New study looks at role of sleep disruption in dogs with dementia
IMAGE: WOOFUS, A PARTICIPANT IN THE SLEEP STUDY, GETS ELECTRODES PLACED. view more
CREDIT: JOHN JOYNER, NC STATE UNIVERSITY
Dogs with dementia suffer the same sleep disruptions that humans with dementia do. In a new study, researchers from North Carolina State University performed electroencephalography, or EEGs, on elderly dogs to determine whether brain-wave readings during sleep correlated with signs of cognitive decline. They found that dogs with more advanced dementia suffered more sleep disruptions and slept less overall than dogs with normal cognitive function.
The study – part of an ongoing clinical trial on canine aging and cognition at NC State – looked at 28 elderly dogs: 17 females and 11 males. Prior to the sleep study, the dogs had received complete physicals, undergone cognitive testing, and their owners completed the Canine Dementia Scale (CADES) questionnaire, in order to determine the severity of their cognitive decline.
The researchers used non-invasive techniques to gather their data – the dogs weren’t sedated, and the electrodes were affixed to the skull with sticky gel. The dogs did two sleep sessions in the lab – the first one to acclimate them to the surroundings and electrode placement, and the second to record brain activity during a two hour sleep period.
“Past sleep studies in dogs often involved surgically implanted electrodes,” says Alejandra Mondino, postdoctoral researcher at NC State and lead author of the study. “Non-invasive studies are relatively new. We are one of a handful of groups doing this work.”
The EEG measured four stages of sleep: wakefulness, drowsiness, NREM and REM. NREM, or non-REM, is a deep sleep state prior to REM (which stands for rapid eye movement and is associated with dreaming).
“In NREM, the brain clears toxins, including the beta-amyloid proteins that are involved in diseases like Alzheimer’s,” Mondino says. “REM sleep is when dreams happen, and this stage is very important for memory consolidation.”
The researchers correlated the percentage of time spent in each sleep state with the dogs’ scores on cognitive testing and the CADES questionnaire. The higher the dog’s dementia score, the less time they spent in NREM and REM sleep.
“These dogs have dementia and sleep disruption is part of that,” Mondino says. “In addition to the shorter time spent sleeping, when we look at the EEG, we saw their brain activity during sleep was more akin to wakefulness.
“In other words, when they do manage to sleep, their brains aren’t really sleeping.”
The work is an important part of establishing baselines for identifying cognitive decline in dogs. The researchers hope that the work can lead to early diagnosis and intervention for elderly dogs with signs of cognitive decline.
“We now know that EEG signatures are useful indicators of canine cognitive dysfunction,” says Natasha Olby, the Dr. Kady M. Gjessing and Rahna M. Davidson Distinguished Chair in Gerontology at NC State and corresponding author of the study. “The work further establishes the dog as a model for Alzheimer’s disease. Hopefully therapeutic trials in dogs will help to direct our choices of treatment development for people.”
The work appears in Frontiers in Veterinary Science and was supported by the Kady M. Gjessing and Rahna M. Davidson Distinguished Chair in Gerontology, the Sleep Research Society Foundation (Grant 04-SRG-21) and the Company of Biologists (Grant DMMTF2205727).
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Note to editors: An abstract follows.
“Sleep and cognition in aging dogs. A polysomnographic study”
DOI: 10.3389/fvets.2023.1151266
Authors: Alejandra Mondino, Michael Khan, Claire Ludwig, Margaret Elizabeth Gruen and Natasha J. Olby, North Carolina State University; Magaly Catanzariti, Instituto de Matemática Aplicada del Litoral Santa Fe, Argentina; Diego Martin Mateos, Instituto de Matemática Aplicada del Litoral Santa Fe, Argentina and Universidad Autónoma de Entre Ríos (UADER), Entre Ríos, Argentina; Anna Kis, Research Centre for Natural Sciences, Institute of Cognitive Neuroscience and Psychology, Budapest, Hungary
Published: Apr. 28, 2023 in Frontiers in Veterinary Science
Abstract:
Introduction: Sleep is fundamental for cognitive homeostasis, especially in senior populations since clearance of amyloid beta (key in the pathophysiology of Alzheimer’s disease) occurs during sleep. Some electroencephalographic characteristics of sleep and wakefulness have been considered a hallmark of dementia. Owners of dogs with canine cognitive dysfunction syndrome (a canine analog to Alzheimer’s disease) report that their dogs suffer from difficulty sleeping. The aim of this study was to quantify age-related changes in the sleep-wakefulness cycle macrostructure and electroencephalographic features in senior dogs and to correlate them with their cognitive performance.
Methods: We performed polysomnographic recordings in 28 senior dogs during a 2 h afternoon nap. Percentage of time spent in wakefulness, drowsiness, NREM, and REM sleep, as well as latency to the three sleep states were calculated. Spectral power, coherence, and Lempel Ziv Complexity of the brain oscillations were estimated. Finally, cognitive performance was evaluated by means of the Canine Dementia Scale Questionnaire and a battery of cognitive tests. Correlations between age, cognitive performance and sleep-wakefulness cycle macrostructure and electroencephalographic features were calculated.
Results: Dogs with higher dementia scores and with worse performance in a problem-solving task spent less time in NREM and REM sleep. Additionally, quantitative electroencephalographic analyses showed differences in dogs associated with age or cognitive performance, some of them reflecting shallower sleep in more affected dogs.
Discussion: Polysomnographic recordings in dogs can detect sleep-wakefulness cycle changes associated with dementia. Further studies should evaluate its potential clinical use to monitor the progression of canine cognitive dysfunction syndrome.
JOURNAL
Frontiers in Veterinary Science
ARTICLE TITLE
Sleep and cognition in aging dogs. A polysomnographic study
ARTICLE PUBLICATION DATE
28-Apr-2023
Old dogs with dementia sleep less
deeply, just like people with Alzheimer’s
Dogs with higher dementia scores and worse performance in problem-solving task show changes in brain waves symptomatic of shallow sleep
In people with Alzheimer’s, the earliest symptoms are commonly disruptions in sleep rhythms. These include daytime sleepiness, showing agitation or confusion around dusk, staying awake longer, and waking up often at night. These changes are thought to result from damage to sleep-regulating areas in the brain. Alzheimer patients tend to spend less time in both REM (rapid eye movement) sleep, in which most dreaming occurs, and non-REM (NREM) sleep. But they show the greatest reduction in so-called slow-wave sleep (SWS) – a stage of non-dreaming deep sleep, characterized by slow ‘delta’ brain waves (0.1 to 3.5 Hz) – when day-time memories are consolidated.
Now, scientists have shown that the same reduction in sleep time and delta brain waves occurs in dogs with the canine equivalent of dementia, canine cognitive dysfunction syndrome (CCDS). These dogs thus sleep less and less deeply. The results are published in Frontiers in Veterinary Science.
“Our study is the first to evaluate the association between cognitive impairment and sleep using polysomnography – the same technique as used in sleep studies in people – in aged dogs,” said senior author Dr Natasha Olby, a professor of veterinary neurology and neurosurgery at North Carolina State University.
Old dogs with or without dementia
Olby and colleagues studied 28 female and male senior mixed- and full-breed dogs between 10.4 and 16.2 years of age, which corresponds to between 81% and 106% of their average lifespan, depending on size. Their owners were asked to fill in a questionnaire about their canine companions, to rate the severity of symptoms of CCDS like disorientation, poor social interactions, and house soiling. The researchers also examined the dogs for possible orthopedic, neurological, biochemical, and physiological co-morbidities.
Based on the results, eight dogs (28.5%) were classified as normal, while another eight (28.5%), four (14.3%), and eight (28.5%) had mild, moderate, or severe CCDS, respectively.
The researchers then performed a series of cognitive tests on the dogs, to measure their attention, working memory, and executive control. For example, in the ‘detour task’, a dog had to retrieve a treat from a horizontal transparent cylinder by accessing it from either end – this task is then made more difficult by blocking off her or his preferred side so they have to show cognitive flexibility to detour to the other end of the cylinder.
Sleep clinic for dogs
Then, first author Dr Alejandra Mondino (a postdoctoral fellow in Olby’s research group) and colleagues performed a polysomnography studies in a quiet room with dim light and white noise in a ‘sleep clinic’. The dogs were allowed to spontaneously take an afternoon noon nap, while electrodes measured their brain waves, the electrical activity of the muscles and heart, and eye movements. These measurements lasted up to two hours, but were stopped if the dogs became anxious, attempted to leave the room, or removed the electrodes. 26 (93%) dogs entered drowsiness, 24 (86%) entered NREM sleep, while 15 (54%) entered REM sleep.
The results showed that dogs with higher dementia scores, and dogs who did worse on the detour task, took longer to fall asleep and spent less time sleeping, and this was true for both NREM and REM sleep.
Dogs with poorer memory scores showed changes, such as fewer slow oscillations in their electroencephalograms, during REM sleep, indicating that they slept less deeply during this phase.
“In people, slow brain oscillations are characteristic of SWS and linked to the activity of the so-called ‘glymphatic system, a transport system that removes protein waste products from the cerebrospinal fluid,” said Olby.
“The reduction in slow oscillations in people with Alzheimer’s, and the associated reduced removal of these toxins, has been implicated in their poorer memory consolidation during deep sleep.”
In contrast, dogs with poorer memory had more pronounced fast beta waves, between 15.75 and 19 Hz. Strong beta waves are typical of wakefulness in healthy people and dogs, so are not a normal phenomenon during sleep – again indicating that dogs with CCDS sleep less deeply.
Day sleeping versus night sleeping
Dogs which did worse at the ‘sustained gaze’ task, which measures attention span, showed tighter coupling in delta waves between the two brain hemispheres – a result that has also been found in people with dementia.
The authors concluded that the dogs with CCDS showed changes in the sleep-wakefulness cycle during the experiments that resemble those found in people with Alzheimer’s. But they caution that it’s still unknown if these changes also occur during when dogs sleep at night instead of in the afternoon.
“Our next step will be to follow dogs over time during their adult and senior years to determine if there are any early markers in their sleep-wakefulness patterns, or in the electrical activity of their brain during sleep, that could predict the future development of cognitive dysfunction,” said Olby.
JOURNAL
Frontiers in Veterinary Science
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
Animals
ARTICLE TITLE
Sleep and cognition in aging dogs. A polysomnographic study
ARTICLE PUBLICATION DATE
28-Apr-2023
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