Psychiatric morbidity, cognitive dysfunction and quality of life in drug-naive patients with Parkinson's disease: A comparative study.

BACKGROUND: To better understand the psychiatric disorders and cognition in Parkinson's disease (PD) and its impact on quality of life (QoL), patients need to be studied soon after diagnosis, before initiation of dopamine replacement therapy. AIM: This study aims to compare the nature and frequency of psychiatric morbidity, cognitive dysfunction, and quality of life in drug-naive patients with PD and healthy controls.
MATERIALS AND METHODS: The cross-sectional, comparative study was conducted in tertiary care center. Fifty drug-naive PD patients and fifty healthy controls were included and assessed on Modified Hoehn and Yahr scale, PD Questionnaire 8, Kolkata cognitive screening battery, General Health Questionnaire-12, and Hamilton Anxiety and Depression Rating Scale (HAM-A and HAM-D).
RESULTS: The mean scores of HAM-A and HAM-D of patients with PD were significantly higher than that of the comparison group. The patients with PD had statistically significant impairment in verbal fluency, Mini-Mental State Examination, calculation, memory immediate recall, visuoconstructional ability, and memory (delayed recall and recognition) in comparison to patients without PD. No statistically significant difference was observed with respect to object naming between the two groups.
CONCLUSION: QoL of a PD patient is adversely affected by both the motor and nonmotor symptoms of the disease such as depression, anxiety, apathy, sleep disturbances, and cognitive impairment. The link between nonmotor symptoms and reduced QoL has important implications for the management of PD because the nonmotor symptoms often appear before patients are given anti-parkinsonian therapy. Screening of nonmotor symptoms in early stage of disease will decrease the morbidity and mortality and improve the QoL. Copyright:

Parkinson's disease (PD), a second most common neurodegenerative condition, has been defined by its characteristic motor presentation.[1] Recent studies have focused on nonmotor features of PD which may predate the motor symptoms and have been associated with increased disability and reduced quality of life (QoL).

The reported frequency of any type of psychiatric symptoms in PD is higher than 60%.[2] Approximately 30%–40% of patients with PD have significant depressive symptoms[34] and up to 40% experience anxiety.[567]

Cognitive impairment in PD is heterogeneous in its severity, rate of progression and typically affects the processing speed, executive functioning and visuospatial functioning.[8910]

To what extent psychiatric morbidity and cognitive impairment are attributable to the neurodegenerative process, and to the psychosocial, demographic, or clinical factors, is yet unclear. Hence, this study was conducted with the aim to compare the nature and frequency of psychiatric morbidity, cognitive dysfunction, and QoL in drug-naive patients with PD and healthy controls.

MATERIALS AND METHODS

The present cross-sectional, comparative study was conducted in the outpatient departments of Medicine, Neurology and Psychiatry, Geetanjali Medical College and Hospital, Udaipur. Individuals with a clinical diagnosis of PD confirmed by a consultant neurologist constituted the study sample. The patients with PD included were drug naive and hemodynamically stable to complete the assessment. The study was conducted between June 2017 and July 2018. The present study was initiated after approval from the institutional ethics committee, and informed consent was obtained from all the study participants.

Fifty healthy controls without PD, who are relatives and friends of the patients matched for age and sex, constituted the comparison group.

Participants with a history of primary psychiatric disorder, substance use disorder (other than nicotine and caffeine), and those with other chronic and/or serious medical condition were excluded from the study.

The following tools were employed in the present study:

Modified Hoehn and Yahr scale (H and Y scale):[11] This scale assesses the severity of the PD. In Stage 1, the earliest stage, the symptoms of PD are mild and only seen on one side of the body (unilateral involvement), and there is usually minimal or no functional impairment. Stage 2 is characterized by symptoms on both sides of the body (bilateral involvement) or at the midline without impairment to balance. Stage 3 is considered midstage and is characterized by loss of balance and slowness of movement. Patients with Stage 4 PD may be able to walk and stand unassisted, but they are noticeably incapacitated. At this stage, the patient is unable to live an independent life and needs assistance with some activities of daily living. Stage 5 is the most advanced and is characterized by confinement to a bed or wheelchair

PD Questionnaire 8 (PDQ-8):[12] It is a shorter version derived from PDQ-39. It is a self-administered questionnaire, used to measure Qol in persons with PD

Kolkata cognitive screening battery:[13] It was initially used by Ganguly et al. and validated among urban population in Bengali- and Hindi-speaking population. This cognitive screening battery consists of category-based verbal fluency tests, a 15-item version of the object naming test, mental state examination, calculation tests, visuo-constructional abilities which include drawing the circle and diamond, overlapping rectangles and a box and a set of memory tests which consist of immediate memory, delayed recall and recognition of a 10-item wordlist

General Health Questionnaire-12 (GHQ 12):[1415] It is a self-administered screening questionnaire, designed for use in consulting settings aimed at detecting individuals with a diagnosable psychiatric disorder

Hamilton Anxiety and Depression Rating Scale (HAM-A and HAM-D):[1516] It has been extensively used to assess the severity of anxiety and depression.

The postgraduate resident assisted the patients in administering the tools, and the findings were ratified by the consultant psychiatrist/neurologist. The data obtained were analyzed using Statistical Package for Social Science version 20 (IBM). Descriptive analysis, Chi-square test, Student's t-test, and Pearson's correlation coefficient test were applied.

RESULTS

Patients with PD and the comparison group were comparable with regard to age, gender, religion, domicile, education, and family profile [Table 1]. Using the GHQ-12, 92% of patients with PD and 16% the control group screened positive for a diagnosable psychiatric disorder. The mean scores of HAM-A and HAM-D of patients with PD were significantly higher than that of the comparison group [Table 2a]. Patients with PD had significantly more severe depressive symptoms, whereas no statistically significant difference was observed with regard to severity of anxiety symptoms between the two groups [Table 2b]. The patients with PD had statistically significant impairment in verbal fluency, Mini-Mental State Examination (MMSE), calculation, memory immediate recall, visuoconstructional ability, and memory (delayed recall and recognition) [Table 3] in comparison to healthy controls. No statistically significant difference was observed with respect to object naming between the two groups. A positive, statistically nonsignificant linear correlation was noted between the severity of PD and PDQ-8 scores [Table 4]. Patients with PD with H and Y score of ≤2 and >2 were classified as early–middle stage PD and middle–advanced disease stage, respectively. Both these groups were compared for severity of depression, anxiety, cognitive dysfunction, and QoL, but no statistically significant differences was noted in both the groups except for verbal fluency [Table 5].

Table 1

Distribution of sociodemographic factors in Parkinson’s disease patients and healthy controls

Variables	Parkinson’s disease patients (n=50), n (%)	Healthy controls (n=50), n (%)	χ2, d/f, P
Age group (years)
50-59	7 (14)	8 (16)	0.628, 2, 0.731
60-69	28 (56)	32 (64)
70 and above	15 (30)	12 (24)
Sex
Male	31 (62)	36 (72)	0.724, 1, 0.395
Female	19 (38)	14 (28)
Religion
Hindu	33 (66)	34 (68)	0.304, 2, 0.859
Muslim	7 (14)	8 (16)
Jain	10 (20)	8 (16)
Domicile
Urban	16 (32)	15 (30)	0.000, 1, 1.000
Rural	34 (68)	35 (70)
Education
Illiterate	16 (32)	19 (38)	1.944, 4, 0.746
Secondary	22 (44)	24 (48)
Senior secondary	6 (12)	4 (8)
Graduate	3 (6)	1 (2)
Postgraduate and above	3 (6)	2 (4)
Family type
Nuclear	24 (48)	23 (46)	0.042, 2, 0.979
Joint	24 (48)	25 (50)
Extended	2 (4)	2 (4)
Family size
<5	18 (36)	16 (32)	0.182, 2, 0.913
5-10	30 (60)	32 (64)
>10	2 (4)	2 (4)
Family income (monthly)
<25,000	30 (60)	35 (70)	1.813, 2, 0.404
25,000-50,000	15 (30)	13 (26)
>50,000	5 (10)	2 (4)

Table 2a

Comparison of Hamilton Rating Scale for Depression and Anxiety scores between Parkinson’s disease patients and healthy controls

	n	Mean±SD	t, d/f, P
HAM-D
Parkinson’s disease patients	50	5.88±3.899	5.011, 98, 0.000
Healthy controls	50	2.84±1.788
HAM-A
Parkinson’s disease patients	50	5.78±5.526	2.662, 98, 0.009
Healthy controls	50	3.58±1.902

SD – Standard deviation; HAM-D – Hamilton Rating Scale for Depression; HAM-A – Hamilton Rating Scale for Anxiety

Table 2b

Distribution according to Severity of Depression and Anxiety scores on Hamilton Rating Scale between Parkinson’s disease patients and healthy controls

	n (%)	Mild, n (%)	Moderate, n (%)	Severe, n (%)	χ2, d/f, P
Parkinson’s disease patients	39 (78)	5 (10)	6 (12)	0	9.803, 2, 0.007
Healthy controls	49 (98)	1 (2)	0	0
	Mild, n (%)	Mild-moderate, n (%)	Moderate-severe, n (%)	Severe, n (%)	χ2, d/f, P
Parkinson’s disease patients	45 (90)	4 (8)	1 (2)	0	1.763, 2, 0.414
Healthy controls	48 (96)	2 (4)	0	0

Table 3

Comparison of cognitive dysfunction on Kolkata cognitive screening battery between Parkinson’s disease patients and healthy controls

Areas of functioning	Mean±SD		t, d/f, P
	Parkinson’s disease patients	Healthy controls
Verbal fluency	18.5±3.609	23.18±4.255	−5.931, 98, 0.000
Object naming	14.92±0.395	14.96±0.197	−0.641, 98, 0.523
MMSE	28.34±1.572	29.62±0.696	−5.265, 98, 0.000
Calculation	3.32±1.331	4.66±0.592	−6.505, 98, 0.000
Memory immediate recall	19.26±2.640	24.6±1.511	−12.413, 98, 0.000
Visuoconstructional ability	5.74±3.968	9.84±1.489	−6.841, 98, 0.000
Memory delayed recall	5.66±1.080	7.24±0.916	−7.889, 98, 0.000
Memory delayed recognition	11.24±3.020	15.68±1.867	−8.843, 98, 0.000

MMSE – Mini-Mental Status Examination; SD – Standard deviation

Table 4

Correlation of severity of Parkinson’s disease scores with quality of life scores on Parkinson’s disease questionnaire 8

Parkinson’s disease severity with QoL score (PDQ-8) (n=50)	Score
Pearson correlation	0.329
Significant	0.195

PDQ-8 – Parkinson’s disease questionnaire-8; QoL – Quality of life

Table 5

Comparison of psychiatric morbidity, cognitive dysfunction and quality of life in early-middle Parkinson’s disease patients with middle-advanced Parkinson’s disease patients (Hoehn and Yahr Staging)

Variables	Mean±SD		t, d/f, P
	Hoehn and Yahr Scale Early-Middle (2 or<2)	Hoehn and Yahr scale middle-advance (>2)
HAM-D	6.323±4.065	4.937±3.453	1.177, 48, 0.245
HAM-A	5.617±4.849	6.125±6.917	−0.300, 48, 0.765
Verbal fluency	17.794±3.682	20±3.033	−2.084, 48, 0.043
Object naming	15±0	14.75±0.683	-
MMSE	28.264±1.503	28.5±1.751	−0.491, 48, 0.626
Calculation	3.264±1.188	3.437±1.631	−0.425, 48, 0.673
Memory immediate recall	18.823±2.587	20.187±2.587	−1.739, 48, 0.088
Visuoconstructional ability	5.676±4.087	5.875±3.827	−0.164, 48, 0.871
Memory delayed recall	5.647±1.124	5.687±1.014	−0.121, 48, 0.904
Memory delayed recognition	10.882±2.857	12±3.306	−1.227, 48, 0.226
PDQ-8	34.926±25.147	46.093±26.008	−1.449, 48, 0.154

HAM-D – Hamilton Rating Scale for Depression; HAM-A – Hamilton Rating Scale for Anxiety; MMSE – Mini-Mental Status Examination; PDQ-8 – Parkinson’s Disease Questionnaire 8; SD – Standard deviation

DISCUSSION

Recent researches support that neuropsychiatric symptoms are common in PD, even in the prodromal stage such as visual changes, other autonomic symptoms, and subtle cognitive changes.[1718]

Pathophysiology of neuropsychiatric comorbidities is still unclear; it may be part of disease process, neurodegeneration, biochemical changes, psychosocial factors, etc., Situational stressors along with reaction to motor disability have all been contributing to the neuropsychiatric symptoms. Aarsland et al. 1999 observed that 40% of the patients suffer from symptoms of depression,[19] and in the present study, author found that 22% of patients had depressive symptoms and 10% of patients had anxiety symptoms even at first consultation. According to an Indian study, Rai et al. found higher rate of psychiatric morbidities. Depression was the most frequent neuropsychiatric comorbidity (43.7%) followed by anxiety (36%), suicide risk (31%), and psychosis (24%) in young-onset Parkinson's disease patients.[20] The higher rate of psychiatric morbidities can be explained by the inclusion of individuals who are already on anti-parkinsonian medications. They may have severe form, advanced stages of illness, and drug-induced psychotic symptoms.

Cognitive impairment in PD is heterogeneous in its severity, rate of progression, and affected cognitive domains.[21] It varies from subtle cognitive changes or deficits, from mild cognitive impairment (MCI) to dementia. MCI in PD increases the risk of conversion to dementia, but on longitudinal assessments, some remain stable as MCI and others revert to normal cognition.[892223] Thus, progression to dementia is not inevitable but develops in about 80% of patients with PD durations, especially longer than 20 years.[24] Cognitive deficits in PD typically affect executive functions, attention, visuospatial function, and processing speed.[10] Some people with PD cognitive impairment may have greater memory deficits than nonamnestic dysfunction. Most of the studies have been conducted during the course of treatment which may have bearing on the evolution and impact of nonmotor features in persons with PD.

In the present study, patients with PD have significant impairment in verbal fluency, MMSE score, calculation, memory immediate recall, visuoconstructional ability, memory delayed recall, and memory delayed recognition except for object naming when compared with persons without PD.

People with PD have a progressive loss of function eventually leading to severe disability by both motor and nonmotor symptoms.[2526] Among nonmotor symptoms depression has been recognized as the main health-related QoL (HRQoL) determinant along with other symptoms such as anxiety, cognitive impairment, fatigue, sleep disorders, pain and autonomic dysregulation.[27]

In the present study, author observed that QoL was poor even in early diagnosis and it increased with advance stage of PD, but statistically, it was insignificant. It has been seen that PD patients usually seek help when their QoL or day-to-day activities decline. Many researchers have observed that psychiatric morbidity in PD patients are associated with poorer QoL than severity of motor symptoms in PD.[2829] A large patient's survey has actually found a greater impact of psychiatric-related symptoms on QoL in earlier phases of disease compared with later stages.[30] In India, the important clinical variables found to cause lower QOL were depression, disease severity, disability in off periods, dyskinesias, postural instability, gait disturbances, and cognitive dysfunction. The QoL was also found to be influenced by disease stage, severity, duration, and financial security.[31]

Adhikari et al. identified many risk factors, such as advanced age, male gender, educational status, psychiatric comorbidities, and severity of PD associated with poor cognitive functions.[31] Advanced age came out to be a significant factor only for delayed memory. Poor educational status is associated with poor cognitive functions. Psychiatric morbidity, especially depression is associated with poor cognitive outcome. The present study contradicts with above findings that psychiatric morbidities (depression and anxiety) are not associated with the severity of illness in drug-naïve patients.

The impairment of various cognitive areas in advanced PD patients supports the models describing parkinsonism-related changes in dorsolateral prefrontal regions participating in “cognitive” basal ganglia and thalamocortical circuits.[32] Impairment in verbal learning was observed, possibly reflecting deficient use of encoding strategies. Impairment was also more frequent in conditions of delayed recall than in conditions of delayed recognition, where cues guide retrieval.

In the present study, verbal fluency was significantly impaired in middle–advanced PD than early stage. According to an Indian study conducted by Saptarshi Adhikari and his colleagues, they observed that verbal fluency, MMSE, delayed recall memory, and fund of information were significantly deferred in early and advanced stage of PD.[31]

Limitations

The small sample size, cross-sectional study design, overrepresentation of patients from a rural background, and inclusion of outpatients limit the generalization of the findings. It is plausible that patients with PD and other medical morbidities such as hypertension, diabetes, and thyroid dysfunction may have a different profile with respect to cognitive functioning, QoL, and neuropsychiatric symptoms.

CONCLUSION

Neuropsychiatric manifestation in PD is a rule rather an exception, even in drug-naïve PD patients. In PD, the QoL of a patient is adversely affected by both the motor and nonmotor symptoms of the disease such as depression, anxiety, apathy, sleep disturbances, and cognitive impairment. The link between nonmotor symptoms and reduced QoL has important implications for the management of PD because the early nonmotor symptoms often appear before patients are given anti-parkinsonian therapy. Screening of nonmotor symptoms in early stage of disease will decrease the morbidity and mortality and improve the QoL.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.