Iron in The Brain Might Help Explain Curious Link Between ADHD And Dementia

Older adults with ADHD are at higher risk of age-related dementias like Alzheimer's disease, and an international team of neuroscientists has found a lead on why this might be the case.

Led by medical physicist Jatta Berberat from the University of Geneva, the team has discovered that iron is distributed similarly in the brains of people with these associated disorders, which may help to explain the link.

There's good evidence that as the human brain ages, it continuously accumulates iron, in both the neocortex (which accounts for about 90 percent of our cerebral cortex) and in the quarter of our brain that sits below the cortex, including the hippocampus, the cerebellum, the amygdala and the basal ganglia.

"Excess iron in certain regions of the brain is often observed [in neurodegenerative diseases] and is associated with increased oxidative stress that furthers neuronal degeneration," explains psychiatrist Paul Unschuld from Geneva University Hospitals.

When iron levels build up in these regions, cognitive performance drops. Quite a few studies have found people with neurodegenerative diseases, including Huntington's, Parkinson's, and Alzheimer's, have noticeably high levels of brain iron, which, because of its magnetic properties, can quite easily be detected by MRI scanners.

The team used this technique to map the layout of accumulated iron in the brains of 32 adults with ADHD, and 29 others without the condition.

The team also took blood samples to measure neurofilament light chain protein (NfL) levels, a protein released when axons are damaged or degenerate. At high levels in blood, NfL indicates damage to the neuronal axons that carry information to neighbouring nerves, and is a potential biomarker for dementia.

Finally, study participants answered questions related to ADHD symptoms and lifestyle factors.

Each facet of this small study was designed to pick up on patterns that may distinguish an ADHD brain by its iron, and look for an association with neuronal axon damage signifying neurodegeneration to indicate whether scientists should pursue this track further.

The MRI-based maps suggest this is no dead end. Participants with ADHD had a distinct distribution of brain iron, with particularly elevated levels in the precentral cortex and a number of other regions. The iron landscape of ADHD brains was different enough from the non-ADHD group to be considered significant.

The researchers also found a significant association between raised iron levels in the precentral cortex of ADHD participants, and NfL levels in their blood. This could mean a build-up of brain iron deposits is creating a communication break-down in the area of the brain responsible for pulling the strings on the rest of the body.

Of the ADHD participants, 19 were taking regular medication for the condition, either methylphenidate (Ritalin) or dexamphetamine.

Some scientists suspect long-term use of psychostimulant medications like these could be behind the ADHD dementia link, because recreational stimulant drugs like MDMA and cocaine are known to affect brain iron levels. Other studies suggest ADHD medication may normalize brain iron in people with ADHD, but long-term effects remain unclear.

Unfortunately, this particular study is too small (and was not designed) to tell us if ADHD medications are actively involved in the tangle of associations, or if they're just innocent bystanders trying to help.

Nonetheless, Unschuld hopes the findings will lead to targeted dementia risk reduction strategies for people diagnosed with ADHD later in life.

"This is especially important since there is a well-known correlation between lifestyle and altered iron levels in the brain," he says.

"To achieve this, additional longitudinal studies are required in order to determine if a reduction of iron levels in the brain is a potential treatment pathway for preventing dementia at an advanced age in persons with ADHD."

This research was published in Psychiatry and Clinical Neurosciences.