Summary: A new study finds that synapse quality — specifically the size of dendritic spine heads in the temporal cortex — predicts better episodic memory in older adults. The results challenge the long-standing idea that memory decline in aging is driven mainly by a loss of synapses, suggesting instead that the strength of remaining synapses plays a decisive role.
These findings point toward therapeutic strategies that boost synaptic strength or preserve spine head diameter as promising approaches to support memory in normal aging and in the early stages of Alzheimer’s disease. Enhancing the function of existing synapses may be more effective than attempting to increase synapse number alone.
Key Facts:
- Synapse Quality: Larger dendritic spine head diameters in the temporal cortex are associated with superior episodic memory performance.
- Memory Preservation: Synaptic strength appears more important than synapse count for maintaining memory in older adults.
- Therapeutic Potential: Treatments that support spine head diameter or synaptic strength could offer benefit to older people and those with Alzheimer’s-related memory impairment.
Source: University of Alabama
Memory for personal experiences tends to decline with age, but the reasons for this variability among older adults have remained under investigation. For decades, researchers emphasized the loss of dendritic spines — small protrusions on neuronal dendrites that form synapses — as a primary cause of age-related cognitive decline. The new study led by teams at the University of Alabama at Birmingham (UAB) and Rush University Medical Center offers a different perspective: the remaining synapses’ structural strength matters most for episodic memory.
“This finding changes how we think about memory loss with age,” said Jeremy Herskowitz, Ph.D., associate professor in the UAB Department of Neurology and the study’s corresponding author. He notes that while the normal aging process does involve some reduction in dendritic spines, the synapses that remain can adapt and compensate. That adaptive capacity offers a target for interventions aimed at preserving or improving memory, even in people in their 80s and beyond.
The research used postmortem brain tissue from 128 participants of the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP). Participants, who were clergy aged 65 or older at enrollment and agreed to annual evaluations and brain donation, had an average age of 90.5 years at death. Their cognitive abilities and Alzheimer’s-related neuropathology varied, and each had undergone regular cognitive testing covering episodic memory, perceptual speed, visuospatial ability, semantic memory, and working memory.
From each brain, researchers sampled the temporal cortex — a region critical for long-term and episodic memory — and the frontal premotor cortex. They stained tissue, imaged thin sections, and digitally reconstructed 55,521 individual dendritic spines across 2,157 neurons. Using rigorous statistical models, including machine-learning techniques, the team evaluated 16 spine morphology features against 17 measures of cognitive function, age, and neuropathology.
Their analyses revealed a specific relationship in the temporal cortex: dendritic spine head diameter significantly improved the prediction of episodic memory performance after accounting for β-amyloid plaque burden, neurofibrillary tangle pathology, and sex. By contrast, the sheer number of spines did not provide the same predictive value. Larger spine head diameters correlated with better episodic memory, supporting the idea that synaptic strength — reflected in spine morphology — is a critical determinant of memory in older adults.
Herskowitz emphasized the translational implications: “Focusing on pathways that preserve or enhance spine head diameter and synaptic strength may offer more benefit than strategies aimed only at generating new spines. Such approaches could be especially useful for older adults in preclinical stages of Alzheimer’s disease.”
Dendritic spines are microscopic structures on dendrites that form synapses with incoming axons. Spine heads can expand or shrink as synapses form and strengthen, reflecting the brain’s plasticity. Measuring tens of thousands of spines required painstaking work spanning more than two years and continued through pandemic restrictions.
Co-first authors of the paper “Dendritic spine head diameter predicts episodic memory performance in older adults” are Courtney K. Walker and Evan Liu of the UAB Department of Neurology. Additional authors include researchers from UAB, Rush University Medical Center, Emory University School of Medicine, and SUNY Upstate Medical University.
Funding: The study was supported by multiple National Institutes of Health grants, including NS061788, AG067635, AG061800, AG054719, AG063755, AG068024, AG10161, AG72975, AG15819, AG17917, AG46152, and AG61356.
About this synaptic plasticity research news
Author: Jeffrey Hansen
Source: University of Alabama
Contact: Jeffrey Hansen – University of Alabama
Image: Image credited to Neuroscience News
Original Research: Closed access. “Dendritic spine head diameter predicts episodic memory performance in older adults” by Jeremy Herskowitz et al., Science Advances.
Abstract
Dendritic spine head diameter predicts episodic memory performance in older adults
Episodic memory among older adults varies considerably and has often been linked to the number of synapses or dendritic spines. We examined 2,157 neurons from 128 older participants in the Religious Orders Study and Rush Memory and Aging Project. Analysis of 55,521 dendritic spines using least absolute shrinkage and selection operator regression and nested model cross-validation revealed that dendritic spine head diameter in the temporal cortex — but not in the premotor cortex — improved prediction of episodic memory performance when models included β-amyloid plaque scores, neurofibrillary tangle pathology, and sex. These findings support the view that, in the temporal cortex, synapse strength is more important than synapse quantity for memory in old age.