A special brain imaging technique could help predict if a person will develop dementia later in life, a new study has revealed. 

Scientists at Johns Hopkins University employed a novel MRI scanning method known as quantitative susceptibility mapping (QSM) to track iron levels in the brain over an extended period.

Alzheimer’s disease, which is the primary cause of dementia affecting 7 million Americans, is believed to result from the build-up of detrimental amyloid plaques and tau proteins. These substances interfere with brain cell operations and hinder neuron communication.

But scientists have begun to research how elevated levels of iron in the brain could impact cognition.  

Excessively high iron, referred to as ‘iron overload’, upsets the equilibrium between free radicals—damaging molecules—and antioxidants, which counteract them, thus worsening nerve cell damage.

While traditionally brain iron levels are assessed after death through tissue analysis, QSM allows researchers to measure this vital mineral non-invasively during the patient’s lifetime.

In their research, scientists evaluated QSM MRI data from 158 individuals without cognitive impairments, establishing initial iron level benchmarks for each. Over 7.7 years, they regularly updated these measurements.

Results indicated that higher initial brain iron levels, particularly in regions critical to memory and other cognitive functions, were linked to an increased risk of mild cognitive impairment as the participants aged.

Alzheimer’s disease, which affects more than 7million Americans, is caused by the abnormal build-up of proteins in and around brain cells. And previous research has linked abnormally high levels of iron in the brain (stock image) 

This is a transitional stage preceding Alzheimer’s disease-related dementia. 

The researchers say that their findings provide further evidence of QSM being a promising non-invasive diagnostic tool for Alzheimer’s Disease, detecting abnormal iron accumulation in the brain linked to disease progression before people start to show symptoms.

This will allow for earlier detection and targeted intervention for the disease.

There isn’t a single ‘normal’ brain iron level, as iron distribution varies across brain regions and increases with age, but typical ranges exist for specific areas.

Currently there is no cure for dementia or Alzheimer’s but the team behind the new study say that clinical trials could test iron-targeted therapies. 

Commenting on the findings, the study’s senior author and associate professor of radiology at Johns Hopkins University Dr Xu Li said: ‘QSM can detect small differences in iron levels across different brain regions, providing a reliable and non-invasive way to map and quantify iron in patients, which is not possible with conventional MR approaches.

‘Using QSM, we found higher brain iron in some memory related regions that are linked to a higher risk of developing cognitive impairment and faster cognitive decline.

‘We can use this kind of tool to help identify patients at higher risk of developing Alzheimer’s disease and potentially guide early interventions as new treatments become available.

‘Also, besides serving as a biomarker, brain iron may become a future therapeutic target.

‘At the same time, we hope to make the QSM technology more standardized, faster and more widely accessible in clinical practice.’

The findings were published in Radiology, a journal of the Radiological Society of North America (RSNA).

High levels of iron were first reported in the brains of people with Alzheimer’s disease in 1953 in a postmortem study.

Natalie Ive (pictured) was diagnosed with primary progressive aphasia, a type of frontotemporal dementia, in 2021 at age 48

Gemma Illingworth, from Manchester, was 28-years-old when she was diagnosed with a rare form of dementia called posterior cortical atrophy (PCA). She died three years later

Iron is a prevalent element in the human body and is needed for major biochemical processes such as oxygen transport and DNA synthesis.

The human body obtains iron through various foods, with red meat being one of the best sources, and it is absorbed through the small intestine.

It is important to maintain a delicate balance of iron in the brain; both deficiency and overload can be detrimental. 

Abnormal iron accumulation has been reported in numerous neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, and Multiple Sclerosis, but it’s unclear if increased iron deposition contributes to the development of these diseases or is a secondary effect or by-product.

Previous studies have identified that iron accumulation correlates with amyloid beta – the protein that clumps together in the brains of people with Alzheimer’s.

These clumps form ‘plaques’ that collect between neurons, otherwise known as nerve cells, and disrupt cell function. 

Associations have also been found between iron and neurofibrillary tangles – abnormal accumulations of a protein called tau that collect inside neurons.

These tangles block the neuron’s transport system, which harms the communication between neurons.

Brain maps of healthy control participants and participants with Alzheimer disease. Iron accumulation was associated with cognitive deterioration independently of brain volume loss. (Alzheimer’s disease is associated with higher rates of brain tissue loss than normal ageing.)

Alzheimer’s disease is the most common cause of dementia. The disease can cause anxiety, confusion and short-term memory loss

It is known that deep grey matter structures of patients with Alzheimer’s disease contain higher brain iron concentrations.

Grey matter of the brain is high in neural cell bodies and plays a major part in the central nervous system.

But less is known about the neocortex, the deeply grooved outer layer of the brain that is involved with language, conscious thought and other important functions.

Impaired iron stability for people with Alzheimer’s disease indicates that iron chelation therapy, giving patients drugs that rid the body of iron via urine, in clinical trials might be a promising treatment.