From the Guidelines
The entorhinal cortex is a critical region in the development of Alzheimer's disease, with atrophy in this area being a key indicator of neurodegeneration, as evidenced by volumetric magnetic resonance imaging (MRI) studies 1. The entorhinal cortex plays a crucial role in memory formation, spatial navigation, and temporal organization of experiences, making it a vital area of study in the context of Alzheimer's disease. Some key functions of the entorhinal cortex include:
- Receiving sensory information from association areas and processing it before sending it to the hippocampus for memory consolidation
- Containing specialized grid cells that create a coordinate system for navigation, allowing us to map our environment and remember locations
- Supporting episodic memory, which is the ability to remember personal experiences with their spatial and temporal contexts The entorhinal cortex is one of the first areas affected in Alzheimer's disease, which explains why early symptoms often include disorientation and memory loss, as noted in studies examining the accumulation of Ab and its association with cognitive decline 1. Key points to consider when evaluating the entorhinal cortex in the context of Alzheimer's disease include:
- The accumulation of Ab is associated with an increased risk of developing cognitive decline and progression towards symptomatic AD 1
- The presence of a second elevated marker of either tau pathology or neurodegeneration in an individual demonstrating excess Ab accumulation is associated with greater prognostic predictability 1
- Structural neuroimaging techniques, such as volumetric MRI, can show hippocampal and entorhinal cortex atrophy and cortical thinning during the preclinical phase of AD 1
From the Research
Entorhinal Cortex Function
- The entorhinal cortex plays a crucial role in spatial cognition and memory, with studies suggesting that it acts as a cognitive map for memory-guided navigation 2.
- Single neurons in the human entorhinal cortex have been found to change their spatial tuning to target relevant memories for retrieval, with 'memory-trace cells' encoding discriminable representations of different memories through a memory-specific rate code 3.
- The deep layers of the entorhinal cortex are important for spatial cognition, as well as memory storage, consolidation, and retrieval, with recent circuit-level analyses suggesting complex roles for deep-layer neurons 4.
Entorhinal Cortex and Alzheimer's Disease
- Alzheimer's disease is a neurodegenerative disorder that affects over 45 million people worldwide, with patients with severe AD requiring help with daily activities and showing severe memory impairment 5.
- Donepezil, a reversible cholinesterase inhibitor, has been found to benefit patients with Alzheimer's disease in cognition and global functioning, although high dosages may lead to adverse events 5, 6.
- The entorhinal cortex is affected in Alzheimer's disease, with studies suggesting that damage to this region may contribute to the spatial memory impairments observed in patients with the disease 3, 4.
Spatial Memory and the Entorhinal Cortex
- The medial entorhinal cortex (MEC) is hypothesized to function as a cognitive map for memory-guided navigation, with grid cells in the MEC exhibiting improved spatial tuning consistency and stable phase relationships during learning 2.
- A consistent map in the MEC supports spatial memory, with the establishment of a spatially consistent MEC map across learning correlating with, and being necessary for, successful spatial memory 2.
- Disrupting the spatial consistency of the map in the MEC impairs memory-guided navigation in a well-learned environment, highlighting the importance of the entorhinal cortex in spatial memory 2.