A metabolic obesity profile is associated with decreased gray matter volume in cognitively healthy older adults

Obesity is a risk factor for cognitive decline and gray matter volume loss in aging. Studies have shown that different metabolic factors, e.g., dysregulated glucose metabolism and systemic inflammation, might mediate this association. Yet, even though these risk factors tend to co-occur, they have mostly been investigated separately, making it difficult to establish their joint contribution to gray matter volume structure in aging. Here, we therefore aimed to determine a metabolic profile of obesity that takes into account different anthropometric and metabolic measures to explain differences in gray matter volume in aging. We included 748 elderly, cognitively healthy participants (age range: 60 – 79 years, BMI range: 17 – 42 kg/m2) of the LIFE-Adult Study. All participants had complete information on body mass index, waist-to-hip ratio, glycated hemoglobin, total blood cholesterol, high-density lipoprotein, interleukin-6, C-reactive protein, adiponectin and leptin. Voxelwise gray matter volume was extracted from T1-weighted images acquired on a 3T Siemens MRI scanner. We used partial least squares correlation to extract latent variables with maximal covariance between anthropometric, metabolic and gray matter volume and applied permutation/bootstrapping and cross-validation to test significance and reliability of the result. We further explored the association of the latent variables with cognitive performance. Permutation tests and cross-validation indicated that the first pair of latent variables was significant and reliable. The metabolic profile was driven by negative contributions from body mass index, waist-to-hip ratio, glycated hemoglobin, C-reactive protein and leptin and a positive contribution from adiponectin. It positively covaried with gray matter volume in temporal, frontal and occipital lobe as well as subcortical regions and cerebellum. This result shows that a metabolic profile characterized by high body fat, visceral adiposity and systemic inflammation is associated with reduced gray matter volume and potentially reduced executive function in older adults. We observed the highest contributions for body weight and fat mass, which indicates that factors underlying sustained energy imbalance, like sedentary lifestyle or intake of energy-dense food, might be important determinants of gray matter structure in aging

Association of estradiol and visceral fat with structural brain networks and memory performance in adults

Importance Changes in estradiol during aging are associated with increased dementia risk. It remains unclear how estradiol supports cognitive health and whether risk factors, such as midlife obesity, are exacerbated by estrogen loss. Objectives To assess whether visceral adipose tissue (VAT) moderates the association between age and brain network structure and to investigate whether estradiol moderates the association between VAT and brain network structure. Design, Setting, and Participants Cross-sectional study of data from 974 cognitively healthy adults in Germany who participated in the Health Study of the Leipzig Research Centre for Civilization Diseases, a previously described population-based cohort study. Two moderation analyses were performed, including VAT as the moderator variable between age and brain network structure and estradiol as the moderator variable between VAT and brain network structure. The study was conducted from August 1, 2011, to November 23, 2014. Analyses were conducted from August 2017 to September 201

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

10Kin1day: A Bottom-Up Neuroimaging Initiative.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain