Possible link between Alzheimer's disease and disrupted sleep-dependent memory consolidation?

It has been well established that certain kinds of sleep consolidate certain kinds of memory. Mander and colleagues (2015) discovered that in older adults, beta-amyloid (the main component of amyloid plagues found in Alzheimer's disease) appears to disrupt slow wave activity in the medial frontal cortex during NREM sleep, which then impairs hippocampus-based memory consolidation.

It would also be interesting to investigate possible disruptions in thalamic sleep spindle activity to see how this may further contribute to memory impairment in this population. I wrote about this possibility in my Sleep Medicine Review's paper a few years ago.

Here is Mander et al.'s abstract, which appears under the advanced online publication section of Nature Neuroscience:

Independent evidence associates β-amyloid pathology with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here we show that β-amyloid burden in medial prefrontal cortex (mPFC) correlates significantly with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation was not direct, but instead statistically depended on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly.

Reference:
Mander, B.,A., Marks, S.,M., Vogel, J.,W., Rao, ,Vikram, Lu, ,Brandon, Saletin, J.,M., . . . Walker, M.,P.Beta]-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation.

Lu, W., & Göder, R. (2012). Does abnormal non-rapid eye movement sleep impair declarative memory consolidation? Sleep Medicine Reviews, 16 (4), 389-394 DOI: 10.1016/j.smrv.2011.08.001


Comments

  1. Recently, I overviewed the details of NREM sleep and how dreams are effected in both the NREM and REM sleep. After reading this article about the linkage of dependent memory consolidation and the beta-amyloid causing a disruption in the linkage of wave lengths in NREM sleep, I can’t help but wonder why this linkage would cause a decline in memory of older adults and not younger people. Also, people recalling dreams are more likely to mention dreams after being awaken during REM sleep and not NREM sleep, even though it’s not impossible, but why would this disruption cause a dramatic change in memory consolidation when dreams are already mentioned as not being remembered as often during NREM sleep? The idea of how the beta-amyloid effects the wave lengths and how that is connected to those similar with Alzheimer's seems extremely fascinating but also seems to be a very complex situation.

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    1. Hi Brandi, my feeling is that similar results would be found in younger adults with similar NREM sleep disruptions and amyloid buildup.

      Dream recall is certainly different compared to a list learning and recall task.

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  2. I can completely understand how this disruption of sleep waves can cause people with Alzheimer's to be unable to consolidate memories. First off many people with Alzheimer's also have what is known at sundowner's. That is once the sun goes down and it is time for bed their level of confusion increases greatly. Maybe it is because they are mentally and physically exhausted, but at night time these patients seem like a different person. But think about this, if you are not sleeping well because of confusion and then on top of that the slow waves of sleep are being interrupted, of course these people are confused. My question is this: Is the interrupted sleep waves causing the worsening memory loss or is the confusion causing interrupted sleep.

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    1. Hi Samantha, gotta love the chicken or egg questions. My guess is that it's the former given the hard evidence from the paper, but there could be possibility for the latter explanation. The authors did control for cognitive impairment, however.

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  3. Alzheimer’s is a serious disease that has no treatment. In the past couple of weeks I have learned several things about how the brain works. Recently, we talked about REM and NREM sleep. One thing I have learned about REM and NREM sleep is that REM and NREM sleep are important for consolidating different types of memories. Depriving people of sleep early in the night, most NREM sleep, impairs verbal learning, such as memorizing a list of words, whereas depriving people of sleep during the second half of the night, more REM sleep, impairs consolidation of learned motor skills. After reading this article and looking back on personal experience, I can see how in older adults beta-amyloid appears to disrupt slow wave activity in the medial frontal cortex during NREM sleep. I have had first-hand experience with someone with Alzheimer’s disease. She never slept at night and when she did it was not for very long. The brain is a very complex thing, and I believe we still have a long way to being able to understand the brain and other things such as sleep.

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    1. Hi Brittany, indeed there are different types of memory being consolidated during different types of sleep. I recommend that you read my Sleep Medicine Review's paper from 2012 in which I go into further detail about this distinction.

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  4. Thanks for sharing this post. Alzheimer’s disease is a problem of the brain. The problem often causes modern forgetfulness, as well as taking those who suffer the illness of their perceptive objective. ementias often occurs while the brain is functioning, i.e. controlling progress, or movement, etc, which the feelings are arrested. Alzheimer’s disease treatment in India can now be easily done.

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