Amyloid accumulation in the medial temporal area starts in the mild cognitive impairment stage of Alzheimer’s disease in [18F]flutemetamol positron emission tomography

Abstract

AbstractBackgroundThis study was aimed to evaluate the hierarchical accumulation of amyloid in the Alzheimer’s brain according to clinical stage using [18F]flutemetamol positron emission tomography.MethodThis was a prospective, single‐cohort study of volunteers who lived independently in Itabashi‐ku (Tokyo, Japan). One hundred thirty‐six participants (female/male = 96/40, mean age/standard deviation = 79.2/4.0 years) were recruited. Two subjects, one with meningeal thickening and another with sequelae in the brain, and 17 visually amyloid‐negative MCI subjects who possibly had neurodegenerative disease other than Alzheimer’s disease were excluded from the further analysis. We applied voxel‐based regression slope analysis using composite voxel of interest values calculated with Cortex ID Suite (GE Healthcare) and [18F]flutemetamol positron emission tomography images in three groups: 70 amyloid‐negative cognitively normal (CN) participants, 29 amyloid‐positive cognitively normal (PreC) participants, and 18 amyloid‐positive MCI (MCI+) participants. Statistical Parametric Mapping 12 software was used for analysis.ResultCompared with the CN group, the PreC group showed accelerated amyloid accumulation in a wide area, except for the medial temporal lobe, paracentral sulcus, and medial occipital lobe. In amyloid‐positive subjects, amyloid accumulation was quicker in the paracentral sulcus, occipital cortex, and left medial temporal lobe in the MCI+ group than in the PreC group. Additional voxel of interest analyses were applied to the statistically significant areas. In the right posterior cingulate area, there was no significant difference between the PreC and MCI+ groups; however, the PreC and MCI+ groups showed a significantly quicker amyloid accumulation than the CN group. In contrast, in the left medial temporal area, the increase of amyloid accumulation was greater only in the MCI+ group compared to the PreC and CN groups.ConclusionIn amyloid‐positive subjects, amyloid accumulation in the left medial temporal lobe did not increase in the preclinical stage. In the medial temporal and occipital lobes, which are relatively spared from amyloid accumulation, it is considered to start late in the MCI stage and not in the preclinical stage. Further study of volume and other biomarkers is requreid to evaluate the regional pathophysiological variability of AD.