Combined Biomarker Prognosis of Mild Cognitive Impairment: An 11-Year Follow-Up Study in the Alzheimer's Disease Neuroimaging Initiative - PubMed (original) (raw)
Combined Biomarker Prognosis of Mild Cognitive Impairment: An 11-Year Follow-Up Study in the Alzheimer's Disease Neuroimaging Initiative
Barbara E Spencer et al. J Alzheimers Dis. 2019.
Abstract
Background: Biomarkers may soon be used to predict decline in older individuals. Extended follow-up studies are needed to determine the stability of such biomarker-based predictions.
Objective: To examine the long-term performance of baseline cognitive, neuroimaging, and cerebrospinal fluid (CSF) biomarker-assisted prognosis in patients with mild cognitive impairment.
Methods: Established, biomarker-defined, cohorts of subjects with mild cognitive impairment were examined for progression to dementia. Subjects with a baseline volumetric MRI, lumbar puncture, and Rey Auditory Verbal Learning Test were included. Dementia-free survival time in each biomarker-defined risk group was determined with Kaplan-Meier survival curves. The influence of each risk factor or combination of factors on dementia-free survival was examined with Cox proportional hazard analyses.
Results: 185 subjects were followed longitudinally for a mean (SD) 4.3 (2.8) years. 59% of participants converted within the follow-up period and the median dementia-free survival time was 2.8 years. Each individual risk factor predicted conversion to dementia (HR 1.9-3.7). The joint presence of any two risk factors increased risk for conversion (HR 7.1-11.0), with the presence of medial temporal atrophy and memory impairment showing the greatest risk for decline. Concordant atrophy, memory impairment, and abnormal CSF amyloid and tau was associated with the highest risk for conversion (HR 15.1). The presence of medial temporal atrophy was associated with the shortest dementia-free survival time, both alone and in combination with memory impairment, abnormal CSF amyloid and tau, or both.
Conclusion: These results suggest that baseline biomarker-assisted predictions of decline to dementia are stable over the long term, and that combinations of complementary biomarkers can improve the accuracy of these predictions.
Keywords: Biomarkers; cerebrospinal fluid; dementia; magnetic resonance imaging; mild cognitive impairment; prognosis; rey auditory verbal learning test.
Conflict of interest statement
CONFLICT OF INTEREST/DISCLOSURE STATEMENT
Dr. Brewer has served on advisory boards for Elan, Bristol-Myers Squibb, Avanir, Novartis, Genentech, and Eli Lilly and holds stock options in CorTechs Labs, Inc. and Human Longevity, Inc. Mss. Spencer and Jennings have no conflict of interest to report.
Figures
Figure 1.. Kaplan-Meier survival curves for each individual risk factor.
Kaplan-Meier survival curves, which estimate the probability that a subject will remain dementia free at a given time, are displayed for the entire cohort and stratified by positive (red) or negative (blue) risk for each individual risk factor. The y-axis shows the proportion of stable subjects. The x-axis shows time in years. Vertical drops indicate conversion. Tick marks indicate censoring. Shading represents 95% confidence intervals. Only subjects who have not yet converted or dropped out are considered at risk at a given time point. Abbreviations: AVLT, sum of scores from the 5 immediate learning trials of the Rey Auditory Verbal Learning Test; HOC, hippocampal occupancy score; HC % ICV, hippocampal volume as a percent of intracranial volume.
Figure 2.. Kaplan-Meier survival curves stratified by risk factor combinations.
Kaplan-Meier survival curves estimate the probability that a subject will remain dementia free at a given time. The y-axis shows the proportion of stable subjects. The x-axis shows time in years. Vertical drops indicate conversion. Tick marks indicate censoring. Shading represents 95% confidence intervals. Only subjects who have not yet converted or dropped out are considered at risk at a given time point. Abbreviations: AVLT, sum of scores from the 5 immediate learning trials of the Rey Auditory Verbal Learning Test; HOC, hippocampal occupancy score.
Figure 3.. Median dementia-free survival time stratified by individual risk factors and risk factor combinations.
Positive risk factors are displayed in red; negative risk factors are displayed in blue. All combinations represent concordant positive or negative risk. The x-axis shows time in years. Error bars represent 95% confidence intervals. Due to high survival, three groups (– Aβ; –HOC, AVLT, and t-tau/Aβ ratio; – HOC – t-tau/Aβ ratio) never reached a median dementia-free survival time, and in several groups the upper limit of the 95% confidence interval was undefined past the last timepoint of 11.5 years. Stars represent such undefined estimates past the study completion. Abbreviations: AVLT, sum of scores from the 5 immediate learning trials of the Rey Auditory Verbal Learning Test; HOC, hippocampal occupancy score; HC % ICV, hippocampal volume as a percent of intracranial volume.
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