Alzheimer’s disease has proven to be a difficult enemy to defeat. After all, ageing is the No. 1 risk factor for the disorder, and there’s no stopping that. Most researchers believe the disease is caused by one of two proteins, one called tau, the other beta-amyloid. As we age, most scientists say, these proteins either disrupt signalling between neurons or simply kill them.
Now, a new UCLA study suggests a third possible cause: iron accumulation. Dr. George Bartzokis, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and senior author of the study, and his colleagues looked at two areas of the brain in patients with Alzheimer’s. They compared the hippocampus, which is known to be damaged early in the disease, and the thalamus, an area that is generally not affected until the late stages. Using sophisticated brain-imaging techniques, they found that iron is increased in the hippocampus and is associated with tissue damage in that area. But increased iron was not found in the thalamus.
While most Alzheimer’s researchers focus on the build-up of tau or beta-amyloid that results in the signature plaques associated with the disease, Bartzokis has long argued that the breakdown begins much further ‘upstream.’ The destruction of myelin, the fatty tissue that coats nerve fibres in the brain, he says, disrupts communication between neurons and promotes the build-up of the plaques. These amyloid plaques in turn destroy more and more myelin, disrupting brain signalling and leading to cell death and the classic clinical signs of Alzheimer’s.
Myelin is produced by cells called oligodendrocytes. These cells, along with myelin, have the highest levels of iron of any cells in the brain, Bartzokis says, and circumstantial evidence has long supported the possibility that brain iron levels might be a risk factor for age-related diseases like Alzheimer’s. Although iron is essential for cell function, too much of it can promote oxidative damage, to which the brain is especially vulnerable.
In the current study, Bartzokis and his colleagues tested their hypothesis that elevated tissue iron caused the tissue breakdown associated with Alzheimer’s disease. They targeted the vulnerable hippocampus, a key area of the brain involved in the formation of memories, and compared it to the thalamus, which is relatively spared by Alzheimer’s until the very late stages of disease.
The researchers used an MRI technique that can measure the amount of brain iron in ferritin, a protein that stores iron, in 31 patients with Alzheimer’s and 68 healthy control subjects.
In the presence of diseases like Alzheimer’s, as the structure of cells breaks down, the amount of water increases in the brain, which can mask the detection of iron, according to Bartzokis.
‘It is difficult to measure iron in tissue when the tissue is already damaged,’ he said. ‘But the MRI technology we used in this study allowed us to determine that the increase in iron is occurring together with the tissue damage. We found that the amount of iron is increased in the hippocampus and is associated with tissue damage in patients with Alzheimer’s but not in the healthy older individuals — or in the thalamus. So the results suggest that iron accumulation may indeed contribute to the cause of Alzheimer’s disease.’
But it’s not all bad news from this study, Bartzokis noted.
‘The accumulation of iron in the brain may be influenced by modifying environmental factors, such as how much red meat and iron dietary supplements we consume and, in women, having hysterectomies before menopause,’ he said.
In addition, he noted, medications that chelate and remove iron from tissue are being developed by several pharmaceutical companies as treatments for the disorder. This MRI technology may allow doctors to determine who is most in need of such treatments. University of California – Los Angeles

One night when she was trying to fall asleep, a 60-year-old woman suddenly began hearing music, as if a radio were playing at the back of her head.

The songs were popular tunes her husband recognised when she sang or hummed them. But she herself could not identify them.

This is the first known case of a patient hallucinating music that was familiar to people around her, but that she herself did not recognise, according to Dr. Danilo Vitorovic and Dr. José Biller of Loyola University Medical Center.

The case raises ‘intriguing questions regarding memory, forgetting and access to lost memories,’ the authors write.

Musical hallucinations are a form of auditory hallucinations, in which patients hear songs, instrumental music or tunes, even though no such music is actually playing. Most patients realise they are hallucinating, and find the music intrusive and occasionally unpleasant. There is no cure.

Musical hallucinations usually occur in older people. Several conditions are possible causes or predisposing factors, including hearing impairment, brain damage, epilepsy, intoxications and psychiatric disorders such as depression, schizophrenia and obsessive-compulsive disorder. Hearing impairment is the most common predisposing condition, but is not by itself sufficient to cause hallucinations.

Vitorovic and Biller describe a hearing-impaired patient who initially hallucinated music when she was trying to fall asleep. Within four months, she was hearing music all the time. For example, she would hear one song over and over for three weeks, then another song would begin playing. The volume never changed, and she was able to hear and follow conversations while hallucinating the music.

The patient was treated with carbamazepine, an anti-seizure drug, and experienced some improvement in her symptoms.

The unique feature of the patient was her ability to hum parts of some tunes and recall bits of lyrics from some songs that she did not even recognise. This raises the possibility that the songs were buried in her memory, but she could not access them except when she was hallucinating.

‘Further research is necessary on the mechanisms of forgetfulness,’ Vitorovic and Biller write. ‘In other words, is forgotten information lost, or just not accessible?’

Vitorovic is a former chief neurology resident and Biller is a professor and chair in the Department of Neurology of Loyola University Chicago Stritch School of Medicine. Loyola University Health System

A new way of screening for ovarian cancer is showing ‘potential’, according to researchers in the US. Tumours in the ovaries are hard to detect in the earliest stages meaning it can be too late to treat them effectively by the time they are found. A trial of 4,051 women showed the method could identify those needing treatment. But a huge study taking place in the UK will give a final verdict on the test when it is completed in 2015.
There is a survival rate of up to 90% when ovarian cancer is caught early, compared with less than 30% if it is discovered in the later stages. Unlike other cancers, the symptoms, such as pelvic and abdominal pain or persistent bloating, are often put down to other common ailments and the tumour can be missed. There is no mass screening programme to detect the cancer either.
Scientists already know that levels of a protein in the blood, called CA125, are often higher with ovarian cancer. However, it is too unreliable on its own. It misses some patients and tells others they have the cancer when they are actually healthy.
Researchers are now testing the idea of using the blood test to sort patients in risk groups based on levels of CA125. Instead of going straight for surgery, low-risk patients are tested again in a year, medium-risk ones after three months and high-risk patients have an ultrasound scan to hunt for tumours.
The US study, at the University of Texas, followed post-menopausal women for 11 years on average. Ten women had surgery based on their ultrasound scan and all the cancers detected were at an early stage.
Researcher Dr Karen Lu told the BBC: ‘Clinical practice definitely should not change from our study, but it gives us an insight – we didn’t get a lot of false positives.’
She said the UK study of 50,000 people would give definitive results: ‘There are two big questions – do we see cancers at an earlier stage and do we decrease the number of deaths.’
Dr Sarah Blagden, from the Ovarian Cancer Action research centre, said: ‘Relative to the trial under way in the in the UK , this is a small study, but it does show that effective ovarian screening is possible.
‘In 2015 the results of the UKCTOCs study will become available and the results are eagerly anticipated, more so now that this American study has produced such encouraging results.’ BBC

Researchers have tied mutations in a gene that causes amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders to the toxic build-up of certain proteins and related molecules in cells, including neurons. The research offers a new approach for developing treatments against these devastating diseases.
Scientists at St. Jude Children’s Research Hospital and the University of Colorado, Boulder, led the work.
The findings provide the first evidence that a gene named VCP plays a role in the break-up and clearance of protein and RNA molecules that accumulate in temporary structures called RNA granules. RNAs perform a variety of vital cell functions, including protein production. RNA granules support proper functioning of RNA.
In ALS and related degenerative diseases, the process of assembling and clearing RNA granules is impaired. The proteins and RNAs associated with the granules often build up in nerve cells of patients. This study shows how mutations in VCP might contribute to that process and neurodegenerative disease.
‘The results go a long way to explaining the process that links a variety of neurodegenerative diseases, including ALS, frontotemporal dementia and related diseases of the brain, muscle and bone known as multisystem proteinopathies,’ said the study’s co-corresponding author, J. Paul Taylor, M.D., Ph.D., a member of the St. Jude Department of Developmental Neurobiology. Roy Parker, Ph.D., of the University of Colorado’s Department of Chemistry and Biochemistry and the Howard Hughes Medical Institute (HHMI), is the other corresponding author. St Jude Children’s Research Hospital

Researchers from King’s College London and the University of Nottingham have identified neuroimaging markers in the brain which could help predict whether people with psychosis respond to antipsychotic medications or not.
In approximately half of young people experiencing their first episode of a psychosis (FEP), the symptoms do not improve considerably with the initial medication prescribed, increasing the risk of subsequent episodes and worse outcome. Identifying individuals at greatest risk of not responding to existing medications could help in the search for improved medications, and may eventually help clinicians personalise treatment plans.
In a study, researchers used structural Magnetic Resonance Imaging (MRI) to scan the brains of 126 individuals – 80 presenting with FEP, and 46 healthy controls. Participants had an MRI scan shortly after their FEP, and another assessment 12 weeks later, to establish whether symptoms had improved following the first treatment with antipsychotic medications.
The researchers examined a particular feature of the brain called ‘cortical gyrification’ – the extent of folding of the cerebral cortex and a marker of how it has developed. They found that the individuals who did not respond to treatment already had a significant reduction in gyrification across multiple brain regions, compared to patients who did respond and to individuals without psychosis. This reduced gyrification was particularly present in brain areas considered important in psychosis, such as the temporal and frontal lobes. Those who responded to treatment were virtually indistinguishable from the healthy controls.
The researchers also investigated whether the differences could be explained by the type of diagnosis of psychosis (eg. with or without affective symptoms, such as depression or elated mood). They found that reduced gyrification predicted non-response to treatment independently of the diagnosis.
Dr Paola Dazzan from the Department of Psychosis Studies at King’s College London’s Institute of Psychiatry, and senior author of the paper, says: ‘Our study provides crucial evidence of a neuroimaging marker that, if validated, could be used early in psychosis to help identify those people less likely to respond to medications. It is possible that the alterations we observed are due to differences in the way the brain has developed early on in people who do not respond to medication compared to those who do.’
She continues:’There have been few advances in developing novel anti-psychotic drugs over the past 50 years and we still face the same problems with a sub-group of people who do not respond to the drugs we currently use. We could envisage using a marker like this one to identify people who are least likely to respond to existing medications and focus our efforts on developing new medication specifically adapted to this group. In the longer term, if we were able to identify poor responders at the outset, we may be able to formulate personalised treatment plans for that individual patient.’
Dr Lena Palaniyappan from the University of Nottingham adds: ‘All of us have complex and varying patterns of folding in our brains. For the first time we are showing that the measurement of these variations could potentially guide us in treating psychosis. It is possible that people with specific patterns of brain structure respond better to treatments other than antipsychotics that are currently in use. Clearly, the time is ripe for us to focus on utilising neuroimaging to guide treatment decisions.’ King’s College London