Comparison of Imaging Biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging

Archives of neurology (Impact Factor: 7.42). 05/2012; 69(5):614-22. DOI: 10.1001/archneurol.2011.3029
Source: PubMed


OBJECTIVE To determine whether magnetic resonance imaging measurements observed in the Alzheimer Disease Neuroimaging Initiative (ADNI) convenience sample differ from those observed in the Mayo Clinic Study of Aging (MCSA) population-based sample. DESIGN Comparison of 2 samples. SETTING Fifty-nine recruiting sites for the ADNI in the United States and Canada and the MCSA, a population-based cohort in Olmsted County, Minnesota. PATIENTS Cognitively normal subjects and amnestic subjects with mild cognitive impairment were selected from the ADNI convenience cohort and MCSA population-based cohort. A simple random sample of subjects from both cohorts in the same age range was selected, and a second sample applied matching for age, sex, educational level, apolipoprotein E genotype, and Mini-Mental State Examination score. MAIN OUTCOME MEASURES Baseline hippocampal volumes and annual percentage of decline in hippocampal volume. RESULTS In the population-based sample, MCSA subjects were older, had less education, performed worse on the Mini-Mental State Examination, and had a family history of Alzheimer disease less often than did ADNI subjects. Baseline hippocampal volumes were larger in ADNI compared with MCSA cognitively normal subjects in the random sample, although no differences were observed after matching. Rates of decline in hippocampal volume were greater in the ADNI compared with the MCSA for cognitively normal subjects and those with amnestic mild cognitive impairment, even after matching. CONCLUSIONS Rates of decline in hippocampal volume suggest that ADNI subjects have a more aggressive brain pathologic process than MCSA subjects and hence may not be representative of the general population. These findings have implications for treatment trials that use ADNI-like recruitment mechanisms and for studies validating new diagnostic criteria for Alzheimer disease in its various stages.

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Available from: Clifford R Jack, Feb 17, 2015
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    • "Interestingly, our data show that the BBB integrity in other brain regions including cortical and subcortical regions or the WM remains relatively unaffected during normal aging or aging associated with MCI. Although we did not find significant changes in hippocampal volumes between the young and older NCI and MCI individuals, it is possible that an early and progressive increase in the BBB permeability, as we show in the hippocampus in older NCI and MCI individuals, might precede hippocampal atrophy seen later in AD (Whitwell et al., 2012; Apostolova et al., 2010), particularly in MCI progressing to AD. This would be similar to findings in animal models with a chronic BBB disruption showing that vascular leakages over time lead to hippocampal and cortical atrophy, loss of neurons, and progressive behavioral changes (Bell et al., 2010, 2012; Winkler et al., 2012, 2014). "
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    ABSTRACT: The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens, and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer's disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic contrast-enhanced MRI protocol with high spatial and temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neuron 01/2015; 85(2):296-302. DOI:10.1016/j.neuron.2014.12.032 · 15.05 Impact Factor
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    • "Comparing results in the two datasets, all methods generally showed a more aggressive pathology in the ADNI population than the Mayo Clinic population, agreeing with previous T1-based imaging comparisons between these groups (Whitwell et al., 2012a). Because our ADNI dataset contains relatively younger subjects, these results Fig. 12. Results of each analysis pipeline computing significant FA reductions in 23 AD subjects versus 23 matched controls from ADNI data. "
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    ABSTRACT: Tract-Based Spatial Statistics (TBSS) is a popular software pipeline to coregister sets of diffusion tensor Fractional Anisotropy (FA) images for performing voxel-wise comparisons. It is primarily defined by its skeleton projection step intended to reduce effects of local misregistration. A white matter “skeleton” is computed by morphological thinning of the inter-subject mean FA, and then all voxels are projected to the nearest location on this skeleton. Here we investigate several enhancements to the TBSS pipeline based on recent advances in registration for other modalities, principally based on groupwise registration with the ANTS-SyN algorithm. We validate these enhancements using simulation experiments with synthetically-modified images. When used with these enhancements, we discover that TBSS's skeleton projection step actually reduces algorithm accuracy, as the improved registration leaves fewer errors to warrant correction, and the effects of this projection's compromises become stronger than those of its benefits. In our experiments, our proposed pipeline without skeleton projection is more sensitive for detecting true changes and has greater specificity in resisting false positives from misregistration. We also present comparative results of the proposed and traditional methods, both with and without the skeleton projection step, on three real-life datasets: two comparing differing populations of Alzheimer's disease patients to matched controls, and one comparing progressive supranuclear palsy patients to matched controls. The proposed pipeline produces more plausible results according to each disease's pathophysiology.
    NeuroImage 01/2014; 94:65–78. · 6.36 Impact Factor
    • "There is some evidence that population-based MCI samples outperform clinic samples (solely based on MMSE) possibly because participants from clinics have a more aggressive or advanced form of MCI [6] [7] [12]. By contrast, others found no difference between clinic and population samples on the MMSE, memory tasks, or executive function tasks [8] or found that clinic samples performed better possibly due to higher levels of cognitive reserve although this result was not corrected for differences in sample age and education [3]. Potential cognitive differences merit further investigation. "
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    ABSTRACT: We examined whether differences in findings of studies examining mild cognitive impairment (MCI) were associated with recruitment methods by comparing sample characteristics in two contemporaneous Australian studies, using population-based and convenience sampling. The Sydney Memory and Aging Study invited participants randomly from the electoral roll in defined geographic areas in Sydney. The Australian Imaging, Biomarkers and Lifestyle Study of Ageing recruited cognitively normal (CN) individuals via media appeals and MCI participants via referrals from clinicians in Melbourne and Perth. Demographic and cognitive variables were harmonized, and similar diagnostic criteria were applied to both samples retrospectively. CN participants recruited via convenience sampling were younger, better educated, more likely to be married and have a family history of dementia, and performed better cognitively than those recruited via population-based sampling. MCI participants recruited via population-based sampling had better memory performance and were less likely to carry the apolipoprotein E ε4 allele than clinically referred participants but did not differ on other demographic variables. A convenience sample of normal controls is likely to be younger and better functioning and that of an MCI group likely to perform worse than a purportedly random sample. Sampling bias should be considered when interpreting findings.
    Annals of epidemiology 10/2013; 24(1). DOI:10.1016/j.annepidem.2013.10.005 · 2.00 Impact Factor
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