Dementia profoundly influences memory recall over time by disrupting the brain’s normal processes of encoding, storing, and retrieving memories. This decline is not simply a matter of forgetting but involves complex changes at molecular, cellular, and network levels in the brain, which progressively impair the ability to access previously formed memories and to form new ones.
Memory formation and maintenance in a healthy brain involve a cascade of molecular “timers” and gene-regulating programs that unfold over time across different brain regions. Initially, memories are formed in the hippocampus, a critical structure for encoding new information. Over time, these memories are gradually reorganized and stabilized in cortical areas through a series of molecular events involving transcriptional regulators such as Camta1, Tcf4, and Ash1l. These regulators support the persistence and durability of memories by promoting functional connections between brain regions and remodeling chromatin to maintain memory traces long-term[1].
In dementia, particularly Alzheimer’s disease (AD), this process is disrupted. One key problem is that while memories may be encoded, the retrieval mechanisms fail. Research using animal models of AD shows that neurons tagged during learning fail to reactivate properly during recall, leading to memory retrieval deficits rather than encoding failures. Chemogenetic reactivation of these learning-tagged neurons in the entorhinal cortex and dentate gyrus can restore memory performance, indicating that the memory traces exist but are inaccessible through natural cues alone[2]. This suggests that dementia impairs the brain’s ability to reactivate the specific neural ensembles necessary for recalling memories.
Another important factor in dementia-related memory loss is the degradation of perineuronal nets (PNNs), which are mesh-like structures surrounding neurons that help maintain proper neuronal communication and support social memory formation. In Alzheimer’s disease, the breakdown of PNNs, particularly in the CA2 region of the hippocampus, correlates with social memory loss, such as forgetting familiar faces and loved ones. Experimental inhibition of enzymes called matrix metalloproteinases (MMPs), which degrade PNNs, has been shown to preserve these nets and protect social memory in mouse models of AD. This mechanism appears to be independent of the classic amyloid-beta pathology and offers a new therapeutic target for preventing memory decline in dementia[3][7].
Dementia also affects the semantic and episodic aspects of memory. Older adults, including those with dementia, tend to rely more on the gist or general meaning of experiences rather than detailed recall. Studies show that semantic centrality—the importance of an event within a narrative—supports memory retrieval, but dementia can reduce the ability to recall central details over time, leading to more fragmented and less accurate memories[4]. This decline in detailed episodic memory is linked to the progressive deterioration of hippocampal and cortical networks.
Spatial memory, which depends heavily on the hippocampus and entorhinal cortex, is also impaired early in dementia. The accumulation of amyloid-beta plaques and neurofibrillary tangles in these regions disrupts neural activation patterns and reduces the fidelity of spatial representations. This leads to difficulties in navigation and spatial orientation, common symptoms in dementia patients. Research indicates that the stability of neural activation patterns in the CA1 region of the hippocampus is crucial for spatial memory, and its disruption correlates with memory decline in both normal aging and dementia[5].
At the cellular level, astrocytes—supportive glial cells in the brain—also influence memory. Recent studies have found sex-specific effects of astrocytic receptors on memory, with certain receptor levels enhancing memory in older females. While this research is still emerging, it suggests that cellular support mechanisms may also be altered in dementia, contributing to memory impairments[6].
In summary, dementia influences memory recall over time through multiple intertwined mechanisms: disruption of molecular timers and gene regulation that stabilize memories, failure to reactivate learning-specific neurons during recall, degradation of protective neuronal structures like perineuronal nets, and progressive damage to hippocampal and cortical networks essential for detailed episodic and spatial memory. These changes lead to a gradual erosion of the ability to retrieve both recent and remote memories, including social memories of loved ones, profoundly affecting the lives of those with dementia.
Sources:
[1] Medical Xpress, 2025
[2] NIH PMC, Chemogenetic manipulation study
[3] Neuroscience News, Alzheimer’s social memory and PNNs
[4] Nature Scientific Reports, semantic memory and aging
[5] PNAS, spatial memory and hippocampal remapping
[6] Cornell Chronicle, astrocytes and memory
[7] News Medical, Alzheimer’s and social memory nets
