Automated analysis of MR images may identify early Alzheimer’s disease

22 may 2009--Analyzing MRI studies of the brain with software developed at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) may allow diagnosis of Alzheimer's disease and of mild cognitive impairment, a lesser form of dementia that precedes the development of Alzheimer's by several years. In their report that will appear in the journal Brain and has been released online, the MGH/Martinos team show how their software program can accurately differentiate patients with mild cognitive impairment or Alzheimer's disease from normal elderly individuals based on anatomic differences in brain structures known to be affected by the disease.

"Traditionally Alzheimer's has been diagnosed based on a combination of factors – such as a neurologic exam, detailed medical history and written tests of cognitive functioning – with neuroimaging used primarily to rule out other diseases such as stroke or a brain tumor," says Rahul Desikan MD, PhD, of the Martinos Center and Boston University School of Medicine, lead author of the Brain paper. "Our findings show the feasibility and importance of using automated, MRI-based neuroanatomic measures as a diagnostic marker for Alzheimer's disease."

The researchers note that mild cognitive impairment occurs in about 20 percent of elderly individuals – as many as 40 percent of those over 85 – 80 percent of whom develop Alzheimer's within five or six years. Since drugs that may slow the progression of Alzheimer's are in development, the ability to treat patients in the earliest stages of the disease may significantly delay progression to dementia. To investigate whether MR imaging can produce diagnostic markers for mild cognitive impairment and Alzheimer's disease, the research team used FreeSurfer – an openly available imaging software package developed at the Martinos Center and the University of California at San Diego – to examine a number of neuroanatomic regions across a range of normal individuals and patients with mild cognitive impairment and Alzheimer's disease.

In the first phase of the study, the investigators examined MR images of 97 elderly individuals, some who had been determined to have mild cognitive impairment and others who were cognitively normal. Analyzing those images identified three regions of the brain where structural differences distinguished the normal controls from participants with mild cognitive impairment with an accuracy of 91 percent. Earlier pathological and imaging studies have found evidence of early Alzheimer's disease in these three areas – the hippocampus, entorhinal cortex and the supramarginal gyrus.

To validate the accuracy and assess the reliability of the first-phase observations, the investigators analyzed imaging data from 216 individuals in the Alzheimer's Disease Neuroimaging Database – 94 of whom were normal, 58 who had mild cognitive impairment at the time of imaging and went on to develop dementia, and 65 who had probable Alzheimer's based on their clinical symptoms. These participants also had a series of neuropsychological tests, and samples of cerebrospinal fluid were available for many of them.

Automated MRI measures of the same three areas identified in the first phase – entorhinal cortex, hippocampus, and supramarginal gyrus – discriminated individuals with mild cognitive impairment from normal elderly controls with 95 percent accuracy, and patients with Alzheimer's were discriminated from normal controls with 100 percent accuracy. The MRI measures also were significantly correlated with clinical and cognitive tests of dementia, particularly memory decline, and with biomarkers of cellular pathology such as the Alzheimer's-associated forms of the tau and amyloid proteins.

"Our results indicate that these automated MRI measures are one effective way of identifying individuals in the earliest stages of Alzheimer's disease, but before this technology can be used clinically, several follow-up studies need to be done," says Desikan. "Those include determining whether these automated MRI measures can accurately predict which individuals with mild cognitive impairment will progress to Alzheimer's; seeing if they can differentiate Alzheimer's from other neurodegenerative diseases; assessing how these measures do at early diagnosis, compared to other measures such as cellular biomarkers; and then validating all of these findings against the gold standard for diagnosis, postmortem examination of brain tissue."

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Bruce Fischl, PhD, of the Martinos Center is the senior author of the Brain study. Additional co-authors are Nicholas Schmansky, Douglas Greve and David Salat of the Martinos Center; Howard Cabral, Boston University School of Public Health; Christopher Hess, William Dillon, Christine Glastonbury and Michael Weiner, University of California, San Francisco; and Randy Buckner, Harvard University and Howard Hughes Medical Institute. Support for the study came from the American Federation for Aging Research, the National Center for Research Resources, the National Institute for Biomedical Imaging and Bioengineering, the Mental Illness and Neuroscience Discovery Institute, the National Institute on Aging, the National Institute for Neurologic Disorders and Stroke and several other organizations.

Older Brain Really May Be a Wiser Brain

By SARA REISTAD-LONG
21 may 2008--When older people can no longer remember names at a cocktail party, they tend to think that their brainpower is declining. But a growing number of studies suggest that this assumption is often wrong.
Instead, the research finds, the aging brain is simply taking in more data and trying to sift through a clutter of information, often to its long-term benefit.
The studies are analyzed in a new edition of a neurology book, “Progress in Brain Research.”
Some brains do deteriorate with age. Alzheimer’s disease, for example, strikes 13 percent of Americans 65 and older. But for most aging adults, the authors say, much of what occurs is a gradually widening focus of attention that makes it more difficult to latch onto just one fact, like a name or a telephone number. Although that can be frustrating, it is often useful.
“It may be that distractibility is not, in fact, a bad thing,” said Shelley H. Carson, a psychology researcher at Harvard whose work was cited in the book. “It may increase the amount of information available to the conscious mind.”
For example, in studies where subjects are asked to read passages that are interrupted with unexpected words or phrases, adults 60 and older work much more slowly than college students. Although the students plow through the texts at a consistent speed regardless of what the out-of-place words mean, older people slow down even more when the words are related to the topic at hand. That indicates that they are not just stumbling over the extra information, but are taking it in and processing it.
When both groups were later asked questions for which the out-of-place words might be answers, the older adults responded much better than the students.
“For the young people, it’s as if the distraction never happened,” said an author of the review, Lynn Hasher, a professor of psychology at the University of Toronto and a senior scientist at the Rotman Research Institute. “But for older adults, because they’ve retained all this extra data, they’re now suddenly the better problem solvers. They can transfer the information they’ve soaked up from one situation to another.”
Such tendencies can yield big advantages in the real world, where it is not always clear what information is important, or will become important. A seemingly irrelevant point or suggestion in a memo can take on new meaning if the original plan changes. Or extra details that stole your attention, like others’ yawning and fidgeting, may help you assess the speaker’s real impact.
“A broad attention span may enable older adults to ultimately know more about a situation and the indirect message of what’s going on than their younger peers,” Dr. Hasher said. “We believe that this characteristic may play a significant role in why we think of older people as wiser.”
In a 2003 study at Harvard, Dr. Carson and other researchers tested students’ ability to tune out irrelevant information when exposed to a barrage of stimuli. The more creative the students were thought to be, determined by a questionnaire on past achievements, the more trouble they had ignoring the unwanted data. A reduced ability to filter and set priorities, the scientists concluded, could contribute to original thinking.
This phenomenon, Dr. Carson said, is often linked to a decreased activity in the prefrontal cortex. Studies have found that people who suffered an injury or disease that lowered activity in that region became more interested in creative pursuits.
Jacqui Smith, a professor of psychology and research professor at the Institute for Social Research at the University of Michigan, who was not involved in the current research, said there was a word for what results when the mind is able to assimilate data and put it in its proper place — wisdom.
“These findings are all very consistent with the context we’re building for what wisdom is,” she said. “If older people are taking in more information from a situation, and they’re then able to combine it with their comparatively greater store of general knowledge, they’re going to have a nice advantage.”