My grandparents have had a small apartment at an assisted living center in my town for the past couple of years. Papa is now a common figure in our town’s pharmacy and convenience store, always buying scratch tickets, chatting with people and creating enough errands for himself to fill up each day. Meanwhile back at the living center Nana manages to maintain the same warm, welcoming glow that she has always had. That she can do this – still be tender and earnest and eager – continues to be more impressive each day as Alzheimer’s mercilessly pursues its degradation of her neurological functioning.

Two days ago I woke up to a long text from my mom about Nana and Papa. The message was an update: my large extended family had finally decided on a new living arrangement for Nana. She would soon be moving to a 24/7 “memory care” facility in the town over from us. Simultaneously Papa would move to a one-room studio apartment in the same assisted living center as before.

My thoughts for the rest of the day remained with my grandparents, and my mind wandered to sleeping, dreaming, and dementia when I began pondering topics to write about for this post. As I started searching key terms, a narrative of dementia’s complex and ever-evolving relationship with sleep and dreaming gradually took form.

First I needed to refresh my understanding of Alzheimer’s, which is the most common form of dementia. Alzheimer’s is a neurodegenerative disease that slowly damages and then kills brain cells. Essentially, the neurons that are needed for normal brain function begin to die prematurely. Neuroscientists studying Alzheimer’s have developed and continued to develop several theories about the onset and cause of Alzheimer’s, but the most robust findings to date regard brain abnormalities (Alzheimer’s Association).

Protein plaques build up between the nerve cells of Alzheimer’s patients and intrusive microscopic tangles of protein also form. As the amount of plaques and tangles increases, there is a loss of connection between cells and one’s brain tissue begins to deteriorate. Meanwhile, the fluid-filled spaces in the brain grow larger and larger. As these changes occur, the basic brain functions that we constantly rely on – like executive planning and memory formation – are threatened and, with time, eradicated. To navigate through the Alzheimer’s Association’s “Brain Tour” and learn more about the neurological impact of Alzheimer’s, click here.

It is not surprising then, with such drastic changes to the brain, that sleep and dreaming are also affected as dementia takes over. In a 2004 research review, Dr. Donald Bliwise reports that as dementia becomes more severe, sleep wakefulness after sleep onset has been found to increase, nocturnal total sleep time has been found to decrease, and sleep efficiency (which is the time one actually spends fully asleep in bed) has also been found to decrease. In line with unstable sleep patterns, napping during the day and sleepiness have also been found to increase.

The same review reports that the amount of rapid eye movement (REM) sleep decreases in people with Alzheimer’s, and that the onset of the first REM episode is pushed back to later in one’s sleep. As Bliwise explains, REM relies largely on cholinergic neurotransmission; so, when the brain’s cholinergic system is damaged
during dementia, REM sleep may be negatively affected. In turn, Bliwise wonders whether or not acetylcholinesterase inhibitors – the drugs most commonly used to slow down cognitive loss in people with dementia – could potentially increase REM.

Subsequently, various researchers have taken on the task of further studying acetylcholinesterase inhibitors (AChEIs) and REM. Walter dos Santos Moraes and colleagues researched the REM sleep outcomes of mild to moderate Alzheimer’s patients who were given either the AChEI drug Donepezil or a placebo (dos Santos Moraes et al., 2005). Donepezil is one of the “second generation” AChEIs that has been developed to treat Alzheimer’s in the past two decades, and because it is regarded as having the best pharmacological profile of any dementia medications, much clinical research continues to be done with it (Cacabelos, 2007). As with other AChEIs, Donepezil works to inhibit acetylcholine degradation in the space between neurons so that normal neural connectivity and function may be maintained (Cacabelos, 2007).

Walter dos Santos Moraes and collaborators found that REM sleep percentage increased after three and six months for participants in the Donepezil treatment group compared to the placebo group. These results aligned with the findings of other studies (such as Mizuno et al., 2004), and thus over time the idea that AChEIs relate to increased REM in people with dementia has taken hold.

Naturally, conclusions about REM sleep in people with dementia led me to think about dreaming. We’ve learned from past research that REM sleep is strongly associated with dreaming (Hobson, 2009); so, I wondered, if REM sleep increases when AChEIs like Donepezil are taken, does dreaming increase too?

While I searched online for answers to my question, I happily pictured Nana entering a peaceful dreamland each evening in her sleep. Unfortunately, this wishful image was rather dashed by what I ended up finding; people with dementia who take AChEIs can and do indeed dream, but their typically very vivid dreams are often extremely unusual, abnormal, and even nightmarish (Cacabelos, 2007). In fact, researchers have found that the closer to bedtime that people with Alzheimer’s take Donepezil, the higher the likelihood is that they will have a nightmare (Singer et al., 2005).

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With these findings in mind, I think I will still hold onto the optimistic hope that – if she dreams – Nana’s dreams aren’t nightmarish but rather pleasant jaunts at the farm where she grew up or lingering remembrances of a bustling home full of her many children and grandchildren. After all, as we have discussed in class, dream research is exceptionally subjective.

After delving into this topic I have come away with many more questions than I began with and I can only imagine that researchers feel the same way. So, to that end, I will also hold onto the optimistic hope that sometime soon the puzzle that is dementia will be solved and all can sleep easy.

Header Image: “On the Way Home” by Mary H. Created as part of the Alzheimer’s Association’s Memories in the Making art therapy program. 

Sources

Bliwise, Donald L. (2004). Sleep disorders in Alzheimer’s disease and other dementias. Clinical Cornerstone: Neurodegenerative Diseases, 6(1A), S16-S28.

Cacabelos, R. (2007). Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics. Neuropsychiatric Disease and Treatment, 3(3), 303-333.

dos Santos Moraes, W. A., Poyares, D. R., Guilleminault, C., Ramos, L. R., Bertolucci, P. F., & Tufik, S. (2006). The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: A double-blind placebo-controlled study. Sleep: Journal of Sleep and Sleep Disorders Research, 29(2), 199-205.

Hobson, J. A. (2009). REM sleep and dreaming: Towards a theory of protoconsciousness. Nature Reviews Neuroscience, 10(11), 803-813.

Mizuno S, Kameda A, Inagaki T, et al. 2004. Effects of donepezil on Alzheimer’s disease: the relationship between cognitive function and rapid eye movement sleep. Psychiatry Clinical Neuroscience, 58(6), 660–5.

Singer M, Romero B, Koenig E, et al. 2005. Nightmares in patients with Alzheimer’s disease caused by donepezil. Therapeutic effect depends on the time of intake. Nervenartz, 76(9), 1127–9.

“What We Know Today About Alzheimer’s Disease and Dementia.” (n.d.) Alzheimer’s Association. Retrieved from http://www.alz.org/research/science/alzheimers_research.asp