The imaging-based method of brainAGE aims to characterize an individual's vulnerability to age-related brain changes. The present study systematically reviewed brainAGE findings in neuropsychiatric conditions and discussed the potential of brainAGE as a marker for biological age. A systematic PubMed search (from inception to March 6th, 2023) identified 273 articles. The 30 included studies compared brainAGE between neuropsychiatric and healthy groups (n≥50). We presented results qualitatively and adapted a bias risk assessment questionnaire. The imaging modalities, design, and input features varied considerably between studies. While the studies found higher brainAGE in neuropsychiatric conditions (11 mild cognitive impairment/ dementia, 11 schizophrenia spectrum/ other psychotic and bipolar disorder, six depression/ anxiety, two multiple groups), the associations with clinical characteristics were mixed. While brainAGE is sensitive to group differences, limitations include the lack of diverse training samples, multi-modal studies, and external validation. Only a few studies obtained longitudinal data, and all have used algorithms built solely to predict chronological age. These limitations impede the validity of brainAGE as a biological age marker.

Original languageEnglish
Article number105581
JournalNeuroscience and Biobehavioral Reviews
StatePublished - Apr 2024


  • Anxiety
  • Biological age
  • Bipolar disorder
  • Dementia
  • Depression
  • Machine-learning
  • Neurodegeneration
  • Neuroimaging
  • Neuropsychiatric disorders
  • Paradox of biomarkers
  • Prediction
  • Schizophrenia
  • Serious mental illness


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