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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Elucidating the Risk Factors for Progression from Amyloid-Negative Amnestic Mild Cognitive Impairment to Dementia

Author(s): Hyung-Ji Kim, Jae-Hong Lee*, E-nae Cheong, Sung-Eun Chung, Sungyang Jo, Woo-Hyun Shim and Yun J. Hong

Volume 17 , Issue 10 , 2020

Page: [893 - 903] Pages: 11

DOI: 10.2174/1567205017666201130094259

Price: $65


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 on 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 amyloid-negative 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 diseaselike 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 disease-mimicking dementia are warranted.

Keywords: Mild cognitive impairment, amyloid deposit, Alzheimer’s disease, image processing, disease progression, neuropsychological test, risk factor, cerebellum.

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