Assessment of Self-reported Sleep Duration and Quality in Relation to the Cognitive Status of Older Adults: A Case-controlled Study

BACKGROUND

Sleep is essential for the amalgamation of procedural memory. Sleep-related consolidation of memory involves an interaction of different memory systems.^1,2 Sleep can affect many sub-domains of cognition, such as complex attention, memory, reasoning, language, and executive functioning. Sleep disturbance is common in older adults because of age-related increase in prevalence of multimorbidity, polypharmacy, psychosocial factors, and certain primary sleep disorders.^3,4 Almost 40–70% of older adults are estimated to have chronic sleep-related problems of whom nearly 50% remain undiagnosed.⁵ While much is known regarding age-related changes in cognitive functioning very little is known on the impact of sleep on late-life cognitive function.

Advanced age has been found related to normative declines in sleep and cognitive function. Enough evidence in literature points to an inherent connection between sleep and cognition. Data from observational studies support the part of sleep disturbances (mainly sleep duration, sleep fragmentation, and sleep-disordered breathing) in the development of cognitive decline.^2,6 Sleep difficulties combined with age-related cognitive decline, can contribute to poorer performance in daily activities necessary for independence, quality of life, and successful aging. Longer day time sleep is associated with a steeper decline in visuospatial reasoning and processing speed.⁷ However, very few studies have correlated the association of duration and sleep patterns with different cognition domains in older adults.

The proportion of older people has increased exponentially in recent decades. This proportion is estimated to be more than 20% of population by 2050.⁸ Therefore, the number of older adults suffering from cognitive decline and dementia has rapidly increased over the last few decades.⁹

Dementia is a common late life serious disorder. It is a very important contributor to a large proportion of disability and mortality in older people. Long-term care of these people has become burdensome for particularly the families and the society at large.¹⁰

Till date, there is no effective treatment available to treat dementia; thus, developing dementia prevention strategies is a priority.^11,12 Decline in cognition during the long preclinical phase of dementia, is regarded as a cardinal marker. Thus, identifying risk factors for cognitive decline, including poor duration and quality of sleep is important for dementia prevention.

OBJECTIVES

This study primarily compared the duration and quality of sleep in relation to cognitive function in various domains in patients of ≥65 years of age. The secondary objective was to compare the Pittsburgh Sleep Quality Index (PSQI) outcome in patients diagnosed with mild cognitive impairment (MCI) with healthy older adults. To identify specific blood biomarkers (lipid profile, vitamin D, vitamin B 12, and folic acid) in cognitively impaired older adults that may be linked to poor quality or duration of sleep.

MATERIALS AND METHODS

RESULTS

A total of 156 consecutive patients were recruited from geriatric medicine OPD, with informed consent to participate. A baseline cognitive assessment and assessment of global PSQI and its individual components were done (Fig. 2).

DEMOGRAPAHIC DETAILS OF THE STUDY PARTICIPANTS

A total of 156 participants were included in the study, of which 78 older adults had cognitive impairment – CDR 0.5 (cases) and 78 participants had normal cognition – CDR 0 (controls). Among the cases 57 were male (73%) and 21 were female (26%) whereas in the control group 55 were male (70%) and 23 were female (29%). The mean age for the cases was 71 years (66, 73) and 70 years (67, 77) for the controls (Table 1).

Demographic details of the case and control group were compared, there was a significant difference in the number of participants with no formal education with patients in control group having a larger group with no formal education (p = 0.034) (Table 1).

The most common comorbidity in cases was type 2 Diabetes mellitus (T2DM) (38%), followed by hypertension (HTN) (24%), coronary artery disease (CAD) (6%), chronic obstructive pulmonary disease (COPD) (4%). The most common comorbidity in the control group was T2DM (42%), followed by HTN (17%), CAD (11%), and COPD (5%). There was no significant difference in comorbidities between the 2 groups (Table 1).

DISCUSSION

The objective of this study was to examine the association of sleep duration and quality with cognition. There were two groups in this study population. Group I (control) comprised individuals with normal cognition (with a CDR of 0) and group II (cases) comprised individuals with MCI (with a CDR of 0.5). The mean age of the participants with CDR 0 was 70 years (66–73), Median (IQ1–IQ3), while the mean age of the patients with CDR 0.5 was 71 years (67–77). There was no significant difference in age between the two groups (p = 0.084). However, it was noted that participants in group II were slightly older than those in group I. There was no significant difference in sex among participants of the two groups (p = 0.772), although most were male.

There was a significant difference in educational status between people in group I with normal cognition and those with MCI group II (p = 0.034). There was no significant variation in the major comorbidities between the groups.

On assessing the groups by applying the geriatric depression scale (GDS), there was a significant difference in the absolute value of the GDS among the groups. Patients in the group with MCI had higher scores than the patients with normal cognition (group I) (p < 0.001). Similar findings were observed in studies performed by Morimoto et al., Preuss et al., Gutzmann and Qazi, and Koboyashi and Kato suggestive of an association of cognitive impairment with depression.^13–16

However, these values were not high enough to label as depression. If the score (GDS) was > 8, these were recorded as cases of depression and were excluded from the study.

This was significant because some older adults with late-life depression could present with cognitive impairment mimicking dementia, i.e., pseudodementia syndrome.¹³

There was a significant difference in the absolute value of 6 CIT with patients having MCI with consistently higher values in 6 CIT as compared with participants with normal cognition among both groups (p < 0.001). This is consistent with other similar studies by Dr. Brooke and Dr. Sheehan, reported in the literature.^17,18 The tool used in this study (6 CIT, a screening tool) has a sensitivity and specificity of 78 and 100%, respectively. It was used to rule out MNCD.^17,18 This was further confirmed by performing CDR on these participants.

Anxiety among the participants could be a confounder leading to poor sleep duration and quality of sleep. Hence, GAD-7 (generalized anxiety disorder scale) was applied to participants of both groups, and the participants with GAD > 4 (suggestive of anxiety) were removed. There was no significant difference in the absolute value of GAD-7 among the groups. The reliability coefficient Cronbach’s α for GAD-7 scale is 0.895, greater than the recommended value of 0.80, suggesting reliability for application in this study.¹⁷

There was no association established between fasting lipid profile and cognitive status in this study, for LDL, TG, TC, and HDL, respectively. This result was inconsistent with findings from studies like one by Iqbal et al. which found lowering LDL, TG, and TC level could prevent cognitive impairment. However, while higher HDL levels have been shown associated with improved cognitive performance, there is a dearth of studies establishing a negative association between lipid profile and cognition in the Indian population. More studies are thus, required to analyze findings in this regard. The groups (CDR 0 and CDR 0.5) also showed no significant difference in serum lipid profile between the participants who had impaired sleep for LDL, TG, TC, and HDL, respectively. This result was inconsistent with previous studies, like one by Merlino which has shown an inverse U relationship between blood HDL cholesterol levels and sleep duration, i.e., individuals with both less and excess sleep duration had low serum HDL.¹⁹ Another study by Kaneita reported that high triglyceride levels and low HDL levels were associated with short and prolonged sleep duration.²⁰ These results could be explained based on the presence of confounders like high BMI and OSA in the participants of these studies and hence further studies are required to establish this association.

The average value of serum vitamin B12 in all the recruited patients was 230 pg/mL. In comparison, the average value in MCI patients was 260 pg/mL (within the normal range but lower than the optimum 300 pg/mL). There was no significant association established between serum levels of vitamin B12 and cognitive status established in this study (p = 0.483). There was no difference of serum vitamin B12 levels between participants with normal (CDR 0) and impaired cognition (CDR 0.5) (p = 0.847). The findings were consistent with other studies that have not been able to establish a steady association between serum vitamin B12 levels, cognition, and sleep duration or quality. A study by Paayal et al. has shown an inverse relationship between serum vitamin B12 and sleep quality.²¹ Another study by Al-Musharaf found that higher levels of serum B12 were related to better sleep quality. These findings, however, could not be extended to global PSQI scores or total serum B12 levels.²² Our observation in this study was in line with these findings in literature.

There are controversies regarding the association of vitamin D deficiency with poor sleep quality or sleep disorder risk and cognition. Metanalysis and systematic reviews by Meehan and Penckofer, suggest an increased risk of sleep disorders and unhealthy sleep related to vitamin D deficiency.²³ Yet another study Larsen et al. suggested no consistent relationship of vitamin D supplementation on sleep even in vitamin deficient population.²⁴ A similar lack of association was established between individuals of both groups with high PSQI scores (>5) in our study (p = 0.837). The average serum 25OH vitamin D value in MCI patients recruited in our study was normal (30.36 ng/mL). The average value in all participants was 30.93 ng/mL (normal range in older adults 20–30 ng/mL). There was no significant relation established between vitamin D and cognitive status in our study (p = 0.159).

It is hypothesized in studies that folic acid supplementation could reduce oxidative stress and telomere shortening induced by insomnia, improving sleep quality.²¹ However, a similar association could not be established in our study (p = 0.356). The average value of folic acid in all participants was 10.0 ng/mL, while the average value in MCI patients was 9.9 ng/mL (normal range 3–17.5 ng/mL). There was no association between folic acid and cognitive status in our study (p = 0.990).

There are inconsistencies with regard to association of biomarkers with sleep and cognitive impairment, while some suggest a positive association yet others refute such claims. A larger multicentric study with a more uniform method of assessment is thus required to ascertain these findings.

With regards to the association of sleep parameters, there was a significant association between global PSQI scores and poor cognition (<0.001), wherein patients with MCI had higher PSQI scores (>5) as compared with those with normal cognition. Similar observations were reported in other studies by Potvin and Tworoger on older adults in the community, comparing global sleep quality to cognitive status.^25,26 The variation between the two groups regarding total sleep duration was statistically significant (p = 0.018). The total period of sleep score is a scale used to quantify the total sleep duration as categorical variables. The total number of participants with more than 7 hours of sleep (i.e., low TDS score) was found to be significantly different in the two groups (1 = 35.9%) vs (2 = 26.92%) of participants (p = 0.013). Group I had a significantly longer duration of sleep more than 7 hours). Similar findings were reported in other studies by Potvin, Tworoger, and Gildner with both a lack of sleep (<5 hours) and excess sleep (>9 hours) associated with incidents of dementia.^25–27

Variation in sleep latency between the two groups was statistically significant (p = 0.045). Sleep latency was greater in participants of group II. However, there was no statistical difference in the individual sleep latency scores. Similar outcomes were reported in other studies comparing cognitive impairment in older adults to sleep latency.²⁶ A significant difference was reported in the total number of sleep disturbances among the groups (p < 0.001). This finding was similar to other studies, like one by Tworoger that compared women in the age group of 70–80 years, belonging to the nurse’s cohort, who showed a decline in cognitive test scores associated with sleep interruptions (snoring) and less sleep duration.²⁶ In another study by Potvin examining the impact of sleep in cognitively healthy older adults between 60 and 70 years of age from Quebec City, Canada, followed up over 12 months, higher sleep disturbance scores and poor overall PSQI scores were related to incident amnestic and non-amnestic MCI.²⁵

There was no difference in the number of sleep medications used by the two groups of participants. There was a significant difference in the incidence of daytime sleepiness among participants of the two groups (p < 0.001). There was variation in this observation in different studies. In a study by Merlino, that recruited 750 Italian older adults with dementia, daytime somnolence was found in up to 30% of the participants.¹⁹ In another study by Tworoger involving women from the nurse’s cohort, no significant association was found between cognitive scores and daytime sleepiness.²⁶ There was no statistical difference in self-reported sleep quality (reported as per the Likert scale) by participants to their overall cognitive status in this study. However, other studies, like one by Gildner including a longitudinal sample of older adults from six different countries as a part of the SAGE study, found that self-reported sleep quality had a positive correlation with cognitive Z scores.²⁷

Regression bivariate analysis of PSQI against cognitive status was statistically significant (p < 0.001). Higher global PSQI scores were related to poor cognition (MCI). Several studies observed similar outcomes, including the previously discussed study in older women of the nurse’s cohort. Multivariate analysis of cognitive function across various sleep parameters showed that shorter sleep duration and sleep interruptions were linked to poor cognition. Similarly, in a prospective study by Potvin and Tworoger examining Canada’s community-dwelling older adults, higher global PSQI scores were linked to cognitive impairment.^25,26

There was a difference in sleep latency in participants of both groups (p = 0.038). There was a statistical difference in the regression analysis between daytime sleepiness and participants’ cognitive status (p ≤ 0.001). A significant difference was reported in the regression analysis of sleep disturbance against cognitive status (p = 0.001). These results were once again comparable to findings reported in several studies, including data from the SAGE study, which found that individuals with shorter and poorer self-reported sleep quality had worse cognitive scores.²⁷

There was no significant variation in the total duration of sleep, TDS score, abnormal sleep quality, use of sleep medication and sleep latency score between the groups.

In comparing various subdomains of CDR to different components of the PSQI, there was a significant association between deficit in the cognitive subdomain of memory and higher global PSQI scores (p < 0.01), in cognitively impaired older adults (CDR 0.5/MCI).

No similar outcome was observed in terms of overall PSQI score in other studies. However, a statistically significant association (p < 0.05) was reported on comparing poor working/verbal memory to sleep duration: short sleep (less than 5 hours) and long sleep (>9 hours) (p < 0.05) in a study by Lo et al.^19,28

There was a statistically important relation between poor orientation and reduced sleep duration and quality (p = 0.028). Although not specific to orientation, multiple studies by Potvin, Tworoger, Gildner, and Lo, did report a significant association between poor sleep duration and quality in multiple cognitive domains.^25–28 There was a statistically significant relation between impaired judgment and problem-solving and poor sleep duration and quality (p = 0.048). Other studies established a similar association between excess or lack of sleep and executive function and processing speed (p < 0.05).²⁹ In a study by Tai et al., confirmatory factor analysis of 5 cognitive tasks was used to analyze executive function (EF) and found that 7 hours or more sleep was related to high EF scores.²⁹ A significant relation was observed between low scores in the subdomain home and hobbies and poor sleep duration and quality (p = 0.017). This could be substantiated by the overall poor cognitive function scores, especially in areas of executive function and processing speed associated with abnormal sleep duration. Similar findings were observed in a systematic review and meta-analysis by Lo et al., involving 35 publications (11 cross-sectional and 7 cohorts) that showed extreme sleep durations were linked to poor multidomain performance, including executive function, working, and verbal memory.²⁸ Although the primary objective of establishing an relationship between self-reported sleep duration and quality with cognitive status in older adults was satisfied in this study, large multicentric studies are required in the future to confirm these results.

CONCLUSION

This study found that individuals with MCI had shorter duration and poor overall quality of sleep compared with older adults with healthy cognition. Participants with MCI had significantly higher global PSQI scores than participants with normal cognition. There was a statistically significant association of poor performance in subdomains of memory, orientation, judgment and problem-solving, home and hobbies with higher global PSQI scores. This was suggestive of a significant association between poor performance in these subdomains of clinical dementia rating (CDR) and poor sleep duration and quality. No statistically significant association was found between serum fasting lipid profiles, serum 25OH (D), serum vitamin B12, and serum folic acid levels within cognitively impaired adults with poor sleep duration or quality.

ORCID

Shreya Biswal https://orcid.org/0000-0001-7652-8360

REFERENCES

1. Born J, Wagner U. Awareness in memory: Being explicit about the role of sleep. Trends Cogn Sci 2004;8(6):242–244. DOI: 10.1016/j.tics.2004.04.010.

2. Brienne Mine. Sleep in the ageing population. Sleep Med Clin 2017;12(1):31–38. DOI: 10.1016/j.jsmc.2016.10.008.

3. Seidel S, Dal-Bianco P, Pablik E, et al. Depressive symptoms are the main predictor for subjective sleep quality in patients with mild cognitive impairment—A controlled study. PLoS One 2015;10(6):e0128139. DOI: 10.1371/journal.pone.0128139.

4. Avidan AY. Normal sleep in humans. In: Haay KM, Richard B, editors. At Clin Sleep Med 2nd Edition. Philadelphia, PA: Saunders; 2014. Chapter 13, pp 83-116.e1.

5. Dzierzewski JM, Dautovich N, Ravyts S. Sleep and cognition in older adults. Sleep Med Clin 2018;13(1):93–106. DOI: 10.1016/j.jsmc.2017.09.009.

6. Kristine Y, Cherry MF, Tina H. Connections between sleep and cognition in older adults. Lancet Neurol 2014;13(10):1017–1028. DOI: 10.1016/S1474-4422(14)70172-3.

7. Cox SR, Ritchie SJ, Allerhand M, et al. Sleep and cognitive aging in the eighth decade of life. Sleep 2019;42(4):zsz019. DOI: 10.1093/sleep/zsz019.

8. United Nations Department of Economic and Social Affairs Population Division. World Population Prospects: The 2015 Revision: Key Findings and Advance Tables United Nations Working Paper ESA/P/WP.241. Accessed August 12, 2020.

9. Prince M, Comas-Herrera A, Knapp M, et al. World Alzheimer Report 2016: Improving healthcare for people living with dementia: coverage, quality and costs now and in the future. Alzheimer’s Dis Int 2016. Accessed August 12, 2020. Available from: https://www.alzint.org/resource/world-alzheimer-report-2016/#:~:text=The%20World%20Alzheimer%20Report%202016,improved%20and%20made%20more%20efficient.

10. Alzheimer’s Association. 2018 Alzheimer’s disease facts and figures. Alzheimers Dement 2018;14(3):367–429. Available from: https://www.alz.org/alzheimers-dementia/facts-figures.

11. Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia in the United States: The aging, demographics, and memory study. Neuroepidemiology 2007;29(1–2):125–132. DOI: 10.1159/000109998.

12. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet 2017;390(10113):2673–2734. DOI: 10.1016/S0140-6736(17)31363-6.

13. Morimoto SS, Kanellopoulos D, Alexopoulos GS. Cognitive impairment in depressed older adults: Implications for prognosis and treatment. Psychiatr Ann 2014;44(3):138–142. DOI: 10.3928/00485713-20140306-05.

14. Gutzmann H, Qazi A. Depression associated with dementia. Z Gerontol Geriatr 2015; 48(4):30511. DOI: 10.1007/s00391-015-0898-8.

15. Preuss UW, Siafarikas N, Petrucci M, et al. Depressive Störungen bei Demenzen und milder kognitiver Beeinträchtigung: Komorbidität, Ursache oder Risikofaktor? [Depressive disorders in dementia and mild cognitive impairments: Is comorbidity a cause or a risk factor?]. Fortschr Neurol Psychiatr 2009;77(7):399–406. DOI: 10.1055/s-0028-1109454.

16. Kobayashi T, Kato S. Depression-dementia medius: Between depression and the manifestation of dementia symptoms. Psychogeriatrics 2011;11(3):177–182. DOI: 10.1111/j.1479-8301.2011.00363.x.

17. Brooke P, Bullock R. Validation of a 6-item cognitive impairment test with a view to primary care usage. Int J Geriatric Psychiatry 1999;14(11):936–940. PMID: 10556864.

18. Sheehan B. Assessment scales in dementia. Ther Adv Neurol Disord 2012;5(6):34958. DOI: 10.1177/1756285612455733.

19. Merlino G, Piani A, Gigli GL, et al. Daytime sleepiness is associated with dementia and cognitive decline in older Italian adults: A population-based study. Sleep Med 2010;11(4):372–377. DOI: 10.1016/j.sleep.2009.07.018.

20. Kaneita Y, Uchiyama M, Yoshiike N, et al. Associations of usual sleep duration with serum lipid and lipoprotein levels. Sleep 2008;31(5):645–652. DOI: 10.1093/sleep/31.5.645.

21. Paayal C, Ganesh U, Shaantanu D. Indian perspective on clinical aspects, usage, and guidelines of folic Acid. J Obstet Gynaecol India 2014;64(5):328–331. DOI: 10.1007/s13224-014-0526-3.

22. Al-Musharaf S, Alabdulaaly A, Bin Mujalli H, et al. Sleep quality is associated with vitamin B12 status in female Arab students. Int J Environ Res Public Health 2021;18(9):4548. DOI: 10.3390/ijerph18094548.

23. Meehan M, Penckofer S. The role of vitamin D in the aging adult. J Aging Gerontol 2014;2(2):60–71. DOI: 10.12974/2309-6128.2014.02.02.1.

24. Larsen AU, Hopstock LA, Jorde R, et al. No improvement of sleep from vitamin D supplementation: Insights from a randomized controlled trial. Sleep Med 2021;3:100040. DOI: 10.1016/j.sleepx.2021.100040.

25. Potvin O, Lorrain D, Forget H, et al. Sleep quality and 1-year incident cognitive impairment in community-dwelling older adults. Sleep 2012;35(4):491–499. DOI: 10.5665/sleep.1732.

26. Tworoger SS, Lee S, Schernhammer ES, et al. The association of self-reported sleep duration, difficulty sleeping, and snoring with cognitive function in older women. Alzheimer Dis Assoc Disord 2006;20(1):41–48. DOI: 10.1097/01.wad.0000201850.52707.80.

27. Gildner TE, Liebert MA, Kowal P, et al. Associations between sleep duration, sleep quality, and cognitive test performance among older adults from six middle income countries: Results from the study on global ageing and adult health (SAGE). J Clin Sleep Med 2014;10(6):613–621. DOI: 10.5664/jcsm.3782.

28. Lo JC, Groeger JA, Cheng GH, et al. Self-reported sleep duration and cognitive performance in older adults: A systematic review and meta-analysis. Sleep Med 2016;17:87–98. DOI: 10.1016/j.sleep.2015.08.021.

29. Tai XY, Chen C, Manohar S, et al. Impact of sleep duration on executive function and brain structure. Commun Biol 2022;5(1):201–209. Available from: https://www.nature.com/articles/s42003-022-03123-3.