Hippocampal damage, by DTI or MR volumetry, and PET hypoperfusion of precuneus/posterior cingulate cortex (PC/PCC) were proposed as biomarkers of conversion from preclinical (MCI) to clinical stage of Alzheimer's disease (AD). This study evaluated structural damage, by DTI and MR volumetry, of hippocampi and tracts connecting hippocampus to PC/PCC (hipp-PC/PCC) in 10 AD, 10 MCI, and 18 healthy controls (CTRL). Normalized volumes, mean diffusivity (MD), and fractional anisotropy (FA) were obtained for grey matter (GM), white matter (WM), hippocampi, PC/PCC, and hipp-PC/PCC tracts. In hippocampi and hipp-PC/PCC tracts, decreased volumes and increased MD were found in AD versus CTRL ( ). The same results with lower significance ( ) were found in MCI versus CTRL. Verbal memory correlated ( ) in AD with left hippocampal and hipp-PC/PCC tract MD, and in MCI with FA of total WM. Both DTI and MR volumetry of hippocampi and hipp-PC/PCC tracts detect early signs of AD in MCI patients. 1. Background Preclinical detection of Alzheimer’s disease (AD) is important to start an early therapeutic treatment, and it will be even more crucial in the next few years, as soon as new drugs will be available. Mild cognitive impairment (MCI) is often the preclinical stage of AD. However, some patients with MCI revert to normal cognitive status, while others, with slow disease progression, remain in this prodromic stage without presenting dementia in their life [1]. To detect which patients with MCI will convert in AD in the immediate future, an in vivo biomarker is not currently available. CSF tau, phospho-tau, and amyloid measurements are in development [2, 3] but require lumbar puncture; therefore, a noninvasive imaging marker is more appealing for screening outpatients without hospital admission. With this purpose, volumetric MRI measures of mesiotemporal atrophy demonstrated to have some prognostic value [4, 5]. Compared to these volumetric measures of macrostructural damage, diffusion tensor imaging (DTI) indexes of microstructural damage within mesiotemporal lobe have shown to better discriminate MCI from controls [6, 7] and to better detect MCI converters [8–10]. DTI is sensitive to both grey and white matter subtle abnormalities. While in AD degeneration mainly affects grey matter [11], recent evidences also found an early white matter involvement [12, 13]. It is a matter of debate whether degeneration directly affects the myelin, but a secondary wallerian degeneration certainly drives disconnection of associative cortical areas from the medial temporal lobe. In MCI, the
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