Year: 2019
Type: article
Study design: Observational Study
Abstract: Dysregulation of the neurovascular system and lower synchronicity of resting state fMRI (rsfMRI) signal between the hippocampus and default mode network (DMN) occurs early in the pathogenesis of Alzheimer's disease (AD). Metabolic syndrome (MetS), a condition characterized by a cluster of vascular risk factors, is an established risk factor for AD. Our study evaluated whether MetS-related vascular risk factors are associated with hippocampal DMN disconnectivity, and whether the effect of these risk factors is additive in cognitively intact older adults. We obtained rsfMRI and T1-weighted volumetric scans on 23 USC Alzheimer's Disease Research Center (ADRC) participants (66.4 ± 8.3 years old; Siemens Prisma 3T) having a Clinical Dementia Rating global score of 0 and available scores for the MetS components listed below. We identified the DMN using a posterior-cingulate cortex (PCC) seed-based analysis, and calculated mean hippocampal z-scores using FreeSurfer-generated hippocampal masks for each individual. In a subset of participants who had available MetS-associated measures (systolic and diastolic blood pressure, body mass index (BMI), and fasting plasma measures of glucose, HDL cholesterol, A1C, and triglycerides). We generated a continuous measure of additive metabolic risk by summing the z-transformed value of each MetS marker after inverting the sign of HDL cholesterol. We used linear regression (adjusting for age, sex, APOE4 carrier status) to relate the additive MetS risk score to bilateral mean hippocampal connectivity. In a subsequent analysis, we performed multiple linear regression to investigate whether any individual MetS marker was significantly associated with hippocampal connectivity. A higher additive MetS risk score - but no individual MetS component - was associated with lower bilateral mean hippocampal DMN synchronicity (β=−0.38, partial p=0.007, omnibus p=0.049).
Source: Alzheimer s & Dementia
Authors: Meral A. Tubi, Jianhang Zhou, Nalini Hazra, Joshua D. Liu, Giselle Kim, Sharon H. Shin, Melanie D. Sweeney, Xinhui Wang, Lon S. Schneider, Elizabeth B. Joe, Hussein N. Yassine, John M. Ringman, Meng Law, Arthur W. Toga, Michael G. Harrington, Berislav V. Zlokovic, Helena C. Chui, Meredith N. Braskie
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2980475486