. 2024 May 9;16(1):102.

doi: 10.1186/s13195-024-01446-3.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory

Kitty K Lui^{1

2}, Abhishek Dave^{2

3}, Kate E Sprecher^{4

5

6

7}, Miranda G Chappel-Farley^{8

9}, Brady A Riedner¹⁰, Margo B Heston^{6

7}, Chase E Taylor¹¹, Cynthia M Carlsson^{6

7

12

13}, Ozioma C Okonkwo^{6

7

12

13}, Sanjay Asthana^{6

7

12

13}, Sterling C Johnson^{6

7

12

13}, Barbara B Bendlin^{6

7

12

13}, Bryce A Mander^{14

15

16}, Ruth M Benca^{17

18

19

20

21}

Affiliations

¹ San Diego State University/University of California San Diego, Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
² Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
³ Department of Cognitive Sciences, University of California, Irvine, CA, USA.
⁴ Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA.
⁵ Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.
⁶ Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA.
⁸ Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
⁹ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
¹⁰ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
¹¹ Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
¹² Wisconsin Alzheimer's Institute, Madison, WI, USA.
¹³ Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.
¹⁴ Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA. bmander@uci.edu.
¹⁵ Department of Cognitive Sciences, University of California, Irvine, CA, USA. bmander@uci.edu.
¹⁶ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA. bmander@uci.edu.
¹⁷ Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA. rbenca@wakehealth.edu.
¹⁸ Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA. rbenca@wakehealth.edu.
¹⁹ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA. rbenca@wakehealth.edu.
²⁰ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA. rbenca@wakehealth.edu.
²¹ Department of Psychiatry and Behavioral Medicine, Wake Forest University, Winston-Salem, NC, USA. rbenca@wakehealth.edu.

PMID: 38725033
PMCID: PMC11080222
DOI: 10.1186/s13195-024-01446-3

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory

Kitty K Lui et al. Alzheimers Res Ther. 2024.

. 2024 May 9;16(1):102.

doi: 10.1186/s13195-024-01446-3.

Authors

Affiliations

¹ San Diego State University/University of California San Diego, Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
² Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
³ Department of Cognitive Sciences, University of California, Irvine, CA, USA.
⁴ Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA.
⁵ Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.
⁶ Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA.
⁸ Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
⁹ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA.
¹⁰ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
¹¹ Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
¹² Wisconsin Alzheimer's Institute, Madison, WI, USA.
¹³ Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.
¹⁴ Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA. bmander@uci.edu.
¹⁵ Department of Cognitive Sciences, University of California, Irvine, CA, USA. bmander@uci.edu.
¹⁶ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA. bmander@uci.edu.
¹⁷ Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA. rbenca@wakehealth.edu.
¹⁸ Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA. rbenca@wakehealth.edu.
¹⁹ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA. rbenca@wakehealth.edu.
²⁰ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA. rbenca@wakehealth.edu.
²¹ Department of Psychiatry and Behavioral Medicine, Wake Forest University, Winston-Salem, NC, USA. rbenca@wakehealth.edu.

PMID: 38725033
PMCID: PMC11080222
DOI: 10.1186/s13195-024-01446-3

Abstract

Background: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk.

Methods: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined.

Results: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers.

Conclusion: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

PubMed Disclaimer

Conflict of interest statement

Dr. Mander has served as a consultant for Eisai Co., Ltd. Dr. Benca has served as a consultant for Eisai, Genomind, Idorsia, Jazz, Merck, and Sunovion. Dr. Riedner has several patents related to sleep technology jointly held by the Wisconsin Alumni Research Foundation and Philips Healthcare, and in addition to grant support, has given several lectures sponsored by Philips Healthcare.

Figures

**Fig. 1**
Scatter plots showing the relationships of (A) AHI, (B) RDI, and (C) ODI during REM sleep to RAVLT total learning scores while controlling for age, sex, time between assessments, years of education, BMI, and *APOE4* status

**Fig. 2**
Scatter plots showing the relationships of REM-NREM (A) AHI, (B) RDI, and (C) ODI ratios to RAVLT total learning scores while controlling for age, sex, time between assessments, years of education, BMI, and *APOE4* status

**Fig. 3**
Scatter plots showing the relationships of (A) AHI, (B) RDI, and (C) ODI during REM sleep to RAVLT long-delay scores while controlling for age, sex, time between assessments, years of education, BMI, and *APOE4* status

**Fig. 4**
Scatter plots showing the relationships of REM-NREM (A) AHI, (B) RDI, and (C) ODI ratios to RAVLT long-delay scores while controlling for age, sex, time between assessments, years of education, BMI, and *APOE4* status

**Fig. 5**
A The association between REM-NREM ODI ratio and RAVLT total learning scores was significantly moderated by *APOE4* status. Only the *APOE4* carriers showed that more oxyhemoglobin saturations during REM sleep as opposed to NREM sleep was related to worse learning performance. B The association between REM ODI and RAVLT total learning scores was moderated by age. A significant moderating effect was present at the mean age and 1 SD above the mean age (in 80% of the sample). C The association between REM-NREM RDI ratio and RAVLT long-delay recall score was moderated by *APOE4* status. A significant moderating effect was observed for only *APOE4* carriers in that, more respiratory events during REM sleep than in NREM sleep was associated with fewer words remembered after a 20-min delay

See this image and copyright information in PMC

Update of

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity and verbal memory.
Lui K, Dave A, Sprecher K, Chappel-Farley M, Riedner B, Heston M, Taylor C, Carlsson C, Okonkwo O, Asthana S, Johnson S, Bendlin B, Mander B, Benca R. Lui K, et al. Res Sq [Preprint]. 2023 Dec 2:rs.3.rs-3683218. doi: 10.21203/rs.3.rs-3683218/v1. Res Sq. 2023. Update in: Alzheimers Res Ther. 2024 May 9;16(1):102. doi: 10.1186/s13195-024-01446-3. PMID: 38076899 Free PMC article. Updated. Preprint.

References

1. Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Annu Rev Med. 1976;27:465–484. doi: 10.1146/annurev.me.27.020176.002341. - DOI - PubMed
1. Shi L, Chen S-J, Ma M-Y, Bao Y-P, Han Y, Wang Y-M, et al. Sleep disturbances increase the risk of dementia: a systematic review and meta-analysis. Sleep Med Rev. 2018;40:4–16. doi: 10.1016/j.smrv.2017.06.010. - DOI - PubMed
1. Emamian F, Khazaie H, Tahmasian M, Leschziner GD, Morrell MJ, Hsiung G-YR, et al. The association between obstructive sleep apnea and Alzheimer’s disease: a meta-analysis perspective. Front Aging Neurosci. 2016;8:78. doi: 10.3389/fnagi.2016.00078. - DOI - PMC - PubMed
1. Bubu OM, Umasabor-Bubu OQ, Turner AD, Parekh A, Mullins AE, Kam K, et al. Self-reported obstructive sleep apnea, amyloid and tau burden, and Alzheimer’s disease time-dependent progression. Alzheimers Dement. 2021;17:226–245. doi: 10.1002/alz.12184. - DOI - PMC - PubMed
1. Macey PM, Prasad JP, Ogren JA, Moiyadi AS, Aysola RS, Kumar R, et al. Sex-specific hippocampus volume changes in obstructive sleep apnea. NeuroImage Clin. 2018;20:305–317. doi: 10.1016/j.nicl.2018.07.027. - DOI - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory

Affiliations

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Update of

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical