MRI predictors of cognitive change in a diverse and carefully characterized elderly population

Abstract

Background: Trajectories of cognitive decline among elderly individuals are heterogeneous, and markers that have high reliability for predicting cognitive trajectories across a broad spectrum of the elderly population have yet to be identified.

Method: This study examined the utility of a variety of MRI-based brain measures, obtained at baseline, as predictors of subsequent declines in domain-specific measures of cognitive function in a cohort of 307 community-dwelling elderly individuals with varying degrees of cognitive impairment who were diverse across several relevant demographic variables and were evaluated yearly. Psychometrically matched measures of cognition were used to assess episodic memory, semantic memory, and executive function. Relationships between baseline MRI measures, including the volumes of the brain, hippocampus, and white matter hyperintensities (WMH), and cognitive trajectories were assessed in mixed effects regression models that modeled MRI effects on cognitive performance at baseline and rate of change as well as interindividual variability in cognitive baseline and rate of change.

Results: Greater baseline brain volume predicted slower subsequent rate of decline in episodic memory and smaller WMH volume predicted slower subsequent rate of decline in executive function and semantic memory. Baseline hippocampal volume, while strongly related to baseline cognitive function, was not predictive of subsequent change in any of the cognitive domains.

Conclusions: Baseline measures of brain structure and tissue pathology predicted rate of cognitive decline in a diverse and carefully characterized cohort, suggesting that they may provide summary measures of pre-existing neuropathological damage or the capacity of the brain to compensate for the impact of subsequent neuropathology on cognition. Conventional MRI measures may have use for predicting cognitive outcomes in highly heterogeneous elderly populations.

Figure 1

Example longitudinal trajectory of episodic memory, and the effect of brain volume in modifying that trajectory. Each line represents the estimated cognitive trajectory for a Hispanic female with mean educational attainment (12.6 years), mean WMH (9.10 cm³), and mean HC (3.62 cm³). The three lines per plot represent the estimated trajectories of an individual that exhibits these characteristics along with differing levels of BV: the population mean, the mean plus one standard deviation, and the mean minus one standard deviation. The episodic memory score is scaled as a z-score; the mean value over the entire population is 0 and a one-unit difference represents a difference of one standard deviation.

Figure 2

Example longitudinal trajectories of executive function and semantic memory, and the effect of WMH volume in modifying those trajectories. Each line represents the estimated cognitive trajectory for a hispanic female with mean educational attainment (12.6 years), mean BV (919.1 cm³), and mean HC (3.62 cm³). The three lines per plot represent the estimated trajectories of an individual that exhibits these characteristics along with differing levels of BV: the population mean, the mean plus one standard deviation, and the mean minus one standard deviation. The executive function and semantic memory scores are scaled as z-scores; the mean of these measures over the entire population is 0 and a one-unit difference represents a difference of one standard deviation.

Figure 3

Characteristic slices from MRI scans of individuals who had the minimum, median, and maximum values of left hippocampal volume, WMH volume, and brain volume. The left hippocampus is annotated by a red-to-white overlay on sagittal slices of T1-weighted images, and WMHs are annotated by a white overlay on axial slices of FLAIR images. Note that in the statistical analysis, brain and hippocampal volume were adjusted to account for inter-individual differences in intracranial volume.

Figure 4

Episodic memory measurements and model-predicted linear episodic memory trajectories for 81 randomly-selected subjects. Each cell plots the real episodic memory measurements for a single subject as a function of time using circles; each line represents the predicted trajectory of episodic memory for the individual based on the mixed effects statistical model with demographic and MRI predictors.