Alzheimer‐like glucose hypometabolism predicts subsequent dementia in amyloid‐negative mild cognitive impairment

Abstract

AbstractBackgroundPatients with mild cognitive impairment (MCI) are at‐risk of progression to Alzheimer’s dementia (AD), particularly if they have elevated amyloid (Aβ), the hallmark pathology of AD. However, a proportion of Aβ‐negative MCI also progress to dementia in clinical practice. We sought to investigate (1) whether subthreshold Aβ load, brain metabolism, or atrophy could predict progression to dementia in patients with Aβ‐negative MCI, and (2) whether the regional pattern was distinct from patients with Aβ‐positive MCI.MethodSeventy‐nine older adults underwent [18F]‐FDG‐PET to estimate their brain metabolism, [18F]‐Flutemetamol‐PET to assess their Aβ load, and 3D‐T1 MRI. Aβ load was expressed in Centiloids and a threshold of 43 corresponding to visual assessment was used to define Aβ positivity. FDG data were expressed as Standardized Uptake Value ratios (SUVr) scaled on pons with partial volume correction. MRI‐PET co‐registration was performed with PetSurfer. Eight Aβ‐negative MCI progressed to dementia after four years. We compared their FDG and thicknesses maps to 25 Aβ‐negative normal older adults, 31 Aβ‐negative stable MCI, and 15 Aβ‐positive MCI who also progressed to AD dementia after four years. Demographics and follow‐up durations are provided in Table1.ResultSubthreshold Aβ did not predict progression to dementia among Aβ‐negative MCI (p=0.81). Vertex‐wise analyses highlighted temporo‐parietal hypometabolism in the Aβ‐negative MCI who progressed to dementia, compared to stable Aβ‐negative controls (Fig. 1), and to a lesser extent compared to stable Aβ‐negative MCI patients (Fig. 2). However, their cerebral metabolism was similar to the one observed in Aβ‐positive MCI (Fig.3). Finally, the regional pattern of cortical thinning in progressive Aβ‐negative MCI was less typical of AD (Fig.4). Adjusting for age, sex, e4 status, or Aβ did not modify these observations.ConclusionTemporoparietal FDG predicts subsequent dementia in Aβ‐negative MCI patients, suggesting a close association with clinical progression. The FDG regional pattern is however not specific of Aβ pathophysiology.