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Abstract Details

Nonlinear and Non-Monotonic Relationship between Default Mode Network Connectivity and Hippocampal Volumes across the ADNI Cohort Cross-Sectionally and Longitudinally
Aging and Dementia
P06 - (-)
025
BACKGROUND: The human brain forms a complex network to exchange information that is dependent on multiple scales spanning the genetic/molecular to the systems/behavioral level. Alzheimer's disease (AD) disrupts this highly interdependent, multi-scale organization. This AD-related disruption has been investigated at the systems level using task-free fMRI (TF-fMRI), demonstrating increased connectivity in frontal networks (i.e. aDMN) and decreased connectivity in parietal networks (i.e. pDMN). However, these findings are not universally reproducible in TF-fMRI studies that use group-wise comparisons to detect changes in connectivity (i.e. control vs. MCI vs. AD). Therefore, we used TF-fMRI data from ADNI to investigate the relationship between connectivity and a continuous measure of the structural integrity of the brain's complex network (hippocampal volumes) across all diagnostic categories.
DESIGN/METHODS: All ADNI subjects with adequate quality TF-fMRI and structural MRI were included in the analysis. Standard preprocessing of data was performed. Coherence based regional homogeneity values were extracted from the aDMN and pDMN. Given the inverse relationship of the aDMN and pDMN these were converted to aDMN/pDMN ratios and modeled against normalized hippocampal volumes using natural splines and localized regression.
RESULTS: The natural spline fit of baseline data excluding extreme atrophy was significant (F=2.79, p = 0.0294), non-monotonic and nonlinear. Longitudinal data followed the trajectory predicted by the fit of baseline cross-sectional data. Localized regression of the entire cohort followed the same trajectory.
CONCLUSIONS: This nonlinear relationship between DMN connectivity and hippocampal volume has significant implications for the design of studies to investigate the impact of AD on the systems level organization of the brain. Traditional comparison between diagnostic categories will have highly variable results depending on the composition of the cohorts selected, which may explain conflicting reports in the literature pertaining to the magnitude and direction of connectivity changes in the aDMN and pDMN.
Authors/Disclosures
David T. Jones, MD (Mayo Clinic)
PRESENTER 		Dr. Jones has stock in Cephlodyne Neurotechnologies, Inc.. Dr. Jones has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
Jeffery Gunter (Mayo Clinic and Foundation) The institution of Jeffery Gunter has received research support from NIH. Jeffery Gunter has received intellectual property interests from a discovery or technology relating to health care.
Prashanthi Vemuri, PhD (Mayo Clinic) The institution of Dr. Vemuri has received research support from NIH.
No disclosure on file
No disclosure on file
Bradley F. Boeve, MD, FAAN (Mayo Clinic) Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.
David S. Knopman, MD, FAAN (Mayo Clinic) Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH.
No disclosure on file
Ronald C. Petersen, MD, PhD, FAAN (Mayo Clinic) Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co.. Dr. Petersen has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai, Inc.. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has a non-compensated relationship as a Board of Directors with American Brain Foundation that is relevant to AAN interests or activities.
Michael W. Weiner, MD Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Dolby Family Ventures. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmaceuicals. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acumen Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Guidepoibnt. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Owkin France. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quantum Leap Health. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sai MedPartners. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MEDA Corp.. Dr. Weiner has stock in Anven. Dr. Weiner has stock in Alzeca. Dr. Weiner has stock in Alzheon, Inc.. Dr. Weiner has stock in ALZpath. The institution of Dr. Weiner has received research support from NIH/NIA; National Institutes of Health/National Institutes of Aging. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Speaker/Presenter with Merck Sharp & Dohme. Dr. Weiner has received personal compensation in the range of $0-$499 for serving as a Speaker/Presenter with BrightFocus Foundation. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Speaker/Presenter with Banner Health.
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia) The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS/ Celgene. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/ Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIAL PD. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerVoice. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung Biosys. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion/ Janssen Pharmaceuticals. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS/ Celgene. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/ EMD Serono. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic Therapeutics. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris/ Mylan. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi/ Genzyme. The institution of Dr. Montalban has received research support from Merck/ EMD Serono. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva Pharmaceuticals. The institution of Dr. Montalban has received research support from Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received research support from BMS/ Celgene.
Clifford R. Jack, Jr., MD (Mayo Clinic) The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.