Impact of sleep quality on cognitive functions in Parkinson’s disease

Saurav Aggrawal; Birinder Singh Paul; Gagandeep Singh; Rajinder Kumar Bansal

doi:10.4103/AOMD.AOMD_58_20

ORIGINAL ARTICLES

Year : 2021 | Volume : 4 | Issue : 1 | Page : 28-33

Impact of sleep quality on cognitive functions in Parkinson’s disease

Saurav Aggrawal, Birinder Singh Paul, Gagandeep Singh, Rajinder Kumar Bansal
Oswal Hospital, Ludhiana, Punjab, India

Date of Submission	26-Nov-2020
Date of Decision	12-Jan-2020
Date of Acceptance	06-Mar-2021
Date of Web Publication	17-Apr-2021

Correspondence Address:
Prof. Birinder Singh Paul
Department of Neurology, Dayanand Medical College and Hospital, Ludhiana, Punjab.
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AOMD.AOMD_58_20

Abstract

BACKGROUND: Sleep disorders lead to cognitive deficits in healthy people and are thought to have significant impact on cognition in Parkinson’s disease (PD). OBJECTIVE: To study the sleep pattern and its relationship to cognitive functioning in non-demented PD cohort. MATERIALS AND METHODS: Sleep was evaluated by Pittsburg Sleep Quality Index (PSQI) in a cohort of PD patients. Comprehensive assessment of cognitive domains including attention, executive functions, short/long-term verbal memory, visual memory, and visuospatial functioning was done by battery of neuro-physiological tests on patients in “ON” state. Based on the component PSQI sleep score, patients were grouped as having "good quality sleep" (PSQI score ≤ 5) or "poor quality sleep" (PSQI score > 5). The demographic profile, disease characteristics, treatment, and cognitive tests were then compared between the two groups. RESULTS: Of 130 patients with diagnosis of PD, 85 patients were included. 63 (74.1%) had good sleep quality while 22 (25.9%) had poor sleep quality. Mean age and disease characteristic were comparable between two groups except that females had statistically significant (P = 0.001) poor sleep quality as compared to men. Poor sleep quality had significant effect on cognitive functions including generativity, inhibition, set-shifting, perseveration, and attention but there was no impact of sleep on verbal memory, visual memory, and visuospatial abilities. CONCLUSION: PD patients with poor sleep quality on PSQI questionnaire should be carefully screened for presence of any cognitive impairment especially executive impairment, as these two may be inter-related. Intervention to improve sleep would have far reaching benefits to improve the quality of life of PD patients.

Keywords: Cognitive functions, Parkinson’s disease, Pittsburg Sleep Quality Index, sleep quality

How to cite this article:
Aggrawal S, Paul BS, Singh G, Bansal RK. Impact of sleep quality on cognitive functions in Parkinson’s disease. Ann Mov Disord 2021;4:28-33

How to cite this URL:
Aggrawal S, Paul BS, Singh G, Bansal RK. Impact of sleep quality on cognitive functions in Parkinson’s disease. Ann Mov Disord [serial online] 2021 [cited 2023 Mar 23];4:28-33. Available from: https://www.aomd.in/text.asp?2021/4/1/28/313945

Introduction

Parkinson’s disease (PD) is the second most common, chronic progressive neuro-degenerative disorder characterized by motor and nonmotor symptoms and has a profound effect on quality of life. Sleep problems are one of the earliest nonmotor symptoms of PD, affecting up to 20–80% of the patients and the incidence increases as the disease progresses.^[1],[2]

Sleep and cognition are potentially interactive, and impaired sleep may have implications for the presence and worsening of cognitive function in PD.^[3] Cross-sectional studies have reported that rapid eye movement (REM) sleep behavior disorder is associated with impaired cognitive profile.^[4] Furthermore, poor sleep in PD patients has been linked longitudinally to accelerated rates of cognitive decline and increased incidence of dementia.^[5]

Cognitive impairment may not only arise directly through the pathology of PD, but also indirectly via the mechanism of chronic sleep disruption.^[6] Studies on sleep disturbances and cognition in PD, however, paint a variable correlation, with many reporting no relationship between sleep and neuropsychological performance and other showing their interdependence.^[7]

Hence, we aimed to study the co-existence of impairment of sleep and cognition in PD and also to identify the domains of cognition primarily affected by the presence of sleep disturbances.

Materials and Methods

This was a hospital-based prospective observational study conducted at the tertiary center in the Department of Neurology. All consecutive patients with diagnosis of PD diagnosed by the neurologist visiting the OPD were enrolled. Detailed neuropsychological evaluation was done by the neuropsychologist in the department.

Collection of data

Patients satisfying the UK Parkinson’s Disease Society Brain Bank diagnostic criteria^[8] for PD and who were able to read and write (studied up to 10th standard) were included in the study conducted over a period of 2 years. The ethical approval was obtained from the Institutional Review Board of the hospital. Written informed consent was taken from all the patients prior to their recruitment.

Patients with associated medical disorders known to affect sleep quality such as chronic kidney disease, chronic liver disease, and chronic pulmonary disease or history of sedatives or psychiatric medications were excluded. PD patients with MMSE <23 (n = 15 patients) and secondary Parkinsonism ^{More Details} (n = 24) such as multisystem atrophy (n = 13), progressive supra nuclear palsy (n = 10), and cortico-basal ganglionic degeneration (n = 1) were also excluded from the study.

Demographic and clinical parameters including gender, age of onset, duration of disease, and H&Y stage of disease were recorded on a predesigned Performa. Details of treatment included anti-parkinsonian drugs with calculation of levodopa equivalent dose (LED) using the accepted conversion factor formula.^[9] We also analyzed the patients who were receiving dopamine agonist separately.

Sleep measure

Pittsburgh Sleep Quality Index (PSQI) is widely used as a measure of sleep quality and has good internal consistency.^[10] PSQI assesses several sleep domains by 19 self-rated questions combined to form a “seven-component score” including (1) subjective sleep quality (one item); (2) sleep latency (two items); (3) sleep duration (one item); (4) habitual sleep efficiency (three items); (5) sleep disturbances (nine items); (6) use of sleeping medication (one item); and (7) daytime dysfunction (two items).

All patients were requested to fill the PSQI self-rated questionnaire in their native language (Hindi version-Mapi Research Trust).

Caregivers were actively involved in helping the patients in filling up the questionnaires for complete assessment of sleep quality as per the standard guidelines.

The patients were classified into two groups based on their component sleep score as “good quality sleep” (PSQI score ≤ 5) or “poor quality sleep” (PSQI score> 5) as used in the previous studies.^[11],[12] The demographic profile, disease characteristics, and treatment and neurophysiological tests were then compared between the two sleep groups.

Cognitive assessment

Comprehensive evaluation of all the cognitive domains known to be involved in PD and sleep disorders was done. The cognitive domains evaluated by applying a battery of neuropsychological tests to all included patients in their “ON” state of disease were (i) attention and working memory; (ii) executive functions; (iii) memory; and (iv) visuospatial functions.

i) Attention and working memory: In the present study, we used digit span backward and days/months’ backward test.

ii) Executive functions: The tests for executive functions included verbal fluency task (FAS and category naming), the Stroop color–word test (inhibition), Wisconsin card sort test (Set shifting response), and Luria fist-edge-palm test (perseveration).

iii) Memory tests: The tests for memory included short-term verbal recall; Benton Visual Retention Test (short-term visual), and long-term verbal recall.

iv) Visuospatial functions: For testing this cognitive domain, we used figure composition subscale of SCOPA-COG.

Statistical analysis

The statistical analysis was done using “version 17” of Statistical Package for Social Science (SPSS). The mean and standard deviation were used for quantitative variables. χ² and Student’s t-test were used for comparison of different categorical and discrete variables. Severity of disease (H&Y) was represented as median and range. The contribution of demographic, disease, and treatment factors on sleep quality was analyzed. Summary scores were calculated for each cognitive domain (memory, paired learning, attention, executive function, and visuospatial function) deviation of more than 2 from the standard considered to have impaired cognitive functioning. Pearson’s correlations were used to examine associations between sleep measures and summary scores in PD patients. P-value less than 0.05 was considered significant.

Results

Out of the 130 patients with diagnosis of PD enrolled from the OPD, 85 were included in the study. Among the 45 excluded, 20 patients had medical conditions affecting sleep pattern and 25 were on sedative medications for sleep disturbances. The non-demented cohort of 85 patients had a mean age of 61.45 ± 9.28 years and 58 (68.2%) patients were males. The median H&Y stage of disease was 2 (range 1–5), and 96% of the patients belonged to mild or early stage of PD. The mean LED was 385 ± 162 mg, and 24 (28.2%) patients were receiving dopamine agonists with a mean dose of 0.92 ± 0.56 mg. The other demographic and clinical characteristics of the patients are listed in [Table 1].

Table 1: Comparison of demographic and clinical characteristics between different sleep quality groups

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Sleep quality and characteristics of PD

Among the cohort of 85 PD patients, 63 (74.1%) had good sleep quality (PSQI ≤ 5; group-I), whereas 22 (25.9%) had poor sleep quality (PSQI >5; group-II). The clinical characteristics such as age, disease duration, age of onset of disease, LED, and dopamine agonist dose were comparable between the two groups, as shown in [Table 2]. There was statistically significant gender difference (P=0.001) in the sleep quality, with females having poor sleep quality when compared with men. There was also a trend of poor sleep quality with increasing severity of the disease, demonstrated by a median H&Y stage of 2 (range 1–4) in those with good sleep quality and of 3 (range 1–5) in the poor sleep quality group. Also, the mean duration of the disease was higher in the poor sleep quality group (3.3 ± 2.25 years) when compared with the good sleep quality group (2.81 ± 2.66 years).

Table 2: Comparison of cognitive functions and sleep quality of PD patients

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Cognitive functions

On assessing the attention and executive cognitive domains, abnormal functioning in the decreasing order of frequency was letter fluency in 36 (42.4%), digit span backwards in 35 (41.2%), Luria’s fist-edge-palm test in 34 (40%), semantic fluency in 31 (36.5%), Stroop testing in 24 (28.2%), and Wisconsin card sort test in 13 (15.3%) patients. While in memory test abnormalities in short-term verbal memory, short-term visual, long-term verbal recall, and visuospatial domains abnormalities were noted in 9 (10.5%), 8 (9.4%), 8 (9.4%) and 7(8.2%), respectively [Table 2].

Sleep and cognition correlation

Neuropsychological testing showed significant effect of sleep quality on the cognitive domains such as generativity, inhibition, set-shifting, perseveration, and attention tests. Patients with poor sleep quality showed poor performance on attention and executive functions (P = 0.001). When cognition was measured using memory (p 0.45) and visuospatial measures (P = 0.49), no significant effect on sleep quality was noted [Figure 1].

Figure 1: Correlation of sleep quality and cognitive function in PD

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This reveals that sleep was a strong factor influencing abnormalities in attention and executive functions (P < 0.01).

Discussion

The present study evaluated sleep pattern and its relationship to cognitive functioning in a cohort of 85 patients. The cohort was divided as either good sleep quality group or poor sleep quality group based on the component score of PSQI, which has been validated in the previous literature and shown to have good internal consistency and homogeneity.^[10] The mean PSQI score in this study was 4.29±3.61, and 22 (25.9%) had poor sleep quality. Sleep disorders are very common in PD but there is paucity of consensus in the literature on the existence of a distinct cognitive profile in non-demented PD patients based on their sleep quality. Studies in literature have also reported that sleep disruption is one of the reasons affecting cognitive impairment apart from other contributory factors such as age, gender, side of onset of disease, and duration of disease. However, the results of these studies paint a mixed picture with variable relationship between sleep and cognition.^[13] Many of these studies have methodical limitations as MMSE or frontal assessment battery (FAB) had been used for neuropsychological assessment.^{[14],[15],[16]} These tests have poor sensitivity to measure sleep-related cognitive deficits in PD, which could explain divergent results. In this study, we tried to overcome the limitation and measured the impact of sleep pattern on cognitive domains using extensive neurophysiological tests evaluating attention and executive functioning, memory (short term, long term, verbal, and visual), and visuospatial ability.

We also observed that women with PD had poor sleep pattern than men, and this statistical significant difference may be because women are actively involved in nurturing their family and carrying out most of the household activities which has a physiological impact causing poor sleep. There is no previous report in literature on gender difference of sleep pattern in patients with PD. Fatima et al.^[17] also reported gender difference in sleep pattern using PSQI. In their study of 3778 adults found, females had high frequency of poor sleep quality when compared with males even after adjusting socioeconomic factors and medical problems (odds ratio 1.53; 95% confidence interval 1.23–1.90). However, there was no difference in the presence of cognitive abnormalities between the genders with regard to sleep quality.

Jozwiak et al.^[18] showed a probable association between the presence of REM sleep behavior disorder in PD and poor performance on cognitive tests, namely, attention, executive functions, episodic verbal memory, and visuospatial abilities. This association may be partly attributed to sharing of the same neuropathological substrate and neurotransmitter, dopamine, which impacts both sleep and cognition.

Goldman et al.^[19] explored overall sleep quality using PSQI and reported that both memory and executive functions were impaired in the poor sleep group of PD patients. These results are, however, contrary to our results that show there was predominant involvement of executive domain with sparing of the memory and visuospatial functions in patients with poor sleep quality. Involvement of executive functions occurs early in the disease course^[20],[21] and may not relate to disease severity.^[22] In contrast, memory dysfunction is seen in later stages and is directly correlated with disease severity.^[19] Our cohort of PD patients had milder disease (mean H&Y<3) with short duration, which may be one of the factors for predominant involvement of executive and attention domains with sparing of memory involvement. Sleep quality and cognition may be more impaired with the progression of PD. Anderson and Horne^[23] studied sleep in adults and pointed out that sleep was particularly important for walking functions of frontal cortex, more precisely the prefrontal cortex. This association of sleep with executive functions is particularly important in patients with PD because PD is characterized by frontal compromise. Hence, in addition to frontal compromise, the impact of sleep loss may be detrimental to higher mental functions, as noted in our study. This theory is further supported by results of Bolitho et al.,^[24] who quantified sleep quality using actigraphy. They concluded that those patients with PD who had excessive nap during the day had greater fronto-subcortical dysfunction in the domain of attention, semantic verbal fluency, and processing speed, highlighting a possible inter-relationship between sleep and cognitive circuit representing a common pathology. There was a trend of higher stage and duration of disease in the poor sleep quality group; although this was not statistically significant, this suggests that stage and duration of disease also influence sleep and cognition.

In contrast, we observed no relation between sleep and memory or visuospatial domains. The reason may be that explicit memory and visuospatial functioning are related to the posterior cortical area that probably involves non-dopaminergic circuits and are hence uninfluenced by the quality of sleep.^[25]

Our study had certain limitations. First, though polysomnography is the gold standard for the assessment of sleep, we used PSQI, a self-reported questionnaire. The validated version of this scale available in native language of our population was, however, an advantage. Secondly, different types of sleep disorder were not analyzed because PSQI screens and measures the severity of overall sleep quality of PD patients and not Rapid eye movement sleep Behavior Disorder (RBD) disorders. Thirdly, our cohort included non-demented PD patients and the number is also small; hence, generalization of results to those having advanced PD, depression, or on sedative treatment needs to be with caution.

In conclusion, about one-fourth of the PD patients had poor sleep quality and this was more common in females. Poor sleep quality as assessed by PSQI had a significant effect across most of the cognitive functions including attention and executive functioning, but there was no association of the sleep quality with memory including verbal (short and long term), visual, and visuospatial abilities.

Understanding the relationship between PD and sleep is important because sleep problems are amenable to treatment. PD patients with poor sleep quality should be carefully screened for the presence of any cognitive impairment as these two may be inter-related. Improving sleep through behavioral therapy can have a positive impact on cognitive function also. This knowledge is essential for reducing the risk of cognitive impairment and in slowing the progression of cognitive decline in PD patients, hence improving their quality of life.^[23] Further studies in future are needed to investigate the neuro-anatomical substrates underlying sleep and cognitive functioning in this disorder.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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