IC‐P‐127: AGE AND WMH HAVE INDEPENDENT ASSOCIATIONS WITH WHOLE BRAIN AND HIPPOCAMPAL ATROPHY RATES

Hippocampal and whole-brain atrophy rates are important markers in measuring Alzheimer's disease (AD) progression with hippocampal rates being a specific marker of AD. Ageing and white matter hyperintensity (WMH) lesions are two factors associated with progressive tissue loss in the brain. Understanding whether the associations of age and WMH on whole-brain and hippocampal atrophy rates are statistically independent is important in understanding underlying disease processes. This study extends previous work by examining the independent relationships of age and WMH with hippocampal and whole-brain atrophy rates using multiple serial scans up to 36 months from baseline. Alzheimer's Disease Neuroimaging Initiative 1 participants were included: 154 AD, 345 mild cognitive impairment (MCI) and 198 controls. Separate mixed-effect linear regression models were used to assess the association between baseline log 2 WMH volume (predictor) on whole-brain and hippocampal atrophy rates (outcome measures) in each diagnostic group (model 1). These models were repeated with age replacing log 2 WMH, to assess the effect of age on atrophy rates (model 2). Finally, models including both log 2 WMH and age as predictors were fitted to assess whether each had independent associations with atrophy rates (model 3). Analyses were adjusted for intracranial volume. Higher WMH was associated with greater whole-brain atrophy rates (greater loss) in controls and higher hippocampal rates in controls and MCI (Tables). Increasing age was associated with higher hippocampal rates in controls and lower brain rates in MCI and AD subjects. In models with both log 2 WMH and age as predictors, these relationships remained significant. Further, in MCI, the age-adjusted association between higher WMH and greater whole-brain rates was borderline significant and the WMH-adjusted association between higher age and lower hippocampal rates was significant. These results suggest that effects of age and WMH on atrophy rates are independent. The relationship between greater WMH and higher atrophy rates is not explained by age effects in controls or MCI. Further, increasing WMH does not explain the positive relationship between age and atrophy rates in controls. The negative association between age and atrophy rate in MCI and AD may be due to more aggressive disease in younger AD subjects.