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A focus on structural brain imaging in the Alzheimer's disease neuroimaging initiative.

ABSTRACT: In recent years, numerous laboratories and consortia have used neuroimaging to evaluate the risk for and progression of Alzheimer's disease (AD). The Alzheimer's Disease Neuroimaging Initiative is a longitudinal, multicenter study that is evaluating a range of biomarkers for use in diagnosis of AD, prediction of patient outcomes, and clinical trials. These biomarkers include brain metrics derived from magnetic resonance imaging (MRI) and positron emission tomography scans as well as metrics derived from blood and cerebrospinal fluid. We focus on Alzheimer's Disease Neuroimaging Initiative studies published between 2011 and March 2013 for which structural MRI was a major outcome measure. Our main goal was to review key articles offering insights into progression of AD and the relationships of structural MRI measures to cognition and to other biomarkers in AD. In Supplement 1, we also discuss genetic and environmental risk factors for AD and exciting new analysis tools for the efficient evaluation of large-scale structural MRI data sets such as the Alzheimer's Disease Neuroimaging Initiative data.

SUBMITTER: Braskie MN

PROVIDER: S-EPMC4019004 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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A focus on structural brain imaging in the Alzheimer's disease neuroimaging initiative.

Braskie Meredith N MN Thompson Paul M PM

Biological psychiatry 20131128 7

In recent years, numerous laboratories and consortia have used neuroimaging to evaluate the risk for and progression of Alzheimer's disease (AD). The Alzheimer's Disease Neuroimaging Initiative is a longitudinal, multicenter study that is evaluating a range of biomarkers for use in diagnosis of AD, prediction of patient outcomes, and clinical trials. These biomarkers include brain metrics derived from magnetic resonance imaging (MRI) and positron emission tomography scans as well as metrics deri ...[more]

PMID: 24367935

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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

A focus on structural brain imaging in the Alzheimer's disease neuroimaging initiative.

Publications

A focus on structural brain imaging in the Alzheimer's disease neuroimaging initiative.

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