Doctors may soon be using a variety of brain scans to diagnose and treat Alzheimer’s long before major symptoms appear. Several new studies add to evidence that scanning technology is powerful enough to detect minor brain changes that appear early in the course of the disease.
“One of the most challenging questions in dementia research is how to diagnose patients in the presymptomatic stages, when an effective treatment will assert the most powerful impact,” says Liana Apostolova, a neurologist at the University of California, Los Angeles and a member of one of several groups worldwide working on methods of early diagnosis.
Her research focuses on using magnetic resonance imaging (MRI) to catalog changes in the hippocampus, an area known to degrade early in the Alzheimer’s process. In one new study, Apostolova’s research team examined MRI scans from ten cognitively normal subjects, with an average age of 69, who retained their cognitive abilities over a seven-year period. Apostolova compared those scans with MRIs from seven other subjects who had developed mild cognitive impairment (MCI) after about three years and Alzheimer’s after about seven.
MCI is the term given to mental declines that are more severe than those that occur during normal aging but less drastic than those seen in full-blown Alzheimer’s. In Apostolova’s study, atrophy of the hippocampus seen at the study’s onset predicted who would develop MCI—including a loss of memory capacity—and eventually Alzheimer’s.
Furthermore, Apostolova was able to pinpoint the precise locations of the hippocampal atrophy (figure at right) and demonstrate that the spread of degenerative changes into particular regions of the hippocampus predicts a future diagnosis of Alzheimer’s. The research was published online ahead of print in Neurobiology of Aging in September 2008. In 2009 another MRI study of atrophy in certain cortical brain regions (mesial and lateral temporal, isthmus cingulate, and orbitofrontal areas) reported similar findings.
Other research teams are using positron emission tomography (PET) to investigate the causes and course of Alzheimer’s. PET may even reveal genes that predispose certain individuals toward the disease.
For example, a research team led by Mony de Leon at New York University recently used PET scans to measure glucose metabolism in the brain, relating differences in metabolism to a maternal history of Alzheimer’s.
De Leon’s team studied 75 cognitively normal people between the ages of 50 and 82, some of whom had seen Alzheimer’s on their mother’s side of the family and some of whom had not. The results, published in Neurology in February 2009, revealed reduced glucose metabolism among the former group, occurring in the same brain regions—the parieto-temporal, posterior cingulate, and medial temporal cortices—as typically seen among patients already diagnosed with Alzheimer’s.
The researchers suspect that such metabolic changes may increase the risk of Alzheimer’s among individuals with a maternal history. This raises the possibility that PET scans might provide a means of early diagnosis for those at risk.
Traditionally, the neurodegenerative processes of Alzheimer’s have been considered separate and distinct from vascular dementia, the loss of cognitive ability that may follow either a major stroke or a series of “ministrokes.” But scans reveal that many patients exhibit both neurodegenerative and vascular changes in tandem.
It “appears that there is a spectrum, ranging from patients with pure vascular dementia to patients with pure Alzheimer’s disease and including a large number of patients with contributions from both Alzheimer and vascular pathology,” Anand Viswanathan of Massachusetts General Hospital writes in the January 27, 2009, issue of Neurology. This overlap, Viswanathan asserts, suggests a reclassification of the various forms of dementia.
In the August 11 issue of Neurology, José Luchsinger of Columbia University Medical Center in New York presents some supporting evidence. His team conducted a study of 679 people—average age 80—all without dementia at the beginning of the study. The scientists interviewed the subjects and tested them for memory, language skills, speed of information processing, and visual-spatial ability. The team diagnosed MCI in 171 participants: 94 of them had MCI with loss of memory capacity, while 74 did not show memory-related symptoms.
MRI scans of these subjects’ brain showed an important difference. Those who had infarcts (regions of dead tissue that appear after the blood supply to an area is blocked completely, usually due to stroke) were more likely to experience MCI without memory loss. Infarcts were instead related to diminished skills in information processing, visual and spatial abilities and language.
In contrast, subjects with a condition of the nerve fibers called white matter hyperintensities (WMH), commonly seen in areas of poor blood circulation in the brain (but not tissue death), generally earned lower scores on memory tasks than did those with infarcts, including word recognition and retrieval tests. So pronounced was the effect that the WMH patients were nearly twice as likely to have MCI with memory loss, compared with those whose scans showed infarcts only. The distinction is a crucial bit of information, the researchers say, because MCI with memory loss is more likely to progress to Alzheimer’s than the non-memory-loss type.
This connection raises some important questions, says Viswanathan, who was not involved in Luchsinger’s research. “Do the WMHs somehow influence the Alzheimer’s disease process?” he asks. “Do the WMHs influence [brain] pathways that have not previously been implicated in memory?”
Prevention and early diagnosis
As methods of detecting such changes become more precise, researchers are moving towards finding ways to prevent them—thus hopefully reducing cases of cognitive impairment and Alzheimer’s.
For instance, several clinical studies are underway to determine whether controlling high blood pressure, diabetes and elevated cholesterol, which are risk factors for heart disease and stroke, will also reduce the risk of Alzheimer’s. “Maybe treating these things ... will actually reduce the number of patients developing Alzheimer’s in the future,” Viswanathan says.
“As an Alzheimer’s researcher I feel that we are racing against time,” Apostolova adds. “As the baby boomers age, Alzheimer’s will soon gain epidemic proportions. We need new or improved tools to diagnose Alzheimer’s as near to its inception as possible. Studies such as ours deliver a promise that preclinical diagnosis of Alzheimer’s will soon be feasible.”