A special brain imaging technique could help predict if a person will develop dementia later in life, a new study has revealed.
Researchers from Johns Hopkins University used a special MRI technique called quantitative susceptibility mapping (QSM) in a long-term investigation to measure levels of iron in the brain.
Alzheimer’s disease, the leading cause of dementia that affects 7million Americans, is thought to be caused by the accumulation of harmful amyloid plaque and tau proteins, which disrupt brain cell function and obstruct communication between neurons.
But scientists have begun to research how elevated levels of iron in the brain could impact cognition.
‘Iron overload,’ or extremely high levels of the mineral, disrupt the balance of free radicals – harmful molecules in the body – and antioxidants – substances that fight free radicals. This exacerbates nerve cell death.
Iron levels are typically measured in the brain post-mortem by analyzing brain tissue samples, but QSM allows scientists to measure the mineral non-invasively while a patient is still alive.
In the study, researchers looked at QSM MRI data from 158 cognitively unimpaired patients and established baseline readings for iron for each subject. Then, the scientists followed participants for 7.7 years, collecting updated readings throughout.
Findings revealed that higher levels of brain iron in the initial readings, especially in the brain regions important to memory and other cognitive function, were linked to an increased risk of mild cognitive impairment later in life.
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.
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