While much is known about the cognitive deterioration that occurs in Alzheimer's Disease (AD), less is known about the effects of AD pathology on the emotional systems in the brain. Damage to the mediotemporal lobe (MTL) occurs early in AD, and damage to the hippocampal formation within the MTL has been very closely linked with the decline in declarative memory that is often one of the first symptoms of AD. The hippocampal formation is interconnected with the amygdala, an MTL limbic brain structure believed to be involved in a number of emotional processing functions, including the enhancement of memory by emotional content, the discrimination of odors, and fear conditioning. The amygdala also is damaged very early in the course of AD, but the effects of this damage, as well as its relationship to damage in the hippocampal formation, are not well understood. We propose to conduct a cross-sectional study to evaluate the relative structural and functional status of these two systems in the earliest stages of AD.
The specific aims of this study are to contrast MRI-derived volumes of neural structures involved in declarative memory (hippocampal formation) with those of neural structures involved in emotional processing (amygdala, orbitofrontal region, and anterior cingulate gyrus) in participants with mild AD, mild cognitive impairment (MCI, a group known to be at high risk for AD), and normal age- and gender-matched controls. We also will use various pertinent neuropsychological and psychometric tests to assess the functional status of these two neural systems in the three groups of subjects. Research participants will include a total of 90 elderly individuals between 60 to 75 years of age and 50 percent female, consisting of 30 elderly individuals in each of the three groups. In addition, 30 young normal individuals between 18 to 30 years of age, and 50 percent female will be included to study the effects of age and age-by-gender interactions on the systems under study. With this research, we hope to better understand the effects of early AD pathology on specific amygdala and emotional brain functions in order to help clarify the diagnosis of early AD, as well as to form the basis for future longitudinal studies of emotional brain function in AD.
