Detecting Early Hippocampal Dysfunction in Alzheimer's Using The Mnemonic Similarity Task

Abstract

The hippocampus plays a central role in learning and in the formation and retrieval of episodic memories—memories tied to personal and unique experiences with contextual details [1]. One of its key subregions, the dentate gyrus, is crucial for pattern separation, the cognitive process that allows individuals to distinguish between experiences or stimuli that are similar but not identical. People may have trouble correctly recalling similar events when this function starts to deteriorate, as seen in neurodegenerative diseases like Alzheimer's Disease (AD). AD is a progressive neurological disorder which often causes deterioration of hippocampal subfields such as the dentate gyrus and CA3 leading to episodic memory loss, impaired spatial navigation, and difficulty with pattern separation. Since such deficits often emerge before global memory decline, pattern separation has been proposed as a potential early cognitive marker of hippocampal dysfunction. The Mnemonic Similarity Task (MST) is an object recognition task designed to indirectly assess hippocampal pattern separation by evaluating a subject’s ability to discriminate between repeated, similar (lure), and novel items. Performance is commonly quantified using the Lure Discrimination Index (LDI), which reflects the capacity to correctly identify lure items as similar rather than identical. This literature review synthesizes behavioral and neuroimaging evidence showing that performance on MST, particularly LDI scores, declines with age and cognitive impairment and is positively correlated with hippocampal volume [2]. These findings highlight the MST’s sensitivity to subtle changes in memory function. Neuroimaging research further revealed that reduced lure discrimination ability is associated with diminished white matter integrity in memory-related neural pathways, as shown through a diffusion tensor imaging analysis, while functional MRI studies demonstrate hyperactivity in the CA3/dentate gyrus region, which has been interpreted as either an early neuropathological change or a compensatory response. Longitudinal results imply that MST performance could be used to monitor the development of cognitive deterioration over time [3]. Given its non-invasive nature, sensitivity to early hippocampal dysfunction, and compatibility with imaging biomarkers, the MST holds promise as a cognitive tool for the early detection and monitoring of Alzheimer’s disease.

References

[1] K. S. Anand and V. Dhikav, “Hippocampus in health and disease: An overview,” Ann Indian Acad Neurol, vol. 15, no. 4, pp. 239–46, Oct. 2012. doi: 10.4103/0972-2327.104323.

[2] S. L. Leal and M. A. Yassa, “Neurocognitive Aging and the Hippocampus across Species,” Trends Neurosci, vol. 38, no. 12, pp. 800–812, Dec. 2015. doi: 10.1016/j.tins.2015.10.003.

[3] S. M. Stark and C. E. L. Stark, “Age-related deficits in the mnemonic similarity task for objects and scenes,” Behavioural brain research, vol. 333, pp. 109–117, Aug. 2017. doi: 10.1016/j.bbr.2017.06.049.