Diversity in verbal fluency performance and its associations with MRI-informed brain age matrices in normal ageing and neurocognitive disorders

Introduction: Category verbal fluency test (CVFT) has been widely used to assess and monitor the cognitive capacities in epidemiological studies and clinical trials. Pronounced discrepancy in CVFT performance has been found in individuals with different cognitive statuses. This study aimed to combine the psychometric and morphometric approaches to decode the complex verbal fluency performance in senior adults with normal ageing and neurocognitive disorders.Methods: This study adopted a two-stage cross-sectional design involving quantitative analyses of neuropsychological and neuroimaging data. In study I, capacity- and speed-based measures of CVFT were developed to evaluate the verbal fluency performance in normal ageing seniors (n = 261), those with mild cognitive impairment (n = 204), and those with dementia (n = 23) whose age range is from 65 to 85 years. In study II, structural magnetic resonance imaging-informed gray matter volume (GMV) and brain age matrices were calculated in a subsample (n = 52) from Study I through surface-based morphometry analysis. With age and gender as covariates, Pearson's correlation analysis was used to examine the associations of CVFT measures, GMV, and brain age matrices.Results: Speed-based measures showed extensive and stronger associations with other cognitive functions than capacity-based measures. The component-specific CVFT measures showed shared and unique neural underpinnings with lateralized morphometric features. Moreover, the increased CVFT capacity was significantly correlated with younger brain age in mild neurocognitive disorder (NCD) patients.Conclusion: We found that the diversity of verbal fluency performance in normal ageing and NCD patients could be explained by a combination of memory, language, and executive abilities. The component-specific measures and related lateralized morphometric correlates also highlight the underlying theoretical meaning of verbal fluency performance and its clinical utility in detecting and tracing the cognitive trajectory in individuals with accelerated ageing.