Study Objectives Although short sleep could promote neurodegeneration, long sleep may be a marker of ongoing neurodegeneration, potentially as a result of neuroinflammation. The objective was to evaluate sleep patterns with age of expected Alzheimer's disease (AD) onset and neuroinflammation.Methods We tested 203 dementia-free participants (68.5 +/- 5.4 years old, 78M). The PREVENT-AD cohort includes older persons with a parental history of AD whose age was nearing their expected AD onset. We estimated expected years to AD onset by subtracting the participants' age from their parent's at AD dementia onset. We extracted actigraphy sleep variables of interest (times of sleep onset and morning awakening, time in bed, sleep efficiency, and sleep duration) and general profiles (sleep fragmentation, phase delay, and hypersomnia). Cerebrospinal fluid (CSF) inflammatory biomarkers were assessed with OLINK multiplex technology.Results Proximity to, or exceeding, expected age of onset was associated with a sleep profile suggestive of hypersomnia (longer sleep and later morning awakening time). This hypersomnia sleep profile was associated with higher CSF neuroinflammatory biomarkers (IL-6, MCP-1, and global score). Interaction analyses revealed that some of these sleep-neuroinflammation associations were present mostly in those closer/exceeding the age of expected AD onset, APOE4 carriers, and those with better memory performance.Conclusions Proximity to, or exceeding, parental AD dementia onset was associated with a longer sleep pattern, which was related to elevated proinflammatory CSF biomarkers. We speculate that longer sleep may serve a compensatory purpose potentially triggered by neuroinflammation as individuals are approaching AD onset. Further studies should investigate whether neuroinflammatory-triggered long sleep duration could mitigate cognitive deficits. Graphical Abstract

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study’s core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition protocol for all 27 HBCD Study recruitment sites to measure brain structure, function, microstructure, and metabolites. Acquisition parameters of individual modalities have been matched across MRI scanner platforms for harmonized acquisitions and state-of-the-art technologies are employed to enable faster and motion-robust imaging. Here, we provide an overview of the HBCD MRI protocol, including decisions of individual modalities and preliminary data. The result will be an unparalleled resource for examining early neurodevelopment which enables the larger scientific community to assess normative trajectories from birth through childhood and to examine the genetic, biological, and environmental factors that help shape the developing brain.

We present the Canadian Open Neuroscience Platform (CONP) portal to answer the research community's need for flexible data sharing resources and provide advanced tools for search and processing infrastructure capacity. This portal differs from previous data sharing projects as it integrates datasets originating from a number of already existing platforms or databases through DataLad, a file level data integrity and access layer. The portal is also an entry point for searching and accessing a large number of standardized and containerized software and links to a computing infrastructure. It leverages community standards to help document and facilitate reuse of both datasets and tools, and already shows a growing community adoption giving access to more than 60 neuroscience datasets and over 70 tools. The CONP portal demonstrates the feasibility and offers a model of a distributed data and tool management system across 17 institutions throughout Canada.

Background Rare diseases are estimated to affect 150-350 million people worldwide. With advances in next generation sequencing, the number of known disease-causing genes has increased significantly, opening the door for therapy development. Rare disease research has therefore pivoted from gene discovery to the exploration of potential therapies. With impending clinical trials on the horizon, researchers are in urgent need of natural history studies to help them identify surrogate markers, validate outcome measures, define historical control patients, and design therapeutic trials. Results We customized a browser-accessible multi-modal (e.g. genetics, imaging, behavioral, patient-determined outcomes) database to increase cohort sizes, identify surrogate markers, and foster international collaborations. Ninety data entry forms were developed including family, perinatal, developmental history, clinical examinations, diagnostic investigations, neurological evaluations (i.e. spasticity, dystonia, ataxia, etc.), disability measures, parental stress, and quality of life. A customizable clinical letter generator was created to assist in continuity of patient care. Conclusions Small cohorts and underpowered studies are a major challenge for rare disease research. This online, rare disease database will be accessible from all over the world, making it easier to share and disseminate data. We have outlined the methodology to become Title 21 Code of Federal Regulations Part 11 Compliant, which is a requirement to use electronic records as historical controls in clinical trials in the United States. Food and Drug Administration compliant databases will be life-changing for patients and families when historical control data is used for emerging clinical trials. Future work will leverage these tools to delineate the natural history of several rare diseases and we are confident that this database will be used on a larger scale to improve care for patients affected with rare diseases.

The Cuban Human Brain Mapping Project (CHBMP) repository is an open multimodal neuroimaging and cognitive dataset from 282 young and middle age healthy participants (31.9 ± 9.3 years, age range 18–68 years). This dataset was acquired from 2004 to 2008 as a subset of a larger stratified random sample of 2,019 participants from La Lisa municipality in La Habana, Cuba. The exclusion criteria included the presence of disease or brain dysfunctions. Participant data that is being shared comprises i) high-density (64–120 channels) resting-state electroencephalograms (EEG), ii) magnetic resonance images (MRI), iii) psychological tests (MMSE, WAIS-III, computerized go-no go reaction time), as well as iv,) demographic information (age, gender, education, ethnicity, handedness, and weight). The EEG data contains recordings with at least 30 minutes in duration including the following conditions: eyes closed, eyes open, hyperventilation, and subsequent recovery. The MRI consists of anatomical T1 as well as diffusion-weighted (DWI) images acquired on a 1.5 Tesla system. The dataset presented here is hosted by Synapse.org and available at https://chbmp-open.loris.ca .

To move Alzheimer Disease (AD) research forward it is essential to collect data from large cohorts, but also make such data available to the global research community. We describe the creation of an open science dataset from the PREVENT-AD (PResymptomatic EValuation of Experimental or Novel Treatments for AD) cohort, composed of cognitively unimpaired older individuals with a parental or multiple-sibling history of AD. From 2011 to 2017, 386 participants were enrolled (mean age 63 years old ± 5) for sustained investigation among whom 349 have retrospectively agreed to share their data openly. Repositories are findable through the unified interface of the Canadian Open Neuroscience Platform and contain up to five years of longitudinal imaging data, cerebral fluid biochemistry, neurosensory capacities, cognitive, genetic, and medical information. Imaging data can be accessed openly at https://openpreventad.loris.ca while most of the other information, sensitive by nature, is accessible by qualified researchers at https://registeredpreventad.loris.ca. In addition to being a living resource for continued data acquisition, PREVENT-AD offers opportunities to facilitate understanding of AD pathogenesis.

The Tomographic Quantitative Electroencephalography (qEEGt) toolbox is integrated with the Montreal Neurological Institute (MNI) Neuroinformatics Ecosystem as a docker into the Canadian Brain Imaging Research Platform (CBRAIN). qEEGt produces age-corrected normative Statistical Parametric Maps of EEG log source spectra testing compliance to a normative database. This toolbox was developed at the Cuban Neuroscience Center as part of the first wave of the Cuban Human Brain Mapping Project (CHBMP) and has been validated and used in different health systems for several decades. Incorporation into the MNI ecosystem now provides CBRAIN registered users access to its full functionality and is accompanied by a public release of the source code on GitHub and Zenodo repositories. Among other features are the calculation of EEG scalp spectra, and the estimation of their source spectra using the Variable Resolution Electrical Tomography (VARETA) source imaging. Crucially, this is completed by the evaluation of z spectra by means of the built-in age regression equations obtained from the CHBMP database (ages 5-87) to provide normative Statistical Parametric Mapping of EEG log source spectra. Different scalp and source visualization tools are also provided for evaluation of individual subjects prior to further post-processing. Openly releasing this software in the CBRAIN platform will facilitate the use of standardized qEEGt methods in different research and clinical settings. An updated precis of the methods is provided in Appendix I as a reference for the toolbox. qEEGt/CBRAIN is the first installment of instruments developed by the neuroinformatic platform of the Cuba-Canada-China (CCC) project.

The Cuban Human Brain Mapping Project (CHBMP) repository is an open multimodal neuroimaging and cognitive dataset from 282 healthy participants (31.9 ± 9.3 years, age range 18–68 years). This dataset was acquired from 2004 to 2008 as a subset of a larger stratified random sample of 2,019 participants from La Lisa municipality in La Habana, Cuba. The exclusion included presence of disease or brain dysfunctions. The information made available for all participants comprises: high-density (64-120 channels) resting state electroencephalograms (EEG), magnetic resonance images (MRI), psychological tests (MMSE, Wechsler Adult Intelligence Scale -WAIS III, computerized reaction time tests using a go no-go paradigm), as well as general information (age, gender, education, ethnicity, handedness and weight). The EEG data contains recordings with at least 30 minutes duration including the following conditions: eyes closed, eyes open, hyperventilation and subsequent recovery. The MRI consisted in anatomical T1 and T2 as well as diffusion weighted (DWI) images acquired on a 1.5 Tesla system. The data is available for registered users on the LORIS database which is part of the MNI neuroinformatics ecosystem.

I read with interest the Null Hypothesis article by Meyer et al.(1) In 2001, Weggen et al.(2) suggested that flurbiprofen and ibuprofen had an effect on gamma secretase not shared by other cyclooxygenase inhibitors. This finding, along with several other failed studies of anti-inflammatory mechanisms in Alzheimer disease (AD), suggests that the widely replicated epidemiologic findings of nonsteroidal anti-inflammatory drug (NSAID) benefit for decreasing AD risk could be related to the effect on gamma-secretase, not inflammation. A flurbiprofen study failed to show a benefit for patients with AD,(3) but a considerable number of studies suggest that the NSAID-related benefit requires years of treatment before dementia develops, which the study by Meyer et al.(1) was appropriately targeting. However, the question remains as to whether ibuprofen is the drug to test, not naproxen.

Objective To evaluate the safety and efficacy of low-dose naproxen for prevention of progression in presymptomatic Alzheimer disease (AD) among cognitively intact persons at risk. Methods Investigation of Naproxen Treatment Effects in Pre-symptomatic Alzheimer9s Disease (INTREPAD), a 2-year double-masked pharmaco-prevention trial, enrolled 195 AD family history–positive elderly (mean age 63 years) participants screened carefully to exclude cognitive disorder (NCT-02702817). These were randomized 1:1 to naproxen sodium 220 mg twice daily or placebo. Multimodal imaging, neurosensory, cognitive, and (in ∼50%) CSF biomarker evaluations were performed at baseline, 3, 12, and 24 months. A modified intent-to-treat analysis considered 160 participants who remained on-treatment through their first follow-up examination. The primary outcome was rate of change in a multimodal composite presymptomatic Alzheimer Progression Score (APS). Results Naproxen-treated individuals showed a clear excess of adverse events. Among treatment groups combined, the APS increased by 0.102 points/year (SE 0.014; p < 10−12), but rate of change showed little difference by treatment assignment (0.019 points/year). The treatment-related rate ratio of 1.16 (95% confidence interval 0.64–1.96) suggested that naproxen does not reduce the rate of APS progression by more than 36%. Secondary analyses revealed no notable treatment effects on individual CSF, cognitive, or neurosensory biomarker indicators of progressive presymptomatic AD. Conclusions In cognitively intact individuals at risk, sustained treatment with naproxen sodium 220 mg twice daily increases frequency of adverse health effects but does not reduce apparent progression of presymptomatic AD. Classification of evidence This study provides Class I evidence that, for people who are cognitively intact, low-dose naproxen does not significantly reduce progression of a composite indicator of presymptomatic AD.

Clinical trials in populations at risk for cognitive disorders often use the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to track cognitive changes over time. Participants from the INTREPAD trial (NCT#02702817) took either English or French version of the assessment. Due to concerns about equivalency of forms, we investigated whether alternate forms of the French version differed among Quebec-French speakers. We then developed adjustments for the French RBANS version in this population. In a randomized trial of preventive intervention (INTREPAD, NCT02702817; Breitner, 2016), we applied the RBANS norms for ages 60-69 to repeated cognitive measures, as we are interested in testing for within-person change over a 2-year period. We chose these norms to avoid "correcting" for age and because participants' mean and median were in fact in the 60-69 age range (Table 1). We administered French RBANS form A at baseline and one of three alternate forms (B, C, D) 3 months later to 133 individuals (Table 2). We computed a linear mixed effect model using 2 time points and dummy variables for the alternate forms. We used bootstrapping because of the small sample size. The mean estimates resulting from these models were used to develop adjustment factors for the French RBANS forms. We then applied these models to adjusted data to verify the removal of form effect. We provide a set of basic suggestions for to reduce form specific effects in longitudinal analysis of the Canadian-French RBANS. Adjustment factors are provided for all 5 cognitive index sub-scores (Table 3). Inasmuch as we have observed significant form effects, we recommend evaluating translated cognitive batteries to ensure that the initial sessions are equivalent in cross-cultural studies. It is likely that longitudinal studies in other language/cultural groups could use this method to correct for test form differences, especially in designs that do not randomize alternate forms.

Data sharing is becoming more of a requirement as technologies mature and as global research and communications diversify. As a result, researchers are looking for practical solutions, not only to enhance scientific collaborations, but also to acquire larger amounts of data, and to access specialized datasets. In many cases, the realities of data acquisition present a significant burden, therefore gaining access to public datasets allows for more robust analyses and broadly enriched data exploration. To answer this demand, the Montreal Neurological Institute has announced its commitment to Open Science, harnessing the power of making both clinical and research data available to the world (Owens, 2016a,b). As such, the LORIS and CBRAIN (Das et al., 2016) platforms have been tasked with the technical challenges specific to the institutional-level implementation of open data sharing, including: Comprehensive linking of multimodal data (phenotypic, clinical, neuroimaging, biobanking, and genomics, etc.) Secure database encryption, specifically designed for institutional and multi-project data sharing, ensuring subject confidentiality (using multi-tiered identifiers). Querying capabilities with multiple levels of single study and institutional permissions, allowing public data sharing for all consented and de-identified subject data. Configurable pipelines and flags to facilitate acquisition and analysis, as well as access to High Performance Computing clusters for rapid data processing and sharing of software tools. Robust Workflows and Quality Control mechanisms ensuring transparency and consistency in best practices. Long term storage (and web access) of data, reducing loss of institutional data assets. Enhanced web-based visualization of imaging, genomic, and phenotypic data, allowing for real-time viewing and manipulation of data from anywhere in the world. Numerous modules for data filtering, summary statistics, and personalized and configurable dashboards. Implementing the vision of Open Science at the Montreal Neurological Institute will be a concerted undertaking that seeks to facilitate data sharing for the global research community. Our goal is to utilize the years of experience in multi-site collaborative research infrastructure to implement the technical requirements to achieve this level of public data sharing in a practical yet robust manner, in support of accelerating scientific discovery.

Highlights Reliable functional brain network subtypes accompany cognitive impairment in AD Symptom-related subtypes exist in the default-mode, limbic and salience networks A limbic subtype is associated with a familial risk of AD in healthy older adults Limbic subtypes also associate with beta amyloid deposition and ApoE4 In Brief We found reliable subtypes of functional brain connectivity networks in older adults, associated with AD-related clinical symptoms in patients as well as several AD risk factors/biomarkers in asymptomatic individuals. Summary The heterogeneity of brain degeneration has not been investigated yet for functional brain network connectivity, a promising biomarker of Alzheimer’s disease. We coupled cluster analysis with resting-state functional magnetic resonance imaging to discover connectivity subtypes in healthy older adults and patients with cognitive disorders related to Alzheimer’s disease, noting associations between subtypes and cognitive symptoms in the default-mode, limbic and salience networks. In an independent asymptomatic cohort with a family history of Alzheimer’s dementia, the connectivity subtypes had good test-retest reliability across all tested networks. We found that a limbic subtype was overrepresented in these individuals, which was previously associated with symptoms. Other limbic subtypes showed associations with cerebrospinal fluid Aβ 1-42 levels and ApoE4 genotype. Our results demonstrate the existence of reliable subtypes of functional brain networks in older adults and support future investigations in limbic connectivity subtypes as early biomarkers of Alzheimer’s degeneration.

In preclinical stages of Alzheimer’s disease (AD), questions remain about relationships in cerebrospinal fluid (CSF) between amyloid beta (Aβ) or tau proteins and other markers of AD pathogenesis. In the PREVENT-AD cohort of cognitively normal older adults with a parental history of AD-like dementia, we assessed distributions of CSF Aβ and tau and their relation to brain integrity and cognitive function. We assessed levels of Aβ1-42 and phosphorylated tau (181P-tau) in 93 individuals (age: 63y. s.d. 5.57). Using cut-offs at the 25th percentile, we dichotomized participants as having high (CSF Aβ1-42<869) or low (CSF Aβ1-42>869) Aβ pathology (Fig.1). We then ran general linear models to assess CSF proteins and AD markers using age as a covariate. We measured hippocampal volume (adjusted for intracranial volume) as an important indicator of brain integrity. We relied on total score from the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), and self-report of the participant’s memory compared to 20 years ago to indicate objective and subjective cognitive status respectively. The association between levels of Aβ1-42 and P-tau was clearly dependent on APOE-e4 status (interaction p<0.01, Fig. 2). In e4 carriers, we observed an expected relationship of higher Aβ pathology (lower CSF values) with higher P-tau, but the inverse was found in non-carriers. The association between lower hippocampal volume and higher CSF P-tau was driven by participants with Aβ pathology (interaction p=0.017, Fig. 3). The association between higher P-tau and the presence of a subjective cognitive complaint was also driven by individuals with Aβ pathology (interaction, p=0.04). There was no interaction between Aβ groups and P-tau on cognitive performance, although total RBANS score declines with elevated P-tau (p=0.013, Fig. 4). Our results suggest that in cognitively normal elderly at risk of AD, individuals with both high P-tau and low Aβ1-42 levels already present associations between CSF measurements and brain integrity or subjective cognitive assessment. Aβ1-42 and P-tau CSF markers, when used conjointly, might therefore be valuable markers to identify candidates for preventive trials. Distribution of CSF Aβ42 (left) and phosphorylated tau (right). Regression analysis showing an interactive effect between P-tau and APOE4 on CSF Aβ42. p values: P-tau, ns; ApoE4, ns; interaction P-tau*ApoE4, p < 0.01. Regression analysis showing an interactive effect between P-tau and Aβ1-42 on hippocampal volume (HV). p values: P-tau, ns; Aβ, ns; interaction P- tau*Aβ, p = 0.017. Low Aβ pathology = CSF value > 869 ; High Aβ pathology = CSF value < 869. Regression analysis showing a significant effect of P-tau on RBANS total score. p values: P-tau, p = 0.013; Aβ, ns; P-tau*Aβ, ns. Low Aβ pathology = CSF value > 869 ; High Aβ pathology = CSF value < 869.

Neuroimaging has been facing a data deluge characterized by the exponential growth of both raw and processed data. As a result, mining the massive quantities of digital data collected in these studies offers unprecedented opportunities and has become paramount for today's research. As the neuroimaging community enters the world of "Big Data", there has been a concerted push for enhanced sharing initiatives, whether within a multisite study, across studies, or federated and shared publicly. This article will focus on the database and processing ecosystem developed at the Montreal Neurological Institute (MNI) to support multicenter data acquisition both nationally and internationally, create database repositories, facilitate data-sharing initiatives, and leverage existing software toolkits for large-scale data processing.

How to use the DICOM anonymizer step by step

Accumulating evidence links inflammation and cholesterol homeostasis to the pathogenesis of Alzheimer’s disease (AD) (Heppner et al. 2015; Wan et al. 2015). Glial cells react to inflammation (e.g., reactive gliosis) and may thus induce grey matter (GM) alterations. Preliminary findings from the PREVENT-AD cohort show that some CSF inflammatory proteins may predict cross-sectional GM integrity (Figure 1). We therefore investigated whether initial concentrations of CSF inflammatory or other proteins predicted longitudinal GM change in different stages of AD. Cross-sectional CSF inflammatory biomarkers predict regional GM mean diffusivity (MD) in the PREVENT-AD cohort (N=45) Significant regional effect of VEGF, MCP-1 and IL-10 (age adjusted, FDR corrected) are shown in red for increased MD and in blue for reduced MD. Reduced mean diffusivity is consistent with restriction of water movement due to gliosis. We analyzed data from 137 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants with up to 7 years of follow-up and initial CSF protein concentrations available. Regional average GM density was calculated using SPM12 tissue segmentations (www.fil.ion.ucl.ac.uk/spm) for 78 regions covering all the brain’s gray matter (Klein and Tourville, 2012). A linear mixed model, including initial age, gender and diagnosis was independently calculated for each combination of brain regions and proteins available (N=83). Statistical associations of the proteins with GM change over time were corrected for multiple comparisons (FDR; p<0.05). High concentration of the T-Cell-Specific protein RANTES and Apolipoprotein A-I (ApoA-I) were associated with diffuse increase in GM density over time (uncorrected p < 0.0008). High levels of heart Fatty Acid-Binding protein (FABP) predicted accelerated decline (uncorrected p < 0.0009) in GM regions associated with AD (Figure 2). Post-hoc analyses revealed that normal controls had higher concentration of RANTES (p = 0.04), while MCI and AD patients had higher concentrations of FABP (p < 0.001), as did APOEe4 carriers in all diagnostic groups (p=0.015). Effect of the CSF proteins on the change of GM over time a) Average regional effect of the proteins having the strongest influence b) Regional effect of the proteins surving FDR correction. NB. For FABP, only the right parahippocampal region effect survive FDR correction. Effect for region with T>2 are show because of their role in AD. The observed association of inflammatory RANTES with GM density over time may reflect reactive gliosis. ApoA-I, a reverse cholesterol transporter in the periphery that is not produced in the brain, also predicted increased GM density over time. Accelerated GM loss with increasing concentration of the lipid transporter FABP is consistent with a role for cholesterol homeostasis in AD. Additional studies may elucidate the possible relationship between early inflammatory processes and impaired lipid transport in the brain.

In contrast with other imaging modalities, there is presently a scarcity of fully open resources in magnetoencephalography (MEG) available to the neuroimaging community. Here we present a collaborative effort led by the McConnell Brain Imaging Centre of the Montreal Neurological Institute, and the Université de Montréal to build and share a centralised repository to curate MEG data in raw and processed form for open dissemination. The Open MEG Archive (OMEGA, omega.bic.mni.mcgill.ca) is bound to become a continuously expanding repository of multimodal data with a primary focus on MEG, in addition to storing anatomical MRI volumes, demographic participant data and questionnaires, and other forms of electrophysiological data such as EEG. The OMEGA initiative offers both the technological framework for multi-site MEG data aggregation, and serves as one of the largest freely available resting-state and eventually task-related MEG datasets presently available.

Table of contents I1 Introduction to the 2015 Brainhack Proceedings R. Cameron Craddock, Pierre Bellec, Daniel S. Margules, B. Nolan Nichols, Jörg P. Pfannmöller A1 Distributed collaboration: the case for the enhancement of Brainspell’s interface AmanPreet Badhwar, David Kennedy, Jean-Baptiste Poline, Roberto Toro A2 Advancing open science through NiData Ben Cipollini, Ariel Rokem A3 Integrating the Brain Imaging Data Structure (BIDS) standard into C-PAC Daniel Clark, Krzysztof J. Gorgolewski, R. Cameron Craddock A4 Optimized implementations of voxel-wise degree centrality and local functional connectivity density mapping in AFNI R. Cameron Craddock, Daniel J. Clark A5 LORIS: DICOM anonymizer Samir Das, Cécile Madjar, Ayan Sengupta, Zia Mohades A6 Automatic extraction of academic collaborations in neuroimaging Sebastien Dery A7 NiftyView: a zero-footprint web application for viewing DICOM and NIfTI files Weiran Deng A8 Human Connectome Project Minimal Preprocessing Pipelines to Nipype Eric Earl, Damion V. Demeter, Kate Mills, Glad Mihai, Luka Ruzic, Nick Ketz, Andrew Reineberg, Marianne C. Reddan, Anne-Lise Goddings, Javier Gonzalez-Castillo, Krzysztof J. Gorgolewski A9 Generating music with resting-state fMRI data Caroline Froehlich, Gil Dekel, Daniel S. Margulies, R. Cameron Craddock A10 Highly comparable time-series analysis in Nitime Ben D. Fulcher A11 Nipype interfaces in CBRAIN Tristan Glatard, Samir Das, Reza Adalat, Natacha Beck, Rémi Bernard, Najmeh Khalili-Mahani, Pierre Rioux, Marc-Étienne Rousseau, Alan C. Evans A12 DueCredit: automated collection of citations for software, methods, and data Yaroslav O. Halchenko, Matteo Visconti di Oleggio Castello A13 Open source low-cost device to register dog’s heart rate and tail movement Raúl Hernández-Pérez, Edgar A. Morales, Laura V. Cuaya A14 Calculating the Laterality Index Using FSL for Stroke Neuroimaging Data Kaori L. Ito, Sook-Lei Liew A15 Wrapping FreeSurfer 6 for use in high-performance computing environments Hans J. Johnson A16 Facilitating big data meta-analyses for clinical neuroimaging through ENIGMA wrapper scripts Erik Kan, Julia Anglin, Michael Borich, Neda Jahanshad, Paul Thompson, Sook-Lei Liew A17 A cortical surface-based geodesic distance package for Python Daniel S Margulies, Marcel Falkiewicz, Julia M Huntenburg A18 Sharing data in the cloud David O’Connor, Daniel J. Clark, Michael P. Milham, R. Cameron Craddock A19 Detecting task-based fMRI compliance using plan abandonment techniques Ramon Fraga Pereira, Anibal Sólon Heinsfeld, Alexandre Rosa Franco, Augusto Buchweitz, Felipe Meneguzzi A20 Self-organization and brain function Jörg P. Pfannmöller, Rickson Mesquita, Luis C.T. Herrera, Daniela Dentico A21 The Neuroimaging Data Model (NIDM) API Vanessa Sochat, B Nolan Nichols A22 NeuroView: a customizable browser-base utility Anibal Sólon Heinsfeld, Alexandre Rosa Franco, Augusto Buchweitz, Felipe Meneguzzi A23 DIPY: Brain tissue classification Julio E. Villalon-Reina, Eleftherios Garyfallidis

Cerebral perfusion decreases in normal individual at risk of Alzheimer's disease who eventually progress to AD (Johnson, 2000). Similarly perfusion is known to be reduced in AD and, to a lesser extent, in MCI. This phenomenon is most evident in precuneus and bilateral parietal cortices as regions of interest (ROI) (Binnewijzend, 2013). Such hypoperfusion may reflect reduced metabolic demand in regions undergoing neuronal loss. Neurodegeneration may also be revealed by deficits in olfactory identification, especially in AD where olfactory loss correlates with neuropathology and severity of clinical symptoms. If olfactory impairments reflect reduced neural mass and AD pathology, they should be related to cerebral blood-flow (CBF). Hence, we hypothesized that olfactory identification would be associated with CBF in a cohort at risk of pre-symptomatic AD. Cognitively normal subjects with a parental history of AD were scanned using MPRAGE T1 and pCASL sequences. Their odor identification performance was assessed with the 40-item University of Pennsylvania Smell Identification Test. Neurolens software was used for ASL analysis. After pre-processing (motion-correction, subtraction of tagged images from the control images and spatial smoothing of 6 mm, a GLM was fitted to the flow series and CBF was computed. Individual grey matter (GM) probability masks were created from the T1 scan using CIVET automatic segmentation algorithms. Anterior and posterior cingulate cortices (ACC, PCC) and precuneus were defined as ROIs using the AAL template and multiplied by the GM mask. Resulting ROI masks were registered to the ASL space and used for average CBF extraction. Due to noise, we were unable to investigate hippocampal, and entorhinal perfusion. In age adjusted robust-fit regression analyses, olfactory identification correlated with global average CBF in GM (fig.1a), precuneus (fig.1b) and PCC (fig.1c), but not in ACC (fig.1d). Olfactory circuitry parallels major arteries in the medial brain and may be associated with cardiovascular health, as we also found a correlation between olfaction and systolic blood pressure (fig.2). Scatterplot graphs of partial regression analysis for smell identification and perfusion for GM, precuneus, PCC, ACC. Scatterplot graphs show partial robust fit regression plots showing CBF association with olfactory identification, after removing the effect of age: a) overall GM CBF is positively associated to UPSIT scores (F=8.74, p= 2.07e-05, r2=0.144 n=158); b) precuneus CBF is positively associated to UPSIT(F=12, p=1.47e-05 r2=0.133, n=159); c) PCC CBF is positively associated to UPSIT (F=11.8, p= 1.71e-05, r2=0.134, n=156); d) ACC CBF is not associated to UPSIT as correlation is driven by age (F=l 1.3, p=2.5e-05, r2=0.124, n=163). Scatter plot graph of correlation between smell identification and systolic blood pressure. Scatterplot graph shows an inverse correlation between olfactory identification and systolic blood pressure (F=26.8, p = 5.7e-07, r2=0.1124, n=192). Impaired olfactory identification is associated with reduced CBF in the overall GM and in key ROIs vulnerable to early changes in AD (Iturria-Medina, 2014). Olfactory identification deficits therefore hold interest as potential markers of pre-symptomatic AD.