Patients with Alzheimer disease (AD) exhibited accelerated asymmetric thinning of the cerebral cortex, according results of a study published in Nature Communications.

Magnetic resonance imaging (MRI) data were acquired from multiple lifespan longitudinal studies which were combined to form discovery, replication, and AD cohorts. The discovery cohort included 2577 scans from 1084 healthy adults sourced from the Lifespan Changes in Brain and Cognition (LCBC) database. The replication cohort consisted of pooled data from 4 studies (Cambridge Centre for Ageing and Neuroscience [Cam-CAN], Berlin Aging Study II [BASE-II], BETULA, and Dallas Lifespan Brain Study [DLBS]) which featured 2909 scans from 1862 adults. The AD cohort came from the Australia Imaging Biomarkers and Lifestyle Study of Aging (AIBL) study which had 545 scans from 169 patients with AD. MRI scans were assessed for longitudinal asymmetrical changes and cognitive decline was assessed by the California Verbal Learning Test and the Matrix Reasoning subtest.

From the discovery cohort, the investigators derived patterns of age-related thinning in prefrontal, anterior/middle temporal, lateral parietal, and insular cortex brain regions. These asymmetrical regions clustered into 3 groups (mean silhouette width, 0.46). Cluster 1 included leftward loss in dorsolateral frontal, medial, orbitofrontal, and anterior temporal cortexes. Cluster 2 had a mixed loss of weaker effects. Cluster 3 had rightward loss in the lateral temporal, insular cortex, and caudal anterior cingulate regions.

These patterns of age-related thinning were validated with the replication cohort. As compared with random (0.1), 3 of the cohort components replicated these findings (Cam-CAN: 0.54; BASE-II: 0.56; BETULA: 0.50; P <.001), and the DLBS data partially confirmed these patterns (0.41).

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Among the discovery and validation cohorts, the patterns of brain region thinning did not significantly associate with cognitive decline (verbal memory: P =.86; fluid reasoning: P =.84).

The AD cohort had comparatively more leftward asymmetry in anterior temporal cortex and frontal cortical regions. These asymmetries indicated patients with AD exhibited accelerated changes occurring among healthy adults.

These findings were potentially biased by the fact that cortical myelination could affect estimation of cortical thickness. These differential patterns may have included some anatomically important differences of myelination in addition to cortical thicknesses.

These data indicated patients with AD had accelerated asymmetrical cortical thinning with aging compared with healthy adults. These changes may be responsible, at least in part, for the decline of higher-order cognition among patients with AD.


Roe JM, Vidal-Piñeiro D, Sørensen Ø, et al. Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s disease. Nat Commun. 2021;12(1):721. doi:10.1038/s41467-021-21057-y