White matter diffusion abnormalities observed in cognitively normal elderly before conversion to mild cognitive impairment

Abstract

AbstractBackgroundDifferences in white matter (WM) microstructure, as measured with diffusion tensor imaging (DTI), have been observed between cognitively normal, mild cognitively impaired (MCI), and Alzheimer’s disease (AD) patient groups. With increased focus on early intervention for AD, detection of preclinical changes is paramount; however, due to difficulties in predicting future conversion, few studies have investigated WM deterioration prior to symptom onset. Using DTI data from the Vallecas project (an 8‐year longitudinal study of healthy elderly individuals), we determine if WM changes can be found in cognitively normal individuals before conversion to MCI.MethodsFrom a baseline cohort of 824 cognitively normal 70‐85 year olds, 65 individuals converted to MCI over the study duration (mean age 77.0±4.29 years, 58% female). 65 non‐converters were matched by age, sex, and years of education to act as controls. DTI scans from one year before conversion were analysed using tract‐based spatial statistics implemented in FSL. Fractional anisotropy (FA), mean diffusivity (MD), and mode of anisotropy (MO) were compared between groups using non‐parametric permutation tests. A second comparison between future converters and all 759 non‐converters (mean age 74.0±3.92 years, 65% female) was also conducted, using age, sex, and years of education as covariates.ResultsIn the unmatched comparisons, controls had higher FA in the left forceps minor (ForMin) and anterior corona radiata (CR) (p<0.05), and higher MO along the corpus callosum (CC) and ForMin (p<0.01). Future converters had higher FA in the left posterior CR and corticospinal tract (p<0.05), higher MD in the left anterior CR (p<0.05), and higher MO along the bilateral projection fibres (p<0.01). In the matched comparison, only MO differences were observed, with higher MO in controls along the body of the CC (p<0.05), and higher MO in future converters in the left projection fibres and the splenium of the CC (p<0.01). All significant results were FWE‐corrected.ConclusionsOur results suggest that frontal commissural fibres begin to deteriorate in cognitively normal subjects destined to convert to MCI, whilst also demonstrating selective preservation of projection fibres. We also find that MO is a sensitive measure of white matter microstructural changes presaging cognitive decline, even in preclinical populations.