The Effects of Subjective Memory Impairment on Brain Function and Structure: Meg, Mri, Apo E Genotype and Longitudinal Follow-Up Studies

Early diagnosis is the basic policy for managing neurodegenerative diseases. Amnestic mild cognitive impairment (aMCI) has been considered as an intermediate state between normal aging and Alzheimer’s disease (AD). There are many studies that have devoted to identifying the predictive factors in patients with aMCI conversion to AD. Alterations of brain structures and functions occur even prior to the diagnosis of aMCI, whereas the current objective cognitive evaluation could not detect these subtle changes. Subjective memory impairment (SMI) is likely a clinical indicator of pre-MCI cognitive decline. The more understanding of the brain’s structural and functional changes, the better we could monitor the clinical progression of this disease spectrum. However, up to the date, there is no literature to integrate different imaging modalities or research tools to comprehensively examine SMI. Therefore, the present 3-year proposal plans to use magnetoencephalography (MEG) in conjunction with magnetic resonance imaging (MRI), blood tests (Apo E genotype, and inflammatory factors such as IL1, IL6) and neuropsychological assessments to study patients with aMCI, SMI and healthy older adults. Specifically, in the first year, we will recruit healthy controls and SMI subjects. At the same time, we will establish a reliable experimental procedure, including parameter settings and analysis pipelines. In the second year, we start to recruit patients with aMCI, and try to determine the significant parameters (among functional and structural neuroimaging indices, blood tests and neuropsychological assessments) that can differentiate SMI from healthy controls or/and aMCI patients. We will also attempt to determine the potential factors that reflect medical responsiveness in patients with aMCI (aMCI stable vs. aMCI conversion to AD). In the final year, through longitudinal follow-up, we will analyze data in SMI who convert to AD to aMCI or AD, and to retrospectively find the predictive or associative parameters measured at the baseline. Another novelty of the present proposal lies in the full consideration of clinical applications. It is very frustrating to request patients to cooperate with the tasks in the functional neuroimaging research. The age-related attenuated attention, motivation and persistence usually contaminate the quality of data. Thus, the present study aims to apply three pre-attentive neurophysiological signals without participants’ overt behavioral responses, while still can reflect basic cognitive processing: (1) mismatch negativity/magnetic mismatch negativity, (2) sensory gating, and (3) resting-state functional connectivity. The aforementioned imaging indices have been widely used in the studies of neurodegenerative diseases, and have potentials to serve as candidates from bench to bedside.

Project ID:PC10601-1111
External Project ID:MOST105-2628-B182-004-MY3