REM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology

So your doctor needs a sleep protocol for you to prevent Alzheimers. 

Your risk of dementia, has your doctor told you of this?  Your doctor is responsible for preventing this!

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018

REM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology

• Zsófia Zavecz,
• Vyoma D. Shah,
• Olivia G. Murillo,
• Raphael Vallat,
• Bryce A. Mander,
• Joseph R. Winer,
• William J. Jagust &
• Matthew P. Walker 

BMC Medicine volume 21, Article number: 156 (2023) Cite this article

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Abstract

Background

Alzheimer’s disease (AD) pathology impairs cognitive function. Yet some individuals with high amounts of AD pathology suffer marked memory impairment, while others with the same degree of pathology burden show little impairment. Why is this? One proposed explanation is cognitive reserve i.e., factors that confer resilience against, or compensation for the effects of AD pathology. Deep NREM slow wave sleep (SWS) is recognized to enhance functions of learning and memory in healthy older adults. However, that the quality of NREM SWS (NREM slow wave activity, SWA) represents a novel cognitive reserve factor in older adults with AD pathology, thereby providing compensation against memory dysfunction otherwise caused by high AD pathology burden, remains unknown.

Methods

Here, we tested this hypothesis in cognitively normal older adults (N = 62) by combining ¹¹C-PiB (Pittsburgh compound B) positron emission tomography (PET) scanning for the quantification of β-amyloid (Aβ) with sleep electroencephalography (EEG) recordings to quantify NREM SWA and a hippocampal-dependent face-name learning task.

Results

We demonstrated that NREM SWA significantly moderates the effect of Aβ status on memory function. Specifically, NREM SWA selectively supported superior memory function in individuals suffering high Aβ burden, i.e., those most in need of cognitive reserve (B = 2.694, p = 0.019). In contrast, those without significant Aβ pathological burden, and thus without the same  need for cognitive reserve, did not similarly benefit from the presence of NREM SWA (B = -0.115, p = 0.876). This interaction between NREM SWA and Aβ status predicting memory function was significant after correcting for age, sex, Body Mass Index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity (p = 0.042).

Conclusions

These findings indicate that NREM SWA is a novel cognitive reserve factor providing resilience against the memory impairment otherwise caused by high AD pathology burden. Furthermore, this cognitive reserve function of NREM SWA remained significant when accounting both for covariates, and factors previously linked to resilience, suggesting that sleep might be an independent cognitive reserve resource. Beyond such mechanistic insights are potential therapeutic implications. Unlike many other cognitive reserve factors (e.g., years of education, prior job complexity), sleep is a modifiable factor. As such, it represents an intervention possibility that may aid the preservation of cognitive function in the face of AD pathology, both present moment and longitudinally.

Peer Review reports

Background

The prevalence of Alzheimer’s disease (AD) shows an almost exponential increase with age (currently averaging around 10% in individuals above the age of 65), causing the number of individuals affected by it to escalate as life expectancy increases [1, 2]. Further, Alzheimer’s disease and its associated pathologies of β-amyloid (Aβ) and tau are typified by cognitive impairment [3,4,5,6,7,8,9,10]. Consistent with this, individuals with high Aβ burden (Aβ positive, Aβ+) have a worse cognitive function and undergo faster cognitive decline than those with low Aβ burden (Aβ negative, Aβ- [3,4,5,6]).

However, a paradox has become increasingly clear: some individuals with high amounts of Aβ pathology suffer marked memory impairment, while others with the same degree of pathology burden show little impairment [11]. Why is this? One proposed explanation is cognitive reserve [12, 13], i.e., factors that offer compensation against the effects of substantive AD pathology.

Cognitive reserve factors identified to date include a greater number of years of education [14,15,16], higher occupational complexity [17, 18], and higher levels of physical activity [19, 20]. Nevertheless, even when combining all reserve factors identified to date, they explain only a modest degree of the full magnitude of cognitive reserve expressed across individuals [21]. This indicates that other such factors must exist that have yet to be identified.

Here, we propose that one novel and currently unexplored factor supporting cognitive reserve in the face of Aβ pathology burden is sleep, and specifically the quality of non-rapid eye movement slow wave sleep (NREM SWS). Five lines of evidence support this hypothesis.

First, a robust literature has demonstrated the beneficial effect of sleep on cognitive performance, particularly for hippocampal-dependent learning and memory [22, 23]. Second, manipulations of NREM SWS and the electroencephalographic (EEG) quality of NREM SWS (indexed in slow wave activity, SWA) causally enhance cognitive function in older adults, and in those with mild cognitive impairment [24, 25]. Third, selective deprivation of NREM SWA in older adults causally impairs hippocampal activity and associated learning, especially for item-based memory [26]. Fourth, Aβ burden is associated with impairments in NREM SWA, which in turn, predicts worse memory performance [27]. Fifth, degraded memory performance is associated with worse sleep efficiency, most prominently in individuals with high Aβ burden [28].

Despite such converging evidence, the possibility that NREM SWA represents a neurophysiological cognitive reserve factor that supports superior memory function under conditions of high Aβ burden remains untested. Of note, the proposal of NREM SWA as a cognitive reserve factor is dissociable from existing findings that show that impaired sleep is associated with worse and declining memory in older adults, and in those with AD pathology. Instead, the current hypothesis describes the opposite scenario: when facing severe AD pathology burden, NREM SWA beneficially mitigates against that high AD pathological state and supports superior cognitive function as a result. That is, we propose a new pathway through which sleep and cognitive function are connected in AD, namely a cognitive reserve pathway wherein NREM SWA confers protective compensation against existing AD pathology burden.

We tested this overarching hypothesis by combining ¹¹C-PiB (Pittsburgh compound B) positron emission tomography (PET) scanning, which offers in vivo estimates of Aβ burden, with sleep EEG recordings quantifying NREM SWA, and a behavioral test of sleep-dependent hippocampal-related learning, focusing on item-based memory [26]. This design offered a test of the prediction that NREM SWA moderates the effect of Aβ pathology burden on memory function, such that NREM SWA supports superior cognitive performance under circumstances of high need for cognitive reserve, i.e., high Aβ burden. Thus, the study addressed the three formal components that have been described in the characterization of cognitive reserve [12, 13]: 1) a feature or disease measurement known to impact cognition (here, Aβ), 2) a measure of cognition (here, memory function), and 3) a variable that influences the relationship between Aβ and memory (here, NREM SWA).

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