Magnetic Resonance Spectroscopic Imaging Detects Metabolic Changes within the Medial Temporal Lobe in aMCI

There is a critical need for reliable diagnosis of Alzheimer's Disease (AD) at an early stage, as disease modifying agents are being developed, likely to be most efficient when lesions are minimal. Using Magnetic Resonance Spectroscopy (MRS), reflecting metabolic change, the NAA/mIno-ratio has been shown to be reduced in AD and to be associated with the severity of AD pathology on postmortem brain tissue. However, it is not clear if this ratio is reduced in the early stages of AD, especially within the mesial temporal lobe (MTL), where tau pathology first develops in AD. Within the MTL, neurofibrillary tangles, related to clinical signs, first affect the anterior subhippocampal cortex, then the hippocampus during the limbic stage. In the monkey, experimental studies show that the sub-hippocampal cortex is crucial for visual recognition memory (VRM). We previously found that aMCI-patients that are impaired on a VRM task have features of early AD. We assessed metabolic changes by measuring NAA/mIno-ratios within the MTL of patients with amnestic MCI (aMCI), at risk for AD, using MRS Imaging. The MTL was sampled at different levels in order to evaluate its subcomponents. The NAA/mIno-ratio was reduced in the MTL of aMCI patients. However, while these ratios in aMCI-patients with normal VRM did not differ from controls, the subgroup of aMCI patients with impaired VRM scores had reduced MTL NAA/mIno ratios. Moreover, VRM performance was correlated with NAA/mIno levels within the anterior MTL. In addition, clinical follow-up data suggests that patients with impaired VRM are more likely to develop probable AD and MCI converters were found to have metabolic changes in the MTL at baseline in comparison with controls. This confirms that MRS may be useful for the detection of AD at the predementia stage of the disease and that NAA/mIno could be considered as a further biomarker of AD. Moreover, taking into account the cognitive profile is crucial in order to select aMCI patients at very high risk for AD. Finally, this study supports the role of anterior MTL structures in VRM.