BrainAGE, brain health, and mental disorders: A systematic review

Neurosci Biobehav Rev. 2024 Apr:159:105581. doi: 10.1016/j.neubiorev.2024.105581. Epub 2024 Feb 13.

Abstract

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.

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

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Aging / physiology
  • Brain* / diagnostic imaging
  • Brain* / physiopathology
  • Humans
  • Mental Disorders* / physiopathology
  • Neuroimaging