Cognitive performance modulates regional brain age differences in clinical anxiety and depression
Owen M Vega1, Phoebe Imms2, Nikhil N Chaudhari3
1Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90089, USA.
Journal of Affective Disorders
|July 9, 2026
Summary
Anxiety and depression are linked to advanced brain age (BA), but cognitive function explains some of this difference. Accounting for cognition changes how we interpret brain aging in mental health conditions.
Area of Science:
- Neuroimaging
- Cognitive Neuroscience
- Psychiatry
Background:
- Anxiety and depression correlate with advanced brain age (BA) and impaired cognition.
- The extent to which diagnostic status versus cognitive variability drives these brain aging differences is unclear.
Purpose of the Study:
- To investigate if cognitive performance explains regional brain age differences in individuals with anxiety and depression.
- To differentiate between diagnostic and cognitive contributions to brain aging.
Main Methods:
- Utilized UK Biobank data (N=21,424) with structural MRI for local brain age (LBA) estimation.
- Analyzed local LBA gap (LBAG) using multivariate testing and mixed-effects models, with and without adjustment for cognitive performance.
- Assessed global brain age gap (GBAG) and regional LBAG across diagnostic groups.
Main Results:
- Elevated GBAG observed in anxiety and depression, indicating a transdiagnostic pattern.
- Widespread regional LBAG elevations were found, reduced by ~20-25% after adjusting for cognitive performance.
- Higher cognitive performance was associated with lower LBAG, particularly in psychiatric groups.
Conclusions:
- Brain aging differences in anxiety and depression are partly attributable to cognitive variability, not solely diagnosis.
- Adjusting for cognition significantly alters the interpretation of brain aging effects in neuropsychiatric populations.
- Integrating cognitive measures is crucial for accurate brain aging models in psychiatric research.
More Related Videos
Related Concept Videos
01:30Cognitive Development During Adulthood
Cognitive development continues throughout adulthood, undergoing significant shifts across early, middle, and late stages. Individual transition occurs from adolescent idealism to pragmatic and adaptable thinking in early adulthood. During this period, individuals learn to integrate personal beliefs with the recognition that other perspectives are equally valid. Exposure to the complexities of modern society, diverse experiences, and higher education contribute to this adaptive thought process,...
01:29The Influence of Cognition on Affect
Cognition plays a pivotal role in shaping emotional experiences, as demonstrated by Schachter and Singer’s two-factor theory of emotion. According to this model, emotion arises from a combination of physiological arousal and cognitive interpretation. The body’s physiological response to stimuli is ambiguous and only gains emotional significance through cognitive labeling. For instance, an increased heart rate and adrenaline surge while standing near an attractive person may be interpreted as...
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function. They...