Individuals with certain signatures on MRI scans are at greatly increased risk of developing Alzheimer's disease, according to two independent studies.
In one, cognitively normal adults with low cortical thickness parameters characteristic of Alzheimer's disease went on to develop the disease at a 55% rate, compared with 0% among similar people with higher-than-average cortical thickness (P<0.005).
The other study showed that similar MRI-based measurements could predict which patients with mild cognitive impairment would progress to full-blown Alzheimer dementia during the following year, with an odds ratio of 7.2 (P not reported) comparing the highest with the lowest quartiles of cortical volume scores.
The authors of both studies concluded that, in many patients who develop Alzheimer's disease, their brains show physical changes characteristic of the condition long before clinical symptoms qualify them for a diagnosis.
In fact, according to the first study, published online in Neurology, those changes were detectable in apparently healthy people as much as 11 years before diagnosis.
Brad Dickerson, MD, of Massachusetts General Hospital in Boston, and colleagues performed MRI scans in two independent samples of cognitively normal adults in their late 60s and 70s.
The first sample included eight people who went on to receive an Alzheimer's diagnosis a mean of 11.1 years later and 25 whose cognitive performance remained normal. In the second sample, 32 cognitively normal individuals were scanned, including seven who converted to Alzheimer's disease after a mean of 7.1 years.
Ten brain regions were scanned to produce a composite cortical thickness score, measured in millimeters. In both groups, those who went on to develop Alzheimer's disease had scores that were about 0.2 mm lower than participants remaining cognitively normal (P<0.05), Dickerson and colleagues reported.
Also, for each standard deviation of cortical thickness score relative to the mean, the hazard ratio for developing Alzheimer's disease was 3.4 (P<0.0005), the researchers indicated.
The second study was published online in Neuroradiology by Linda McEvoy, PhD, of the University of California San Diego, and colleagues. They performed MRI scans in 203 normal controls, 164 people with mild Alzheimer's disease, and 317 with mild cognitive impairment, all with mean ages of about 75.
As in the study by Dickerson and colleagues, MRI measures of different cortical regions were combined into an overall score. Scores for the cognitively normal and Alzheimer's disease groups were then incorporated into a model applied to the participants with mild cognitive impairment.
In the latter group, nearly 90% had at least 18 months of follow-up. The average one-year rate of conversion to Alzheimer's disease in patients with mild cognitive impairment was 17%.
Among patients in the highest quartile of risk according to the baseline MRI scans, the one-year conversion rate was 40%, versus 3% in the lowest quartile, McEvoy and colleagues reported.
The study also included a second set of MRI scans performed one year after the baseline scans, the researchers indicated. After excluding patients who did not complete a full year of follow-up after the second round of scans or who had converted to Alzheimer's disease during the first year, the analysis covered 170 participants with mild cognitive impairment.
When these results were incorporated into the risk-prediction model, the highest-risk participants with mild cognitive impairment converted to Alzheimer's disease at a one-year rate of 69%, compared with 3% among the lowest-risk participants (odds ratio 12.0, P=0.001).
McEvoy and colleagues acknowledged that predicting which individuals would progress to Alzheimer's disease would have limited clinical value in the absence of treatments that can halt or delay the process.
On the other hand, they wrote, "such predictive prognostic information will be critical if disease-modifying therapies become available."
For their part, Dickerson and colleagues said their findings suggest that MRI markers should be included in research criteria now being developed for so-called preclinical Alzheimer's disease.
Again, although such a designation would have little clinical relevance at present, the research community is eager for a standard, objective definition that could be used to recruit participants for trials of disease-modifying therapies aimed at preventing onset of clinical symptoms.
Both groups of authors indicated that their studies were limited by uncertainties in the baseline characterizations of patients as cognitively normal and in the clinical diagnoses. Additionally, the Neurology study had relatively small sample sizes, whereas McEvoy and colleagues noted that their samples were not representative of the general clinical population.
Also, neither study reported standard diagnostic accuracy measures such as sensitivity, specificity, or positive/negative predictive values for their risk scoring systems.
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