Rates of brain atrophy over time in autopsy-proven frontotemporal dementia and Alzheimer disease

Rates of brain loss have been shown to accelerate over time in early Alzheimer disease (AD); however the trajectory of change in frontotemporal lobar degeneration with ubiquitin immunoreactive-changes (FTLD-U) is unknown. This study compared the progression of atrophy over multiple MRI in subjects with autopsy-confirmed AD and FTLD-U. Nine subjects with autopsy-confirmed FTLD-U and nine with autopsy-confirmed AD were identified that had three or more serial MRI. The boundary-shift integral was used to calculate change over time in whole-brain and ventricular volume. A hierarchical regression model was used to estimate the slope of volume change in AD and FTLD-U over time and to estimate differences in the slopes across the subject groups. Whole-brain volume loss did not deviate from a linear rate over time in both AD and FTLD-U subjects, although this may be due to limited sample size. The FTLD-U subjects had a faster rate (23 ml/year) than the AD subjects (10 ml/year). The rate of ventricular expansion accelerated over time. At the point when each subject had a Clinical Dementia Rating Sum-of-Boxes score of 6, the annual rate was 7 ml/year in FTLD-U and 5 ml/year in AD. These rates of change increased by an estimated 1.66 ml/year in FTLD-U and 0.44 ml/year in AD, although these estimates were not significantly different between the two groups. The trajectories of brain and ventricular changes were similar in AD and FTLD-U suggesting that it is independent of pathology, although subjects with FTLD-U show a more rapidly progressive decline.