Regional cortical network atrophy predicts progression to dementia in the Lewy body diseases

Abstract

Introduction: The timeline from symptom onset to the loss of independent functioning varies across patients with Lewy body disease (LBD). Here, we investigate whether the magnitude of cortical atrophy within functional networks that subserve cognitive and affective functions has utility in predicting progression to dementia in LBD.

Methods: Forty-six LBD patients with intact instrumental and basic activities of daily living at baseline underwent brain magnetic resonance imaging scans and longitudinal clinical assessments. Cortical atrophy was estimated in LBD patients relative to an amyloid-negative control group.

Results: Multivariate Cox regression analysis demonstrated that atrophy in the affective salience and limbic networks, but not in cognitive, motor, or visual networks, predicted progression to dementia after controlling for disease duration, diagnosis, amyloid beta status, and baseline cognitive severity.

Discussion: Baseline atrophy in the salience and limbic networks is an important predictor of progression to dementia and may have value in identifying early-stage LBD patients at risk for faster progression.

Highlights: In this longitudinal study of the Massachusetts Alzheimer's Disease Research Center's Memory and Aging Cohort, although the magnitude of cortical atrophy in the early stages of Lewy body disease (LBD) was highly variable at the individual level, atrophy in the salience-limbic network predicted progression to dementia in LBD. In the early stages of LBD, each one standard deviation increase in salience-limbic atrophy doubled the risk of dementia. These findings were robust to adjustment for disease duration, diagnosis, amyloid beta status, and baseline cognitive severity.

Keywords: Lewy body disease; Parkinson's disease; brain network atrophy; dementia; longitudinal; mild cognitive impairment with Lewy bodies.

FIGURE 1

Brain networks of interest. The visual, somatomotor, dorsal attention, ventral attention (largely overlapping with the salience network), limbic, and frontoparietal networks are defined by the Yeo atlas. The somatosensory region extracted from the Glasser atlas served as a control region.

FIGURE 2

Spatial topography of cortical atrophy in the Lewy body diseases. (A) Cortical network atrophy scores (inverted W‐scores) are displayed at each vertex on the cortical surface maps. Higher atrophy scores indicate greater atrophy at baseline in patients with Lewy body disease relative to amyloid‐negative cognitively normal controls. (B) Bar graph indicates the percentage of all vertices showing atrophy scores above 0.5 at the group level falling within the boundaries of each functional network of interest.

FIGURE 3

Hazard ratios from univariate Cox regression analyses to predict time of progression to dementia in Lewy body disease. (See Figure 1 for a description of networks.)

FIGURE 4

Latent network factors identified by factor analysis of atrophy scores in seven functional brain networks. Factor analysis identified three uncorrelated latent factors in the dataset: (1) the visual‐motor‐DAN factor, (2) the DMN‐FPN factor, and (3) the salience–limbic factor. These three factors jointly explained 84.1% of the total variance. DAN, dorsal attention network; DMN‐FPN, default mode network–frontoparietal network.

FIGURE 5

Predictive value of atrophy in the salience–limbic networks for progression to dementia in Lewy body disease. Multivariate Cox regression model controlling for disease duration, clinical diagnosis, amyloid positivity, and baseline cognitive severity. Individuals with baseline cortical thickness in this network more than one standard deviation below controls are those at highest risk, as indicated with the red line.