Early Neural Predictor of Cognitive Impairment

Early neural predictors of cognitive impairment are important both for determining the biological causes of dementia and for identifying individuals at high risk for cognitive decline as early as possible. Researchers at the University of California, Davis, looked at two areas of the brain that are part of the circuitry associated with cognitive decline in order to determine if there were any identifiable changes in these areas that might predict later cognitive impairment. A group of 102 cognitively normal elderly participants with no indications of cognitive impairment were recruited to take part in a longitudinal study in which they received multiple MRIs over an average of four years. Of these, 18 participants progressed to having mild cognitive impairment and 2 developed Alzheimer’s Disease. Early MRI scans of these participants were then compared with scans of the participants who did not experience any cognitive impairment to determine which brain regions best predicted the observed cognitive decline.

Extensive research on memory and the brain has examined the important role of the hippocampus (Latin for seahorse), which has been repeatedly shown to play a crucial role in memory. However, it is important to also recognize that the hippocampus is just one part in a complex chain of brain circuitry that is necessary for memory recall and formation. Another, less studied brain area that has been shown to be part of the brain’s memory circuitry is the fornix (Latin for arch). The fornix is a band of nerve fibers that connects the hippocampus and other areas of the brain. The researchers wanted to determine whether changes in the fornix or the hippocampus could be predictors of eventual cognitive impairment.

When they compared the participants who developed cognitive impairment to those who did not, researchers found that fornix volume and the integrity of the axons in the fornix both predicted eventual cognitive impairment, while, somewhat surprisingly, the volume of the hippocampus did not. A statistical standard deviation’s difference in fornix size was associated with a 53 percent reduction in risk of cognitive impairment.

The findings here suggest that changes in the fornix are promising biomarkers for predicting cognitive decline among individuals who are showing no outer symptoms of cognitive decline. Since diseases that involve cognitive impairment are most effectively prevented or slowed when treated early, conducting MRIs of the fornix prior to any observed cognitive decline could lead to better cognitive outcomes and higher quality of life by enabling treatment of problems before they become clinically visible. While this is the most immediate likely impact of this study, this research also suggests exciting possibilities for better understanding the mechanisms for cognitive decline. Additionally, the fornix itself may become a target for treatments targeting cognitive impairment. Preliminary studies have shown that electrical stimulation of the fornix can lead to cognitive improvements or slow the rate of cognitive decline.


Fletcher E, Raman M, Huebner P, et al. Loss of fornix white matter volume as a predictor of cognitive impairment in cognitively normal elderly individuals. JAMA Neurology. (2013). DOI:10.1001/jamaneurol.2013.3263

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