Longitudinal age effects in microstructures of the hippocampal subfields.

Abstract

AbstractBackgroundThe human brain undergoes considerable morphologic change with age, which is one of the primary risk‐factors for Alzheimer’s disease (AD). Age‐related microstructural changes in the brain may be quantified by advanced diffusion MRI (dMRI) with compartment modeling. In this longitudinal study, we aimed to investigate the effects of age on the hippocampal subfields, one of the brain regions vulnerable to the early stages of AD.MethodThirty‐seven cognitively normal older adults (70.6 ± 6.7 years) were recruited from the Indiana ADRC. Participants received a baseline and a follow‐up MRI scan over 24 ± 11.7 months with a Siemens 3T Prisma scanner using a 64‐channel head coil. We applied grey‐matter‐specific multi‐compartment diffusion model (cortical‐neurite orientation dispersion and density imaging) to derive diffusion microstructural metrics, namely orientation dispersion index (ODI), volume fractions of fast isotropic diffusion (VFISO), and intracellular‐space (VFIC) in the hippocampal‐subfields (CA1‐3, CA4 and dentate gyrus (CA4‐DG), and subiculum) [1]. To study the longitudinal age effects, we investigated the rate of change in the diffusion metrics and the association between the rate of change and age. Linear regression analysis was performed using SPSS software and adjusted for sex, education, APoE e4 status, and subfield volumes (Table 1).ResultAll subjects had normal cognition (i.e., MoCA and MMSE, Table 1). The volumes of CA1‐3 and subiculum significantly decreased between the baseline and follow‐up MRI scans, (p<0.05, Table 1). During this period, while significantly increased ODI within subject was observed in CA4‐DG, significantly decreased VFISO in all the subfields and increased VFIC in the subiculum were noted (Figure 1). The decreasing rate of VFISO in CA4‐DG was significantly associated with age (Table 2), suggesting the reduction in VFISO accelerated over age.ConclusionWe demonstrated that diffusion metrics are sensitive to microstructural alterations in the hippocampal subfields of cognitively normal older adults. The cornu ammonis region 4 and dentate gyrus is the most vulnerable region affected by aging with increased tissue dispersion and age‐accelerated reduction in fast isotropic diffusion. Future studies will focus on the effects of the initial microstructural condition to its rate of change with aging.