Regional microstructural alteration of the corpus callosum in preclinical Alzheimer’s disease

Abstract

AbstractBackgroundWhile previous studies consistently reported regional microstructural changes of the cerebral white matter (WM) in Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI), little information is available for such changes in the preclinical stage of AD. We first aimed to investigate regional microstructural alteration of the WM in cognitively normal (CN) older adults with amyloid‐beta (Aβ) deposition. We also tried to develop a prediction model for Aβ positivity in CN using information on WM microstructural alteration and clinical variables that can be easily obtained in memory clinics.MethodSeventy‐five CN older adults from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer’s disease (KBASE) cohort were included in the analyses. All Participants underwent comprehensive clinical and neuropsychological assessment, T1 MRI, diffusion tensor imaging (DTI), and [11C]PiB‐PET. All CN subjects were divided into Aβ positive (CN+) and negative (CN‐) based on the level of cerebral Aβ retention on [11C]PiB‐PET. Multivariate stepwise logistic regression analyses were conducted to develop Aβ positivity prediction models.ResultWhen compared to CN‐, CN+ showed high mean diffusivity (MD) value of the genu of the corpus callosum (CC_genu) (F(1,73) = 6.357, p = 0.014, Figure 1). The area under the curve (AUC) of the receiver operating characteristics curve for the Aβ positivity prediction model only using MD of the CC_genu was 0.653 [confidence interval (CI) = 0.511‐0.794]. Model with MD of the CC_genu, age, and word list recall and constructional recall test scores were finally selected. The AUC of the final model was 0.851 [CI = 0.765‐0.937] (Figure 2).ConclusionThe findings indicate that microstructural alteration of the CC_genu occurs even in the stage of preclinical AD. When taken together with episodic memory scores commonly available in clinical practice, information about such regional WM microstructural alteration can be used to screen preclinical AD.