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Cognitive impairment in idiopathic Parkinson's disease
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.181533
Background: Cognitive symptoms are common in advanced Parkinson's disease (PD). However, assessment of cognitive impairment is difficult in PD because of accompanying motor symptoms and the coexistence of nonmotor symptoms. Specific subdomains affected in the disease are not reflected in the conventional scales used for assessing cognition. Keywords: Cognitive impairment; Parkinson disease; postural instability and gait disorder; scales for outcomes in Parkinson's disease-cognition
Over the past few years there has been an increasing awareness that the clinical spectrum of Parkinson's disease (PD) is much broader. Apart from the known motor features, it also encompasses nonmotor domains, including cognition. The spectrum of cognitive impairment in PD ranges from very subtle impairment to frank dementia. The cognitive impairment has a profound effect on the patient's quality of life and also imposes considerable burden on the caregiver. However, the motor impairment makes it difficult to administer cognitive tests in these patients, which often require good motor skills. Very few studies have attempted to study the cognitive impairment in PD, particularly from India. The lack of proper definition of cognitive impairment in PD and nonuniformity of the scales used to assess it in these studies has led to confusing results. In a recent hospital-based prospective study from India, Sanyal et al., reported that among 250 PD patients, 36.8% had no cognitive impairment (PD-normal), 27.2% had PD with dementia (PDD), and 36% had mild cognitive impairment (PD-MCI) at baseline. After 7 years of evaluation, 32 new patients, 12 patients from the PD-MCI group, and nine patients from the PD-normal group were diagnosed with dementia. The 7-year prevalence rate for dementia was estimated to be 49.28%.[1] Few Indian studies have so far appropriately addressed the issue of cognitive dysfunction in PD in a systematic manner using validated scales. Aim and objectives To analyze the spectrum of cognitive impairment in various phenotypes and stages of PD and to assess the correlation of this impairment of cognition with motor and various nonmotor symptoms of PD.
Study design This was an observational, cross-sectional study carried out in a tertiary neurology referral center in Eastern India. Fifty PD patients fulfilling the United Kingdom PD Society Brain Bank criteria were included after obtaining an explicit consent. One of the inclusion criteria was that the patients were able to read English as well as the local language Bengali. The patients were assessed clinically and scored according to various scales used in this study. Patients with aided visual acuity of ≤6/18 or with a significant hearing difficulty were excluded from the study. An ethical clearance for the above mentioned study was obtained from the Institutional Ethical Committee and written consent from the patients was obtained before the study was undertaken. Assessments In this study, sociodemographic and historical data were obtained from each patient. In addition, validated scales devised by the Leiden University Medical Center, Department of Neurology, Leiden, the Netherlands, as a part of the Scales for Outcomes of PD (SCOPA) project, were used. These are specifically suited for assessment of PD patients. We have used three scales: Short Parkinson's evaluation scale (SPES)-SCOPA for motor symptoms (motor evaluation, activities of daily living, and motor complications),[2] SCOPA-cognition (SCOPA-COG)[3] for cognitive domains (memory, attention, executive function, and visuospatial function), and SCOPA-psychiatric complications (SCOPA-PC)[4] for psychotic symptoms and impulse control disorders. A mean score for tremor was calculated as the mean of the following items from the SPES-SCOPA motor scale: Rest tremor (right and left) and postural tremor (right and left). Similarly, a mean score for postural instability and gait disorder (PIGD) was calculated as the mean of postural instability, freezing during the ''on,'' phenomenon, gait score, and walking score. Patients with a ratio of mean tremor score/mean PIGD score ≥1.5 were classified as tremor dominant, whereas patients with a ratio of <1.5 were classified as PIGD dominant. In order to assess the stage of motor impairment, the modified Hoehn and Yahr staging was applied. Stage 4 and 5 are referred to as “severe impairment,” Stage 3 as “moderate impairment,” and others were labeled as having “mild impairment.”[5] PD was considered as “Early Onset” when the disease started below 40 years of age and “late-onset” when the disease started above 40 years of age. Cognitive assessment was done by SCOPA-COG [3] and mini-mental state examination (MMSE).[6] There are various components in SCOPA-COG scale, each having a maximum possible score. The lower the score, more is the impairment. The various components include memory (total score 22), attention (total score 4), executive functions (total score 12) and visuospatial functions (total score 5). The maximum possible total score in SCOPA-COG is 43, whereas the maximum possible total score in MMSE is 30. We used Beck's Depression Inventory (BDI) to assess the severity of the depressive symptoms. Before using BDI in our study population, we had translated and validated it. The original BDI was translated into Bengali by a neurologist, a psychiatrist, and a psychologist independently. These translations were pooled together, and a final version was prepared. The Bengali version was then translated back into English. The translation-retranslation reliability was found to be satisfactory. The Bengali version was then used for the study. Patients with a BDI score ≥17 were classified into the group labeled as “patients with depression.” Others were labeled as belonging to the “no depression” group. SCOPA-PC was applied to record the psychotic and impulse disorders. Statistical analysis International Business Machine's Statistical Package for the Social Sciences by V 19 was used to perform the statistical analysis. Frequencies and descriptive statistics were examined for each patient. To analyze the correlation between impairment of cognition with motor and nonmotor symptoms, the Pearson's correlation coefficient was used. To analyze the relative contribution of variables such as age, duration of illness, SPES-SCOPA score, depression score, and psychotic symptoms score in influencing the SCOPA-COG scores, the linear regression model was applied. The Student's t-test was used to analyze if there was a significant difference between the groups of “early-onset” and “late-onset” patients, between the mean cognitive scores of “mild” and “moderate” patients, as well as between the mean cognitive scores of tremor-predominant and PIGD patients.
The total study population comprised 41 men and 9 women. The mean age of the male population was 59.61 years (standard deviation [SD] =9.716) and that of women was 50.78 years (SD = 6.534). The mean duration of illness was 5.18 years (SD = 4.231). The majority of the study population had tremor-predominant PD (n = 46) and PIGD patients comprised a minority (n = 4). Seventy-eight percent of the PD patients were in the mild Hoehn and Yahr stage (≤2.5) whereas 22% were in the moderate stage (Stage 3). The cognitive profile of the study population was best reflected when the patients were assessed by the SCOPA-COG scale in contrast to the MMSE. In the study population, the median scores in the various subdomains were 6, 2, 6.5, and 3 for memory, attention, executive, and visuospatial functions, respectively, and the median total score in the population was 18.5 [Figure 1]. In MMSE, the median scores of the various domains were 10 for orientation, 3 for registration, 6 for attention and recall, and 8 for language, and the median score of MMSE was 26.5 [Figure 2]. Thus, it is appreciable that in most of the study population, the scores in MMSE were almost normal. None of our PD patients were found to be suffering from dementia.
The comparison between the groups was done according to the age of onset, disease phenotype, and stage of disease. Student's t-test failed to reveal a statistically reliable difference between the mean cognitive scores of “early-onset” (mean = 18, SD = 5.627) and “late-onset” patients (mean = 17.56, SD = 6.041), t (48) = 0.181, P = 0.857, and α = 0.05 [Figure 3]; similarly, we did not find any difference between the mean cognitive scores of “mild” (mean = 18.21, SD = 5.859) and “moderate” patients (mean = 15.55, SD = 5.959), t (48) =1.324, P = 0.192, and α = 0.05 [Figure 4]; and, between the mean cognitive scores of tremor-predominant (mean = 17.76, SD = 5.801) and PIGD patients (mean = 16, SD = 8.124), t (48) =0.566, P = 0.574, and α = 0.05) [Figure 5].
As seen from the matrix [Figure 6], there is a decreasing trend of cognitive scores with increasing age, duration of illness, increasing motor scores, psychotic symptoms, and depressive scores. Levels of significance have been attained for the SPES-SCOPA, SCOPA-PC, and BDI scores.
From the study, an attempt was made to see the relative contribution of variables like age, duration of illness, SPES-SCOPA scores, depression scores, and psychotic symptoms scores in influencing the SCOPA-COG scores by the linear regression model. This regression model was statistically significant (P = 0.38) with the standard error of the estimate being 5.50, and the model was able to predict about 14% variance in the dependent variables from the independent variables with the larger contribution being from depression followed by the SPES-SCOPA and SCOPA-PC scores.
In this study, we have found that in the PD patients, cognitive impairment is quite common in the early stages of the disease. The deficits are commonly observed in a few selected domains and the conventional MMSE is not sensitive enough to pick up the deficits. In contrast, the use of scales specifically designed to study the affected domains in PD were best suited to detect the deficits. This may reflect the pathophysiology of the disease itself. The difficulties in assessing cognitive impairment in PD patients are manifold. The motor symptoms limit the ability of the patients in performing various cognitive tasks, which require a certain amount of motor functioning. The presence of other associated nonmotor symptoms like depression and psychoses may contribute to the cognitive impairment. Finally, the effect of antiparkinsonian drugs may interfere with the proper cognitive assessment. The impairment is more in the PIGD phenotype compared to the tremor phenotype, though the difference is not statistically significant. In this study, we have tried to analyze the various factors which might be important to predict the onset of cognitive deficits, such as disease severity, motor symptoms, associated depression, and psychotic symptoms. The underlying pathology of cognitive deficits and dementia associated with PD has been a matter of controversy, both in terms of the site and the type of pathology. Studies of clinicopathological associations in demented patients with PD can be broadly classified into three groups on the basis of pathological changes such as subcortical pathology, limbic or cortical Lewy-body-type degeneration, and those suggesting coincident Alzheimer's disease-type pathology.[7] In a study by Muslimovic et al.,[8] it was seen that compared to either healthy control subjects or normative data, PD patients exhibited impaired performance on a wide range of standardized neuropsychological tests. However, further analysis of individual test performances revealed that deficits in the domains of memory, attention, and executive function constituted the core impairment. The relationship between PIGD and dementia has been investigated in only a few studies. These have shown that PIGD is more prevalent in demented than in nondemented patients with PD, and that impairment of speech and balance at baseline predicts the incident dementia in PD patients followed longitudinally.[9],[10] In a study by Alves et al.,[11] it was seen that in patients with persistent tremor dominant Parkinsonism More Details, the MMSE scores were stable during the entire study period, while in those patients who transformed from the 'tremor dominant' to the 'PIGD motor' subtype, this transition was associated with a more than 3-fold increase in the rate of MMSE decline. These findings may indicate that the PIGD subtype and the cognitive decline in PD are caused by common or parallel neuropathological changes. Similarly, in the CamPaIGN study [12] of incident PD, the severity of nontremor type (like mixed, or PIGD type) motor symptoms was associated with a higher risk for the development of dementia that was independent of age. Cognitive dysfunction in early PD patients may reflect neuropathological changes that are distinct from those responsible for the motor disorder.[13],[14],[15],[16],[17],[18] Further support for this assumption is deduced by the lack of association between cognitive impairment and dopaminergic medication. Cognitive deficits in PD are traditionally seen as subcortical in nature as several studies have demonstrated that there is a significant impairment in executive functions such as poor planning, sequencing, cognitive flexibility, and problem-solving capacities.[12],[19],[20],[21],[22],[23] Memory impairments including encoding, recall, and procedural memory are also affected. Several risk factors for PDD have been proposed, including certain predominant motor features such as rigidity and gait instability, minimal cognitive impairment, and the presence of visual hallucinations.[24],[25] It has been estimated that bulbar dysfunctions and gastroenterological and urological disorders, suggestive of autonomic dysfunction, are predictors of the risk for development of dementia in PD.[26],[27] Older age is widely accepted as a risk factor for dementia in PD.[28],[29] Some authors have found parameters such as disease duration, age of onset, and severity of motor symptoms to be significant risk factors, but the published data are at times contradictory.[30],[31],[32] There are only few studies conducted in India to assess the cognitive impairment in patients with PD [Table 1]. The investigators of these studies have worked on the subject looking from different angles using various scales. Ours is the first attempt from India to study the subject in a comprehensive manner with the use of standard scales.
Limitations of the study A few limitations of our study are worth mentioning. This being a tertiary care-centered clinic-based cross-sectional study, it might not reflect the true picture in the community and the progression of symptoms over time cannot be studied from the present design. The sample size was small with mostly male patients with the majority of patients being in the mild and moderate stages. Hence, the deficits represented in this study are not characteristic of the entire spectrum of the disease. Most of the patients were already on dopaminergic medications by the time they presented to us and that may have played a contributory role in the impaired cognitive performance. We would like to continue this study to include more patients and incorporate patients in the advanced stages and in different age groups. They will be subsequently followed up over time so that we can have a clear picture of the burden of these symptoms in the population and follow the evolution of symptoms over time.
From our study, we conclude that the commonly affected subdomains in PD are memory and executive functioning. Cognitive impairment was more in the groups labeled as late-onset compared to early onset, moderate disease to mild disease, and PIGD to tremor-dominant subgroups but the levels did not achieve statistical significance. A decreasing performance on the cognitive assessment scales was observed with increasing age and duration of the illness. A significant correlation was obtained with increased motor disability, psychotic symptoms, and depression. Acknowledgment We wish to thank Mrs. Trishita Das for her kind support in finalizing the document. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.[34]
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1]
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