Associations of Baseline Sleep Microarchitecture with Cognitive Function After 8 Years in Middle-Aged and Older Men from a Community-Based Cohort Study

Figures & data

Figure 1 FAMAS clinic and sleep study assessments and cognitive function testing.

Abbreviations: FAMAS, Florey Adelaide Male Ageing Study; CATI, computer-assisted telephone interview; PSG, polysomnography.

Table 1 Baseline Participant Characteristics Stratified by Participation in Cognitive Follow-Up Examination

Baseline Participant Characteristics	Cognitive Follow-Up Examination Participation		p-values
	Participants (n=139)	Non-Participants (n=236)
Age (years), % (n)
<50	17.3 (24)	25.7 (61)	0.61
50–59	36.0 (50)	29.3 (71)	0.84
60–69	34.5 (48)	21.7 (50)	0.003
≥70	12.2 (17)	23.2 (54)	0.029
Financial stress, % (n)
Spends >earns	12.2 (17)	17.0 (40)	0.52
Highest education, % (n)
≥Diploma, certificate, trade, bachelor‘s degree or higher	75.2 (104)	70.3 (166)	0.28
Married/partner, % (n)	89.8 (125)	80.4 (190)	0.018
BMI (kg/m^2), % (n)
<25 (underweight/normal)	19.1 (26)	21.4 (51)	0.69
25 to <30 (overweight)	45.9 (64)	45.7 (108)	0.32
≥30 (obese)	35.0 (49)	33.0 (77)	0.34
Diabetes mellitus, % (n)	8.3 (11)	5.1 (12)	0.67
Hypertension % (n)	58.6 (81)	59.4 (140)	0.80
CVD, % (n)	5.8 (8)	9.7 (23)	0.21
Insomnia, % (n)	12.2 (17)	15.3 (36)	0.50
SEIFA IRSD, % (n)
Quintile 1 (highest disadvantage)	21.0 (29)	23.6 (56)	0.86
Quintile 2	10.8 (16)	9.4 (22)	0.93
Quintile 3	28.0 (39)	29.0 (68)	0.95
Quintile 4	27.4 (38)	24.6 (58)	0.68
Quintile 5 (lowest disadvantage)	12.7 (17)	13.4 (32)	0.97
Current smokers, % (n)	14.6 (20)	20.2 (48)	0.15
Sedentary physical activity	18.5 (26)	25.0 (59)	0.86
Mean (SD)
Cognitive baseline data
TMT-A, seconds	15.4 (5.2)	16.2 (7.1)	0.14
TMT-B, seconds	75.3 (26.1)	80.0 (37.6)	0.12
EEG relative spectral power
NREM sleep
Delta	81.2 (6.4)	81.5 (7.1)	0.66
Theta	8.2 (2.8)	8.0 (2.7)	0.63
Alpha	5.3 (2.4)	5.2 (2.5)	0.65
Sigma	2.0 (0.9)	2.0 (1.0)	0.52
Beta	3.3 (1.6)	3.3 (2.3)	0.98
Median (IQR)
EEG Slowing ratio	9.0 (6.4, 12.7)	9.0 (6.9, 12.2)	0.51
Mean (SD)
REM sleep
Delta	69.7 (8.7)	70.5 (10.3)	0.44
Theta	11.9 (3.5)	11.6 (4.4)	0.45
Alpha	6.9 (2.4)	6.7 (2.6)	0.45
Sigma	3.0 (1.1)	2.8 (1.1)	0.16
Beta	8.4 (3.4)	8.3 (4.2)	0.77
Median (IQR)
Slowing ratio	4.5 (3.4, 6.2)	4.5 (3.6, 6.6)	0.54
Mean (SD)
N2 sleep spindle metrics
Occurrence	213.8 (157.0)	221 (165.6)	0.67
Overall density	1.0 (0.7)	1.1 (0.7)	0.90
Fast density	0.4 (0.3)	0.4 (0.3)	0.83
Slow density	0.7 (0.5)	0.7 (0.5)	0.76
Average frequency	12.8 (0.3)	12.8 (0.3)	0.85
Amplitude	13.8 (3.1)	13.8 (4.4)	0.98
N3 spindle metrics
Occurrence	43.9 (64.4)	34.0 (43.0)	0.10
Overall density	0.6 (0.7)	0.5 (0.6)	0.23
Fast density	0.1 (0.2)	0.1 (0.2)	0.65
Slow density	0.5 (0.6)	0.4 (0.5)	0.22
Average frequency	12.4 (1.5)	11.9 (2.9)	0.039
Amplitude	12.7 (4.7)	13.3 (7.8)	0.40

Notes: Baseline participant characteristics: Participants: Includes those who participated in the follow-up cognitive examination. Non-participants: Includes those who only participated in the baseline cognitive examination, not follow-up. p-values: Those <0.05 are boldfaced to indicate a statistically significant between-group difference in the variable of interest. BMI: body mass index categorised according to international criteria from the World Health Organization (<25 kg/m² [underweight/normal], 25 to <30 kg/m² [overweight], and ≥30 kg/m² [obese]). Cardiovascular disease: self-reported, doctor-diagnosed myocardial infarction, angina, transient ischemic attack, or stroke. Diabetes mellitus: self-reported, doctor-diagnosed, fasting plasma glucose ≥7.0 mmol/L (126 mg/dL), haemoglobin A1C ≥6.5%, or reported antidiabetic medication use (oral hypoglycaemic agents and/or insulin). Insomnia: difficulty initiating or maintaining sleep occurring at least three nights/week (PSQI dimensions) and significant daytime fatigue defined as a score one SD below the mean on the 36-item short-form survey instrument (SF-36) Vitality Scale. Hypertension: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or reported antihypertensive medication use. Cardio-metabolic conditions: one or more of hypertension, diabetes mellitus, or cardiovascular disease. EEG relative spectral powers: delta: 0.5–4 Hz; theta: 4.5–8 Hz; alpha: 8–12 Hz; sigma: 12–15 Hz; beta: 15–32 Hz. EEG slowing ratio: calculated as a ratio of slow to fast EEG frequencies [(delta+theta)/(alpha+sigma+beta)]. N2 and N3 sleep spindle metrics: occurrence (11–16 Hz, total events), overall density (11–16 Hz, number/minute), fast density (13–16 Hz, number/minute), slow density (11–13 Hz, number/minute), average frequency (Hz, oscillations/second), and amplitude (µV).

Abbreviations: BMI, body mass index; SD, standard deviation; IQR, interquartile range; SEIFA IRSD, Socio-Economic Indexes for Areas Index of Relative Socio-Economic Disadvantage; TMT-A, trail-making test A; TMT-B, trail-making test B; CVD, cardiovascular disease; NREM, non-rapid eye movement sleep; REM, rapid eye movement sleep; N2, stage 2 sleep; N3, stage 3 sleep.

Table 2 Baseline Sleep Microarchitecture Parameters Stratified by Standard Deviation Reduction in TMT Performance from Baseline to Follow-Up

Follow-Up Cognitive Performance Domains	Cognitive Follow-Up Examination Participants
	Visual Attention and Processing Speed (TMT-A)			Executive Function (TMT-B)
Cognitive Performance Subgroups	<0.5 SD Reduction (n=121)	≥0.5 SD Reduction (n=18)	p-values	<0.5 SD Reduction (n=121)	≥0.5 SD Reduction (n=18)	p-values
EEG relative spectral power Mean (SD)
NREM sleep
Delta	80.9 (6.4)	82.7 (5.6)	0.21	81.1 (6.5)	81.4 (6.2)	0.81
Theta	8.1 (2.5)	7.7 (2.0)	0.43	8.2 (2.9)	8.1 (2.4)	0.88
Alpha	5.4 (2.4)	4.8 (2.5)	0.24	5.3 (2.4)	5.3 (2.5)	0.97
Sigma	2.1 (1.0)	1.8 (0.7)	0.083	2.1 (0.9)	2.0 (1.0)	0.61
Beta	3.4 (1.7)	3.1 (0.9)	0.36	3.3 (1.6)	3.2 (1.4)	0.75
Median (IQR)
Slowing ratio	8.9 (6.3, 11.9)	10.3 (7.6, 14.5)	0.15	8.9 (6.4, 12.5)	9.5 (6.7, 13.1)	0.67
REM sleep
Mean (SD)
Delta	70.2 (9.0)	67.2 (6.7)	0.11	69.6 (8.9)	70.4 (7.8)	0.66
Theta	11.8 (3.6)	12.6 (3.0)	0.28	11.9 (3.5)	11.9 (3.2)	0.95
Alpha	6.5 (2.5)	7.6 (2.2)	0.11	6.9 (2.4)	6.9 (2.5)	0.95
Sigma	3.0 (1.2)	3.3 (1.0)	0.12	3.0 (1.1)	2.9 (1.2)	0.63
Beta	8.3 (3.5)	9.2 (2.8)	0.22	8.5 (3.6)	8.0 (2.9)	0.40
Median (IQR)
Slowing ratio	4.6 (3.4, 6.6)	3.9 (3.0, 5.4)	0.071	4.3 (3.3, 6.6)	4.8 (3.6, 6.1)	0.63
N2 sleep spindle metrics
Occurrence	229.7 (161.2)	151.9 (121.0)	0.022	219.4 (153.8)	200.6 (166.8)	0.55
Overall density	1.1 (0.7)	0.8 (0.6)	0.027	1.1 (0.7)	1.0 (0.8)	0.52
Fast density	0.4 (0.3)	0.3 (0.3)	0.24	0.4 (0.3)	0.4 (0.4)	0.52
Slow density	0.7 (0.5)	0.5 (0.4)	0.022	0.7 (0.5)	0.6 (0.5)	0.64
Average frequency	12.8 (0.3)	12.8 (0.2)	0.35	12.8 (0.3)	12.8 (0.3)	0.22
Amplitude	14.0 (3.0)	13.5 (3.5)	0.49	14.2 (3.2)	12.8 (2.6)	0.033
N3 sleep spindle metrics
Occurrence	47.0 (67.7)	32.3 (48.6)	0.30	45.9 (67.5)	38.2 (53.9)	0.55
Overall density	0.7 (0.7)	0.4 (0.5)	0.044	0.7 (0.7)	0.6 (0.7)	0.69
Fast density	0.1 (0.2)	0.1 (0.2)	0.68	0.1 (0.2)	0.1 (0.2)	0.93
Slow density	0.6 (0.6)	0.3 (0.3)	0.002	0.5 (0.6)	0.5 (0.6)	0.66
Average frequency	12.4 (1.2)	12.7 (0.4)	0.29	12.4 (1.3)	12.2 (2.2)	0.40
Amplitude	4.6 (6.6)	13.1 (4.9)	0.095	13.1 (4.9)	11.3 (3.8)	0.060

Notes: Cognitive follow-up examination participants: Includes baseline sleep microarchitecture results for men who participated in both the baseline and follow-up cognitive assessments. Cognitive performance subgroups: divided into participants who showed a <0.5 SD reduction versus a ≥0.5 SD reduction in TMT-A or TMT-B performance from baseline to follow-up. Visual attention and processing speed (TMT-A): Includes baseline sleep microarchitecture by TMT-A performance subgroups. Executive function (TMT-B): Includes baseline sleep microarchitecture by TMT-B performance subgroups. <0.5 SD reduction: Includes baseline sleep microarchitecture for men who showed a <0.5 SD reduction in TMT-A or TMT-B performance between the baseline and follow-up cognitive assessments. ≥0.5 SD reduction: Includes baseline sleep microarchitecture for men who showed a ≥0.5 SD reduction in TMT-A or TMT-B performance between the baseline and follow-up cognitive assessments. Boldfaced p-values: statistically significant between-group difference in the variable of interest. BMI: body mass index categorised according to international criteria from the World Health Organisation (<25 kg/m² [underweight/normal], 25 to <30 kg/m² [overweight], and ≥30 kg/m² [obese]). Cardiovascular disease: self-reported, doctor-diagnosed myocardial infarction, angina, transient ischemic attack, or stroke. Diabetes mellitus: self-reported, doctor-diagnosed, fasting plasma glucose ≥7.0 mmol/L (126 mg/dL), haemoglobin A1C ≥6.5%, or reported antidiabetic medication use (oral hypoglycaemic agents and/or insulin). Insomnia: difficulty initiating or maintaining sleep occurring at least three nights/week (PSQI dimensions) and significant daytime fatigue defined as a score one standard deviation below the mean on the 36-item short-form survey instrument (SF-36) Vitality Scale. Hypertension: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or reported antihypertensive medication use. Cardio-metabolic conditions: one or more of hypertension, diabetes mellitus, or cardiovascular disease. Psychotropic medication(s): Use of one or more of opiates, antipsychotics, antiepileptics, antidepressants, or benzodiazepines. EEG relative spectral powers: delta: 0.5–4 Hz; theta: 4.5–8 Hz; alpha: 8–12 Hz; sigma: 12–15 Hz; beta: 15–32 Hz. EEG slowing ratio: calculated as a ratio of slow to fast EEG frequencies [(delta+theta)/(alpha+sigma+beta)]. N2 and N3 sleep spindle metrics: occurrence (11–16 Hz, total events), overall density (11–16 Hz, number/minute), fast density (13–16 Hz, number/minute), slow density (11–13 Hz, number/minute), average frequency (Hz, oscillations/second), and amplitude (µV). All PSG measures were scored according to AASM 2007 Alternative scoring criteria in which an AHI of 10/h is approximately equivalent to an AHI of 5/h used to define sleep-disordered breathing by the AASM 2007 Recommended scoring criteria.

Abbreviations: SD, standard deviation; IQR, interquartile range; NREM, non-rapid eye movement sleep; REM, rapid eye movement sleep; N2, stage 2 sleep; N3, stage 3 sleep; TMT-A, trail-making test A; TMT-B, trail-making test B.

Table 3 Unadjusted and Adjusted Associations of Baseline Sleep Microarchitecture Parameters with Standardized (z-Score) Follow-Up TMT-A Performance

	Unadjusted Model		Adjusted Model 1		Adjusted Model 2
	B (95% CI)	p	B (95% CI)	p	B (95% CI)	p
NREM sleep
Delta	0.002 (−0.02, 0.03)	0.86	0.001 (−0.02, 0.03)	0.97	0.006 (−0.02, 0.03)	0.61
Theta	0.008 (−0.05, 0.07)	0.79	0.008 (−0.05, 0.07)	0.78	−0.004 (−0.06, 0.05)	0.87
Alpha	−0.008 (−0.08, 0.06)	0.82	−0.005 (−0.07, 0.06)	0.89	−0.02 (−0.08, 0.04)	0.42
Sigma	−0.13 (−0.31, 0.06)	0.18	−0.05 (−0.23, 0.12)	0.54	−0.07 (−0.23, 0.08)	0.34
Beta	−0.004 (−0.11, 0.011)	0.94	−0.005 (−0.11, 0.10)	0.92	−0.002 (−0.09, 0.09)	0.97
Slowing ratio	0.07 (−0.78, 0.91)	0.87	0.005 (−0.77, 0.78)	0.99	0.18 (−0.52, 0.88)	0.61
REM sleep
Delta	−0.02 (−0.04, −0.001)	0.042	−0.01 (−0.03, 0.006)	0.19	−0.004 (−0.02, 0.01)	0.61
Theta	0.05 (−0.001, 0.09)	0.057	0.04 (−0.005, 0.08)	0.081	0.02 (−0.02, 0.06)	0.32
Alpha	0.08 (0.01, 0.15)	0.024	0.04 (−0.02, 0.11)	0.21	0.02 (−0.04, 0.08)	0.54
Sigma	0.10 (−0.05, 0.24)	0.21	0.03 (−0.11, 0.17)	0.69	−0.004 (−0.13, 0.12)	0.95
Beta	0.03 (−0.02, 0.08)	0.25	0.01 (−0.03, 0.06)	0.60	−0.003 (−0.05, 0.04)	0.88
Slowing ratio	−0.004 (−0.04, 0.03)	0.80	−0.005 (−0.04, 0.03)	0.76	0.003 (−0.03, 0.03)	0.86
N2 spindles
Occurrence	−0.001 (−0.002, −0.0002)	0.017	0.0007 (−0.001, 0.001)	0.90	−0.0002 (−0.001, 0.001)	0.74
Overall density	−0.29 (−0.52, −0.06)	0.014	0.005 (−0.24, 0.25)	0.97	−0.03 (−0.25, 0.20)	0.80
Fast density	−0.30 (−0.79, 0.18)	0.22	0.23 (−0.24, 0.71)	0.33	0.15 (−0.30, 0.58)	0.52
Slow density	−0.43 (−0.76, −0.11)	0.010	−0.11 (−0.44, 0.23)	0.54	−0.13 (−0.43, 0.18)	0.42
Frequency	0.30 (−0.33, 0.92)	0.35	0.43 (−0.16, 1.02)	0.15	0.48 (−0.05, 1.02)	0.077
Amplitude	−0.03 (−0.08, 0.03)	0.33	0.03 (−0.03, 0.08)	0.29	0.02 (−0.03, 0.07)	0.44
N3 spindles
Occurrence	−0.001 (−0.004, 0.001)	0.33	0.0002 (−0.002, 0.003)	0.86	0.0005 (−0.002, 0.003)	0.68
Overall density	−0.25 (−0.49, −0.009)	0.042	−0.01 (−0.26, 0.23)	0.92	0.002 (−0.22, 0.23)	0.98
Fast density	−0.14 (−1.11, 0.82)	0.77	0.64 (−0.28, 1.56)	0.17	0.62 (−0.22, 1.46)	0.15
Slow density	−0.33 (−0.61, −0.05)	0.023	−0.08 (−0.36, 0.21)	0.60	−0.06 (−0.32, 0.21)	0.68
Frequency	0.17 (0.08, 0.27)	0.16	0.18 (0.07, 0.29)	0.18	0.11 (0.03, 0.19)	0.34
Amplitude	−0.02 (−0.06, 0.02)	0.28	0.01 (−0.02, 0.05)	0.45	0.006 (−0.03, 0.04)	0.70

Notes: Coefficients: unstandardized beta (B) coefficients (95% confidence interval) from univariable and multivariable regression models are reported. Estimates: estimates represent the change in follow-up TMT-A scores corresponding to a 1% increase in baseline relative EEG spectral power and a one-unit increase in baseline logarithmically (10-base) transformed EEG slowing ratio. Boldfaced p-values: statistically significant at the 0.05 level. EEG relative spectral powers: delta: 0.5–4 Hz; theta: 4.5–8 Hz; alpha: 8–12 Hz; sigma: 12–15 Hz; beta: 15–32 Hz. EEG slowing ratio: calculated as a ratio of slow to fast EEG frequencies [(delta+theta)/(alpha+sigma+beta)]. N2 and N3 sleep spindle metrics: occurrence (11–16 Hz, total events), overall density (11–16 Hz, number/minute), fast density (13–16 Hz, number/minute), slow density (11–13 Hz, number/minute), average frequency (Hz), and amplitude (µV). Adjusted Model 1: adjusted for baseline age, AHI, highest educational attainment, socio-economic disadvantage, marital status, BMI, and cardio-metabolic conditions (one or more of cardiovascular disease, diabetes mellitus, or hypertension). Adjusted Model 2: additionally adjusted for baseline cognitive task performance. Spindle occurrence (adjusted Model 1 and 2): additionally adjusted for total sleep time.

Abbreviations: NREM, non-rapid eye movement; REM, rapid eye movement; CI, confidence interval.

Table 4 Unadjusted and Adjusted Associations of Baseline Sleep Microarchitecture Parameters with Standardized (z-Score) Follow-Up TMT-B Performance

	Unadjusted Model		Adjusted Model 1		Adjusted Model 2
	B (95% CI)	p	B (95% CI)	p	B (95% CI)	p
NREM sleep
Delta	0.01 (−0.02, 0.04)	0.47	0.01 (−0.02, 0.04)	0.40	0.009 (−0.01, 0.03)	0.40
Theta	−0.02 (−0.09, 0.04)	0.43	−0.03 (−0.09, 0.03)	0.27	−0.02 (−0.07, 0.03)	0.43
Alpha	−0.01 (−0.08, 0.06)	0.75	−0.02 (−0.09, −0.05)	0.62	−0.02 (−0.07, 0.04)	0.59
Sigma	−0.11 (−0.29, 0.07)	0.23	−0.06 (−0.24, 0.12)	0.49	−0.07 (−0.22, 0.08)	0.38
Beta	−0.02 (−0.13, 0.09)	0.70	−0.02 (−0.12, 0.09)	0.78	−0.03 (−0.12, 0.06)	0.46
Slowing ratio	0.19 (−0.67, 1.00)	0.69	0.18 (−0.63, 0.98)	0.66	0.20 (−0.47, 0.87)	0.55
REM sleep
Delta	−0.005 (−0.02, 0.02)	0.64	0.002 (−0.02, 0.02)	0.80	0.007 (−0.009, 0.02)	0.41
Theta	0.004 (−0.05, 0.05)	0.87	−0.007 (−0.06, 0.04)	0.79	−0.002 (−0.04, 0.04)	0.91
Alpha	0.03 (−0.04, 0.10)	0.47	−0.009 (−0.08, 0.06)	0.80	−0.02 (−0.08, 0.04)	0.45
Sigma	0.02 (−0.13, 0.17)	0.82	−0.04 (−0.19, 0.11)	0.60	−0.07 (−0.19, 0.06)	0.28
Beta	0.01 (−0.04, 0.06)	0.67	−0.0004 (−0.05, 0.05)	0.99	−0.02 (−0.06, 0.02)	0.28
Slowing ratio	0.002 (−0.03, 0.04)	0.90	0.004 (−0.03, 0.04)	0.80	0.004 (−0.02, 0.03)	0.76
N2 spindles
Occurrence	−0.001 (−0.002, 0.0004)	0.24	0.0005 (−0.001, 0.002)	0.43	0.0002 (−0.001, 0.001)	0.74
Overall density	−0.16 (−0.40, 0.08)	0.18	0.09 (−0.16, 0.34)	0.49	0.03 (−0.18, 0.24)	0.77
Fast density	−0.17 (−0.65, 0.32)	0.50	0.34 (−0.15, 0.83)	0.17	0.16 (−0.26, 0.57)	0.46
Slow density	−0.24 (−0.57, 0.09)	0.16	−0.0005 (−0.35, 0.35)	0.99	−0.02 (−0.31, 0.28)	0.91
Frequency	−0.11 (−0.74, 0.52)	0.72	0.09 (−0.52, 0.70)	0.76	−0.06 (−0.57, 0.46)	0.83
Amplitude	−0.02 (−0.08, 0.03)	0.38	0.01 (−0.04, 0.07)	0.67	−0.002 (−0.05, 0.04)	0.92
N3 spindles
Occurrence	−0.001 (−0.003, 0.002)	0.69	0.0004 (−0.002, 0.003)	0.78	−0.0004 (−0.002, 0.002)	0.97
Overall density	−0.04 (−0.29, 0.21)	0.74	0.15 (−0.10, 0.40)	0.23	0.08 (−0.14, 0.29)	0.49
Fast density	0.26 (−0.71, 1.23)	0.59	1.06 (0.13, 2.00)	0.026	0.57 (−0.24, 1.38)	0.17
Slow density	−0.08 (−0.36, 0.21)	0.59	0.11 (−0.19, 0.40)	0.48	0.05 (−0.20, 0.30)	0.70
Frequency	0.24 (−0.18, 0.65)	0.26	0.32 (−0.07, 0.70)	0.10	0.01 (−0.33, 0.35)	0.95
Amplitude	−0.03 (−0.07, 0.007)	0.11	−0.007 (−0.04, 0.03)	0.71	−0.02 (−0.05, 0.01)	0.20

Notes: Coefficients: unstandardized beta (B) coefficients (95% confidence interval) from univariable and multivariable regression models are reported. Estimates: estimates represent the change in follow-up TMT-A and TMT-B scores corresponding to a 1% increase in baseline relative EEG spectral power and a one-unit increase in baseline logarithmically (10-base) transformed EEG slowing ratio. Boldfaced p-value: statistically significant at the 0.05 level. EEG relative spectral powers: delta: 0.5–4 Hz; theta: 4.5–8 Hz; alpha: 8–12 Hz; sigma: 12–15 Hz; beta: 15–32 Hz. EEG slowing ratio: calculated as a ratio of slow to fast EEG frequencies [(delta+theta)/(alpha+sigma+beta)]. N2 and N3 sleep spindle metrics: occurrence (11–16 Hz, total events), overall density (11–16 Hz, number/minute), fast density (13–16 Hz, number/minute), slow density (11–13 Hz, number/minute), average frequency (Hz), and amplitude (µV). Adjusted Model 1: adjusted for baseline age, AHI, highest educational attainment, socio-economic disadvantage, marital status, BMI, and cardio-metabolic conditions (one or more of cardiovascular disease, diabetes mellitus, or hypertension). Adjusted Model 2: additionally adjusted for baseline cognitive task performance. Spindle occurrence (Adjusted Model 1 and 2): additionally adjusted for total sleep time.

Abbreviations: NREM, non-rapid eye movement; REM, rapid eye movement; CI, confidence interval.

Table 5 Unadjusted and Adjusted Associations of Baseline Sleep Microarchitecture Parameters with Baseline to Follow-Up Change in TMT-A Performance

	Unadjusted Model		Adjusted Model 1		Adjusted Model 2
	OR (95% CI)	p	OR (95% CI)	p	OR (95% CI)	p
NREM sleep
Delta	1.05 (0.97, 1.13)	0.21	1.06 (0.97, 1.16)	0.19	1.06 (0.97, 1.16)	0.19
Theta	0.93 (0.77, 1.12)	0.43	0.91 (0.73, 1.15)	0.45	0.92 (0.73, 1.16)	0.47
Alpha	0.89 (0.73, 1.08)	0.24	0.86 (0.67, 1.09)	0.20	0.86 (0.68, 1.09)	0.20
Sigma	0.62 (0.36, 1.07)	0.087	0.62 (0.32, 1.20)	0.15	0.62 (0.32, 1.20)	0.16
Beta	0.86 (0.62, 1.19)	0.36	0.73 (0.46, 1.15)	0.17	0.73 (0.46, 1.15)	0.17
Slowing ratio	3.84 (0.44, 33.2)	0.22	5.68 (0.42, 77.7)	0.19	5.56 (0.40, 76.6)	0.20
REM sleep
Delta	0.96 (0.91, 1.01)	0.12	0.97 (0.91, 1.04)	0.38	0.97 (0.91, 1.04)	0.36
Theta	1.07 (0.95, 1.21)	0.28	1.11 (0.94, 1.31)	0.20	1.12 (0.95, 1.33)	0.18
Alpha	1.16 (0.97, 1.38)	0.12	1.11 (0.89, 1.39)	0.37	1.11 (0.89, 1.39)	0.35
Sigma	1.36 (0.93, 1.99)	0.12	1.10 (0.69, 1.73)	0.70	1.09 (0.69, 1.73)	0.70
Beta	1.08 (0.96, 1.23)	0.22	1.02 (0.87, 1.18)	0.83	1.02 (0.87, 1.19)	0.83
Slowing ratio	1.04 (0.96, 1.13)	0.37	1.05 (0.95, 1.15)	0.39	1.04 (0.95, 1.15)	0.40
N2 spindles
Occurrence	0.996 (0.99, 1.00)	0.025	1.001 (0.997, 1.005)	0.66	1.001 (0.997, 1.006)	0.63
Overall density	0.42 (0.19, 0.93)	0.031	1.16 (1.08, 1.26)	0.75	1.17 (0.47, 2.90)	0.73
Fast density	0.40 (0.08, 1.88)	0.24	2.36 (0.45, 12.5)	0.31	2.51 (0.47, 13.6)	0.28
Slow density	0.25 (0.07, 0.84)	0.025	0.84 (0.21, 3.29)	0.80	0.84 (0.21, 3.32)	0.81
Frequency	2.19 (0.42, 11.4)	0.35	5.39 (0.55, 53.3)	0.15	5.31 (0.53, 53.1)	0.16
Amplitude	0.95 (0.82, 1.10)	0.48	1.10 (0.91, 1.33)	0.32	1.10 (0.91, 1.32)	0.33
N3 spindles
Occurrence	0.99 (0.98, 1.00)	0.29	1.001 (0.99, 1.01)	0.84	1.001 (0.99, 1.01)	0.86
Overall density	0.37 (0.14, 0.99)	0.047	0.83 (0.30, 2.34)	0.73	0.82 (0.29, 2.33)	0.71
Fast density	0.57 (0.04, 8.16)	0.68	7.73 (0.34, 175.2)	0.20	8.38 (0.36, 193.5)	0.18
Slow density	0.24 (0.07, 0.85)	0.027	0.56 (0.14, 2.27)	0.42	0.55 (0.13, 2.23)	0.40
Frequency	2.22 (0.43, 11.5)	0.34	2.82 (0.83, 9.54)	0.096	3.01 (0.87, 10.5)	0.083
Amplitude	0.84 (0.72, 0.99)	0.036	0.94 (0.78, 1.14)	0.55	0.94 (0.78, 1.14)	0.56

Notes: Coefficients: odds ratios (95% confidence intervals) from univariable and multivariable binary logistic regression models are reported. Estimates: estimates represent odds of decline in TMT-A and TMT-B scores corresponding to a 1% increase in relative EEG spectral power at baseline and a one-unit increase in logarithmically (10-base) transformed EEG slowing ratio at baseline. Boldfaced p-values: statistically significant at the 0.05 level. EEG relative spectral powers: delta: 0.5–4 Hz; theta: 4.5–8 Hz; alpha: 8–12 Hz; sigma: 12–15 Hz; beta: 15–32 Hz. EEG slowing ratio: calculated as a ratio of slow to fast EEG frequencies (delta+theta)/(alpha+sigma+beta). N2 and N3 sleep spindle metrics: occurrence (11–16 Hz, total events), overall density (11–16 Hz, number/minute), fast density (13–16 Hz, number/minute), slow density (11–13 Hz, number/minute), average frequency (Hz), and amplitude (µV). Adjusted Model 1: adjusted for baseline age, AHI, highest educational attainment, socio-economic disadvantage, marital status, BMI, and cardio-metabolic conditions (one or more of cardiovascular disease, diabetes mellitus, or hypertension). Adjusted Model 2: additionally adjusted for baseline cognitive task performance. Spindle occurrence (Adjusted Model 1 and 2): additionally adjusted for total sleep time.

Abbreviations: NREM, non-rapid eye movement; REM, rapid eye movement; CI, confidence interval; OR, odds ratio.

Table 6 Unadjusted and Adjusted Associations of Baseline Sleep Microarchitecture Parameters with Baseline to Follow-Up Change in TMT-B Performance

	Unadjusted Model		Adjusted Model 1		Adjusted Model 2
	OR (95% CI)	p	OR (95% CI)	p	OR (95% CI)	p
NREM sleep
Delta	1.01 (0.95, 1.07)	0.81	1.00 (0.93, 1.07)	0.95	1.00 (0.92, 1.07)	0.89
Theta	0.99 (0.86, 1.14)	0.88	1.01 (0.86, 1.20)	0.87	1.02 (0.87, 1.21)	0.80
Alpha	1.00 (0.85, 1.17)	0.96	1.00 (0.82, 1.21)	0.97	1.00 (0.82, 1.22)	0.97
Sigma	0.89 (0.58, 1.38)	0.60	1.01 (0.61, 1.68)	0.97	1.02 (0.61, 1.70)	0.94
Beta	0.96 (0.74, 1.24)	0.75	1.00 (0.74, 1.36)	0.98	1.00 (0.74, 1.35)	0.99
Slowing ratio	1.34 (0.19, 9.18)	0.77	1.08 (0.11, 10.3)	0.95	1.03 (0.11, 9.99)	0.98
REM sleep
Delta	1.01 (0.97, 1.06)	0.66	1.03 (0.97, 1.09)	0.30	1.03 (0.98, 1.10)	0.25
Theta	0.99 (0.89, 1.12)	0.95	0.99 (0.86, 1.14)	0.93	0.99 (0.86, 1.15)	0.94
Alpha	0.99 (0.85, 1.17)	0.95	0.92 (0.75, 1.12)	0.39	0.91 (0.74, 1.11)	0.35
Sigma	0.92 (0.65, 1.30)	0.62	0.77 (0.50, 1.16)	0.21	0.75 (0.49, 1.15)	0.18
Beta	0.95 (0.84, 1.07)	0.40	0.90 (0.78, 1.04)	0.16	0.89 (0.77, 1.03)	0.12
Slowing ratio	1.01 (0.94, 1.09)	0.79	1.01 (0.92, 1.10)	0.95	1.00 (0.92, 1.10)	0.98
N2 spindles
Occurrence	1.00 (0.997, 1.002)	0.55	1.002 (0.99, 1.005)	0.24	1.002 (0.99, 1.005)	0.25
Overall density	0.82 (0.46, 1.48)	0.51	1.47 (0.72, 2.99)	0.29	1.46 (0.71, 2.98)	0.30
Fast density	0.66 (0.19, 2.30)	0.52	2.05 (0.49, 8.57)	0.33	1.98 (0.47, 8.38)	0.35
Slow density	0.82 (0.36, 1.87)	0.64	1.47 (0.57, 3.78)	0.43	1.48 (0.57, 3.82)	0.42
Frequency	0.40 (0.09, 1.75)	0.22	0.46 (0.07, 2.87)	0.41	0.44 (0.07, 2.73)	0.38
Amplitude	0.85 (0.74, 0.99)	0.036	0.89 (0.75, 1.06)	0.19	0.89 (0.75, 1.06)	0.25
N3 spindles
Occurrence	1.00 (0.99, 1.005)	0.55	1.00 (0.99, 1.01)	0.90	1.00 (0.99, 1.01)	0.89
Overall density	0.88 (0.48, 1.62)	0.69	1.37 (0.69, 2.72)	0.37	1.36 (0.68, 2.69)	0.39
Fast density	0.90 (0.09, 8.98)	0.93	5.53 (0.41, 74.6)	0.20	4.93 (0.35, 69.2)	0.24
Slow density	0.85 (0.42, 1.74)	0.66	1.32 (0.59, 2.94)	0.50	1.31 (0.59, 2.93)	0.51
Frequency	1.05 (0.40, 2.70)	0.93	0.31 (0.43, 3.95)	0.64	1.18 (0.37, 3.76)	0.78
Amplitude	0.88 (0.76, 1.01)	0.065	0.92 (0.79, 1.09)	0.34	0.92 (0.78, 1.08)	0.30

Notes: Coefficients: odds ratios (95% confidence intervals) from univariable and multivariable binary logistic regression models are reported. Boldfaced p-value: statistically significant at the 0.05 level. Estimates: estimates represent odds of decline in TMT-A and TMT-B scores corresponding to a 1% increase in relative EEG spectral power at baseline and a one-unit increase in logarithmically (10-base) transformed EEG slowing ratio at baseline. EEG relative spectral powers: delta: 0.5–4 Hz; theta: 4.5–8 Hz; alpha: 8–12 Hz; sigma: 12–15 Hz; beta: 15–32 Hz. EEG slowing ratio: calculated as a ratio of slow to fast EEG frequencies (delta+theta)/(alpha+sigma+beta). N2 and N3 sleep spindle metrics: occurrence (11–16 Hz, total events), overall density (11–16 Hz, number/minute), fast density (13–16 Hz, number/minute), slow density (11–13 Hz, number/minute), average frequency (Hz), and amplitude (µV). Adjusted Model 1: adjusted for baseline age, AHI, highest educational attainment, socio-economic disadvantage, marital status, BMI, and cardio-metabolic conditions (one or more of cardiovascular disease, diabetes mellitus, or hypertension). Adjusted Model 2: additionally adjusted for baseline cognitive task performance. Spindle occurrence (Adjusted Model 1 and 2): additionally adjusted for total sleep time.

Abbreviations: NREM, non-rapid eye movement; REM, rapid eye movement; N2, stage 2 sleep; N3, stage 3 sleep; CI, confidence interval.