TY - JOUR T1 - Regional Neuronal Network Failure and Cognition in Late-Onset Sporadic Alzheimer Disease JF - American Journal of Neuroradiology JO - Am. J. Neuroradiol. SP - S18 LP - S30 DO - 10.3174/ajnr.A3895 VL - 35 IS - 6 suppl AU - S.F. Carter AU - K.V. Embleton AU - J.M. Anton-Rodriguez AU - A. Burns AU - M.A.L. Ralph AU - K. Herholz Y1 - 2014/06/01 UR - http://www.ajnr.org/content/35/6_suppl/S18.abstract N2 - BACKGROUND AND PURPOSE: The severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function. The current investigation studied the breakdown of the structure and function in regional networks involving the Papez circuit and extended neocortical association areas. MATERIALS AND METHODS: Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with 18F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls. RESULTS: Atrophy of the medial temporal lobes was the strongest and most consistent abnormality in patients with mild cognitive impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal regions was most strongly related to episodic memory deficits, while deficits in semantic cognition were also strongly related to reductions of glucose metabolism in the posterior cingulate cortex and temporoparietal regions. Changes in fractional anisotropy within white matter tracts, particularly in the left cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus, were significantly associated with the cognitive deficits in multiple regression analyses. Posterior cingulate and orbitofrontal metabolic deficits appeared to be related to microstructural changes in projecting white matter tracts. CONCLUSIONS: Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the most prominent lesion, with associated impairment of the uncinate and cingulum white matter microstructures and hippocampal and posterior cingulate metabolic impairment. ACE-RAddenbrooke's Cognitive Examination-RevisedADAlzheimer diseaseFAfractional anisotropyHCMPhippocampusMCImild cognitive impairmentMTLmedial temporal lobePCCposterior cingulate cortexTBSSTract-Based Spatial Statistics ER -