Table 2.
Descriptive Study Characteristics and Main Findings: Obstructive Sleep Apnea, and Mild Cognitive Impairment (MCI) and/or Alzheimer’s disease (AD).
| Authors, Year Published | Study Design | Subjects |
OSA assessment | Cognitive Domains | Adjusted Variables | Major findings | ||
|---|---|---|---|---|---|---|---|---|
| N | Age (Mean ± SD) | Gender | ||||||
| OSA and MCI/AD (Cross-sectional Studies) Older Adults (Mean Age: 60 and older) | ||||||||
| Dlugaj et al., 2014 [95] | Cross- sectional, population-based | 1793 | 63.8 (7.5) | 919M 874F | AHI | Memory, executive function | Age, sex, education | ■ SDB not associated with MCI or MCI subtypes (amnestic and non-amnestic) |
| Hoch et al., 1986 [97] | Cross-sectional | 80 | 71.5 (8.1) | 33M 57F | AHI | DSM-III | None | Significant association |
| Hoch et al., 1989 [99] | Cross-sectional | 27 | 74.5 (5.1) | 7M 20F | AHI | NICNDS-ADRDA, DSM-III | N/A | No association between OSA and dementia |
| Kim et al., 2011 [96] | Cross-sectional, clinic | 30 | 67.4 (3.8) | 42M 18W | AHI | Executive function, Language, Memory, Visuospatial construction | N/A | ■ ↑AHI associated with language with MCI |
| Reynolds et al., 1985 [98] | Cross-sectional | 61 | 69.7 (6.8) | 19M 42F | AI, AHI | DSM 3, Hamilton rating, Folstein score, and a modified Hachinski Ischemia score | Gender | Significant association between sleep apnea and dementia in women |
| Reynolds et al., 1987 [100] | Cross-sectional | 30 | 73.3 (9.1) | 3M 12F | 24 Channel polygraphs | DSM 3, Hamilton rating, Folstein score, and a modified Hachinski Ischemia score | N/A | No association between OSA and dementia |
| Smallwood et al., 1983 [101] | Cross-sectional | 55 | Range: 23–81 y | 45M 10F | AHI | DSM 3, neurological examination | Age, sex | No relationship between dementia and apnea severity |
| OSA and AD, All-cause MCI or Dementia (Longitudinal studies) | ||||||||
| Middle Aged (Mean Age: 30–59) | ||||||||
| Chang et al., 2013 [107] | Longitudinal, community based | Controls 7070 OSA 1414 | 55.5 (4.78) | M: 5034 F: 3450 | Clinical diagnosis (according to AASM guidelines) | ICD-9 CM Dementia diagnosis | Age, sex, CVD comorbidities, urbanization level, income | OSA was associated with increased Dementia risk than for the comparison group, and is an age, time, and gender dependent. |
| Older Adults (Mean Age: 60 and older) | ||||||||
| Lee et al., 2019 [122] | Longitudinal, Community | Controls: 3635 SDB: 727 | Range: 40–79 | M: 3332 F: 1030 | NHIS record of clinical diagnosis | ICD-10:G30 | Sex, age, CVD, hypertension, Type 2 DM, depression, BMI, smoking status, physical activity, and drinking | Those with SDB were 1.575 times more likely to develop AD |
| Lutsey et al., 2018 [105] | Longitudinal, Community | Controls: 849 OSA: 1100 | 63 (5.4) | M: 1073 F: 876 | Home PSG | TICSm, hospitalization codes). Neurocognitive exam | age, sex, field center, education, physical activity, ethanol intake, smoking status, leisure time physical activity, and APOE e4, BMI | Late-midlife OSA was associated with all-cause and Alzheimer’s disease dementia in later life. |
| Osorio et al., 2015 [106] | Prospective | 2285 | 74 (6.6) | 1101F | Self-reported | Self-report; diagnosis by clinician | APOE e4 status, sex, education, BMI, depression, cardiovascular disease, hypertension, diabetes, and age | Significant association between SDB and earlier age at cognitive decline |
| Yaffe et al., 2011 [103] | Longitudinal, Community | Controls: 193 SDB:105 | 82.3 (3.2) | Women only | AHI: ≥15 | Global, Attention, Executive Function, Memory | Age, race, BMI, education, smoking, diabetes, hypertension, antidepressant use, benzodiazepine use, non-diazepam anxiolytics use | ■ SDB: ↑hypoxemia had ↑risk of developing MCI or dementia over five year follow-up Sleep fragmentation and duration not associated with cognition |
| Yaffe et al., 2015 [104] | Longitudinal | AD: 4107 Dementia: 14380 | 67.7 (1.1) | Men Only | Not specified; clinical diagnosis | AD & Dementia (classified using ICD-9 codes) | Age, CVD comorbidities, obesity, depression, income, education | Those with a sleep apnea had a 20% and 27% increased risk for AD and dementia respectively |
| OSA and Cognition (RCT studies) | ||||||||
| Older Adults (Mean Age: 60 and older) | ||||||||
| Ancoli-Israel et al., 2008 [125] | RCT | 52 | 78.2 (7.2) | 39M 13F | Rechtschaffen and Kales criteria | Neuropsychological test battery | None | CPAP improved some cognitive functioning |
| Chong et al., 2006 [126] | RCT | 39 | 78.0 (7.04) | 29M 10F | RDI | NINCDS-ADRDA criteria | None | CPAP reduces sleepiness in those with AD and OSA |
| Cooke et al., 2009a [123] | RCT | 52 | 77.8 (7.3) | 39M 13F | Rechtschaffen and Kales criteria | NINCDS-ADRDA criteria, MMSE | None | After one night of CPAP use: deeper sleep, affects for three weeks |
| Cooke et al., 2009b [124] | RCT | 10 | 75.7 (5.9) | 7M 3F | AHI, PSQI, ESS, FOSQ | Neuropsychological test battery | None | Sustained CPAP use associated with less cognitive decline |
| Moraes et al., 2008 [127] | RCT | 23 | Control: 72.6 (11.0) Treatment: 76.9 (6.2) | 8M 15F | Rechtschaffen and Kales and AASM criteria | ADAS-cog | None | Donepezil treatment in AD individuals: improved AHI, oxygen saturation, and sleep duration |
Abbreviations: AASM: American academy of sleep medicine; Aβ40/42, amyloid beta-40/42; AD, Alzheimer’s disease; ADAS-cog: Alzheimer’s disease assessment scale-cognitive; AHI ≥ 15, apnea hypopnea index of 15 or more events per hour of sleep; APOE, apolipoprotein epsilon4; BMI, body mass index, CDR, clinical dementia rating, CPAP, continuous pulmonary ambulatory pressure, CRP, c-reactive protein, CSF, cerebrospinal fluid; CVD, cardiovascular disease, DSM-IIIR/IV-TR, diagnostic and statistical manual of mental disorders; third edition/fourth edition, text revised; EDS, Excessive daytime sleepiness; ESS, Epworth sleepiness scale; F, female, FOSQ: functional outcomes sleep questionnaire; GDS, global dementia scale, ICD-9/10, international classification of diseases ninth/tenth edition AD criteria; IADL, instrumental activities of daily living, IQ, intelligence quotient, M, male, MCI, mild cognitive impairment, MMSE: mini mental state examination; MRI, magnetic resonance imaging; N, number of participants; NA, not applicable; N/A, not available; NC, normal cognition, NINCDS-ADRDA, national institute of neurological and communicative disorders and stroke and the Alzheimer’s disease and related disorders association; ODI: oxygen desaturation index; OSA, obstructive sleep apnea, OSAS, obstructive sleep apnea syndrome; PSQI: Pittsburg sleep quality index; RCT: randomized clinical trial; RDI, respiratory disturbance index, SaO2, saturated arterial oxygen, SCI, subjective cognitive decline, SDB, sleep disordered breathing; SSRI, selective serotonin reuptake inhibitor, TICSm: Telephone interview for cognitive status TMT: trail making test; WAIS-R, Wechsler adult intelligence scale revised.