Increased adiposity is related to reduced neurite complexity in the hippocampus, fornix, and uncinate fasciculus of cognitively unimpaired adults

Abstract

AbstractBackgroundObesity is a risk factor for dementia. However, results from studies associating obesity to volume in the hippocampus and parahippocampal gyrus, regions underpinning memory, are inconsistent. Null findings could be due to the insensitivity of volumetric MRI to detect early neurodegenerative change. The neurite orientation dispersion and density imaging (NODDI) model provides unique information about neurite microstructure that may be relevant to the earliest stages of neurodegeneration. In cognitively healthy participants, we used NODDI to examine if body mass index (BMI) and waist circumference (WC) were related to the microstructure of the hippocampus and parahippocampal gyrus and white matter (WM) tracts linking these gray matter (GM) regions to the brain (i.e., hippocampal cingulum, uncinate fasciculus, and fornix).MethodParticipants were enrolled in the Wisconsin Alzheimer’s Disease Research Center (ADRC) Clinical Core, had T‐1 weighted and multi‐shell diffusion MRI, and lacked history of stroke and cognitive impairment (Table 1). Microstructure was assessed using neurite density (NDI) and orientation dispersion (ODI) indices obtained from the NODDI model. Higher NDI indicates higher neurite density; higher ODI reflects lower neurite coherence and greater neurite dispersion. N=383 had NODDI indices, height, weight and covariate data. Waist circumference (WC) (n=382) was dichotomized according to sex‐specific thresholds for cardiovascular/diabetes disease risk (females >88cm; males >102cm). Linear regression tested the relationship of BMI and WC to NDI and ODI in regions of interest controlling for age, sex, education, diabetes, hypertension, depression, and APOE4 carrier status.ResultIndividuals with higher BMI and in the higher‐risk WC category had significantly lower hippocampal ODI and fornix NDI when adjusting for covariates (Table 2, Figure 1). Higher BMI was also related to higher uncinate fasciculus ODI.ConclusionIncreased adiposity was related to lower neurite dispersion in the hippocampus and lower neurite density in the fornix. BMI alone was associated with lower neurite coherence in the uncinate fasciculus. These results suggest that increased adiposity may be related to less complex neurite microstructure in regions important for memory. Additional research is needed to determine if adiposity‐related microstructural differences in GM and WM are related to memory decline and presage future development of dementia.