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Background: The hypothetical model of dynamic biomarkers for Alzheimer's disease (AD) describes high amyloid eposition and hypometabolism at the mild cognitive impairment (MCI) stage. However, it remains unknown whether brain myloidosis and hypometabolism follow the same trajectories in MCI individuals. We used the concept of early MCI (EMCI) nd late MCI (LMCI) as defined by the Alzheimer's disease Neuroimaging Initiative (ADNI)-Go in order to compare the iomarker profile between EMCI and LMCI. Objectives: To examine the global and voxel-based neocortical amyloid burden and metabolism among individuals who are ognitively normal (CN), as well as those with EMCI, LMCI and mild AD. Methods: In the present study, 354 participants, including CN (n = 109), EMCI (n = 157), LMCI (n = 39) and AD (n = 49), were nrolled between September 2009 and November 2011 through ADNI-GO and ADNI-2. Brain amyloid load and metabolism were estimated using [18F]AV45 and [18F]fluorodeoxyglucose ([18F]FDG) PET, respectively. Uptake ratio images of [18F]AV45 nd [18F]FDG were calculated by dividing the summed PET image by the median counts of the grey matter of the erebellum and pons, respectively. Group differences of global [18F]AV45 and [18F]FDG were analyzed using ANOVA, while he voxel-based group differences were estimated using statistic parametric mapping (SPM). Results: EMCI patients showed higher global [18F]AV45 retention compared to CN and lower uptake compared to LMCI. PM detected higher [18F]AV45 uptake in EMCI compared to CN in the precuneus, posterior cingulate, medial and dorsal ateral prefrontal cortices, bilaterally. EMCI showed lower [18F]AV45 retention than LMCI in the superior temporal, inferior arietal, as well as dorsal lateral prefrontal cortices, bilaterally. Regarding to the global [18F]FDG, EMCI patients showed no ignificant difference from CN and a higher uptake ratio compared to LMCI. At the voxel level, EMCI showed higher metabolism in precuneus, hippocampus, entorhinal and inferior parietal cortices, as compared to LMCI. Conclusions: The present results indicate that brain metabolism remains normal despite the presence of significant amyloid ccumulation in EMCI. These results suggest a role for anti-amyloid interventions in EMCI aiming to delay or halt the eposition of amyloid and related metabolism impairment. [ABSTRACT FROM AUTHOR]

The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer’s disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer’s disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer’s disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior cingulate and frontal regions only in the Alzheimer’s group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Background: The hypothetical model of dynamic biomarkers for Alzheimer's disease (AD) describes high amyloid deposition and hypometabolism at the mild cognitive impairment (MCI) stage. However, it remains unknown whether brain amyloidosis and hypometabolism follow the same trajectories in MCI individuals. We used the concept of early MCI (EMCI) and late MCI (LMCI) as defined by the Alzheimer's disease Neuroimaging Initiative (ADNI)-Go in order to compare the biomarker profile between EMCI and LMCI., Objectives: To examine the global and voxel-based neocortical amyloid burden and metabolism among individuals who are cognitively normal (CN), as well as those with EMCI, LMCI and mild AD., Methods: In the present study, 354 participants, including CN (n = 109), EMCI (n = 157), LMCI (n = 39) and AD (n = 49), were enrolled between September 2009 and November 2011 through ADNI-GO and ADNI-2. Brain amyloid load and metabolism were estimated using [(18)F]AV45 and [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET, respectively. Uptake ratio images of [(18)F]AV45 and [(18)F]FDG were calculated by dividing the summed PET image by the median counts of the grey matter of the cerebellum and pons, respectively. Group differences of global [(18)F]AV45 and [(18)F]FDG were analyzed using ANOVA, while the voxel-based group differences were estimated using statistic parametric mapping (SPM)., Results: EMCI patients showed higher global [(18)F]AV45 retention compared to CN and lower uptake compared to LMCI. SPM detected higher [(18)F]AV45 uptake in EMCI compared to CN in the precuneus, posterior cingulate, medial and dorsal lateral prefrontal cortices, bilaterally. EMCI showed lower [(18)F]AV45 retention than LMCI in the superior temporal, inferior parietal, as well as dorsal lateral prefrontal cortices, bilaterally. Regarding to the global [(18)F]FDG, EMCI patients showed no significant difference from CN and a higher uptake ratio compared to LMCI. At the voxel level, EMCI showed higher metabolism in precuneus, hippocampus, entorhinal and inferior parietal cortices, as compared to LMCI., Conclusions: The present results indicate that brain metabolism remains normal despite the presence of significant amyloid accumulation in EMCI. These results suggest a role for anti-amyloid interventions in EMCI aiming to delay or halt the deposition of amyloid and related metabolism impairment.