Hippocampal Mean Diffusivity for the Diagnosis of Dementia and Mild Cognitive Impairment in Primary Care.

BACKGROUND: Hippocampal mean diffusivity (MD) measured by Diffusion-Tensor Imaging is a promising diagnostic marker for Mild Cognitive Impairment (MCI) and dementia. Its performance has yet to be evaluated in primary care patients, who vary systematically from patients visiting specialized care settings. OBJECTIVE: We assessed the diagnostic accuracy of hippocampus diffusivity for detecting MCI and dementia in a sample recruited from primary care, compared to a sample from specialized care. METHOD: One sample was recruited from a primary care intervention trial (DelpHi-MV) (n=70), and the other sample was recruited from our memory clinic (n=70). The samples were matched pairwise for diagnosis, MMSE, age, gender, and education. They included dementia patients, MCI patients and healthy subjects. Mean MD was calculated for the left and right hippocampus, corrected for partial volume effects. Within each sample, left or right hippocampal MD served as predictor for diagnostic group in logistic regressions, which were additionally controlled for white matter lesions. RESULTS: In the primary care sample, hippocampal MD detected dementia with high cross-validated accuracy (left: AUC=.92; right: AUC=.85), but did not classify MCI with an accuracy above chance (left: AUC=.58; right: AUC=.44). In the memory clinic sample, hippocampal MD classified both dementia (left: AUC=.91; right: AUC=.91) and MCI (left: AUC=.86; right: AUC=.83) with high cross-validated accuracy. CONCLUSION: Hippocampal MD supported the identification of dementia but did not contribute to the detection of MCI in the primary care patient population.

Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance of partial volume correction.

Mean diffusivity (MD) measured by diffusion tensor imaging can reflect microstructural alterations of the brain's gray matter (GM). Therefore, GM MD may be a sensitive marker of neurodegeneration related to Alzheimer's Disease (AD). However, due to partial volume effects (PVE), differences in MD may be overestimated because of a higher degree of brain atrophy in AD patients and in cases with mild cognitive impairment (MCI). Here, we evaluated GM MD changes in AD and MCI compared with healthy controls, and the effect of partial volume correction (PVC) on diagnostic utility of MD. We determined region of interest (ROI) and voxel-wise group differences and diagnostic accuracy of MD and volume measures between matched samples of 39 AD, 39 MCI and 39 healthy subjects before and after PVC. Additionally, we assessed whether effects of GM MD values on diagnosis were mediated by volume. ROI and voxel-wise group differences were reduced after PVC. When using these ROIs for predicting group separation in logistic models, both PVE corrected and uncorrected GM MD values yielded a poorer diagnostic accuracy in single predictor models than regional volume. For the discrimination of AD patients and healthy controls, the effect of GM MD on diagnosis was significantly mediated by volume of hippocampus and posterior cingulate ROIs. Our results suggest that GM MD measurements are strongly confounded by PVE in the presence of brain atrophy, underlining the necessity of PVC when using these measurements as specific metrics of microstructural tissue degeneration. Independently of PVC, regional MD was not superior to regional volume in separating prodromal and clinical stages of AD from healthy controls.