Forgetting where you parked may be a familiar sign of aging, but scientists are still working to understand why memory becomes less reliable over time. A new study from the University of California, Berkeley, links memory decline to disruptions in the brain waves that occur during deep sleep and to the accumulation of tau, a protein associated with Alzheimer’s disease. The findings suggest that tau in the frontal cortex is associated with changes in the coordinated electrical activity that helps consolidate memories overnight.
How deep sleep helps store memories
Episodic memory allows people to recall events from their lives, from childhood milestones such as the first day of elementary school to experiences that occurred only minutes earlier, such as parking a car. These memories contribute to long-term memory, but the ability to retrieve the sights, sounds and other details of past experiences often weakens with age.
Some memory loss is a normal part of aging. For people who develop Alzheimer’s disease, however, the changes can be substantially more severe. The new study offers clues about the processes that may connect normal aging, sleep and the disease.
Neuroscientist Omar Sharon and his colleagues, led by former Berkeley sleep researcher Matthew Walker, examined the relationship between disrupted brain waves during deep sleep, memory decline and tau accumulation. The study was published in Nature Neuroscience.
“This is the first time we have shown a link between tau and how it influences memory consolidation by attenuating progressive slow waves originating from the frontal lobe,” said Sharon, a postdoctoral fellow at the Center for Human Sleep Science at the University of California, Berkeley.
Sleep has several stages, each associated with distinct patterns of brain activity. Rapid eye movement, or REM, sleep is especially recognizable because the eyes move beneath closed eyelids and most dreaming occurs during this stage. Non-REM, or NREM, sleep is also important for maintaining healthy brain function.
During deep NREM sleep, large groups of neurons temporarily become inactive and then reactivate in a coordinated sequence. These synchronized changes produce slow brain waves that typically begin in the frontal cortex and spread across the brain.
“Each slow wave reflects a huge number of neurons turning off and back on again at the same time,” Sharon said. “Our study shows that it is important for memory that these events cascade sequentially across large parts of the brain. This coordinated shutdown has only been observed during deep sleep, and it may be one of the reasons we sleep.”
As tau accumulates in the aging brain, this carefully coordinated activity appears to become less organized. Instead of traveling together across broad regions, the waves become more dispersed and cover shorter distances. These changes are associated with reduced memory consolidation, cognitive decline and Alzheimer’s disease.
Tau is linked to disrupted brain waves
To investigate the relationship, the researchers used electroencephalography (EEG) to record brain activity during sleep. They compared cognitively healthy adults in their early 20s with older participants ranging from their mid-60s to mid-70s.
The difference was pronounced. In younger participants, groups of slow waves traveled together across a distance roughly equal to the width of a hand on the scalp. In older participants, the waves generally traveled shorter distances and appeared more independently rather than moving as coordinated groups.
The researchers then examined whether the changes were associated with tau accumulation. Working with William Jagust, professor emeritus of public health and neuroscience at the University of California, Berkeley, they used positron emission tomography (PET) scans to examine the brains of older participants. PET imaging uses radioactive tracers introduced into the bloodstream to show the distribution and biological activity of specific substances.
The scans showed that greater tau accumulation in the frontal cortex was associated with the breakdown of traveling waves typically seen during deep sleep.
Importantly, these changes were also found in people who did not develop Alzheimer’s disease.
“These people didn’t have Alzheimer’s disease,” Sharon said. “Although tau was present in their brains, there were potential effects. Their memory decline was within normal limits for their age.”
Sharon explained that the severity of changes associated with early Alzheimer’s disease can vary widely. Even when a person’s memory remains within the expected range for their age, the amount of tau in the brain is associated with cognitive performance.
“Lonely waves” are associated with memory loss
The researchers next investigated whether altered sleep activity corresponded to measurable differences in memory.
In the evening, participants learned pairs of related words. The following day, they were asked to recall the pairs, allowing the researchers to assess how effectively the memories had been retained overnight.
Participants whose slow waves traveled shorter distances and appeared more isolated generally remembered fewer word associations. The researchers referred to these disconnected patterns as “lonely waves.”
The team also followed some participants for several years to track changes over time. Among people with elevated tau levels in the frontal cortex, the researchers observed difficulty regulating slow waves and a reduced ability to retain newly learned information overnight.
Together, the observations support an association between tau accumulation, changes in deep-sleep brain activity and deterioration of episodic memory. They do not establish that tau directly causes memory loss or that disrupted waves are the cause of the decline.
Spinal-fluid tests support the findings
Because PET scans are expensive and require specialized equipment, the researchers looked for another way to examine the relationship between Alzheimer’s-related proteins and sleep activity.
In collaboration with Yoel Ju, a neurologist at Washington University in St. Louis, they analyzed spinal fluid from a separate group of older adults. The goal was to determine whether protein measurements produced results similar to those from the brain-imaging study.
Unlike PET scans, spinal-fluid analysis could not identify tau accumulation specifically in the frontal cortex. However, the results pointed in the same direction. People whose brains produced more isolated slow waves during sleep had higher ratios of tau to amyloid in their spinal fluid. Amyloid is another protein closely associated with Alzheimer’s disease.
The consistency across independent participant groups and testing methods strengthened the evidence for the association.
“I think that increases the strength of the evidence because it was collected in a completely different location and in a different cohort,” Sharon said.
Sleep recordings, brain scans, spinal-fluid analysis and memory assessments together suggest that tau accumulation is associated with specific disruptions in brain activity during deep sleep.
“This long-term correlation suggests that Alzheimer’s disease pathology is associated with disruption of this key sleep function,” Sharon said.
What deep sleep may reveal about brain aging
Memory often declines with age, but the research suggests that the process may involve more than aging alone. Alzheimer’s-related changes, particularly tau accumulation in regions involved in generating widespread slow waves, may help explain why some people have greater difficulty retaining memories.
“It’s not just about age,” Sharon said. “It’s how many lesions are in the frontal region where the global wave originates.”
Sleep quality may also play a role. Although the composition and movement of slow brain waves can be difficult to define or measure precisely, they may provide indicators of how efficiently the brain performs its nighttime memory functions.
The findings raise the possibility that changes in deep-sleep activity could eventually help researchers identify or better understand early memory problems. They may also point to potential targets for treatments intended to preserve memory during aging.
For now, important questions remain unanswered. Scientists must determine whether tau accumulation contributes to the disruption of synchronized sleep waves, whether changes in those waves influence tau accumulation, or whether other processes help explain the relationship.
“We see tau and lone waves rising together over time,” Sharon said. “What we can’t say yet is which will lead, and that question will determine how we design our interventions.”
Additional co-authors include Shi Chen, James Westphal, Chelsea Brown and Viyoma D. Shah of the University of California, Berkeley, and Jason Dude of Washington University in St. Louis.
The research was funded by a grant from the National Institutes of Health’s National Institute on Aging. Sharon also received support from a Glenn Medical Research Foundation Postdoctoral Fellowship and a Weill Neurohub Fellowship.
Source: www.sciencedaily.com
