The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100+ years of age. HCP-D is enrolling 1300+ healthy children, adolescents, and young adults (ages 5–21), and HCP-A is enrolling 1200+ healthy adults (ages 36–100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200+ participants, aged 22–35), but some imaging- related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain.

Background The fornix is the predominant outflow tract of the hippocampus, a brain region known to be affected early in the course of Alzheimer’s disease (AD). The aims of the present study were to: 1) examine the cross-sectional relationship between fornix DTI measurements (fractional anisotropy (FA), and mean (MD), axial (DA) and radial (DR) diffusivities), hippocampal volume, and memory performance, and 2) compare fornix DTI measures to hippocampal volumes as predictors of progression and transition from amnestic mild cognitive impairment (MCI) to AD dementia. Methods 23 MCI participants with baseline hippocampal volumetry and diffusion tensor imaging received detailed evaluations at baseline, 3, 6, 12 months, and 2.5 years. Six participants converted to AD over the follow-up. Fornix and posterior cingulum DTI measurements and hippocampal volumes were ascertained using manual measures. Random effects models assessed each of the neuroimaging measures as predictors of decline on the MMSE, CDR-Sum of boxes and Memory z-scores; ROC analyses examined the predictive value for conversion to AD. Results There was a significant correlation between fornix FA and hippocampal volumes. However, only the fornix measurements (FA, MD, DR, DA) were cross-sectionally correlated with memory z-scores. Both fornix FA and hippocampal volumes were predictive of memory decline. Individually, fornix FA and MD and hippocampal volumes were very good predictors of progression with likelihood ratios>83, and better than 90% accuracy. Conclusion Fornix FA both cross-sectionally correlated with and longitudinally predicted memory decline and progression to AD. Manually-drawn fornix ROI shows comparable promise to hippocampal volume as a predictive biomarker of progression and warrants replication in a larger study.

Background-A blood-based biomarker of Alzheimer disease (AD) would be superior to CSF and neuroimaging measures in terms of cost, invasiveness and feasibility for repeated measures. We previously reported blood ceramides varied in relation to timing of memory impairment in a population-based study. The present objective was to examine whether plasma ceramides varied by AD severity in a well-characterized clinic sample and were associated with cognitive decline and hippocampal volume loss over one year.Methods-Participants included 25 normal controls (NC), 17 amnestic Mild Cognitive Impairment (MCI), and 21 early probable AD. A thorough neuropsychological battery and neuroimaging with hippocampal volume determination were conducted at baseline and one year later. Plasma ceramides were assayed at baseline using HPLC-coupled electrospray ionization tandem mass spectrometry. : 443-326-5174, Fax: 410-550-1407, mmielke1@jhmi.edu. Disclosure: All authors report no conflicts of interest. The corresponding author had full access to all the data in the study and had final responsibility of the decision to submit for publication.Disclosure Statement: While funding for the neuroimaging and participant follow-up was partially obtained through a grant from GlaxoSmithKline, the authors had access to the data at all times and retain the data. Funding for the plasma lipids were obtained from NIH grants. All authors report no conflicts of interests with regards to GlaxoSmithKline or any other organization. All participants provided informed consent and the study was approved by the Johns Hopkins University Institutional Review Board.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-While all saturated ceramides were lower in MCI compared to AD at baseline, Ceramides C22:0 and C24:0 were significantly lower in the MCI group compared to both NC and AD groups (p<0.01). Ceramide levels did not differ (p>0.05) in AD versus NC. There were no cross-sectional associations between ceramides C22:0 and C24:0 and either cognitive performance or hippocampal volume among any group. However, among the MCI group, higher baseline ceramide C22:0 and C24:0 levels were predictive of cognitive decline and hippocampal volume loss one year later. NIH Public AccessAuthor Manuscript Alzheimers Dement. Author manuscript; available in PMC 2011 September 1. Conclusion-Resultssuggest that very long-chain plasma ceramides C22:0 and C24:0 are altered in MCI and predict memory loss and right hippocampal volume loss among subjects with MCI. These plasma ceramides may be early indicators of AD progression.

This paper examines morphometry of MRI biomarkers derived from the network of temporal lobe structures including the amygdala, entorhinal cortex and hippocampus in subjects with preclinical Alzheimer's disease (AD). Based on template-centered population analysis, it is demonstrated that the structural markers of the amygdala, hippocampus and entorhinal cortex are statistically significantly different between controls and those with preclinical AD. Entorhinal cortex is the most strongly significant based on the linear effects model (p < .0001) for the high-dimensional vertex- and Laplacian-based markers corresponding to localized atrophy. The hippocampus also shows significant localized high-dimensional change (p < .0025) and the amygdala demonstrates more global change signaled by the strength of the low-dimensional volume markers. The analysis of the three structures also demonstrates that the volume measures are only weakly discriminating between preclinical and control groups, with the average atrophy rates of the volume of the entorhinal cortex higher than amygdala and hippocampus. The entorhinal cortex thickness also exhibits an atrophy rate nearly a factor of two higher in the ApoE4 positive group relative to the ApoE4 negative group providing weak discrimination between the two groups.

Technologies for multi-atlas brain segmentation of T1-weighted MRI images have rapidly progressed in recent years, with highly promising results. This approach, however, relies on a large number of atlases with accurate and consistent structural identifications. Here, we introduce our atlas inventories (n = 90), which cover ages 4 – 82 years with unique hierarchical structural definitions (286 structures at the finest level). This multi-atlas library resource provides the flexibility to choose appropriate atlases for various studies with different age ranges and structure-definition criteria. In this paper, we describe the details of the atlas resources and demonstrate the improved accuracy achievable with a dynamic age-matching approach, in which atlases that most closely match the subject’s age are dynamically selected. The advanced atlas creation strategy, together with atlas pre-selection principles, are expected to support the further development of multi-atlas image segmentation.