Vascular and Alzheimer's disease markers independently predict brain atrophy rate in Alzheimer's Disease Neuroimaging Initiative controls

Josephine Barnes,Owen T Carmichael,Kelvin K Leung,Christopher Schwarz,Gerard R Ridgway,Jonathan W Bartlett,Ian B Malone,Jonathan M Schott,Martin N Rossor,Geert Jan Biessels,Charlie Decarli,Nick C Fox

doi:10.1016/j.neurobiolaging.2013.02.003

Abstract

This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Aβ1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Aβ1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Aβ1-42 (p < 0.001) and tau (p = 0.04) were associated with BSI. There was no evidence of independent effects of WMH or CSF measures on BSI in AD. These data support findings that vascular damage is associated with increased brain atrophy in the context of AD pathology in pre-dementia stages.

Highlights

Alzheimer’s disease (AD) is the most common primary pathological cause of dementia, and vascular disease has been reported as the second most common (Brayne et al, 2009; Jellinger, 2006)
The primary goal of Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early AD
We found that both increased White matter hyperintensities (WMH) volume and decreased cerebrospinal fluid (CSF) Ab level were independently associated with an increase in brain volume loss in control subjects

Summary

Introduction

Alzheimer’s disease (AD) is the most common primary pathological cause of dementia, and vascular disease has been reported as the second most common (Brayne et al, 2009; Jellinger, 2006). Some studies have shown that AD and vascular pathologies are prevalent and that they can often co-occur (Brayne et al, 2009; Jellinger, 2006; Schneider et al, 2007; White et al, 2002). WMHs have multiple histopathological correlates, including ependymal loss, cerebral ischemia, demyelination, microcystic infarcts, venous collagenosis, and gliosis (Gouw et al, 2011; Kim et al, 2008) They increase with age and vascular risk factors (DeCarli et al, 2001; Jeerakathil et al, 2004; Nordahl et al, 2006; Yoshita et al, 2006).

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