Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

Jiu Chen1, Zhijun Zhang1, Shijiang Li2

1Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing 210009, China
2Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA
Corresponding authors: Zhijun Zhang and Shijiang Li. E-mail:,

Impaired structure and function of the hippocampus is a valuable predictor of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). As a part of the medial temporal lobe memory system, the hippocampus is one of the brain regions affected earliest by AD neuropathology, and shows progressive degeneration as aMCI progresses to AD. Currently, no validated biomarkers can precisely predict the conversion from aMCI to AD. Therefore, there is a great need of sensitive tools for the early detection of AD progression. In this review, we summarize the specific structural and functional changes in the hippocampus from recent aMCI studies using neurophysiological and neuroimaging data. We suggest that a combination of advanced multi-modal neuroimaging measures in discovering biomarkers will provide more precise and sensitive measures of hippocampal changes than using only one of them. These will potentially affect early diagnosis and disease-modifying treatments. We propose a new sequential and progressive framework in which the impairment spreads from the integrity of fibers to volume and then to function in hippocampal subregions. Meanwhile, this is likely to be accompanied by progressive impairment of behavioral and neuropsychological performance in the progression of aMCI to AD.

Keywords: Alzheimer’s disease; amnestic mild cognitive impairment; hippocampus; episodic memory; functional magnetic resonance imaging; structural magnetic resonance imaging; diffusion tensor imaging; multi-modal MRI biomarker

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