Barbara B. Bendlin, PhD – Slide of the Week

Barbara B. Bendlin, PhD - Slide of the Week

Title: Diffusion-weighted imaging metrics are sensitive to microstructural alterations related to amyloid and tau pathology among cognitively intact adults

Legend: Alzheimer’s disease is characterized by accumulation of amyloid and neurofibrillary tangles, and this pathology can be detected using neuroimaging or fluid biomarkers prior to the development of dementia. The Alzheimer’s disease process also involves neurodegeneration which eventually leads to cognitive decline and dementia, however typical approaches for measuring neurodegeneration (such as T1-weighted imaging), may not be sensitive to neurodegeneration in the asymptomatic disease stage. Here, we used multi-shell diffusion weighted imaging to demonstrate that amyloid and tau pathology measured among cognitively intact research participants are associated with microstructural alterations. On left are shown the regions of interest that
were studied based on their vulnerability to Alzheimer’s disease. In the middle, are shown the significant interactions between amyloid and tau pathology on neurite density derived from diffusion-weighted imaging. On right, these effects were not observed when examining cortical thickness derived with T1-weighted imaging, suggesting diffusion-weighted imaging may provide a more sensitive measure of neurodegeneration.

Citation: Vogt NM, Hunt JFV, Adluru N, Ma Y, Van Hulle CA, Iii DCD, Kecskemeti SR, Chin NA, Carlsson CM, Asthana S, Johnson SC, Kollmorgen G, Batrla R, Wild N, Buck K, Zetterberg H, Alexander AL, Blennow K, Bendlin BB. Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults. Alzheimers Dement. 2021 May 13. doi: 10.1002/alz.12364. Epub ahead of print. PMID: 33984184.

Abstract: Introduction: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer’s disease prior to cognitive impairment. Methods: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42 /Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. Results: We observed a significant CSF Aβ42 /Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. Discussion: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.

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.

Slide of the Week Archives