Background:
Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true
Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable
Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited
number of studies had been conducted this subpopulation in terms of clinical progression.
Objective:
We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative
amnestic mild cognitive impairment (MCI).
Methods:
This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36
months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and
fluorine-18[F18]-florbetaben amyloid PET.
Results:
During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with
the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and
hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant
Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced
gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices.
Conclusion:
Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be
caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration
independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.
Optimally-Discriminative Voxel-Based Morphometry significantly increases the ability to detect group differences in schizophrenia, mild cognitive impairment, and Alzheimer's disease