Grant: Project Grant

The human brain, the most complex tissue in nature, and its disease-causing malfunctions are incompletely understood. For example, older patients with schizophrenia show more severe age-related deficits in attention, learning and memory, and planning abilities compared to healthy controls. These deficits significantly affect independence and quality of life. We know that this age-related cognitive decline is not due to a higher frequency of neurodegenerative pathology (such as Alzheimer Disease), but otherwise neuroscientists do not know why it occurs. This project will look at the brain changes that occur in patients with chronic schizophrenia with and without Alzheimer Disease pathology and in neurologically normal controls. Our thought is that inflammation and abnormalities in the cellular composition of the brain will explain how this cognitive decline occurs. To study this, we will compare the microscopic changes that occur in autopsy brain samples of three group of older adults: 1) patients with chronic schizophrenia and extensive clinical evaluation and testing during life, 2) patients with Alzheimer Disease and 3) neurologically normal controls. Specific brain regions important for normal brain functioning will be compared in terms of cellular composition and degree of inflammation using a new technology called Digital Spatial Profiling (DSP). This technology measures up to 96 different tissue markers at the same time in areas defined under the microscope, which was not possible until now. This amount of detail will provide clues as to the differences in brain structure between these groups, and how these relate to cognitive impairment. This information will allow us to look for targets that could be help to follow up clinically or treat cognitive decline in chronic schizophrenia and other psychiatric conditions.