Modeling cholinergic modulation of fMRI memory networks in aging & MCI

Massachusetts General Hospital, Boston MA

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Abstract

This is a revised application for a K23 Mentored Patient-Oriented Research Career Development Award[unreadable] entitled: "Modeling Cholinergic Modulation of fMRI Memory Networks in Aging & MCI". This research[unreadable] proposal aims to combine functional MRI (fMRI), memory testing, medications that affect acetylcholine[unreadable] (ACh), and mathematical modeling to investigate the effects of aging, amnestic-mild cognitive impairment[unreadable] (MCI - a precursor of Alzheimer's disease, AD), and cholinergic changes on critical brain regions and their[unreadable] interactions during the learning of face-name pairs.[unreadable] Learning and remembering the names of new individuals we encounter is a particularly difficult demand in[unreadable] daily life and the most common memory complaint of older individuals visiting memory clinics. Meanwhile,[unreadable] deficits in central cholinergic function occur in the process of normal aging and become increasingly[unreadable] apparent in clinical AD, yet the exact nature and effects of these changes on memory systems in MCI and[unreadable] early AD remain elusive. Acetylcholinesterase inhibitors (AChEl) produce modest overall benefits in AD but[unreadable] their effects in MCI are less clear. The primary research questions in this proposal are: 1) What are the[unreadable] cognitive and fMRI correlates of cholinergic modulation in youth, aging and MCI? 2) Can they sensitively[unreadable] differentiate aging and MCI? 3) Can they serve as biomarkers to predict the 2-year clinical course of MCI?[unreadable] 4) Will combining pharmacological cognitive fMRI with modeling methods increase the ability to delineate the[unreadable] nature, functional integrity and compensatory reserve of memory systems in aging and MCI?[unreadable] As part of the proposed research, the candidate seeks training in: 1) fMRI analysis and modeling techniques;[unreadable] 2) cognitive neruoscience of aging and memory impairment; and 3) ethical clinical research methods. The[unreadable] proposed plan will foster the candidate's development into an independent physician-scientist using cognitive[unreadable] neuroscience, modeling, and pharmacological methods to study the functional neuro-anatomy, physiology,[unreadable] and chemisty of memory changes in aging and MCI.[unreadable] MCI is a condition that will affect increasing numbers of older adults and is thougth to represent a very early[unreadable] manifestation of AD. As more effective treatments are developed, it is an essential matter of public health to[unreadable] diagnose and treat AD at the earliest. This proposal works towards this goal.[unreadable]