Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/catenin, TGF- and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

RATIONALEMetabolomics in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort provides a powerful tool for mapping biochemical changes in AD, and a unique opportunity to learn about the association between circulating blood metabolites and brain amyloid-β deposition in AD.OBJECTIVESWe examined 140 serum metabolites and their associations with brain amyloid-β deposition, cognition, and conversion from mild cognitive impairment (MCI) to AD.FINDINGSSerum-based targeted metabolite levels were measured in 1,531 ADNI participants. We performed association analysis of metabolites with brain amyloid-β deposition measured from [18F] Florbetapir PET scans. We identified nine metabolites as significantly associated with amyloid-β deposition after FDR-based multiple comparison correction. Higher levels of one acylcarnitine (C3; propionylcarnitine) and one biogenic amine (kynurenine) were associated with decreased amyloid-β accumulation. However, higher levels of seven phosphatidylcholines (PC) were associated with increased amyloid deposition. In addition, PC ae C44:4 was significantly associated with cognition and conversion from MCI to AD dementia.CONCLUSIONPerturbations in PC and acylcarnitine metabolism may play a role in features intrinsic to AD including amyloid-β deposition and cognitive performance.

Background: Although shorter telomeres have been associated with Alzheimer's disease (AD), it is unclear whether longitudinal change in telomere length is associated with AD progression. Objective: To investigate the association of telomere length change with AD diagnosis and progression. Methods: In 653 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, T/S ratio (telomere versus single copy gene), a proxy of telomere length, was measured for up to five visits per participant (N = 1918 samples post-QC) using quantitative PCR (qPCR). T/S ratio was adjusted for batch effects and DNA storage time. A mixed effects model was used to evaluate association of telomere length with AD diagnostic group and interaction of age and diagnosis. Another mixed effects model was used to compare T/S ratio changes pre-to post-conversion to MCI or AD to telomere change in participants with stable diagnoses. Results: Shorter telomeres were associated with older age (Effect Size (ES) = -0.23) and male sex (ES = -0.26). Neither baseline T/S ratio (ES = -0.036) nor T/S ratio change (ES = 0.046) differed significantly between AD diagnostic groups. MCI/AD converters showed greater, but non-significant, telomere shortening compared to non-converters (ES = -0.186).