Longitudinal change in cortical thickness and hippocampal volume predicts cognitive decline

Abstract

AbstractBackgroundUsing biomarkers for early detection of Alzheimer disease (AD) is crucial for developing potential treatments. It has been hypothesized that longitudinal change in cortical thickness and hippocampal volume could be used to predict cognitive decline in individuals with AD. Here, using longitudinal MRI data, we evaluated whether changes in cortical thickness and hippocampal volume predicted changes in cognition, as measured by a battery of standardized tests.Method152 Participants (aged: 45‐86) who were enrolled in studies at the Knight ADRC at Washington University were included. Data was obtained through OASIS (www.oasis‐brains.org). Participants were classified as having normal cognition or early symptomatic AD, and were followed for 1‐8 years. Hippocampal volume was extracted, and cortical thickness measures were derived as an average of a set of FreeSurfer cortical regions (Figure 1). A random coefficient model was used to calculate longitudinal change in these biomarkers, and to assess whether these measures predict cognitive decline. Additional correlations between longitudinal changes in cognition and changes in cortical thickness, and hippocampal volume, were calculated using Spearman correlations.ResultWe found that longitudinal change in cortical thickness and hippocampal volume significantly predicted the rate of decline measured from a battery of standardized cognitive tasks (Figure 2). Furthermore, longitudinal changes in these structural biomarkers were strongly correlated with cognitive decline measured by the Logical Memory IIA‐Delayed (Figure 3).ConclusionLongitudinal changes in cortical thickness and hippocampal volume significantly predict cognitive decline on neuropsychological tests that address cognitive domains that are typically impacted by AD. To evaluate brain atrophy in a manner that could easily be examined in a clinical context, we did not limit the study to participants with known amyloid biomarker status. It has been postulated that once therapeutic agents for AD become available, we will have difficulty providing large scale screening tests in populations at risk due to limited availability of PET centers. As MRI is widely available, longitudinal volumetric MRI may potentially be used in the future to screen patients as a first step in a workup and evaluation for participation in clinical trials or, once approved, evaluation for therapy.