|Year : 2019 | Volume
| Issue : 2 | Page : 84-88
The cognitive profile and executive function of progressive supranuclear palsy and multiple system atrophy patients
Divya Goel, Arvind Vyas
Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India
|Date of Submission||11-Nov-2018|
|Date of Decision||05-Mar-2019|
|Date of Acceptance||22-Apr-2019|
|Date of Web Publication||24-May-2019|
Dr. Divya Goel
Department of Neurology, SMS Medical College and Hospital, Jaipur - 302 004, Rajasthan
Source of Support: None, Conflict of Interest: None
Introduction: Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are two relatively common forms of atypical parkinsonism seen in movement disorder clinics. This study provides an insight into the cognitive dysfunction in these two diseases. Aims: This study aims at assessing the cognitive and executive dysfunction and investigating the relationship between age, education, Montreal cognitive assessment (MOCA), and frontal assessment battery (FAB) score in a group of Indian patients with MSA and PSP. Materials and Methods: This is a hospital-based observational study with the recruitment of patients of MSA and PSP based on consensus criteria and The National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria, respectively. A total of 50 patients of MSA and PSP admitted or attending outpatient department in the Department of Neurology, SMS hospital, Jaipur, were analyzed for cognitive and executive functions between December 2016 and December 2018 using MOCA and FAB. The Student's t-test was used. The level of significance was determined as itsP value withP < 0.05 taken as statistically significant. Results: On MOCA, impairment was observed in 24% of cases of MSA and 92% of cases of PSP. On FAB, impairment was observed in 20% of cases of MSA and 72% of cases of PSP.
Conclusions: Cognitive dysfunction is a major finding in PSP and MSA patients. Thus, cognitive dysfunction in a patient does not rule out MSA as considered in the previous literature and is an important diagnostic finding in PSP; yet requires future research on a larger scale.
Keywords: Frontal assessment battery, Montreal cognitive assessment, multiple system atrophy, progressive supranuclear palsy
|How to cite this article:|
Goel D, Vyas A. The cognitive profile and executive function of progressive supranuclear palsy and multiple system atrophy patients. Indian J Med Spec 2019;10:84-8
|How to cite this URL:|
Goel D, Vyas A. The cognitive profile and executive function of progressive supranuclear palsy and multiple system atrophy patients. Indian J Med Spec [serial online] 2019 [cited 2021 Oct 18];10:84-8. Available from: http://www.ijms.in/text.asp?2019/10/2/84/258985
| Introduction|| |
Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), two relatively common forms of atypical Parkinsonism More Details encountered in movement disorders clinic, are both degenerative diseases with Parkinsonian features. In earlier studies, wherein PSP patients have been shown to have cognitive as well as executive dysfunction predominantly affecting attention and verbal fluency.,,, MSA patients have been known to have intact cognition, especially in the early part of the disease. According to the standardized criteria, cognitive or executive dysfunction has not been considered as a diagnostic criterion in either PSP or MSA. Although, a subcortical cognitive impairment has been notified in both the diseases but not frank dementia. Rather, cognitive decline is considered as an exclusion criterion for the diagnosis of MSA. In PSP patients, executive dysfunction is marked in early stages of the disease and cognitive slowing occurs independent of the motor disability, chiefly affecting the domain of attention. In patients of MSA, the emerging studies demonstrate that cognitive impairment is common varying from mild-to-severe affecting single-to-multiple domains. Pathologically, there is striatofrontal deafferentation, cortical, and cerebellar degeneration in MSA. Biopsy reports are suggestive of neuronal loss, astrogliosis, and glial cytoplasmic inclusions in frontotemporal regions of patients affected with MSA. These evidence support that cognitive dysfunction is a common occurrence in MSA. Therefore, the consensus criteria for the diagnosis of MSA need to be revised. Thus, larger prospective studies are required to establish the cognitive and executive dysfunction in patients of MSA and PSP, the aspect that has been essentially ignored in the previously carried out studies. This study aims at exploring the differential involvement of cognitive domains and executive functions in the patients of MSA and PSP to highlight the ignored aspects of the two diseases.
| Materials and Methods|| |
This is a hospital-based observational study of patients with MSA and PSP. Ethics committee approval was taken for this study beforehand. A total of 50 patients were recruited from December 2016 to December 2018 (PSP, n = 25; MSA, n = 25), admitted or attending outpatient department in the Department of Neurology, SMS hospital, Jaipur with a prior informed consent taken from each of them. All patients fulfilled the diagnostic criteria on recruitment. MSA was clinically diagnosed based on the second consensus criteria, PSP was diagnosed based on the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria. No distinction was made between “possible” or “probable” diagnosis. Patients with recent history of encephalitis, alien limb syndrome, cortical sensory deficits, focal frontal or temporoparietal atrophy, hallucinations or delusions unrelated to dopaminergic therapy, cortical dementia of Alzheimer's type (severe amnesia and aphasia or agnosia), early unexplained dysautonomia, asymmetric parkinsonian signs (i.e., bradykinesia), neuroradiological evidence of relevant structural abnormality (i.e., basal ganglia or brainstem infarcts, lobar atrophy), Whipple's disease, confirmed by polymerase chain reaction were excluded from the study. The patients were evaluated clinically for independent signs and symptoms and assessed through modified Hoehn and Yahr staging. The tests used were mini-mental state examination (MMSE), frontal assessment battery (FAB), and Montreal cognitive assessment (MOCA). Prior permission was taken for research purpose from Dr. Ziad Nasreddine, the MOCA copyright owner. MOCA was used to provide a more sensitive assessment of cognitive as well as executive functions with separate measures for visuospatial function (trail making B, cube, and clock drawing), naming, attention (forward/backward digit span, vigilance and serial 7s subtraction), language (repetition and lexical fluency), abstraction, delayed recall, and orientation. The total score was from a maximum of 30 with higher scores indicating better performance. One point was to be added for an individual who had 12 years or fewer of formal education. A final total score of >26 was considered normal. Any score below this cutoff was considered to be suggestive of cognitive impairment. FAB was used to detect executive functions through six measures, i.e., similarities, lexical fluency, motor Luria test, conflicting instructions, go no go test, and prehension; each rated on a 0–3 scale with a maximum score of 18. A cutoff score of 12 on the FAB has a sensitivity of 77% and specificity of 87% in differentiating between frontal dysexecutive type dementias and dementia of Alzheimer's type. Patients were evaluated for dysautonomia, cerebellar signs, pyramidal involvement, bulbar/pseudobulbar palsy and supranuclear gaze palsy. Results were tabulated in the form of mean and analyzed using the Student's t-test, and the level of significance was determined as its P value with P < 0.05 taken as statistically significant.
| Results|| |
[Table 1] shows the basic demographic and clinical characteristics of the patients included in this study. Patients in the PSP group were on an average significantly older than those in the MSA group (P = 0.004). Males were found to dominate both the diseases, but the proportion did not significantly differ in both groups (P = 0.74). The disease duration did not vary much in the two groups (P = 0.11). There was the predominance of cerebellar, dysautonomic, and genitourinary features in MSA and pyramidal involvement, supranuclear gaze palsy, and bulbar/pseudobulbar involvement in PSP patients. There was no observable difference in the mean score of modified Hoehn and Yahr grading among MSA and PSP cases (P = 1.00). MMSE (P = 0.005) and MOCA (P = 0.02) scores were significantly higher in the MSA group, whereas FAB scores (P = 0.18) did not show any statistically significant difference in the two groups [Table 1].
|Table 1: Demographic and clinical details of the multiple system atrophy and progressive supranuclear palsy groups|
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Taking age and education as covariates, [Table 2] shows that PSP group scored significantly lower on all cognitive parameters on MOCA as compared to that of MSA (P = 0.02). The score was comparable for two parameters, i.e., naming and orientation. However, there was marked difference in scores of rest of the parameters with PSP patients exhibiting severe cognitive dysfunction, especially in areas of visuospatial, vigilance, repetition, lexical fluency, and abstraction where the average scores were < 50% of average scores. MSA patients on the other hand too showed some cognitive dysfunction with an average score (24.84) below the cutoff value of 26 and maximum impairment in lexical fluency.
|Table 2: The mean scores of the multiple system atrophy and progressive supranuclear palsy groups on Montreal cognitive assessment|
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[Table 3] shows that PSP patients showed relatively low scores on all FAB measures as compared to MSA (P = 0.18). The average score of MSA patients was above the cutoff value, and PSP patients were below it. PSP patients performed significantly worse in three parameters, i.e., similarities (P = 0.005), conflicting instructions (P = 0.033), and go no go test (P = 0.007).
|Table 3: The mean scores of the multiple system atrophy and progressive supranuclear palsy groups on frontal assessment battery|
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[Table 4] shows the trend of demographic and clinical parameters in the patients with cognitive dysfunction relative to those with preserved cognitive function, i.e., impaired and unimpaired MOCA scores. This shows that the patients with cognitive impairment had a trend toward higher age (P = 0.26 for MSA and 0.07 for PSP), lower education (P = 0.03 in both groups), male predominance, and longer disease duration (P = 0.73 for MSA and 0.41 for PSP). There was a statistically significant difference in the presence of cerebellar signs in patients of MSA with impaired MOCA (P = 0.009) and in bulbar/pseudobulbar palsy in PSP patients with impaired MOCA (P = 0.02). The statistical analysis does not seem to be prudent in this section of this study as the comparator groups in both the diseases, i.e., MSA patients with impaired MOCA (n = 2) and PSP patients with impaired MOCA (n = 6) are too small in number to reach any conclusions. However, the various parameters have been listed for the benefit of the reader.
|Table 4: Demographic and clinical measures in cognitively unimpaired (Montreal cognitive assessment >26) and impaired (Montreal cognitive assessment <26) multiple system atrophy and progressive supranuclear palsy patient groups|
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[Table 5] shows that MMSE was impaired in 20% of MSA and 68% of PSP patients while MOCA was impaired in 24% of MSA and 92% of PSP patients, thus clearly signifying its increased sensitivity to detect cognitive impairment as compared to MMSE. FAB was impaired in 20% of MSA and 72% of PSP groups, thus indicating increased executive dysfunction in PSP group.
|Table 5: Percentage of patients with impaired mini-mental state examination, Montreal cognitive assessment, and frontal assessment battery scores in patients of multiple system atrophy and progressive supranuclear palsy|
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| Discussion|| |
In the current study, the patients with PSP suffered with more cognitive impairment as expected. The MMSE, MOCA, and FAB scores in PSP patients were lower than those in MSA patients with statistical significance. However, this study also revealed significant cognitive impairment in MSA patients. About 24% of MSA patients suffered significant cognitive impairment within 3 years of disease onset. Moreover, MOCA proved to be a more sensitive test in detecting cognitive dysfunction as compared to MMSE and this difference was particularly large in the PSP group.
Earlier studies in MSA have shown mixed results as regards cognitive dysfunction. In a retrospective study by Wenning et al., 38 patients of pathologically proven MSA were enrolled, among which 15.7% of cases were reported to have dementia in comparison to 53% in Parkinson's disease (PD). However, dementia was reported to occur after 5 years of disease onset. In another study by O'Sullivan et al., amongst 83 biopsy-proven patients, dementia was seen in 15%. These studies suggest that cognitive impairment is an active feature in MSA patients though both these studies showed a late occurrence of dementia. Kitayama et al. in a study of 58 patients where dementia was posed as an exclusion criterion for the diagnosis of MSA, found dementia in 10 patients, i.e., 17.2% of cases with clinical features typical of MSA. In another study, a significant degree of cognitive dysfunction is reported only in around 2% of patients with MSA. The largest study on atypical parkinsonism till date had been done by Brown et al. In this study, a substantial evidence that cognitive impairment is consistent with a diagnosis of MSA was found by prospective neuropsychological analysis of 372 MSA patients in a subgroup analysis of the Neuroprotection and Natural History in Parkinson-Plus Syndromes study-a randomized, multi-center, double-blind, placebo-controlled study of the efficacy and safety of riluzole in patients with MSA and PSP). In this study, the Mattis Dementia Rating Scale, a broader and more comprehensive neuropsychological battery, disclosed that 19.6% of MSA patients presented significant cognitive impairment. A single cognitive domain impairment was observed in 28.6% of cases and multiple domain impairment in 13.5% of cases. Moreover, using the FAB, 31.8% of the patients scored below the cutoff score. All these studies point toward the fact that cognitive dysfunction is an important finding in MSA and the same has been corroborated by our study, in which cognitive dysfunction was found in 24% of patients within first 3 years of disease onset.
Cognitive dysfunction has been a major finding in PSP patients and unlike MSA, this has not been an area of dispute. In earlier studies,, patients of PSP have been found to have cognitive impairment in early stages of disease regardless of the duration of disease. In our study, a significant proportion of PSP patients showed cognitive impairment on MOCA, i.e., 92% indicating that cognitive impairment is an integral part of the disease process.
Executive dysfunction is the most common cognitive abnormality in patients of atypical parkinsonism.,, In earlier study of Azoue et al., it was shown that executive and attentive–working memory domains were the most commonly affected cognitive functions in patients of MSA and PSP. In our study, executive dysfunction was a prominent feature in both these diseases. PSP patients exhibited severe executive dysfunction in areas of visuospatial, attention, language, and abstraction with the marked impairment in clock drawing, vigilance, lexical fluency, and backward digit span tasks. MSA patients had maximum impairment in lexical fluency.
Executive functions were also tested through FAB wherein PSP patients, impairment was found in 72% patients and in MSA, impairment was found in 20% of patients. In both MOCA and FAB, maximum impairment was listed in the area of lexical fluency, thus making it a prime test for executive dysfunction. In the earlier study by Brown et al., on the FAB, impairment was observed in 62.0% of patients with PSP and 31.8% of those with MSA. In a study conducted in 2015 by Stamelou et al., the analysis of FAB was done in patients of PSP, MSA and PD and it was concluded that phonemic verbal fluency can help differentiate these disorders, the maximal impairment being in PSP with relative preservation in PD. Impairment of letter fluency had been reported in PSP in studies conducted by Lange et al., Rittman et al., and Soliveri, and in MSA by Pillon et al.
Our findings provide additional support for the superiority of MOCA over MMSE, as MOCA includes the executive parameters such as attention, abstraction, backward digit span, and lexical fluency, unlike the MMSE. Wherein MSA group showed impaired MMSE in 20% of patients, MOCA was found to be impaired in 24%. This difference was marked in PSP, wherein impaired MMSE was found in 68% of patients and impaired MOCA in 92%. This is in accordance with the previous study conducted by Fiorenzato et al. on 130 patients including those of PSP, MSA, and PD. This study analyzed the patients with MMSE and MOCA and concluded that MOCA is superior to MMSE in detecting the cognitive impairment, especially the executive dysfunction in these patients.
Finally, it was observed in this study that age and education contribute to the MMSE, MOCA, and FAB performance. The proportion of patients with impaired parameters in both groups was found to have higher age and lesser education than those who were cognitively unimpaired. Although the proportion of patients with impaired scores were too small for these statistical differences to be prudent.
| Conclusion|| |
This study highlights the cognitive and executive dysfunction in patients of atypical parkinsonism and helps us understand the various domains of mild, moderate, and severe affection through multiple parameters used on MOCA and FAB scales. This study establishes the presence of significant cognitive impairment in MSA patients at an earlier stage of their disease and thus helps us establish that cognitive impairment should not be used as an exclusion criterion for its diagnosis. Finally, MOCA and FAB can be considered useful batteries for assessing cognitive and executive dysfunctions as these have been proved to be more sensitive than the conventionally used MMSE.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Krishnan S, Mathuranath PS, Sarma S, Kishore A. Neuropsychological functions in progressive supranuclear palsy, multiple system atrophy and Parkinson's disease. Neurol India 2006;54:268-72.
] [Full text]
Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: A Frontal assessment battery at bedside. Neurology 2000;55:1621-6.
Maher ER, Smith EM, Lees AJ. Cognitive deficits in the Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). J Neurol Neurosurg Psychiatry 1985;48:1234-9.
Milberg W, Albert M. Cognitive differences between patients with progressive supranuclear palsy and Alzheimer's disease. J Clin Exp Neuropsychol 1989;11:605-14.
Pillon B, Dubois B, Lhermitte F, Agid Y. Heterogeneity of cognitive impairment in progressive supranuclear palsy, Parkinson's disease, and Alzheimer's disease. Neurology 1986;36:1179-85.
Brown RG, Lacomblez L, Landwehrmeyer BG, Bak T, Uttner I, Dubois B, et al.
Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy. Brain 2010;133:2382-93.
Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al.
Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71:670-6.
Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, et al.
Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): Report of the NINDS-SPSP international workshop. Neurology 1996;47:1-9.
Fahn S, Elton RL; Members of the UPDRS Development Committee. Unified Parkinson's disease rating scale. In: Fahn S, Marsden CD, Calne DB, editors. Recent Developments in Parkinson's Disease. Florham Park, NJ: Macmillan Health Care Information; 1987. p. 153-64.
Wenning GK, Ben Shlomo Y, Magalhães M, Daniel SE, Quinn NP. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 1994;117(Pt 4):835-45.
O'Sullivan SS, Massey LA, Williams DR, Silveira-Moriyama L, Kempster PA, Holton JL, et al.
Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. Brain 2008;131:1362-72.
Kitayama M, Wada-Isoe K, Irizawa Y, Nakashima K. Assessment of dementia in patients with multiple system atrophy. Eur J Neurol 2009;16:589-94.
Wenning GK, Seppi K, Scherfler C, Stefanova N, Puschban Z. Multiple system atrophy. Semin Neurol 2001;21:33-40.
Ghosh BC, Rowe JB, Calder AJ, Hodges JR, Bak TH. Emotion recognition in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 2009;80:1143-5.
Donker Kaat L, Boon AJ, Kamphorst W, Ravid R, Duivenvoorden HJ, van Swieten JC. Frontal presentation in progressive supranuclear palsy. Neurology 2007;69:723-9.
Auzou N, Dujardin K, Biundo R, Foubert-Samier A, Barth C, Duval F, et al.
Diagnosing dementia in multiple system atrophy by applying movement disorder society diagnostic criteria for Parkinson's disease dementia. Parkinsonism Relat Disord 2015;21:1273-7.
Dujardin K, Defebvre L, Krystkowiak P, Degreef JF, Destee A. Executive function differences in multiple system atrophy and Parkinson's disease. Parkinsonism Relat Disord 2003;9:205-11.
Lange KW, Tucha O, Alders GL, Preier M, Csoti I, Merz B, et al.
Differentiation of Parkinsonian syndromes according to differences in executive functions. J Neural Transm (Vienna) 2003;110:983-95.
Stamelou M, Diehl-Schmid J, Hapfelmeier A, Kontaxopoulou D, Stefanis L, Oertel WH, et al.
The frontal assessment battery is not useful to discriminate progressive supranuclear palsy from frontotemporal dementias. Parkinsonism Relat Disord 2015;21:1264-8.
Rittman T, Ghosh BC, McColgan P, Breen DP, Evans J, Williams-Gray CH, et al.
The Addenbrooke's cognitive examination for the differential diagnosis and longitudinal assessment of patients with Parkinsonian disorders. J Neurol Neurosurg Psychiatry 2013;84:544-51.
Soliveri P, Monza D, Paridi D, Carella F, Genitrini S, Testa D, et al.
Neuropsychological follow up in patients with Parkinson's disease, striatonigral degeneration-type multisystem atrophy, and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 2000;69:313-8.
Fiorenzato E, Weis L, Falup-Pecurariu C, Diaconu S, Siri C, Reali E, et al.
Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) performance in progressive supranuclear palsy and multiple system atrophy. J Neural Transm (Vienna) 2016;123:1435-42.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]