Ventricular maps in 804 ADNI subjects: Correlations with CSF biomarkers and clinical decline

Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
Neurobiology of aging (Impact Factor: 5.01). 08/2010; 31(8):1386-400. DOI: 10.1016/j.neurobiolaging.2010.05.001
Source: PubMed


Ideal biomarkers of Alzheimer's disease (AD) should correlate with accepted measures of pathology in the cerebrospinal fluid (CSF); they should also correlate with, or predict, future clinical decline, and should be readily measured in hundreds to thousands of subjects. Here we explored the utility of automated 3D maps of the lateral ventricles as a possible biomarker of AD. We used our multi-atlas fluid image alignment (MAFIA) method, to compute ventricular models automatically, without user intervention, from 804 brain MRI scans with 184 AD, 391 mild cognitive impairment (MCI), and 229 healthy elderly controls (446 men, 338 women; age: 75.50 +/- 6.81 [SD] years). Radial expansion of the ventricles, computed pointwise, was strongly correlated with current cognition, depression ratings, Hachinski Ischemic scores, language scores, and with future clinical decline after controlling for any effects of age, gender, and educational level. In statistical maps ranked by effect sizes, ventricular differences were highly correlated with CSF measures of Abeta(1-42), and correlated with ApoE4 genotype. These statistical maps are highly automated, and offer a promising biomarker of AD for large-scale studies.

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    • "One study also reported lesions in the caudate nucleus and lentiform nucleus of AD patients with late-onset depression [45]. Expansion of the lateral ventricles was also correlated with depression, general cognitive decline, and poor outcome [46]. Thus, depression is associated with both gray and white matter atrophy, particularly in specific regions of the prefrontal cortex. "
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    • "Surprisingly, while Aβ load was reduced in entorhinal, cingulate and parietal cortices, improvements in cognitive performance did not correlate with Aβ load [10], suggesting that effects on Aβ are likely not a central mechanism underlying the cognitive benefits of the interventions. However, because Aβ is well established to compromise neuronal health and synaptic function [11], [12], accumulation of Aβ in the aged canine brain is likely not benign, and it must be considered that AB may trigger downstream mechanisms that contribute to declines in brain health and cognitive function with age. "
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    • "Some neuroimaging measures, such as hippocampal and ventricular volume largely meet these criteria as endophenotypes for AD. Both increased ventricular volume [85] [86] [87] [88] and decreased volume of medial temporal lobe structures, especially the hippocampus [87] [88] [89] [90] [91] [92] predict cognitive decline, are moderately to highly heritable [93] [94] [95], and are associated with AD and genetic risk for AD (Table 2). Other measures that show promise in predicting cognitive decline are brain amyloid burden as measured using Pittsburgh Compound B [96] and white matter integrity (in general and perhaps more specifically in the parietal lobe) as measured with diffusion tensor imaging [97] both of which are also highly heritable [98] [99]. "
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