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P4‐584: APOE GENOTYPE INFLUENCE ON HIPPOCAMPAL SUBFIELDS IN COGNITIVELY NORMAL AND ALZHEIMER DISEASE SUBJECTS
Author(s) -
Balaji Kannappan,
Choi Yu Yong,
Lee Jang Jae,
Choi Kyu Yeong,
Lee Kun Ho
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.08.132
Subject(s) - apolipoprotein e , hippocampal formation , atrophy , neuroimaging , dementia , alzheimer's disease , psychology , neuroscience , hippocampus , allele , alzheimer's disease neuroimaging initiative , disease , pathology , medicine , biology , genetics , gene
Background: Neurite orientation dispersion and density imaging (NODDI) is an advanced model applicable to diffusion magnetic resonance imaging (MRI). It provides two reliably interpretable in-vivometrics of white matter (WM) and gray matter (GM) microstructure: (1) neurite density index (NDI), which reflects the proportion of the water diffusion constrained within axons or dendrites; and (2) orientation dispersion index (ODI), which reflects the degree of neurite coherence. This study aimed to apply the NODDI model to assess age effects in a middle to older-aged cognitively unimpaired population. Methods: 525 cognitively-unimpaired individuals (median age 64.4068.13 years, 65.1% female, 37.1% APOE4-positive) underwent multi-shell diffusion MRI (b1⁄4500x9, 800x18, and 2,000x36). Mean NODDI metrics were estimated and extracted from 19 WM and GM regions of interest (ROIs). Regions were selected a priori based on prior studies. Linear regression models were used to determine the crosssectional relationship between NODDImetrics and age (controlling for sex and APOE4 status). Results: All results were Bonferroni corrected for multiple comparisons. In WM, ODI was higher with age in approximately half of the WM ROIs (5 out of 7, with one ROI only showing this effect unilaterally) and NDI was lower with older age in most of the WM ROIs (4 out of 7). In GM, ODI was lower with age in all of the GM ROIs, with the exception of the hippocampus, which showed higher ODI with age. NDI was lower with age in most of the GM ROIs (8 out of 12, with two ROIs only showing this effect unilaterally). Conclusions: The present study demonstrates regional GM and WM microstructural alterations with older age in line with previous aging diffusion MRI studies. Lower NDI and lower ODI in GM suggest age-related loss of dendrites and axons and reduced neurite complexity with older age. In WM, NDI was lower and ODI was higher with higher age, suggesting loss of long-range axons and loss of fiber coherence, respectively. Future directions include performing a true longitudinal assessment of microstructure with increasing age and comparing “normal” age-related microstructural changes to those in diseases such as Alzheimer’s disease.