Affiliations: [a] Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
| [b] Department of Radiology, University of California, San Diego, La Jolla, CA, USA
Correspondence:
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Correspondence to: James B. Brewer, MD, PhD, 9500 Gilman Drive, Mail Code 0949, La Jolla, CA 92093, USA. Tel.: +1 858 534 1237; E-mail: [email protected].
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
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 prognoses 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 magnetic resonance imaging, 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
