Regional rates of neocortical atrophy from normal aging to early Alzheimer disease

Abstract

Objective: To evaluate the spatial pattern and regional rates of neocortical atrophy from normal aging to early Alzheimer disease (AD).

Methods: Longitudinal MRI data were analyzed using high-throughput image analysis procedures for 472 individuals diagnosed as normal, mild cognitive impairment (MCI), or AD. Participants were divided into 4 groups based on Clinical Dementia Rating Sum of Boxes score (CDR-SB). Annual atrophy rates were derived by calculating percent cortical volume loss between baseline and 12-month scans. Repeated-measures analyses of covariance were used to evaluate group differences in atrophy rates across regions as a function of impairment. Planned comparisons were used to evaluate the change in atrophy rates across levels of disease severity.

Results: In patients with MCI-CDR-SB 0.5-1, annual atrophy rates were greatest in medial temporal, middle and inferior lateral temporal, inferior parietal, and posterior cingulate. With increased impairment (MCI-CDR-SB 1.5-2.5), atrophy spread to parietal, frontal, and lateral occipital cortex, followed by anterior cingulate cortex. Analysis of regional trajectories revealed increasing rates of atrophy across all neocortical regions with clinical impairment. However, increases in atrophy rates were greater in early disease within medial temporal cortex, whereas increases in atrophy rates were greater at later stages in prefrontal, parietal, posterior temporal, parietal, and cingulate cortex.

Conclusions: Atrophy is not uniform across regions, nor does it follow a linear trajectory. Knowledge of the spatial pattern and rate of decline across the spectrum from normal aging to Alzheimer disease can provide valuable information for detecting early disease and monitoring treatment effects at different stages of disease progression.

Figure 1 Annual atrophy rates as a function of degree of clinical impairment Annual atrophy rates as a function of degree of clinical impairment (i.e., baseline Clinical Dementia Rating Sum of Boxes score [CDR-SB]). Mean atrophy rates are represented as a percent change in neocortical volume and mapped onto the lateral (left), ventral (middle), and medial (right) pial surface of the left hemisphere. These data demonstrate that atrophy rates are most prominent in posterior brain regions early in the course of disease, spreading to anterior regions as the level of impairment increases, with relative sparing of sensorimotor regions. MCI = mild cognitive impairment; AD = Alzheimer disease.

Figure 2 Annual neocortical atrophy rates in regions of interest Graphs depicting annual neocortical atrophy rates (percent volume change) in regions of interest in the normal control, mild cognitive impairment (MCI)–Clinical Dementia Rating Sum of Boxes score (CDR-SB) 0.5–1, MCI–CDR-SB 1.5–2.5, and early Alzheimer disease (AD) groups.

Figure 3 Cortical surface maps representing the mean difference in atrophy rates early vs later in the course of disease Cortical surface maps representing the mean difference in atrophy rates early (mild cognitive impairment [MCI]–Clinical Dementia Rating Sum of Boxes score [CDR-SB] 0.5–1 − normal) vs later (early Alzheimer disease [AD] − MCI–CDR-SB 1.5–2.5) in the course of disease projected onto the left pial surface. Positive values (red) represent cortical regions showing early > late increases in atrophy rates (i.e., areas in which the difference in atrophy rates between controls and patients with MCI–CDR-SB 0.5–1 was greater than that between patients with MCI–CDR-SB 1.5–2.5 and early AD), whereas negative values (blue) represent cortical areas showing late > early increases in atrophy rates (i.e., areas in which the difference in atrophy rates between patients with MCI–CDR-SB 1.5–2.5 and early AD exceeded that between controls and patients with MCI–CDR-SB 0.5–1). Areas showing no difference in atrophy rates at the early vs later stage of disease, whether due to minimal atrophy or to a constant rate of atrophy across disease stages, do not appear in color on the maps.