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Abstract & Commentary
Source: Scahill RI, et al. Mapping the evolution of regional atrophy in Alzheimer’s disease: Unbiased analysis of fluid-registered serial MRI. Proc Natl Acad Sci U S A. 2002;99:4703-4707.
Serial MRI measurements can be used to map the pattern of regional brain atrophy in a variety of neurologic disease states. Using robust techniques that minimize the subjectivity of morphometric analysis, Scahill and colleagues compared rates and regional distribution of brain atrophy in 4 presymptomatic patients, 10 with mild Alzheimer’s Disease (AD), 12 with moderate AD, and age-matched controls. They found that rates of atrophy varied across brain regions and across stages of the disease in a consistent way. Their findings advance our understanding of the pathophysiology of AD and may be useful for diagnosis as well as in the evaluation of potential disease modifying therapies.
Scahill et al obtained 2 T1-weighted 1.5T MRI scans from each subject at an interval of 1-2 years. They used a fluid registration model and the SPM99 image analysis program to determine the pattern and extent of regional brain atrophy within individuals and across groups over time. In presymptomatic cases that subsequently developed AD, volume loss was largely confined to the hippocampus and precuneous. By the mild stage of the disease, atrophy continued to occur in the hippocampus and precuneous but also involved the anterior frontal lobe, portions of the inferior and lateral temporal lobes, as well as the posterior cingulate region. In moderately affected AD patients, hippocampal atrophy rates were comparable to controls. Neocortical areas lost more volume in the moderate stages, including more extensive portions of the cortical regions described above.
Across AD subjects, slightly more atrophy was noted in the left hemisphere than the right. Areas of expanded volume included the lateral ventricles and the third ventricle. No significant atrophy was found in the cerebellum or primary sensorimotor areas.
As postmortem studies have previously suggested, this study demonstrates that brain atrophy in living AD procedes from the hippocampus and precuneous to the connected neocortical association areas. The hippocampus is devastated early in the disease and having been affected early on, it is relatively unchanged in the more severe stages of AD. The observation of slightly greater left than right-sided atrophy in AD is an interesting one that is not readily explained by existing theories of AD pathogenesis.
The areas of most profound atrophy on MRI correspond to those seen on functional imaging studies with PET of AD patients, even after corrections for brain atrophy are made. Quantitative PET studies are expensive, have lower spatial resolution, and can be technically challenging to perform. Serial MRI measurements use existing MRI scanners and are less expensive to perform, but do require specialized software and expertise for analysis. Is there a niche for the use of this technique in the clinical evaluation of dementia patients? Apart from future use in the evaluation of potential disease modifying therapies, serial atrophy measures may be useful in the evaluation of more challenging cases in which the differential diagnosis remains uncertain after conventional clinical and laboratory techniques are exhausted. —Norman R. Relkin
Dr. Relkin, Associate Professor of Clinical Neurology and Neuroscience, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.