Robust detection of atrophy over short intervals in AD and FTLD

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PROJECT SUMMARY Alzheimer’s disease, Frontotemporal Lobar Degeneration, and other diseases that lead to dementia are one of the 21st century’s major public health problems. This family of neurodegenerative diseases involves the disruption of functional brain circuits and ultimately the death of brain cells. In living people, the standard measure of neurodegeneration is derived from brain MRI scans, which can quantitatively measure the location and amount of atrophy. This is traditionally done, and continues to be done in many studies, over intervals of one year, with one or two scans collected one year apart, estimating annualized rates of brain atrophy. In some clinical trials, scans may be collected more frequently, but in one recent failed phase III trial aiming to slow neurodegeneration they were collected 80 weeks apart. The goal of this work is to demonstrate that new methods we and our colleagues have developed are able to improve the sensitivity to detect atrophy within individuals over short intervals of time, down to as little as 3 months. This is done by making a large number of extremely fast, highly precise repeated measurements at each time point for each individual. We aim to demonstrate the reliability and validity of these new MRI measures of neurodegeneration against traditional MRI measures and externally validated against PET and clinical measures in individuals with Early-onset Alzheimer’s disease or behavioral variant Frontotemporal Dementia. If successful, this work could revolutionize the field and open the door to a new means to track neurodegeneration, potentially greatly facilitating clinical trials.