Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.
Humans
Female
Male
Alzheimer Disease
/ genetics
Middle Aged
Sleep, REM
/ physiology
Aged
Sleep Apnea, Obstructive
/ complications
Polysomnography
Risk Factors
Verbal Learning
/ physiology
Apolipoprotein E4
/ genetics
Memory
/ physiology
Severity of Illness Index
Sleep Apnea Syndromes
/ complications
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
09 May 2024
09 May 2024
Historique:
received:
29
11
2023
accepted:
01
04
2024
medline:
10
5
2024
pubmed:
10
5
2024
entrez:
9
5
2024
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 38725033
doi: 10.1186/s13195-024-01446-3
pii: 10.1186/s13195-024-01446-3
doi:
Substances chimiques
Apolipoprotein E4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102Subventions
Organisme : NIA NIH HHS
ID : F31 AG048732
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG033514
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG027161
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG052698
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG068353
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG052698
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG021155
Pays : United States
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Références
Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Annu Rev Med. 1976;27:465–84.
pubmed: 180875
doi: 10.1146/annurev.me.27.020176.002341
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.
pubmed: 28890168
doi: 10.1016/j.smrv.2017.06.010
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.
pubmed: 27148046
pmcid: 4828426
doi: 10.3389/fnagi.2016.00078
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;17:226–45.
doi: 10.1002/alz.12184
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;20:305–17.
pubmed: 30101062
pmcid: 6083433
doi: 10.1016/j.nicl.2018.07.027
Macey PM, Henderson LA, Macey KE, Alger JR, Frysinger RC, Woo MA, et al. Brain morphology associated with obstructive sleep apnea. Am J Respir Crit Care Med. 2002;166:1382–7.
pubmed: 12421746
doi: 10.1164/rccm.200201-050OC
Findley LJ, Barth JT, Powers DC, Wilhoit SC, Boyd DG, Suratt PM. Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia. Chest. 1986;90:686–90.
pubmed: 3769569
doi: 10.1378/chest.90.5.686
Zimmerman ME, Aloia MS. Sleep-disordered breathing and cognition in older adults.
Bubu OM, Andrade AG, Umasabor-Bubu OQ, Hogan MM, Turner AD, de Leon MJ, et al. Obstructive sleep apnea, cognition and Alzheimer’s disease: a systematic review integrating three decades of multidisciplinary research. Sleep Med Rev. 2020;50:101250.
pubmed: 31881487
doi: 10.1016/j.smrv.2019.101250
Petersen RC, Smith GE, Ivnik RJ, Kokmen E, Tangalos EG. Memory function in very early Alzheimer’s disease. Neurology. 1994;44:867–72.
pubmed: 8190289
doi: 10.1212/WNL.44.5.867
Rabin LA, Paré N, Saykin AJ, Brown MJ, Wishart HA, Flashman LA, et al. Differential memory test sensitivity for diagnosing amnestic mild cognitive impairment and predicting conversion to Alzheimer’s disease. Aging Neuropsychol Cogn. 2009;16:357–76.
doi: 10.1080/13825580902825220
Wong CG, Jeffers SL, Bell SA, Caldwell JZK, Banks SJ, Miller JB. Story memory impairment rates and association with hippocampal volumes in a memory clinic population. J Int Neuropsychol Soc. 2022;28:611–9.
pubmed: 34187612
doi: 10.1017/S1355617721000850
Morrell MJ, McRobbie DW, Quest RA, Cummin ARC, Ghiassi R, Corfield DR. Changes in brain morphology associated with obstructive sleep apnea. Sleep Med. 2003;4:451–4.
pubmed: 14592287
doi: 10.1016/S1389-9457(03)00159-X
Macey PM. Damage to the hippocampus in obstructive sleep apnea: a link no longer missing. Sleep. 2019;42:zsy266.
pubmed: 30615182
pmcid: 6765131
doi: 10.1093/sleep/zsy266
Wallace A, Bucks RS. Memory and obstructive sleep apnea: a meta-analysis. Sleep. 2013;36:203–20.
Varga AW, Kishi A, Mantua J, Lim J, Koushyk V, Leibert DP, et al. Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory. J Neurosci. 2014;34:14571–7.
pubmed: 25355211
pmcid: 4212062
doi: 10.1523/JNEUROSCI.3220-14.2014
Maquet P, Péters J-M, Aerts J, Delfiore G, Degueldre C, Luxen A, et al. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature. 1996;383:163–6.
pubmed: 8774879
doi: 10.1038/383163a0
Nofzinger EA, Mintun MA, Wiseman M, Kupfer DJ, Moore RY. Forebrain activation in REM sleep: an FDG PET study. Brain Res. 1997;770:192–201.
pubmed: 9372219
doi: 10.1016/S0006-8993(97)00807-X
McSharry DG, Saboisky JP, DeYoung P, Jordan AS, Trinder J, Smales E, et al. Physiological Mechanisms of Upper Airway Hypotonia during REM Sleep. Sleep. 2014;37:561–9.
pubmed: 24587579
pmcid: 3920322
doi: 10.5665/sleep.3498
Varga AW, Mokhlesi B. REM obstructive sleep apnea: risk for adverse health outcomes and novel treatments. Sleep Breath. 2019;23:413–23.
pubmed: 30232681
doi: 10.1007/s11325-018-1727-2
Andrade AG, Bubu OM, Varga AW, Osorio RS. The relationship between obstructive sleep apnea and Alzheimer’s disease. J Alzheimers Dis. 2018;64:S255–70.
pubmed: 29782319
pmcid: 6542637
doi: 10.3233/JAD-179936
Kadotani H, Kadotani T, Young T, Peppard PE, Finn L, Colrain IM, et al. Association between apolipoprotein E ∊4 and sleep-disordered breathing in adults. JAMA. 2001;285:2888–90.
pubmed: 11401610
doi: 10.1001/jama.285.22.2888
Ding X, Kryscio RJ, Turner J, Jicha GA, Cooper G, Caban-Holt A, et al. Self-reported sleep apnea and dementia risk: findings from the prevention of Alzheimer’s disease with Vitamin E and Selenium trial. J Am Geriatr Soc. 2016;64:2472–8.
pubmed: 27801937
pmcid: 5173398
doi: 10.1111/jgs.14393
Devita M, Peppard PE, Mesas AE, Mondini S, Rusconi ML, Barnet JH, et al. Associations between the apnea-hypopnea index during REM and NREM sleep and cognitive functioning in a cohort of middle-aged adults. J Clin Sleep Med. 2019;15:965–71.
Nikodemova M, Finn L, Mignot E, Salzieder N, Peppard PE. Association of sleep disordered breathing and cognitive deficit in APOE ε4 carriers. Sleep. 2013;36:873–80.
pubmed: 23729930
pmcid: 3649829
doi: 10.5665/sleep.2714
André C, Kuhn E, Rehel S, Ourry V, Demeilliez-Servouin S, Palix C, et al. Association of sleep-disordered breathing and medial temporal lobe atrophy in cognitively unimpaired amyloid-positive older adults. Neurology. 2023;101:e370–85.
pubmed: 37258299
pmcid: 10435067
doi: 10.1212/WNL.0000000000207421
Rajan KB, Weuve J, Barnes LL, McAninch EA, Wilson RS, Evans DA. Population estimate of people with clinical AD and mild cognitive impairment in the United States (2020–2060). Alzheimers Dement J Alzheimers Assoc. 2021;17:1966–75.
doi: 10.1002/alz.12362
Buckley RF, Mormino EC, Rabin JS, Hohman TJ, Landau S, Hanseeuw BJ, et al. Sex differences in the association of global amyloid and regional tau deposition measured by positron emission tomography in clinically normal older adults. JAMA Neurol. 2019;76:542–51.
pubmed: 30715078
pmcid: 6515599
doi: 10.1001/jamaneurol.2018.4693
Digma LA, Madsen JR, Rissman RA, Jacobs DM, Brewer JB, Banks SJ, et al. Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau. Brain Commun. 2020;2:fcaa025.
pubmed: 32337508
pmcid: 7166251
doi: 10.1093/braincomms/fcaa025
Chapman RM, Mapstone M, Gardner MN, Sandoval TC, McCrary JW, Guillily MD, et al. Women have farther to fall: gender differences between normal elderly and alzheimer’s disease in verbal memory engender better detection of AD in women. J Int Neuropsychol Soc JINS. 2011;17:654–62.
pubmed: 21486518
doi: 10.1017/S1355617711000452
Ye L, Pien GW, Ratcliffe SJ, Weaver TE. Gender differences in obstructive sleep apnea and treatment response to continuous positive airway pressure. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2009;5:512–8.
Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA. 2004;291:2013–6.
pubmed: 15113821
doi: 10.1001/jama.291.16.2013
Basoglu OK, Tasbakan MS. Gender differences in clinical and polysomnographic features of obstructive sleep apnea: a clinical study of 2827 patients. Sleep Breath. 2018;22:241–9.
pubmed: 28197893
doi: 10.1007/s11325-017-1482-9
Zhou L, Kong J, Li X, Ren Q. Sex differences in the effects of sleep disorders on cognitive dysfunction. Neurosci Biobehav Rev. 2023;146:105067.
pubmed: 36716906
doi: 10.1016/j.neubiorev.2023.105067
Qiu K, Mao M, Hu Y, Yi X, Zheng Y, Ying Z, et al. Gender-specific association between obstructive sleep apnea and cognitive impairment among adults. Sleep Med. 2022;98:158–66.
pubmed: 35870305
doi: 10.1016/j.sleep.2022.07.004
Koo BB, Patel SR, Strohl K, Hoffstein V. Rapid eye movement-related sleep-disordered breathing: influence of age and gender. Chest. 2008;134:1156–61.
pubmed: 18812455
doi: 10.1378/chest.08-1311
Votteler S, Knaack L, Janicki J, Fink GR, Burghaus L. Sex differences in polysomnographic findings in patients with obstructive sleep apnea. Sleep Med. 2022;101:429–36.
pubmed: 36516599
doi: 10.1016/j.sleep.2022.11.025
Johnson SC, Koscik RL, Jonaitis EM, Clark LR, Mueller KD, Berman SE, et al. The Wisconsin Registry for Alzheimer’s Prevention: a review of findings and current directions. Alzheimers Dement Diagn Assess Dis Monit. 2017;10:130–42.
Weintraub S, Besser L, Dodge HH, Teylan M, Ferris S, Goldstein FC, et al. Version 3 of the Alzheimer Disease Centers’ neuropsychological test battery in the Uniform Data Set (UDS). Alzheimer Dis Assoc Disord. 2018;32:10–7.
pubmed: 29240561
pmcid: 5821520
doi: 10.1097/WAD.0000000000000223
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 2011;7:270–9.
doi: 10.1016/j.jalz.2011.03.008
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 2011;7:263–9.
doi: 10.1016/j.jalz.2011.03.005
Darst BF, Koscik RL, Racine AM, Oh JM, Krause RA, Carlsson CM, et al. Pathway-specific polygenic risk scores as predictors of β-amyloid deposition and cognitive function in a sample at increased risk for Alzheimer’s disease. J Alzheimers Dis JAD. 2017;55:473–84.
pubmed: 27662287
doi: 10.3233/JAD-160195
Mander BA, Dave A, Lui KK, Sprecher KE, Berisha D, Chappel-Farley MG, et al. Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity. Sleep. 2022;45(9):zsac135.
AAST Titration Technical Guideline 2021 RB 7–30–21.pdf. [cited 2024 Feb 27]. Available from: https://www.aastweb.org/Portals/0/Docs/Resources/Guidelines/AAST%20Titration%20Technical%20Guideline%202021%20RB%207-30-21.pdf . Accessed 27 Feb 2024.
AASM Scoring Manual Updates for 2017 (Version 2.4) | Journal of Clinical Sleep Medicine. [cited 2023 Jul 31]. Available from: https://jcsm.aasm.org/doi/full/10.5664/jcsm.6576 . Accessed 27 Feb 2024.
Kapur VK, Donovan LM. Why a single index to measure sleep apnea is not enough. J Clin Sleep Med. 2019;15(5):683–4.
pubmed: 31053224
pmcid: 6510677
doi: 10.5664/jcsm.7746
Rashid NH, Zaghi S, Scapuccin M, Camacho M, Certal V, Capasso R. The value of oxygen desaturation index for diagnosing obstructive sleep apnea: a systematic review. Laryngoscope. 2021;131:440–7.
pubmed: 32333683
doi: 10.1002/lary.28663
Beaudin AE, Waltz X, Hanly PJ, Poulin MJ. Impact of obstructive sleep apnoea and intermittent hypoxia on cardiovascular and cerebrovascular regulation. Exp Physiol. 2017;102:743–63.
pubmed: 28439921
doi: 10.1113/EP086051
Mokhlesi B, Punjabi NM. “REM-related” obstructive sleep apnea: an epiphenomenon or a clinically important entity? Sleep. 2012;35:5–7.
pubmed: 22215911
pmcid: 3242688
doi: 10.5665/sleep.1570
Siddiqui F, Walters AS, Goldstein D, Lahey M, Desai H. Half of patients with obstructive sleep apnea have a higher NREM AHI than REM AHI. Sleep Med. 2006;7:281–5.
pubmed: 16564214
doi: 10.1016/j.sleep.2005.10.006
Liu Y, Su C, Liu R, Lei G, Zhang W, Yang T, et al. NREM-AHI greater than REM-AHI versus REM-AHI greater than NREM-AHI in patients with obstructive sleep apnea: clinical and polysomnographic features. Sleep Breath. 2011;15:463–70.
pubmed: 20443068
doi: 10.1007/s11325-010-0358-z
Joosten SA, Landry SA, Wong A-M, Mann DL, Terrill PI, Sands SA, et al. Assessing the physiologic endotypes responsible for REM- and NREM-based OSA. Chest. 2021;159:1998–2007.
pubmed: 33197399
doi: 10.1016/j.chest.2020.10.080
Shea SA, Edwards JK, White DP. Effect of wake-sleep transitions and rapid eye movement sleep on pharyngeal muscle response to negative pressure in humans. J Physiol. 1999;520:897–908.
pubmed: 10545152
pmcid: 2269629
doi: 10.1111/j.1469-7793.1999.00897.x
Mokhlesi B, Finn LA, Hagen EW, Young T, Hla KM, Van Cauter E, et al. Obstructive sleep apnea during REM sleep and hypertension. Results of the Wisconsin Sleep Cohort. Am J Respir Crit Care Med. 2014;190:1158–67.
pubmed: 25295854
pmcid: 4299639
doi: 10.1164/rccm.201406-1136OC
Aurora RN, Crainiceanu C, Gottlieb DJ, Kim JS, Punjabi NM. Obstructive sleep apnea during REM sleep and cardiovascular disease. Am J Respir Crit Care Med. 2018;197:653–60.
pubmed: 29112823
pmcid: 6005240
doi: 10.1164/rccm.201706-1112OC
Mokhlesi B, Varga AW. Obstructive sleep apnea and cardiovascular disease. REM sleep matters! Am J Respir Crit Care Med. 2018;197:554–6.
pubmed: 29141154
pmcid: 6005246
doi: 10.1164/rccm.201710-2147ED
Rey A. L’examen psychologique dans les cas d’encéphalopathie traumatique. (Les problems.). [The psychological examination in cases of traumatic encepholopathy. Problems.]. Arch Psychol. 1941;28:215–85.
Estévez-González A, Kulisevsky J, Boltes A, Otermín P, García-Sánchez C. Rey verbal learning test is a useful tool for differential diagnosis in the preclinical phase of Alzheimer’s disease: comparison with mild cognitive impairment and normal aging. Int J Geriatr Psychiatry. 2003;18:1021–8.
pubmed: 14618554
doi: 10.1002/gps.1010
Greenaway MC, Lacritz LH, Binegar D, Weiner MF, Lipton A, Munro CC. Patterns of verbal memory performance in mild cognitive impairment, Alzheimer disease, and normal aging. Cogn Behav Neurol. 2006;19:79.
pubmed: 16783130
doi: 10.1097/01.wnn.0000208290.57370.a3
Twamley EW, Ropacki SAL, Bondi MW. Neuropsychological and neuroimaging changes in preclinical Alzheimer’s disease. J Int Neuropsychol Soc JINS. 2006;12:707–35.
pubmed: 16961952
doi: 10.1017/S1355617706060863
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995;57:289–300.
doi: 10.1111/j.2517-6161.1995.tb02031.x
Hotelling’s t and Steiger’s Z tests. [cited 2022 Sep 6]. Available from: https://blogs.gwu.edu/weissba/teaching/calculators/hotellings-t-and-steigers-z-tests/ . Accessed 27 Feb 2024.
Keselman HJ, Rogan JC. The Tukey multiple comparison test: 1953–1976. Psychol Bull. 1977;84:1050–6.
doi: 10.1037/0033-2909.84.5.1050
Bauer DJ, Curran PJ. Probing interactions in fixed and multilevel regression: inferential and graphical techniques. Multivar Behav Res. 2005;40:373–400.
doi: 10.1207/s15327906mbr4003_5
Esarey J, Sumner JL. Marginal effects in interaction models: determining and controlling the false positive rate. Comp Polit Stud. 2018;51:1144–76.
doi: 10.1177/0010414017730080
Johnson PO, Fay LC. The Johnson-Neyman technique, its theory and application. Psychometrika. 1950;15:349–67.
pubmed: 14797902
doi: 10.1007/BF02288864
Sundermann EE, Biegon A, Rubin LH, Lipton RB, Landau S, Maki PM. Does the female advantage in verbal memory contribute to underestimating AD pathology in women versus men? J Alzheimers Dis JAD. 2017;56:947–57.
pubmed: 28106548
doi: 10.3233/JAD-160716
Neu SC, Pa J, Kukull W, Beekly D, Kuzma A, Gangadharan P, et al. Apolipoprotein E genotype and sex risk factors for Alzheimer disease: a meta-analysis. JAMA Neurol. 2017;74:1178–89.
pubmed: 28846757
pmcid: 5759346
doi: 10.1001/jamaneurol.2017.2188
Cannon-Albright LA, Foster NL, Schliep K, Farnham JM, Teerlink CC, Kaddas H, et al. Relative risk for Alzheimer disease based on complete family history. Neurology. 2019;92:e1745–53.
pubmed: 30867271
pmcid: 6511086
doi: 10.1212/WNL.0000000000007231
Findley LJ, Wilhoit SC, Suratt PM. Apnea duration and hypoxemia during REM sleep in patients with obstructive sleep apnea. Chest. 1985;87:432–6.
pubmed: 3979129
doi: 10.1378/chest.87.4.432
Mander BA, Winer JR, Walker MP. Sleep and human aging. Neuron. 2017;94:19–36.
pubmed: 28384471
pmcid: 5810920
doi: 10.1016/j.neuron.2017.02.004
Li W, Ma L, Yang G, Gan W. REM sleep selectively prunes and maintains new synapses in development and learning. Nat Neurosci. 2017;20:427–37.
pubmed: 28092659
pmcid: 5535798
doi: 10.1038/nn.4479
Louie K, Wilson MA. Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron. 2001;29:145–56.
pubmed: 11182087
doi: 10.1016/S0896-6273(01)00186-6
Djonlagic I, Guo M, Igue M, Malhotra A, Stickgold R. REM-related obstructive sleep apnea: when does it matter? Effect on motor memory consolidation versus emotional health. J Clin Sleep Med. 2020;16(3):377–84.
pubmed: 31992413
pmcid: 7075098
doi: 10.5664/jcsm.8210
Owen JE, Benediktsdottir B, Cook E, Olafsson I, Gislason T, Robinson SR. Alzheimer’s disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea. Sleep. 2021;44:zsaa195.
pubmed: 32954401
doi: 10.1093/sleep/zsaa195
Sharma RA, Varga AW, Bubu OM, Pirraglia E, Kam K, Parekh A, et al. Obstructive sleep apnea severity affects amyloid burden in cognitively normal elderly. A longitudinal study. Am J Respir Crit Care Med. 2018;197:933–43.
pubmed: 29125327
pmcid: 6020410
doi: 10.1164/rccm.201704-0704OC
Daulatzai MA. Evidence of neurodegeneration in obstructive sleep apnea: relationship between obstructive sleep apnea and cognitive dysfunction in the elderly. J Neurosci Res. 2015;93:1778–94.
pubmed: 26301370
doi: 10.1002/jnr.23634
Baril A-A, Gagnon K, Brayet P, Montplaisir J, Carrier J, Soucy J-P, et al. Obstructive sleep apnea during REM sleep and daytime cerebral functioning: a regional cerebral blood flow study using high-resolution SPECT. J Cereb Blood Flow Metab. 2020;40:1230–41.
pubmed: 30465610
doi: 10.1177/0271678X18814106
Braun AR, Balkin TJ, Wesenten NJ, Carson RE, Varga M, Baldwin P, et al. Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study. Brain J Neurol. 1997;120(Pt 7):1173–97.
doi: 10.1093/brain/120.7.1173
Leritz EC, McGlinchey RE, Kellison I, Rudolph JL, Milberg WP. Cardiovascular disease risk factors and cognition in the elderly. Curr Cardiovasc Risk Rep. 2011;5:407–12.
pubmed: 22199992
pmcid: 3245189
doi: 10.1007/s12170-011-0189-x
Spira AP, Blackwell T, Stone KL, Redline S, Cauley JA, Ancoli-Israel S, et al. Sleep-disordered breathing and cognition in older women. J Am Geriatr Soc. 2008;56:45–50.
pubmed: 18047498
doi: 10.1111/j.1532-5415.2007.01506.x
O’Hara R, Schröder CM, Kraemer HC, Kryla N, Cao C, Miller E, et al. Nocturnal sleep apnea/hypopnea is associated with lower memory performance in APOE ε4 carriers. Neurology. 2005;65:642–4.
pubmed: 16116137
doi: 10.1212/01.wnl.0000173055.75950.bf
Johnson DA, Lane J, Wang R, Reid M, Djonlagic I, Fitzpatrick AL, et al. Greater cognitive deficits with sleep-disordered breathing among individuals with genetic susceptibility to Alzheimer disease The Multi-Ethnic Study of Atherosclerosis. Ann Am Thorac Soc. 2017;14:1697–705.
pubmed: 28731362
pmcid: 5711280
doi: 10.1513/AnnalsATS.201701-052OC
Fenton L, Isenberg AL, Aslanyan V, Albrecht D, Contreras JA, Stradford J, et al. Variability in objective sleep is associated with Alzheimer’s pathology and cognition. Brain Commun. 2023;5:fca031.
doi: 10.1093/braincomms/fcad031
Lim ASP, Yu L, Kowgier M, Schneider JA, Buchman AS, Bennett DA. Modification of the relationship of the apolipoprotein E ε4 allele to the risk of alzheimer disease and neurofibrillary tangle density by sleep. JAMA Neurol. 2013;70:1544–51.
pubmed: 24145819
doi: 10.1001/jamaneurol.2013.4215
Striepens N, Scheef L, Wind A, Meiberth D, Popp J, Spottke A, et al. Interaction effects of subjective memory impairment and ApoE4 genotype on episodic memory and hippocampal volume. Psychol Med. 2011;41:1997–2006.
pubmed: 21284913
doi: 10.1017/S0033291711000067
Donix M, Ercoli LM, Siddarth P, Brown JA, Martin-Harris L, Burggren AC, et al. Influence of Alzheimer disease family history and genetic risk on cognitive performance in healthy middle-aged and older people. Am J Geriatr Psychiatry. 2012;20:565–73.
pubmed: 21849821
doi: 10.1097/JGP.0b013e3182107e6a
Young CB, Johns E, Kennedy G, Belloy ME, Insel PS, Greicius MD, et al. APOE effects on regional tau in preclinical Alzheimer’s disease. Mol Neurodegener. 2023;18:1.
pubmed: 36597122
pmcid: 9811772
doi: 10.1186/s13024-022-00590-4
Honea RA, Vidoni ED, Swerdlow RH, Burns JM, Initiative for the ADN. Maternal family history is associated with Alzheimer’s disease biomarkers. J Alzheimers Dis. 2012;31:659–68.
pubmed: 22669011
pmcid: 3608420
doi: 10.3233/JAD-2012-120676
Dickstein DL, Walsh J, Brautigam H, Stockton SD Jr, Gandy S, Hof PR. Role of vascular risk factors and vascular dysfunction in Alzheimer’s disease. Mt Sinai J Med J Transl Pers Med. 2010;77:82–102.
doi: 10.1002/msj.20155
Seshadri S, Wolf PA, Beiser A, Au R, McNulty K, White R, et al. Lifetime risk of dementia and Alzheimer’s disease: the impact of mortality on risk estimates in the Framingham Study. Neurology. 1997;49:1498–504.
pubmed: 9409336
doi: 10.1212/WNL.49.6.1498
Buckley RF, Scott MR, Jacobs HIL, Schultz AP, Properzi MJ, Amariglio RE, et al. Sex mediates relationships between regional tau pathology and cognitive decline. Ann Neurol. 2020;88:921–32.
pubmed: 32799367
pmcid: 7581543
doi: 10.1002/ana.25878
Babulal GM, Quiroz YT, Albensi BC, Arenaza-Urquijo E, Astell AJ, Babiloni C, et al. Perspectives on ethnic and racial disparities in Alzheimer’s disease and related dementias: update and areas of immediate need. Alzheimers Dement. 2019;15:292–312.
pubmed: 30555031
doi: 10.1016/j.jalz.2018.09.009
Dudley KA, Patel SR. Disparities and genetic risk factors in obstructive sleep apnea. Sleep Med. 2016;18:96–102.
pubmed: 26428843
doi: 10.1016/j.sleep.2015.01.015
Dunietz GL, Chervin RD, Burke JF, Conceicao AS, Braley TJ. Obstructive sleep apnea treatment and dementia risk in older adults. Sleep. 2021;44:zsab076.
pubmed: 33769542
pmcid: 8436135
doi: 10.1093/sleep/zsab076
Richards KC, Gooneratne N, Dicicco B, Hanlon A, Moelter S, Onen F, et al. CPAP adherence may slow 1-year cognitive decline in older adults with mild cognitive impairment and apnea. J Am Geriatr Soc. 2019;67:558–64.
pubmed: 30724333
pmcid: 6402995
doi: 10.1111/jgs.15758
Cooke JR, Ayalon L, Palmer BW, Loredo JS, Corey-Bloom J, Natarajan L, et al. Sustained use of CPAP slows deterioration of cognition, sleep, and mood in patients with Alzheimer’s disease and obstructive sleep apnea: a preliminary study. J Clin Sleep Med. 2009;05:305–9.
doi: 10.5664/jcsm.27538
Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE. A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev. 2011;15:343–56.
pubmed: 21652236
pmcid: 3202028
doi: 10.1016/j.smrv.2011.01.003