NEUROCOGNITIVE CONSEQUENCES OF OSA IN THE ELDERLY. Nadia Gosselin, Ph.D. Université de Montréal Hôpital du Sacré-Cœur de Montréal

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1 NEUROCOGNITIVE CONSEQUENCES OF OSA IN THE ELDERLY Nadia Gosselin, Ph.D. Université de Montréal Hôpital du Sacré-Cœur de Montréal

2 CFPC CoI Templates: Slide 1 FACULTY/PRESENTER DISCLOSURE Faculty: Nadia Gosselin Relationships with commercial interests: Grants/Research Support: None Speakers Bureau/Honoraria: None Consulting Fees: None Other: None

3 CFPC CoI Templates: Slide 2 DISCLOSURE OF COMMERCIAL SUPPORT This program has received financial support from Canadian Institutes of Health Research and Fonds de la recherche du Québec Santé in the form of research grant. Potential for conflict(s) of interest: None

4 CFPC CoI Templates: Slide 3 MITIGATING POTENTIAL BIAS Not applicable

5 INTRODUCTION TO OSA

6 WHAT IS OBSTRUCTIVE SLEEP APNEA (OSA)? Obstructive apnea : a decrease > 90% of baseline airflow for at least 10 s accompanied by a sustained or an increased respiratory effort. Obstructive hypopnea : a decrease > 30% of the airflow amplitude for at least 10 s accompanied with either a desaturation higher than 3% or an arousal. 6

7 Sleep Apnea Video:

8 OBJECTIVE MEASURES OF OSA Polysomnography Level 1 Sleep studies Portable monitor Level 3 sleep studies 8

9 9

10 OSA SEVERITY Standard criteria are based on the apnea/hypopnea index (AHI): 5-15 = Mild = Moderate > 30 = Severe * An AHI greater than 30 represents more than 210 respiratory events for a 7-h night. 10

11 RISK FACTORS Obesity (large neck, central distribution of adipose tissue) Age (> 40 yo) Men (8 men for 1 woman) Craniofacial morphology (ex. Receded chin) Diabetes and hypertension Young et al., JAMA,

12 OSA PREVALENCE WITH AGE New studies suggest that the prevalence in older adults could be as high as 58%. 80% are not diagnosed and not treated. Young et al.,

13 OSA DIAGNOSIS - SYMPTOMS Symptoms reported by the patient or his/her bed partner: Snoring Choking during the night Frequent awakenings Non restorative sleep Morning headaches Dry month Daytime sleepiness/drowsiness 13

14 OSA DIAGNOSIS - QUESTIONNAIRES STOP-BANG Low risk of OSA: 0-2 questions Intermediate risk of OSA: 3-4 questions High risk of OSA: 5-8 questions Proprietary to University Health Network. Modified from: Chung et al. Anesthesiology 2008; 108:812-21; Chung et al. Br J Anaesth 2012, 108:768 75; Chung et al. J Clin Sleep Med 2014;10:951-8.

15 OSA DIAGNOSIS - QUESTIONNAIRES Epworth Sleepiness Scale

16 CONSEQUENCES OF OSA ON COGNITION

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18 OSA AND COGNITION Affected Attention Episodic memory Executive functions +/- Affected Psychomotor speed Not affected Language (Gagnon et al., Pathologie-Biologie, 2014)

19 OSA AND COGNITION 19

20 OSA AND COGNITION (Adapté de Vemuri et al., 2011) 20

21 EPIDEMIOLOGICAL EVIDENCE LINKING OSA TO COGNITIVE DECLINE

22 LONGITUDINAL STUDY OF OSTEOPOROTIC FRACTURES (YAFFE ET AL., JAMA, 2011) Question: Determine the prospective relationship between sleep apnea and MCI/dementia Methods: N=298; 82 ± 3.2 yo, community-dwelling women Sleep apnea defined as AHI>15: 105/298 participants Mean follow-up of 4.7 years 107/298 developed MCI/Dementia Results: Women with OSA are at greater odds of MCI/dementia, mostly related to hypoxia at baseline

23 ALZHEIMER DISEASE NEUROIMAGING INITIATIVE (OSORIO ET AL., NEUROLOGY, 2015) Question: Is OSA/SDB associated with younger onset of MCI or AD-dementia? Methods: Self-reported presence of OSA Survival curves of age at onset of MCI or AD-dementia Cox regression model to assess age at onset of MCI or ADdementia (adjusted for APO e4; Sex; education; BMI; age at baseline; depression; cardiovascular disease; HBP; diabetes) Results: OSA+ subjects have a younger onset of MCI; Similar trend for AD

24 PROOF-SYNAPSE (SAINT-MARTIN ET AL., SLEEP, 2015) Objective: To determine whether SDB-related factors affect cognitive changes in healthy elderly subjects Methods: Longitudinal study 8 year follow-up N=559 Results: SBD is associated with attention decline

25 OSA AND DEMENTIA Globally, the effects of OSA on cognition are relatively modest according to large cohort studies, except for older-old. However, when Alzheimer disease is diagnosed, more than 50% of the patients are diagnosed with sleep apnea. There are probably factors (sex, age, lifestyle, comorbidities) that put a person more at risk of suffering for the cognitive impacts of sleep apnea.

26 SCREENING FOR COGNITIVE DECLINE IN OSA

27 MINI-MENTAL STATE EXAMINATION AND MOCA

28 Characteristics NoMCI (n = 32) AOS MCI (n = 16) t and p-values NoMCI (n = 28) Controls MCI (n = 21) (K. Gagnon et al., in prep.) t and p-values Demographic Age (years) 65.1 ± ± 6.9 ns 63.9 ± ± 4.0 ns Sex (nb.) 5F; 27 M 1 F; 15 M 7 F; 21 M 3F; 18 M ns Education (years) 15.3 ± ± 5.3 ns 16.6 ± ± 2.4 t=4.8; p= Cognitive reserve index ± ± 17.4 ns ± ± 12.8 t=3.2; p=0.002 Vascular risk factors Vascular burden 1.6 ± ±1.2 ns 1.2 ± ± 01.5 ns Markers of obesity Body mass index 30.2 ± ± 2.4 ns 26.4 ± ± 2.6 ns Neck circumference (cm) 41.7 ± ± 1.8 ns 38.4 ± ± 2.8 ns Waist circumference (cm) ± ± 5.6 ns 94.2 ± ± 10.0 ns Mood and sleep questionnaires Beck Depression Inventory 8.2 ± ± 4.9 ns 5.2 ± ± 6.1 ns Beck Anxiety Inventory 4.2 ± ± 6.1 ns 3.4 ± ± 4.0 ns Epworth sleepiness scale 10.5 ± ± 4.1 ns 6.9 ± ± 4.6 ns Pittsburgh Sleep Quality Index 6.4 ± ± 3.8 ns 3.7 ± ± 3.2 ns Cognitive complaints Cognitive Failure Questionnaire 32.0 ± ± 8.0 ns 24.2 ± ± 12.7 t=-2.4, p=0.02 QAM for patients 2.2 ± ± 0.4 ns 1.9 ± ± 0.5 t=-2.7, p=0.009 QAM for relatives 2.1 ± ± 0.4 ns 1.6 ± ± 0.7 t=-2.3, p=

29 MINI-MENTAL STATE EXAMINATION AND MOCA The MMSE is not valid to screen for mild cognitive impairment in patients with OSA.

30 MECHANISMS LINKING OSA TO COGNITIVE DECLINE

31 MECHANISMS LINKING OSA TO DEMENTIA Moderate to severe sleep apnea is associated with a greater risk of white matter changes on FLAIR in middle-aged. *statistically controlled for comorbidities (Kim et al., Sleep, 2013)

32 MECHANISMS LINKING OSA TO DEMENTIA Aβ clearance is increased during sleep through the glymphatic system. (Xie et al., Science, 2013)

33 NEUROIMAGING OF OSA

34 NEUROIMAGING OF OSA Parietal hypoperfusions in middle-aged and older adults with severe OSA x = -68 x = -58 x = -36 x = -32 x = 4 x = 10 T-value (Baril et al., Sleep, 2015)

35 NEUROIMAGING OF OSA Hypoxemia, AHI and sleep fragmentation were all associated with increased thickness or gray matter volume, possibly representing a reactive response/oedema. Baril et al., AJRCCM,

36 NEUROIMAGING OF OSA Baril et al., AJRCCM,

37 GM volume GRAY MATTER CHANGES OVER TIME Oedema Neural death Time 37

38 TREATING OSA

39 TREATING OSA Whether OSA treatment can slow down, stop or reverse neurodegenerative processes potentially accentuated by OSA is a crucial question, particularly for patients who start their treatment after the age of 65.

40 TREATING OSA Weight loss Sleep hygiene and lifestyle (caffeine consumption, daytime naps, reduce alcohol consumption, stop smoking, etc.) Mandibular advancement device CPAP

41 EFFETS OF CPAP ON COGNITION IN MIDDLE-AGED (Katia Gagnon et al., Pathologie-Biologie, 2014)

42 CASE STUDY 57 years old man with OSA (AHI of 39.7) before and after 1 year of CPAP Before CPAP After CPAP (Liguori et al., Brain, 2017)

43 EFFECTS OF CPAP ON COGNITION Adults > 65 years old with severe OSA Improvement in speed, short-term memory and verbal fluency after CPAP. CPAP No-CPAP (Dalmases et al., Chest, 2015)

44 EFFECTS OF CPAP ON COGNITION

45 CHALLENGE WITH TREATMENT Weight loss is, most of the time, the best treatment Long-term adherence to CPAP is less than 50% (Baratta et al., Sleep Med, 2018). Reasons evoked: discomfort, airways dryness, inconvenience for the bed partner, etc.

46 CONCLUSIONS TAKE HOME MESSAGES 1) OSA is extremely prevalent after the age of 65. 2) OSA is, most of the time, not diagnosed and not treated. 3) OSA has variable consequences on cognitive/brain health ; factors moderating the association between OSA and cognitive/brain health (ex. Age, sex, genetics, etc.). 4) Treating OSA can have various positive (but no negative) effects on cognition, even in the case of ongoing cognitive decline.

47 ACKNOWLEDGMENTS Graduate students Andrée-Ann Baril Katia Gagnon Maxime Fortin Francis L Heureux Sirin Chami Marie-Ève Dusseault-Martineau Team Hélène Blais Caroline D Aragon Cynthia Thompson Christophe Bedetti Danièle Legault Catherine Chapados-Noreau Marjolaine Lafortune Marie-Josée Quinn Jean Paquet Joëlle Robert Sarah-Hélène Julien Fatma Ben Aissa Frédérique Escudier Collaborators Jacques Montplaisir Alex Desautels Jean-François Gagnon Chantal Lafond Jean-Paul Soucy Anne Décary Serge Gauthier Louis De Beaumont Judes Poirier 47