Dataset Information

Comparison of imaging biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging.

ABSTRACT: 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.Comparison of 2 samples.Fifty-nine recruiting sites for the ADNI in the United States and Canada and the MCSA, a population-based cohort in Olmsted County, Minnesota.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.Baseline hippocampal volumes and annual percentage of decline in hippocampal volume.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.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.

SUBMITTER: Whitwell JL

PROVIDER: S-EPMC3569033 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Comparison of imaging biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging.

Whitwell Jennifer L JL Wiste Heather J HJ Weigand Stephen D SD Rocca Walter A WA Knopman David S DS Roberts Rosebud O RO Boeve Bradley F BF Petersen Ronald C RC Jack Clifford R CR

Archives of neurology 20120501 5

<h4>Objective</h4>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.<h4>Design</h4>Comparison of 2 samples.<h4>Setting</h4>Fifty-nine recruiting sites for the ADNI in the United States and Canada and the MCSA, a population-based cohort in Olmsted County, Minnesota.<h4>Patients</h4>Cognitively normal subjects and ...[more]

PMID: 22782510

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Project description:MRI-derived features of presumed cerebral small vessel disease are frequently found in Alzheimer's disease. Influences of such markers on disease-progression measures are poorly understood. We measured markers of presumed small vessel disease (white matter hyperintensity volumes; cerebral microbleeds) on baseline images of newly enrolled individuals in the Alzheimer's Disease Neuroimaging Initiative cohort (GO and 2) and used linear mixed models to relate these to subsequent atrophy and neuropsychological score change. We also assessed heterogeneity in white matter hyperintensity positioning within biomarker abnormality sequences, driven by the data, using the Subtype and Stage Inference algorithm. This study recruited both sexes and included: controls: [n = 159, mean(SD) age = 74(6) years]; early and late mild cognitive impairment [ns = 265 and 139, respectively, mean(SD) ages =71(7) and 72(8) years, respectively]; Alzheimer's disease [n = 103, mean(SD) age = 75(8)] and significant memory concern [n = 72, mean(SD) age = 72(6) years]. Baseline demographic and vascular risk-factor data, and longitudinal cognitive scores (Mini-Mental State Examination; logical memory; and Trails A and B) were collected. Whole-brain and hippocampal volume change metrics were calculated. White matter hyperintensity volumes were associated with greater whole-brain and hippocampal volume changes independently of cerebral microbleeds (a doubling of baseline white matter hyperintensity was associated with an increase in atrophy rate of 0.3 ml/year for brain and 0.013 ml/year for hippocampus). Cerebral microbleeds were found in 15% of individuals and the presence of a microbleed, as opposed to none, was associated with increases in atrophy rate of 1.4 ml/year for whole brain and 0.021 ml/year for hippocampus. White matter hyperintensities were predictive of greater decline in all neuropsychological scores, while cerebral microbleeds were predictive of decline in logical memory (immediate recall) and Mini-Mental State Examination scores. We identified distinct groups with specific sequences of biomarker abnormality using continuous baseline measures and brain volume change. Four clusters were found; Group 1 showed early Alzheimer's pathology; Group 2 showed early neurodegeneration; Group 3 had early mixed Alzheimer's and cerebrovascular pathology; Group 4 had early neuropsychological score abnormalities. White matter hyperintensity volumes becoming abnormal was a late event for Groups 1 and 4 and an early event for 2 and 3. In summary, white matter hyperintensities and microbleeds were independently associated with progressive neurodegeneration (brain atrophy rates) and cognitive decline (change in neuropsychological scores). Mechanisms involving white matter hyperintensities and progression and microbleeds and progression may be partially separate. Distinct sequences of biomarker progression were found. White matter hyperintensity development was an early event in two sequences.

Dataset Information

Comparison of imaging biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging.

Publications

Comparison of imaging biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging.

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