Home / Archives / Vol 47 No 2 (2021) / Research Articles

Predictors of Parkinson’s Disease Dementia Among Patients in a Tertiary Care Hospital in Bangladesh

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Dr. Mohammad Ibrahim Khalil
Department of Neurology, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh.

Narayan Chandra Kundu
Department of Neurology, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh.

Serajoom Munira
Department of Neurology, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh.

Mahmood-uz-Jahan
Ex-Director, Bangladesh Medical Research Council, Dhaka, Bangladesh.

Md. Ridwanur Rahman
Department of Medicine, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh.

Keywords: Parkinson’s disease, Dementia, Mini mental state examination, Depression.

DOI: 10.3329/bmrcb.v47i2.57779

Abstract

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorders with an estimated prevalence of 2–3% at 65 years and as high as 10% among those 80 years old.^1-3 It increases proportionately with age.⁴ Exact aetiology and underlying mechanisms of PD are still unknown but aggregated Lewy bodies containing alpha-synuclein (aSyn) are believed to play a central role in the pathogenesis.⁵ Similarly, curable treatments are not yet available.⁶ Dementia is used to describe a progressive decline in a person’s functioning with a loss of memory, intellect, emotional reactions, social skills and rationality.⁷ Dementia is six times more prevalent in PD than general population.⁸ Parkinson’s disease dementia (PDD) represent the second most common cause of dementia worldwide.⁹ It is the most devastating nonmotor features of PD causing severe decline in quality of life, increased family burden, economical stain, caregiver burden, mortality, and often require hospitalization.¹⁰ PDD has a unique clinical profile and neuropathology, distinct from Alzheimer’s disease (AD), with notable relative preservation of delayed memory, but severely impaired executive function, attention, and visuospatial skills.^2,9 Not all people with PD will develop dementia. It is estimated that 30-60% non-demented PD patients developed PDD over two to five years.^11,12 A systematic review reports the point prevalence of PDD is about 30%.^8,54 So, it should be recognised early and treated appropriately.² However, effective treatment is currently unclear.¹³ Identifying the factors predictive of PDD is important for the high risk cases in future planning care, counseling and targeted therapeutic interventions.¹⁰ Being able to predict PDD development accurately, would provide opportunities for intervention as well as novel treatments that might prolong survival and improve quality of life.¹⁴ Several demographic, motor and non-motor features have been identified as predictors.¹³ There may have medical comorbidities which may have modification effects.^10,15-18 Thus, information about which patients will eventually develop dementia is an important issue in public health and clinical practice.^15,19 The neurobiological basis for PDD is multifocal, multiple neurotransmitter deficits related to a synergistic effect of á-synuclein deposits.²⁰ There are no specific ancillary investigations for diagnosis. The main structural pathology is the degeneration in cerebral cortex, limbic structures with relative preservation of the medial temporal lobes and the hippocampus.²¹ It is likely that PDD is multifactorial including genetic, demographic, environmental and medical comorbidities.²² Vascular risk factors have been associated with cognitive deficits and dementia in general population, but their role on cognitive dysfunction in PD is still unclear.^23,24 Little researches has examined it as a potential factor that could be controlled.^10,15,17 However, most previous studies have been conducted in western countries and information for Asian PD populations, especially sub- continent are lacking.^15,22 Due to significant sociocultural differences, findings from western populations may not be directly extrapolated to this region. PDD have been shown to vary widely between different countries.²² However, limited information on this topic, the association between PD and the risk of dementia needs to be further explored. Thus the study was designed to estimate the frequency of PPD, and to evaluate clinical, vascular, socioeconomic and demographic aspects that may contribute to PDD among the cases with PD.

Materials and Methods

This was a single centre, cross-sectional, descriptive, comparative study between demented and non- demented PD cases at the Department of Neurology, Shaheed Suhrawardy Medical College and Hospital (ShSMCH), Dhaka, Bangladesh. One hundred thirty- one consecutive PD patients were diagnosed clinically, using UK Parkinson’s Disease Society Brain Bank criteria whoever agree to comply the study procedures. PD symptoms more than one year were included.^25,26 The objectives of the study were explained to the participant/legal guardian in easily understandable local language, then informed written consent was taken prior to data collection. MRI of brain was done in all cases and secondary Parkinsonism including vascular disease, traumatic brain injury, or Alzheimer’s disease and age less than 40 years were excluded. Any disability or unstable disease that might prevent the patient from completing study procedure, significant aphasia affecting participation, refused to participate, other psychiatric disorders non-related to PD, abusive use of alcohol or illicit drugs and symptoms of PD durations less than a year were excluded. Diagnosis of dementia was done by a neurologist based on DSM-IV criteria using a pre- deigned structured clinical face to face interview with mini-mental state examination (MMSE) score ≤24(0– 30 points) and Parkinson’s disease with dementia short screen (PDD-SS) score ≤11(0–22 points).^27-29 The interview was conducted in local language and assessments were made in English by the investigators. Depression was diagnosed according to DSM-IV criteria.^27,30 Severity of PD was evaluated by the Hoehn and Yahr stage (H-Y I to V).³¹ Ethical clearance was obtained from the National Research Ethics Committee of Bangladesh Medical Research Council.

Demographic and other clinical information obtained from the patient, relatives or caregiver. A subject was considered diabetes mellitus (DM) if fasting blood glucose value ≥7.0 mmol/L and/or 2-h post-load glucose concentration ≥11.1 mmol/L or currently receiving treatment for DM. Hypertension (HTN) was considered if clinically diagnosed or currently receiving medication for high blood pressure. The history of angina/infarction (ischemic heart disease-IHD) and atrial fibrillation was considered when there was evidence of a clinical diagnosis for each of these pathologies with the help of ECG, chest X-ray and echocardiography. Tobacco consumption was established according to the WHO as: non-smoker, ex-smoker and current smoker. Variables like hallucination, postural instability, sleep disturbance and family history of dementia was evaluated in a dichromats yes/no. Data were analysed using SPSS version 23. Continuous variables were expressed as mean ± standard deviation and were evaluated by the unpaired Student’s t test. Similarly, categorical variables were expressed as percentage of the total and were evaluated by the chi-square test to measure the level of significance. The relative risk of PDD was estimated as odds ratio (OR) using logistic regression models. A p-value <0.05 was considered statistically significant. We calculated adjusted odds ratio (adj. OR) between two groups, demented (Group A) and non-demented (Group B) PD cases. All significant variables from univariate analysis were entered into a linear regression model in a stepwise fashion and a final fitted model was determined.

Results

One hundred thirty-one PD cases were enrolled and 50 (38.0%) had dementia. The mean (SD) age of dementia and non-dementia was 73.32(8.86) years (range 54 to 95) and 63.98 (6.19) years (range 45 to 86) respectively. Male was slightly predominant (52%vs.68%). The mean (SD) disease duration was 8.53 (3.04) vs 3.76 (1.39) years and age at disease onset was 60.21(6.31) vs 64.79(8.64) years respectively. The frequency of residence, education, smoking status, and family history of dementia was not significance (table I).

Hypertension (66% vs.12%) and depression (76% vs 27%) were detected significantly higher in group A (table II). Daily used levodopa was 596(189) and 364(200) mg which was not significant. The mean (SD) MMSE score was 18.75(4.4) vs 27(1.85) and PDD-SS core was 8.61(2.3) vs 14.75(3.26) between groups respectively.

Univariate logistic regression analysis was first performed for each hypothesized predictor (table III), age ≥70 years[OR=10.45, p<0.001)]; diabetes [OR=2.96, p=0.019]; hypertension [OR=8.54, p<0.001]; diseases duration ≥5 years [OR=18.09, p<0.001] sleep disturbance [OR=2.52, p=0.028]; postural instability [OR=3.68, p=0.021]; hallucination [OR=4.55, p=0.011]; H-Y stage ee3 [OR=16.13, p<0.001] and depression [OR=8.49, p<0.001] were significantly associated with developing PDD.

When all significant variables from univariate were included in multivariate linear logistic regression mode (table IV), age ee70 years [OR=4.25, 95% CI (1.51- 7.86), p=0.031], diabetes [OR=5.37, 95% CI (2.29-10.09); p=0.019], hypertension [OR=7.63, 95% CI (2.69-13.01); p=0.011], disease duration ee5 years [OR=10.01, 95% CI (4.81-21.65); p<0.001], H-Y stage ≥3 [OR= 9.52, 95% CI (4.37-19.06); p<0.001] and depression [OR=8.79, 95% CI (3.95-18.98); p<0.001] were found significantly associated with PDD.

Discussion

In this study of PD patients 38% was found dementia. This finding has similarity with other studies.^33,41,42 There was no sex difference. Age was a determining factor in developing PDD which was reported in many other studies.^32-35,42 As age increases, biological and psychological changes begin to occur. Dopamine levels decrease with age, allowing older individuals to be more susceptible to PDD. This is plausible given that age is the most important risk factor for dementia in the general population also.

H-Y stage was significantly correlated with PDD in our results. In agreement with this, previous studies have found a positive correlation of PDD with the progression of PD.^13,33,38-42 The incidence of PDD was related to disease progression, greater severity of neurological and motor symptoms.³⁷ High severity of extrapyramidal signs with older age poses the highest risk of developing PDD.³⁶ H-Y stage greater than two has been proposed to be a predictor of PDD.⁸ We found that longer disease duration was significantly correlated with PDD. This result is in accordance with others study.^43-47,55 Neuropsychiatric symptoms were associated with more severe dementia and advanced Parkinson’s disease durations.⁴⁸

An interesting and surprising finding was that depression, hypertension and diabetes was significantly associated with PDD in multivariate logistic regression. These factors are modifiable. Depression was important non-motor factors for PDD. Similar findings have been reported previously.^{8,10,23,42,49} Indeed, the role of hypertension has been recently highlighted as one of PDD predictors using an extensive longitudinal evaluation.^10,13,23,50 The effect of diabetes on PDD was also evaluated.^51,52 Diabetes mellitus was independently associated with more severe cognitive impairment in PD.⁵¹ It may exacerbate brain atrophy and cognitive functions in PD with greater vulnerability in the frontal lobes.⁵³

It was a single centre; cross-sectional study, making it less representative for the entire population. This study did not address clinical symptoms, subtypes and severity of dementia. The final limitation was the lack of drug information that may affect cognitive function.

Conclusion

The study shows proportion of PD patients suffer from dementia. PDD was significantly associated with a number of socio-demographic and clinical factors including advancing age, longer disease duration, higher disease stage, diabetes, hypertension and presence of depressive illness. Our overall findings in relation to frequency and PDD predictors, are in keeping what is reported in other populations also. This study showed some unique modifiable factors of PDD such as depression, hypertension and diabetes. These findings need further inquiry whether they are replicated regionally or globally. Further research is required in order to understand underlying mechanisms of dementia in Parkinson’s disease.

Acknowledgments

BMRC for funding support.

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