UC San Diego

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.