Article

Subregional neuroanatomical change as a biomarker for Alzheimer's disease.

Department of Neurosciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2009; 106(49):20954-9. DOI: 10.1073/pnas.0906053106
Source: PubMed

ABSTRACT Regions of the temporal and parietal lobes are particularly damaged in Alzheimer's disease (AD), and this leads to a predictable pattern of brain atrophy. In vivo quantification of subregional atrophy, such as changes in cortical thickness or structure volume, could lead to improved diagnosis and better assessment of the neuroprotective effects of a therapy. Toward this end, we have developed a fast and robust method for accurately quantifying cerebral structural changes in several cortical and subcortical regions using serial MRI scans. In 169 healthy controls, 299 subjects with mild cognitive impairment (MCI), and 129 subjects with AD, we measured rates of subregional cerebral volume change for each cohort and performed power calculations to identify regions that would provide the most sensitive outcome measures in clinical trials of disease-modifying agents. Consistent with regional specificity of AD, temporal-lobe cortical regions showed the greatest disease-related changes and significantly outperformed any of the clinical or cognitive measures examined for both AD and MCI. Global measures of change in brain structure, including whole-brain and ventricular volumes, were also elevated in AD and MCI, but were less salient when compared to changes in normal subjects. Therefore, these biomarkers are less powerful for quantifying disease-modifying effects of compounds that target AD pathology. The findings indicate that regional temporal lobe cortical changes would have great utility as outcome measures in clinical trials and may also have utility in clinical practice for aiding early diagnosis of neurodegenerative disease.

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Available from: Anders M Dale, Jul 07, 2015
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    • "A variety of imaging modalities, including structural and functional ones, has shown distinctive changes in the brains of patients within the AD spectrum [11]. Overt dementia presents marked atrophy in the medial temporal lobe structures [12] [13] along with progressive thinning of the parietotemporal and frontal cortices [14] [15]. The pattern observed in MCI is similar, but to a lesser degree, to that of AD. "
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    • "All magnetic resonance imaging and PET analyses were of previously processed secondary data obtained from ADNI. Hippocampal and whole brain volume data from the Anders Dale Lab (University of California, San Diego, CA) were used, and details on their processing methods are published elsewhere (Holland et al., 2009). For normalization, we used total intracranial volumes calculated automatically from FreeSurfer (Fischl et al., 1999). "
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    • "However, for the individual patient the presence of focal injury (contusions, hemorrhages) also plays a significant role for outcome, but it was beyond the scope of the present paper to evaluate the interaction between focal injuries and the atrophy in different brain structures. It should be noted that the volume change measures obtained using independent NeuroQuant segmentations would not be expected to have the spatial specificity and power to detect subtle change that many across time point registration methods might provide (Holland et al., 2009; Fox et al., 2001; Thompson et al., 2004). On the other hand, NeuroQuant has previously been shown to have results comparable to that of hand segmentation of subregional volumes by anatomical experts (Brewer et al., 2009), and thus provides an identifiable and translatable measure of structure volume. "
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