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Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5\u2010T MRI. CSF A\u03b2<jats:sub>42<\/jats:sub> and total tau were measured (<jats:italic>n =<\/jats:italic> 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain\/hippocampal atrophy rates and (b) CSF A\u03b2<jats:sub>42<\/jats:sub> and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (<jats:italic>P =<\/jats:italic> 0.002) and MCI subjects (<jats:italic>P =<\/jats:italic> 0.03), and with brain atrophy rate in controls (<jats:italic>P =<\/jats:italic> 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (<jats:italic>P<\/jats:italic>\u2009=\u20090.007). 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