New MRI Technique May Predict Progress of Dementias

A new technique for analyzing brain images offers the possibility of using magnetic resonance imaging (MRI) to predict the rate of progression and physical path of many degenerative brain diseases, report scientists at the San Francisco VA Medical Center and the University of California, San Francisco.

The technique, developed by SFVAMC scientists in collaboration with a team led by Bruce Miller, MD, clinical director of the UCSF Memory and Aging Center, also supports mounting evidence that dementias spread through the brain along specific neuronal pathways in the same manner as prion diseases.

The scientists employed new computer modeling techniques to realistically predict the physical progression of Alzheimer’s disease and frontotemporal dementia (FTD) using images of 14 healthy brains. The models were based on whole-brain tractography, an MRI technique that maps the neural pathways, or “communication wires,” that connect different areas of the brain. The spread of disease along those pathways, as predicted by the models, closely matched actual MRI images of brain degeneration in 18 Alzheimer’s patients and 18 FTD patients.

Their study was published in the March 22 edition of Neuron.

“The results need to be replicated, but they suggest that, by using this approach, we can predict the location and course of future brain atrophy in Alzheimer’s, FTD and other degenerative brain diseases, based on just one MRI taken at the outset of the disease,” said senior author Michael Weiner, MD, director of the SFVAMC Center for Imaging of Neurodegenerative Diseases. “This would be extremely useful in planning treatment, and in helping patients and families know what to expect as dementia progresses.”

The progression of Alzheimer’s disease and other dementias

Each person experiences dementia in their own way, but it can be helpful to think of the way the condition progresses as a series of stages. This factsheet outlines the characteristics of early-, middle- and late-stage Alzheimer’s disease and briefly looks at how other forms of dementia progress.

Alzheimer’s disease
Alzheimer’s disease is a progressive illness. This means that the structure and chemistry of the brain become increasingly damaged over time. The person’s ability to remember, understand, communicate and reason will gradually decline. Looking at Alzheimer’s disease as a series of three stages can be a useful way of understanding the changes that occur over time. But it is important to realise that this view of Alzheimer’s can only provide a rough guide to the course of the disease. This is because:

- some symptoms may appear earlier or later than indicated here, or not at all
- the stages may overlap - the person may need help with one task, but may be able to manage another activity on their own
- some symptoms, such as walking about, may appear at one stage and then vanish, while others such as memory loss will worsen over time.

The way that a person experiences Alzheimer’s disease will depend on many factors, including their physical make-up, their emotional resilience, the medication they take and the support they can rely on.

Weiner, who is also a UCSF professor of radiology, medicine, psychiatry and neurology, said that the results were “consistent with an emerging concept that brain damage occurs in these neurodegenerative diseases in a diffusive, prion-like propagation.”

A prion is an infectious, misfolded form of a normal protein. These proteins leave destructive amyloid deposits in the brains in which they develop, causing degeneration and eventual death. They are responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, or “mad cow” disease, in cattle. In 1997, neurologist Stanley B. Prusiner of UCSF was awarded the Nobel Prize in Medicine for discovering and characterizing the prion. His finding overturned a tenet of modern biology, showing that a protein, rather than just the molecules DNA and RNA, could cause infection.

“The idea of a prion-like mode of progression in dementias, which many scientists are beginning to support, is that the misfolded protein in one neuron will infect a neighboring brain cell, causing proteins in that cell to misfold in turn, and that the spread of these misfolded proteins flows along certain networks in the brain,” explained Weiner. “For instance, in Alzheimer’s, there is a spread of amyloid protein along the memory network. This paper reinforces the idea that the damage occurs progressively along that network and others.”

Alzheimer’s disease Early stage

Alzheimer’s disease usually begins gradually with very minor changes in the person’s abilities or behaviour. At the time, such signs are often mistakenly attributed to stress or bereavement or, in older people, to the normal process of ageing. It is often only when looking back that we realise that these signs were probably the beginnings of dementia.
Loss of memory for recent events is a common early sign. Someone with Alzheimer’s may:

forget about recent conversations or events
repeat themselves
become slower at grasping new ideas
lose the thread of what is being said
sometimes become confused
show poor judgement, or find it harder to make decisions
lose interest in other people or activities
develop a readiness to blame others for taking mislaid items
become unwilling to try out new things or adapt to change.

If you are caring for someone with Alzheimer’s disease, there’s a lot you can do in the early stages to help the person you are caring for maintain their independence. It may be tempting to do things for them, but they are more likely to retain their sense of self-worth if they are given the chance to do things for themselves, with support if necessary. (See our factsheet Maintaining everyday skills (521) for more information.)
The person may also become anxious and agitated. They may experience distress over their failure to manage tasks and may need some reassurance. If this is the case, try to talk to them, and give them as much emotional support as you can.

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