Slowing the progression of Alzheimer’s disease

In recent years, the field of neuroscience has experienced a massive boom in the use of magnetic resonance imaging (or MRI) as a tool to uncover some hidden clues about the brain that would otherwise go undetected. Recent neuroimaging research in Oxford has found that by looking at the anatomy of the hippocampus, the brain’s principle memory centre, it may be possible to predict if an elderly individual with mild cognitive impairments is likely to develop Alzheimer’s disease up to 2 years prior to diagnosis.

This research was carried out on a group of elderly people who suffer from mild cognitive impairment (MCI). Thought to be a stepping-stone between healthy aging and Alzheimer’s disease, MCI is usually associated with memory and cognitive deficits. Whilst over 50% of people with MCI go on to develop clinical symptoms of dementia and become diagnosed with Alzheimer’s disease, some remain stable for many years and can even return to a state of healthy ageing. But is there anything that can distinguish between someone who will progress and someone who will not? And how can we tell when the progression will happen?

These questions paved the way for some of the current work being done in Oxford. Led by a team of neuroimaging specialists at the John Radcliffe hospital, the main aim of the research was to look for early indications of Alzheimer’s disease in a group of MCI patients. The researchers scanned stable MCI patients and then kept in touch with them for several years in order to find out if and when their condition progressed to Alzheimer’s disease. The researchers excluded any patients who progressed earlier than 2 years after the MRI scan in order to tightly control the progression’s time window. After several years of follow-up, the team were able to separate their original collection of MRI scans into two groups: a group of stable patients and a group of patients who developed Alzheimer’s disease 2 or more years after the scan.

The team went back to these original MRI scans to look for any anatomical clues that could predict the progression of the disease. They were particularly interested in their patients’ grey matter, brain tissue that is primarily made up of neuron cell bodies and acts as the brain’s hardware. Interestingly, they found that the volume of left hippocampal grey matter was significantly reduced in patients who would later develop Alzheimer’s compared to those who didn’t go on to develop the disorder. The hippocampus is known to be the a major centre for memory in the brain, so you would expect to see degeneration here in Alzheimer’s disease. The fact that they found early signs of degeneration in this area up to 2 years before the symptoms of dementia started is fascinating. When combined with other measures, such as the number of proteins known to be markers of Alzheimer’s disease in the fluid around the brain, the team were able to predict with 91% accuracy if any given patient would develop symptoms of dementia in two years’ time.

This 2-year window could be sufficient to undergo some form of treatment to slow the eventual devastating degeneration of the brain. But what treatments can successfully target the destruction of this tissue? The same research team went on to show that they could slow grey matter loss in the brain of a new group of MCI patients by giving them B vitamin supplements. These unlikely candidates are known to lower homocysteine, a chemical thought to increase the risk of dementia either by stopping neurons growing in the hippocampus or by increasing the number of proteins growing in tangles, both of which are markers of Alzheimer’s disease. Many theories have linked homocysteine and B vitamins to dementia, but this study was the first to directly test the theory. Perhaps most importantly, the B vitamin treatment had no effect in those patients who began the study with low homocysteine levels.

What could this work mean in the larger context of Alzheimer’s treatment? Rather predictably, the researchers called for larger studies sampling from a more diverse elderly population. They were also very clear to highlight that B vitamins were not ‘treating’ the degeneration as such but instead seemed to slow the process by reducing high levels of homocysteine. B vitamins were simply giving as much protection against degeneration as that of someone with naturally low levels of homocysteine. However, as to be expected, there was quite a buzz in the media when the research was published earlier this year, with snappy headlines such as ‘Should you be taking vitamin B to protect against Alzheimer’s?’ and ‘The daily vitamin B pill that halts the ravages of dementia’. The NHS was quick to respond rather negatively by emphasising the problems with this research and arguing that there is no clear evidence that B vitamin supplements present greater benefits than risks to patients.

Although the NHS did not discuss what the potential risks of B vitamin treatment could involve, the response does highlight one of the issues facing clinically-oriented scientific research – statistical significance needs to be understood in the context of clinical significance. Results need to be replicable on a very large scale and tested for any possible adverse effects before they can be considered clinically. The research did show that B vitamins could slow the loss of grey matter in certain brain regions, but how does this translate to a patient’s cognitive abilities? Although the science here is promising, years of expensive large-scale trials will have to take place before anything involving MRI screening and B vitamins can be implemented in the prevention of dementia. Whether or not this is feasible or will actually happen is another question altogether.