Integrity in six key brain regions predicts numeric working memory performance in 30,000 middle-aged and older adults: A UK Biobank magnetic resonance imaging study.

Objective: This study investigated the neuroanatomical correlates of working memory using the UK Biobank Numeric Memory Test (NMT; a visual backward digit-span task) in a large sample of middle-aged and older adults.Volumes of brain regions previously implicated in digit-span tasks were hypothesized to positively correlate with NMT performance; however, some differences were expected due to visual NMT format (e.g., reduced relevance for language regions).A secondary aim was to generate the first normative data set for the NMT.Method: As part of the UK Biobank study, 30,640 healthy adults aged 51-80 completed both NMT and brain magnetic resonance imaging.Linear fixed-effects modeling assessed whether brain volumes (25 regions of interest) could predict NMT performance after accounting for age, sex, education, and head size.Normative data were generated as percentile tables stratified by age/sex/education.Results: Linear fixed-effects modeling revealed that better NMT performance was predicted by larger volumes of total cerebellar cortex, bilateral superior temporal, bilateral insula, left inferior parietal, left hippocampus, and left lateral occipital ( p range: <.001-.048),with a moderate effect size ( f 2 = 0.072).Both linear fixed-effects and normative data revealed that NMT performance decreases with age but increases with education (both p < .001),with no discernible sex differences.Conclusions: The findings support the idea that greater neurostructural integrity correlates with better cognitive performance.While future multimodal longitudinal studies are needed to confirm structure-function associations and more diverse ethnic/socioeconomic groups are needed to improve generalizability, these findings could inform clinical decision making and targeted treatment for working memory dysfunction. Key PointsQuestion: Which brain regions are related to numeric working memory performance in a large sample of >30,000 middle-aged and older adults from the UK Biobank?Findings: Greater integrity (larger volume) in six key brain regions (cerebellum, superior temporal, insula, inferior parietal, hippocampus, lateral occipital) predicted better numeric working memory performance after controlling for the effect of age, sex, education, and head size.Importance: These findings deepen understanding of brainbehavior associations for numeric working memory function, with the identified regions potentially informing targeted treatment to enhance performance for cognitive decline, which may occur in healthy aging, disorder, and disease.Next Steps: Future studies should aim to follow participants over time to investigate the effects of age-related brain changes on numeric working memory performance, ideally using multimodal brain techniques to increase holistic understanding, and more diverse participants (e.g., lower socioeconomic/minority ethnic groups) to improve generalizability.