As people age, remembering everyday experiences such as where a car was parked can become more difficult. A study from the University of California, Berkeley, offers new evidence that this decline is associated with the accumulation of tau, an Alzheimer’s disease-related protein, and with disruptions in the coordinated slow brain waves produced during deep sleep. The findings connect tau in the frontal cortex with weaker overnight memory consolidation, while also showing that the relationship does not necessarily mean a person has Alzheimer’s disease.
How deep sleep helps store memories
Remembering personal experiences depends on episodic memory, which allows people to recall events ranging from childhood milestones to something that happened only minutes earlier. This form of memory contributes to long-term memory, but it often becomes less reliable with age. Sights, sounds and other details associated with past experiences can become harder to retrieve. Although some memory loss is a normal part of aging, the changes can be much more severe in people who develop Alzheimer’s disease.
Neuroscientist Omar Sharon and his colleagues, led by former Berkeley sleep researcher Matthew Walker, investigated how aging affects the brain systems that support memory. They identified an association between disrupted brain waves during deep sleep, memory decline and the accumulation of tau.
The results suggest that tau accumulation in the brain’s frontal cortex is associated with changes in the electrical activity that helps preserve memories overnight.
“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.
The study was published in Nature Neuroscience.
Sleep occurs in several stages, each with its own patterns of brain activity. Rapid eye movement, or REM, sleep is widely recognized because the eyes move beneath closed eyelids and most dreaming occurs during this stage. Non-rapid eye movement, or NREM, sleep is also important for healthy brain function, particularly during its deeper stages.
During deep NREM sleep, large groups of neurons temporarily become inactive before becoming active again in a coordinated sequence. These synchronized changes produce slow waves that usually 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.”
The researchers found that as tau accumulates in the aging brain, this carefully organized activity becomes less coordinated. Rather than traveling together across a broad area, the waves become more dispersed and cover shorter distances. These changes are associated with weaker memory consolidation, cognitive decline and Alzheimer’s disease.
Tau is linked to disrupted sleep waves
To examine the relationship, the scientists used electroencephalography, or EEG, to monitor 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 clear. 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 adults, the waves generally traveled shorter distances and appeared more independently instead of moving in coordinated groups.
The researchers then investigated whether the changes were associated with tau. Working with William Jagust, professor emeritus of public health and neuroscience at the University of California, Berkeley, they used positron emission tomography, or PET, scans to examine the brains of older participants. PET uses radioactive tracers introduced into the bloodstream to show the distribution and biological activity of particular substances.
The scans showed that greater tau accumulation in the frontal cortex was associated with the collapse of the longer-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 changes associated with early Alzheimer’s disease can vary considerably. Even when a person’s memory ability 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 tested 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 information 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 observe changes in their brains over time. People with elevated tau levels in the frontal cortex had greater difficulty regulating their slow waves and were less able to retain newly learned information overnight.
These observations support a relationship between tau accumulation, altered deep-sleep brain activity and the deterioration of episodic memory. However, the study did not establish that tau directly causes memory loss or that disrupted slow waves are the causal mechanism.
Spinal-fluid analysis supports the findings
Because PET scans are expensive and require specialized equipment, the researchers looked for another way to study the relationship between Alzheimer’s disease-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 aim was to determine whether protein measurements in the fluid revealed patterns similar to those found through brain imaging.
Spinal-fluid measurements cannot specifically identify tau accumulation in the frontal cortex. Nevertheless, 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 between the independent participant groups and the different testing methods strengthened the evidence for the relationship.
“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.
Together, sleep recordings, brain scans, spinal-fluid analysis and memory tests 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 reveals about brain aging
Memory often declines with age, but the findings suggest that the process involves more than aging alone. Alzheimer’s disease-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 be part of the explanation. Although the composition and movement of slow brain waves can be difficult to define and measure precisely, they may provide useful indicators of how efficiently the brain performs memory-related functions at night.
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 as people age.
For now, key questions remain unanswered. Scientists still need to determine whether tau accumulation contributes to the disruption of synchronized sleep waves, whether changes in those waves influence tau accumulation, or whether other biological processes account for 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, as well as 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