Brain iron load and neuroaxonal vulnerability in adult attention-deficit hyperactivity disorder

AIM Adult attention deficit hyperactivity disorder (ADHD) may be associated with an increased risk of dementia in old age. Here, we investigated the liability for neurodegenerative brain disease in adult ADHD, possibly reflected by increased brain iron content and associated neuroaxonal vulnerability. METHODS Thirty-two adults with ADHD (35 ± 10 years) and 29 age- and sex-matched controls (32 ± 12 years) underwent magnetic resonance imaging (MRI), standardized psychometric testing and assessment of lifestyle factors. Quantitative susceptibility mapping (QSM) was used to assess magnetic abnormalities indicating local alterations of iron deposition in the brain. By calculating QSM-maps, local iron deposition was tested for statistically significant differences between ADHD and healthy controls. Plasma neurofilament light chain (NfL) levels were measured as an indicator of neuroaxonal integrity by using a fourth-generation ELLA immunoassay. RESULTS Brain iron content differed in persons with ADHD, with strongest effects observable in the right precentral cortex (healthy controls: 0.0033 ± 0.0017ppm; ADHD: 0.0048 ± 0.0016ppm; t(59) = 3.56, P < 0.001). Moreover, right precentral cortex iron in persons with ADHD was associated with increased blood NfL levels (F(1.57) = 13.2, P = 0.001, r$^{2}$ = 0.19). CONCLUSION Our results indicate altered regional iron content in the brains of adults with ADHD. The observed association between increased precentral magnetic susceptibility and increased NfL suggests a connection between local excess of brain iron and neuroaxonal damage in ADHD. Given the limited sample size of the current study and the naturalistic medication plan, further longitudinal studies are needed to establish whether altered brain iron distribution in adults with ADHD may be associated with an increased risk of dementia at old age.