New Marker Could Make Preclinical Diagnosis of Alzheimer’s Possible
Results of a new study using diffusion tensor imaging point to the possibility of using hippocampal changes as a neuroradiologic marker of future cognitive decline.
Researchers report that mean hippocampal diffusivity — a measure often used to look at pathological changes in white and gray matter — predicted decline in a cohort of cognitively healthy individuals, whereas hippocampal volume did not.
“In elderly people with subclinical memory impairment, the hippocampal formation — the region of the brain crucial for normal memory function — is the site of ultrastructural changes,” lead investigator Giovanni Carlesimo, MD, from Tor Vergata University in Rome, Italy, told Medscape Neurology.
“Most currently available markers of Alzheimer’s disease are able to confirm the disease only when the cognitive impairment is clinically relevant and the underlying neuropathological changes are well developed,” Dr. Carlesimo said. Identifying a new marker for future disease progression could open the door to early treatment and alter the course of disease, he explained.”Carlesimo et al have put magnetic resonance imaging (MRI) diffusion high on the list of potential early markers of Alzheimer’s disease with their eloquent study of normal aging,” Norbert Schuff, PhD, from the University of California at San Francisco, writes in an accompanying editorial.
Diffusion tensor imaging is sensitive to the random movement of water molecules on a microscopic scale. The technique is already in widespread use for tractography of white matter fibers and for studies of brain connectivity.
In their study, investigators compared hippocampal volumes of 76 healthy individuals with measures derived from diffusion tensor imaging. Participants were recruited from universities, recreational centers, hospital personnel, and patients’ relatives. They ranged in age from 20 to 80 years.
The researchers used a 3-T MRI protocol with whole-brain T1-weighted and diffusion-weighted scanning. They also conducted neuropsychological assessments, including tests of verbal and visuospatial memory.
Dr. Carlesimo and his team used mean diffusivity to index microstructural variations within the hippocampus. They found that mean diffusivity of the hippocampus predicted verbal and visuospatial memory performance. This was especially the case in those 50 years or older.
The partial correlations of age with performance scores were ?0.42 for verbal and ?0.52 for visuospatial memory (P < .001). Preliminary Findings The researchers observed substantial stability between age and memory scores until the age of 50 years, and then there was a steady decline with increasing age. When the sample was split into those younger than 50 years and those 50 years or older, the partial correlations were significant for the older sample but not for the younger (r = ?0.42 and ?0.34 vs r = ?0.03 and ?0.14). "What we found particularly intriguing in the results of the present study is that the memory performance in healthy elderly individuals did not correlate with the rate of hippocampal atrophy — a very crude index of macroscopical anatomical change — but, rather, with a measure of structural integrity, which is not immediately appreciable at a visual analysis of magnetic resonance images," Dr. Carlesimo said. The investigators emphasize the need for additional studies to confirm these preliminary findings. The team is currently conducting a 3-year follow-up study to verify the predictive value of hippocampal changes in memory deficits.