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Abstract
ABSTRACTThis study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5‐T MRI. CSF Aβ42 and total tau were measured (n = 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 Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 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 (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.
Highlights
Atrophy rate, or rate of tissue loss over time, is one of the markers that reflects disease progression and severity in Alzheimer’s disease (AD) (Fox et al, 1999; Mungas et al, 2002; Jack et al, 2005)
N Mean brain volume adjusted for white matter hyperintensity (WMH), Total Intracranial Volumes (TIV) and gender Mean hippocampal volume adjusted for WMH, TIV and gender Association between WMH and baseline brain volume Association between WMH and baseline hippocampal brain volume
We found novel evidence that WMHs were associated with disproportionately greater hippocampal atrophy in controls and mild cognitive impairment (MCI) subjects relative to whole-brain atrophy
Summary
Rate of tissue loss over time, is one of the markers that reflects disease progression and severity in Alzheimer’s disease (AD) (Fox et al, 1999; Mungas et al, 2002; Jack et al, 2005). Hippocampal atrophy is an early marker of AD pathology (Henneman et al, 2009; Dubois et al, 2014); rates correlate with. Cerebrospinal fluid (CSF) markers of AD (Hampel et al, 2005; Schuff et al, 2009) and with cognitive decline (Jack et al, 2000). One type of vascular damage appears hypointense on T1-weighted MRI and hyperintense on T2-weighted imaging; so-called white matter hyperintensities (WMHs) can be quantified volumetrically (Prins et al, 2004; Carmichael et al, 2010; Schmidt et al, 2012). WMH volume is associated with increasing age (Yoshita et al, 2006), risk of future cognitive decline and dementia (van der Flier et al, 2005; Carmichael et al, 2010). WMHs are associated with numerous potentially modifiable cerebrovascular risk factors (Debette et al, 2011)
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