Abstract
IntroductionSubcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer’s disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, methodological differences, and the contribution of brain atrophy associated with AD pathology have yielded inconsistent results in the literature.MethodsUsing the Lesion Explorer (LE) MRI processing pipeline for SH quantification and brain atrophy, this study examined SH volumes of interest and cognitive function in a sample of patients with AD (n = 265) and normal elderly controls (n = 100) from the Sunnybrook Dementia Study.ResultsCompared with healthy controls, patients with AD were found to have less gray matter, less white matter, and more sulcal and ventricular cerebrospinal fluid (all significant, P <0.0001). Additionally, patients with AD had greater volumes of whole-brain SH (P <0.01), periventricular SH (pvSH) (P <0.01), deep white SH (dwSH) (P <0.05), and lacunar lesions (P <0.0001). In patients with AD, regression analyses revealed a significant association between global atrophy and pvSH (P = 0.02) and ventricular atrophy with whole-brain SH (P <0.0001). Regional volumes of interest revealed significant correlations with medial middle frontal SH volume and executive function (P <0.001) in normal controls but not in patients with AD, global pvSH volume and mental processing speed (P <0.01) in patients with AD, and left temporal SH volume and memory (P <0.01) in patients with AD.ConclusionsThese brain-behavior relationships and correlations with brain atrophy suggest that subtle, yet measurable, signs of small vessel disease may have potential clinical relevance as targets for treatment in Alzheimer’s dementia.
Highlights
Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer’s disease (AD) and normal elderly controls
Since T1-based segmentations may result in misclassified tissue volumetrics due to the relative intensity of subcortical hyperintensity (SH) on T1 [17], an additional proton density (PD)/T2/fluid attenuated inversion recovery (FLAIR)-based SH segmentation is recommended to correct for this error and account for the possible contribution of ischemic vascular injury, with studies examining aging and dementia [19]
Compared with normal elderly controls (NC), patients with AD were found to have less overall brain matter, less gray matter (GM), less white matter (WM), and more sulcal cerebrospinal fluid (sCSF) and ventricular CSF (vCSF), and relatively large effect sizes were demonstrated for overall brain atrophy and all basic tissue type comparisons (BPF%: d = 1.35, GM: d = 1.35, WM: d = 0.92, sCSF: d = 1.24, vCSF: d = 1.01)
Summary
Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer’s disease (AD) and normal elderly controls. Subcortical hyperintensities (SHs) are commonly observed radiological entities on T2-weighted (T2), proton density (PD), and fluid attenuated inversion recovery (FLAIR) magnetic resonance images (MRIs) of the aging brain [1,2]. Often referred to as leukoaraiosis, these diffuse white. SH can be subclassified as periventricular (pvSH) and deep white (dwSH) [14,15,16]. The purpose of the present study is to better understand the complex relationships between MRI measures of small vessel disease, atrophy, and cognition in patients with sporadic Alzheimer’s disease (AD) and cognitively normal elderly controls (NCs). This study used MRI-derived (T1/T2/PD) volumetrics to determine whether regional SH volumes of interest (VOIs) were differentially correlated with atrophy and performance on tasks probing executive function, mental processing speed, and memory
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