Title: Cortical microstructural alterations in mild cognitive impairment and Alzheimer’s disease dementia
Legend: Multi-shell diffusion weighted imaging was used to measure microstructural cortical alterations in Alzheimer’s disease (AD). Participants were recruited from the Wisconsin Alzheimer’s Disease Research Center clinical core and included individuals with AD dementia (N=26), mild cognitive impairment (MCI, N=30)) and cognitively unimpaired controls (N=56). Neurite density (NDI) in cortical gray matter was lower in both MCI (A) and AD dementia (B), compared to controls. Follow-up analyses comparing microstructure and cortical thickness (derived from T1-weighted MRI) indicated that neurite density differences between groups remained, even when controlling for cortical thickness (see manuscript). The results support the use of diffusion-weighted imaging for measuring AD-related neurodegeneration.
Citation: Vogt NM, Hunt JF, Adluru N, Dean DC, Johnson SC, Asthana S, Yu JJ, Alexander AL, Bendlin BB. Cortical Microstructural Alterations in Mild Cognitive Impairment and Alzheimer’s Disease Dementia. Cereb Cortex. 2020 May 14;30(5):2948-2960. doi: 10.1093/cercor/bhz286. PMID: 31833550; PMCID: PMC7197091.
Abstract: In Alzheimer’s disease (AD), neurodegenerative processes are ongoing for years prior to the time that cortical atrophy can be reliably detected using conventional neuroimaging techniques. Recent advances in diffusion-weighted imaging have provided new techniques to study neural microstructure, which may provide additional information regarding neurodegeneration. In this study, we used neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion model, in order to investigate cortical microstructure along the clinical continuum of mild cognitive impairment (MCI) and AD dementia. Using gray matter-based spatial statistics (GBSS), we demonstrated that neurite density index (NDI) was significantly lower throughout temporal and parietal cortical regions in MCI, while both NDI and orientation dispersion index (ODI) were lower throughout parietal, temporal, and frontal regions in AD dementia. In follow-up ROI analyses comparing microstructure and cortical thickness (derived from T1-weighted MRI) within the same brain regions, differences in NODDI metrics remained, even after controlling for cortical thickness. Moreover, for participants with MCI, gray matter NDI-but not cortical thickness-was lower in temporal, parietal, and posterior cingulate regions. Taken together, our results highlight the utility of NODDI metrics in detecting cortical microstructural degeneration that occurs prior to measurable macrostructural changes and overt clinical dementia.
About the Lab: Bendlin’s lab focuses on brain structure and function in middle and late age, especially in people with increased risk of developing AD due to parental family history, genotype and vascular risk factors. Understanding early brain changes in people who may go on to develop AD is expected to lead to earlier diagnosis, prevention, and the development of new therapies for AD. Her current projects use MRI as a tool to understand the effect of risk factors (parental family history, genotype, metabolic syndrome) on brain blood flow and structure. Additionally, she is funded to examine the relationship between cerebrospinal fluid biomarkers and brain structure to learn more about early mechanisms of brain damage in AD.