Cognitive Neuroscience Approaches to Therapy

Therapeutic interventions for Alzheimer’s disease (AD) have been hampered by the lack of a reliable diagnostic technique that allows efficacious interventions to begin as early as possible. The overall purpose of the proposed study is to develop a reliable method for the early diagnosis of AD. We have developed a novel, non-invasive, high resolution functional imaging procedure – perfusion fMRI – that is well suited to attaining this goal. This technique can also contribute to our understanding of cognitive difficulties and to the development of experimental therapies for AD. In the first study, we will compare the pattern of perfusion defect in patients with mild AD with control subjects. The specificity of the AD perfusion defect will be confirmed by comparisons with another cortical dementia, frontotemporal degeneration (FD). We will correlate patterns of cognitive difficulty assessed at the time of perfusion fMRI with the unique patterns of cortical defect seen on fMRI, validating these distinct patterns of brain activity with standardized and experimental neurocognitive measures. We hypothesize that mild AD will be associated with a specific profile of reduced cortical activity in comparison to control subjects , and the anatomic distribution of this defect will differ from the pattern of reduced activity seen in FD. We also expect to observe specific correlations between neurocognitive measures and patterns of reduced cortical activity in AD and FD. In the second study, we will assess the feasibility of identifying a specific profile of perfusion abnormality in non-demented elderly patients with memory complaints. We will obtain neuropsychological and Apolipoprotein E (ApoE) assessments in these patients as well. We hypothesize that a subset of non-demented patients with memory complaints will demonstrate the perfusion profile seen in AD. The early identification and improved understanding of cognitive difficulty in AD has crucial implications for the management of this disorder since patients w ill be able to receive a treatment as early as possible in the course of the condition. This cost-effective approach will optimize the likelihood of responding to preventive strategies, neurotransmitter system supplementation, and other therapeutic interventions that delay end-points such as nursing home entry in AD.