Sleep (and specifically Slow-Wave Sleep), Older Adults, and Memory

So wending it’s way through the news cycle about a week or two ago (briefly) was some neuroscience research from folks at UC Berkeley relating to older adulthood, memory retention, and so-called “slow wave sleep.”

What these researchers did is took two groups of ostensibly healthy young adults (in their 20s) and older adults (in their 70s), and subjected them to a word-pair matching memory task where English words and nonsense words were associated and subject to a subsequent forced-choice recognition memory test (they did administer a number of other neuropsychological tests, but the critical one was the word-pair matching task). They selected the word-pair task because it was found in previous research to be sensitive to the effects of sleep in subjects performing the task.

Subjects were assessed immediately after the task, and then after a typical nights sleep for them (if you call typical when you’re wired up in a sleep lab), they were tested again – but the testing the next morning was done with subjects’ brains being monitored via fMRI.

Before I get to the results – what is sleep? When I was starting graduate school, sleep was an activity subdivided into five distinct identifiable stages according to the so-called Rechtschaffen and Kales sleep scoring criteria – this had been the method for identifying sleep stages for approximately the last 40 years. In 2007 the American Academy of Sleep Medicine got into the mix and simplified matters somewhat and made the practice of polysomnography somewhat more straightforward, by collapsing seven sleep stages into four. Thus, a typical sleep cycle looks like this:

N1 → N2 → N3 → N2 → REM

In both methods for scoring sleep, there was little real change in the objective criteria for identifying so-called Rapid Eye Movement, or REM sleep. N1 and N2 (formerly 1 and 2) were the same across both staging methods (representing N1 / 1 being essentially just drowsing, and N2 / 2 being so-called “alpha wave” sleep – where conscious awareness of the environment disappears).

Slow-wave sleep went from being measured across multiple sleep stages (3 & 4) using the R&K criteria and now is now measured in a single sleep stage (N3).

Below is something called a hypnogram, where sleep can be visually represented across the various sleep stages – typically looks like this (peaks on this graph represent waking periods, with lower points representing increasingly deep sleep).hypnogram

The above hypnogram is a fairly typical looking representation of a young adult’s sleep pattern across an entire night. As is typical, there is more slow-wave sleep during the first ½ of the night and more REM sleep during the second half.

Now let’s look at a hypnogram depicting the same, typical young adults’ sleep with that of a typical older adult (from Lichstein & Morin, 2000; Treatment of Late-Life Insomnia – a great book).

(Note that the hypnograms here are scored using the older R&K criteria).

sleep stages

Note a difference? The term used by the sleep folks is that older adults, even ostensibly healthy ones, tend to show evidence of a “fractured sleep architecture,” characterized by more intrasleep arousals (those are the very highest points represented on the hypnogram), a generally shallower “sleep depth,” and significantly less time spent in NREM sleep (e.g., non-REM sleep). Lack of sleep depth and reductions in NREM sleep tend translate into lack of so-called slow-wave sleep.

Slow-wave sleep (SWS), is referred to as such due to the distinctive pattern of 75microvolt (0.5-2 Hz) waves observable on electroencephalogram (EEG) leads during a polysomnogram, and consist of stages 3 and 4 of the R&K criteria (now just stage N3). SWS is not dreaming sleep and typically when subjects are awoken from SWS they do not report dream activity (unlike REM sleep). It’s considered the most physically restorative sleep period, notable by the fact that production of human growth hormone (HGH) peaks during this time of night. Also, when SWS suffers in otherwise healthy young adults (as is the case in patients suffering from narcolepsy), the result is subjective reports of being physically exhausted, despite sleeping several hours a night, such as this person.

Back when I was a lowly predoctoral intern in psychology at UMDNJ in New Jersey, I did a rotation at the hospital’s sleep lab where we saw a number of patients and offered treatments. One of the “rules of thumb” I learned when I was first learning sleep medicine is that SWS is for resting the body, and REM sleep is for resting the mind.

Of course, sleep is an inordinately complex biological process and while it seems likely that REM sleep plays a role in consolidation of certain types of memories, it now seems clear that SWS plays a role in consolidation of memory, particularly declarative memory, as well.

So, back to Mander, Rao, and Lu et al. (2013; the Berkeley study referenced at the beginning of this post). What these researchers found is that SWS deficits observed in older adults were reliably related to performance deficits on the word pair matching task, and that this SWS deficit observed in older adults, moreover, was related to degeneration of a part of the brain called the medial prefrontal cortex (mPFC, part of the frontal lobes of the brain), and finally, was also related to overactivation of the hippocampus the next day.

The idea, of course, is SWS is the mechanism by which memories stored in the hippocampus (sort of a neurobiological memory buffer) are consolidated and shunted to the cerebral cortex for long-term storage, via the mPFC. If the mPFC is malfunctioning, the memories stay stranded in the hippocampal ‘buffer’ until they are overwritten. Which, of course, then provides us with a fascinating account of how those “senior moments” take place, or worse, how dementia begins to show itself in older adults.

The question is, how is this information of practical use? Interestingly, there are a number of ways to boost SWS. Exercise, hot baths, carbo-loading are some easy, drug-free methods. One of the active ingredients in cannabis, THC, is known to increase the duration of SWS. Transcranial stimulation (also known as EMG) is another method.

Hot baths, exercise, and eating sweet treats sounds nice, but may not do the job on their own. Use of cannabis to boost SWS, while it might be effective and with few side effects (aside from perhaps an increased preference for the aforementioned sweet treats) isn’t a particularly practical treatment given its current legal status. EMG is interesting but even more impractical given the expensive and unwieldy equipment required.

Another treatment option for boosting SWS is a prescription medication called Zyrem, also known as sodium oxybate. Zyrem is basically a chemical analogue of gamma-hydroxy-butyrate, also known as GHB. GHB, of course, is a neurochemical that humans produce endogenously (in our brains) and is thought to be related to the maintenance of the human sleep cycle, particularly as it relates to SWS.

Even there, however, the practicality issue makes use of GHB and GHB analogues difficult – GHB is also an illegal drug, like cannabis, and Zyrem is a drug that is more tightly controlled than many narcotic pain medications, and is only approved for use in narcolepsy.

This is unfortunate. Barring the invention of a cheap and portable version of an EMG machine for use in older adults beginning to show signs of memory problems (or even showing signs of frank dementia), direct methods for stimulation of SWS production in older adults is difficult given the practical (legal) limitations on use of agents like cannabis or GHB.

Of course, we should back up for a moment. It’s certainly possible that boosting SWS in older adults may be a successful treatment for memory problems – but it may not be. Recall that in the Berkeley study (Mander et al.), the reduction in SWS was observed to be related to degeneration of the mPFC (part of the frontal lobes of the brain). Its possible (although it seems unlikely) that boosting SWS may not reverse memory problems in older adults because, after all, it’s unclear how boosting SWS would actually reverse the brain damage we know now is associated with dementia. However, this is interesting information and hopefully there will be research taking place.

The most important document you will never write

An advance health care directive (AHCD) is a legal document designed to tell your doctors and your loved ones exactly how you want your health to be managed at the end of your life. In California, the Office of the Attorney General has put together a very helpful website that explains what an AHCD is, and even provides sample forms you can fill out and distribute to your health care providers and family members, no lawyer required.

Although it is relatively easy to complete an AHCD, a vast majority of people fail to do so. The great mystery is why. Certainly, many people find it uncomfortable to think about end-of-life issues. People who propose the government educate people about AHCDs are accused of wanting to create “death panels.” Also, we commonly segregate the elderly, so that choices concerning death and dying remain on the periphery. As a result, the importance of clearly spelling out end-of-life decisions fades into the hum and buzz of everyday life. Sometimes, it’s just hard to find the time to get your sh*! together.

The importance of completing an AHCD is particularly acute given the standard approach to end-of-life care in our culture. Absent an AHCD, an older adult is likely to be subjected to heroic measures when the adult might consider comfort care more appropriate, instead.

Certainly, the AHCD has its critics, and the form does not always communicate effectively the wishes of the patient at issue. However, the best way to make sure your end-of-life health care wishes are followed is to communicate what you want to those you love. A written document, such as an AHCD, is the best way to make those wishes clear.

“Robot & Frank” (2012): A Review

There’s a small collection of movies out there that offer a particularly notable and meaningful commentary on older adulthood. “Iris,” a bittersweet drama depicting the famous author and philosopher Iris Murdoch’s decline from Alzheimer’s, is a favorite of mine. The film’s depiction of the difficulties (and moments of joy) experienced by her devoted husband were extremely moving. There is also the hilarious fantasy tale in Pixar’s 2009 film “Up,” which so wonderfully and humorously depicts many of the prejudices and difficulties posed by older adults in our culture while at the same time spinning a delightful and eye-popping yarn.

“Robot and Frank” is a 2012 movie directed by the newcomer Jake Schreier in his feature-length debut. It stars Frank Langella who plays an aging, crotchety semi-retired cat burglar named Frank, who seems to be suffering from some early-stage dementia, and is cared for by his well-meaning but often-annoying two children.

The twist to this story (aside from Frank’s criminal tendencies) is that it takes place in the near future, and features a “healthcare robot” that Frank’s son has purchased to encourage Frank’s independence in his home, and to maintain Frank’s health. At first, Frank is hostile to the robot, but soon warms to his presence, particularly after he discovers that he can manipulate the robot into helping him resume his life of crime.  (Peter Sarsgaard plays the robot, FTW. — BT) On the one hand, you might think, “clearly this is a bug in this robot’s programming; why would the manufacturers allow this robot to participate in criminal behavior with their care recipients?” However, the movie explains that the robot does its best to create an individualized care plan for the care recipient, and the highest priority for the healthcare robot is to maintain high functioning in their charges.

Gerontologists will tell you: one of the best ways to slow or prevent cognitive decline in vulnerable elderly is for older adults to remain actively engaged in meaningful activities. The robot initially tries to encourage Frank to engage in activities like gardening and hiking, but this doesn’t quite do it for Frank. So, what we end up with in this movie is a series of hugely entertaining scenes where the robot is trained by Frank to pick locks, taken along with him to do “jobs,” and becomes Frank’s business partner in some of his exploits. As a result, Frank gets his second wind, begins to eat better, displays more excitement for life, and for a time, seems sharper than he has ever been – but as a downside he attracts the interest of the local police.

Throughout the movie, however, we’re reminded that Frank is never really quite well. He seems to be constantly disoriented (misremembering that his son is no longer in college; forgetting that his favorite restaurant has been gone for years), and at the end of the movie when the dramatic (obligatory for a buddy movie) chase scene ensues, he displays a massive lapse in his memory that really demonstrates that Frank’s memory may be beyond remediation.

The brilliance of this movie is that it does many things all at once, both cinematically and as a commentary on aging and dementia care. “Robot and Frank” manages to embed a humorous and fascinating commentary on dementia caregiving within a charming, heartwarming science fiction “buddy movie” storyline. Caregiving for an older adult with memory problems is challenging as any son or daughter with a demented older adult at home can tell you – this movie provides a whimsical way of exploring the challenges. This is quality and timely social commentary in a very fun package.