: Discussionmentioning

confidence: 90%

Section: Insert Table 1 and Figure 1 Herementioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%