Dataset Information

Utility of Molecular and Structural Brain Imaging to Predict Progression from Mild Cognitive Impairment to Dementia.

ABSTRACT: This project compares three neuroimaging biomarkers to predict progression to dementia in subjects with mild cognitive impairment (MCI). Eighty-eight subjects with MCI and 40 healthy controls (HCs) were recruited. Subjects had a 3T magnetic resonance imaging (MRI) scan, and two positron emission tomography (PET) scans, one with Pittsburgh compound B ([11C]PIB) and one with fluorodeoxyglucose ([18F]FDG). MCI subjects were followed for up to 4 y and progression to dementia was assessed on an annual basis. MCI subjects had higher [11C]PIB binding potential (BPND) than HCs in multiple brain regions, and lower hippocampus volumes. [11C]PIB BPND, [18F]FDG standard uptake value ratio (SUVR), and hippocampus volume were associated with time to progression to dementia using a Cox proportional hazards model. [18F]FDG SUVR demonstrated the most statistically significant association with progression, followed by [11C]PIB BPND and then hippocampus volume. [11C]PIB BPND and [18F]FDG SUVR were independently predictive, suggesting that combining these measures is useful to increase accuracy in the prediction of progression to dementia. Hippocampus volume also had independent predictive properties to [11C]PIB BPND, but did not add predictive power when combined with the [18F]FDG SUVR data. This work suggests that PET imaging with both [11C]PIB and [18F]FDG may help to determine which MCI subjects are likely to progress to AD, possibly directing future treatment options.

SUBMITTER: Lan MJ

PROVIDER: S-EPMC5679746 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Utility of Molecular and Structural Brain Imaging to Predict Progression from Mild Cognitive Impairment to Dementia.

Lan Martin J MJ Ogden R Todd RT Kumar Dileep D Stern Yaakov Y Parsey Ramin V RV Pelton Gregory H GH Rubin-Falcone Harry H Pradhaban Gnanavalli G Zanderigo Francesca F Miller Jeffrey M JM Mann J John JJ Devanand D P DP

Journal of Alzheimer's disease : JAD 20170101 3

This project compares three neuroimaging biomarkers to predict progression to dementia in subjects with mild cognitive impairment (MCI). Eighty-eight subjects with MCI and 40 healthy controls (HCs) were recruited. Subjects had a 3T magnetic resonance imaging (MRI) scan, and two positron emission tomography (PET) scans, one with Pittsburgh compound B ([11C]PIB) and one with fluorodeoxyglucose ([18F]FDG). MCI subjects were followed for up to 4 y and progression to dementia was assessed on an annua ...[more]

PMID: 28984586

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Project description:BackgroundAmyloid pathology in subjects with mild cognitive impairment (MCI) is an important risk factor for progression to dementia due to Alzheimer's disease. Predicting the onset of dementia is challenging even in the presence of amyloid, as time to progression varies considerably among patients and depends on the onset of neurodegeneration. Survival analysis can account for variability in time to event, but has not often been applied to MRI measurements beyond singular predefined brain regions such as the hippocampus. Here we used a voxel-wise survival analysis to identify in an unbiased fashion brain regions where decreased gray matter volume is associated with time to dementia, and assessed the effects of amyloid on these associations.MethodsWe included 276 subjects with MCI (mean age 67?±?8, 41% female, mean Mini-Mental State Examination 26.6?±?2.4), baseline 3D T1-weighted structural MRI, baseline cerebrospinal fluid (CSF) biomarkers, and prospective clinical follow-up. We fitted for each voxel a proportional Cox hazards regression model to study whether decreased gray matter volume predicted progression to dementia in the total sample, and stratified for baseline amyloid status.ResultsDementia at follow-up occurred in 122 (44%) subjects over an average follow-up period of 2.5?±?1.5 years. Baseline amyloid positivity was associated with progression to dementia (hazard ratio 2.4, p?<?0.001). Within amyloid-positive subjects, decreased gray matter volume in the hippocampal, temporal, parietal, and frontal regions was associated with more rapid progression to dementia (median (interquartile range) hazard ratio across significant voxels 1.35 (1.32-1.40)). Repeating the analysis in amyloid-negative subjects revealed similar patterns (median (interquartile range) hazard ratio 1.76 (1.66-1.91)).ConclusionsIn subjects with MCI, both abnormal amyloid CSF and decreased gray matter volume were associated with future progression to dementia. The spatial pattern of decreased gray matter volume associated with progression to dementia was consistent for amyloid-positive and amyloid-negative subjects.

Project description:BackgroundMild cognitive impairment is often a precursor to dementia due to Alzheimer's disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment.ObjectiveTo develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings.Design and participants382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study.Main predictors measuresDemographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales.Main outcome measureProgression to probable Alzheimer's disease.Key resultsSubjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer's disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell's c-statistic was 0.71(95% CI: 0.68-0.75). Fourteen percent of subjects with low risk scores (0-2 points, n?=?124) converted to probable Alzheimer's disease over 3 years, compared to 51% of those with moderate risk scores (3-8 points, n?=?223) and 91% of those with high risk scores (9-16 points, n?=?35).ConclusionsAn index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer's disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression.

Project description:BACKGROUND:The previously described and validated Erlangen Score (ES) algorithm enables interpretation of the cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), ordering them on an ordinal scale: from neurochemically normal (ES?=?0) through improbable AD (ES?=?1), possible AD (ES?=?2 or 3), to probable AD (ES?=?4). Here we assess the accuracy of the ES in predicting hazards of progression from the mild cognitive impairment (MCI) stage of AD to the dementia stage of the disease (Alzheimer's disease dementia (ADD)) in a novel, single-center cohort. METHODS:Baseline CSF biomarkers (amyloid beta (A?) 1-42, A?42/40, Tau, and pTau181), interpreted according to the ES, were used to estimate time to progression from the MCI stage of AD to ADD, conditional on age, gender, APOE ?4 genotype, and Mini Mental State Examination score in 144 MCI subjects, using the Extended Cox Model; the subjects were followed-up until they developed dementia or until they had been cognitively stable for at least 2?years. In addition, ES distributions were studied in 168 ADD cases and 66 neurologic controls. Further, we stratified MCI patients into those who progressed to ADD faster (within 3 years, n?=?47) and those who progressed slower (n?=?74). RESULTS:The distributions of the ES categories across the four diagnostic groups (Controls, MCI-Stable, MCI-AD, and ADD) were highly significantly different (Kruskal-Wallis ?2(df?=?3)?=?151.4, p?<?0.001), with significant contrasts between each pair (p?<?0.005), except between the ADD and the MCI-AD groups (p?=?1.0). MCI patients with ES?=?2 or 3 had 6-8 times higher hazards to progress to ADD compared to patients with ES?=?0 or 1 in the first 3 follow-up years, and then their hazards decreased to those of the group with ES?=?0 or 1. Patients with ES?=?4 had hazards 8-12 times higher compared to the ES?=?0 or 1 group. Faster progressors with ES?=?2 or 3 had, in comparison to slower progressors, significantly lower A?1-42, A?1-40, and A?42/40, but comparable Tau and pTau181. A highly significant difference of the ES distributions between these two groups was observed (p?<?0.001). CONCLUSIONS:Our current results reconfirm and extend the conclusions of the previously published report that the Erlangen Score is a useful tool facilitating interpretation of a complex pattern of the CSF AD biomarkers.

Dataset Information

Utility of Molecular and Structural Brain Imaging to Predict Progression from Mild Cognitive Impairment to Dementia.

Publications

Utility of Molecular and Structural Brain Imaging to Predict Progression from Mild Cognitive Impairment to Dementia.

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