Journal List > Dement Neurocogn Disord > v.15(4) > 1120235

Dement Neurocogn Disord. 2016 Dec;15(4):142-146. English.
Published online Dec 31, 2016.
© 2016 Korean Dementia Association
The Association between Motor Laterality and Cognitive Impairment in Parkinson's Disease
Jee Eun Yoon,1 Ji Sun Kim,1 Jae-Young Seo,1 Jin Whan Cho,2 Jun-Sang Sunwoo,1 Kyung Bok Lee,1 Hakjae Roh,1 and Moo-Young Ahn1
1Department of Neurology, Soonchunhyang University School of Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea.
2Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Correspondence: Ji Sun Kim, MD, PhD, Department of Neurology, Soonchunhyang University School of Medicine, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea. Tel: +82-2-709-9224, Fax: +82-2-795-3687, Email:
Received Sep 30, 2016; Revised Dec 02, 2016; Accepted Dec 02, 2016.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background and Purpose

The relationship between the side of motor symptoms and cognitive impairment has rarely been reported in Parkinson’s disease (PD). We aimed to estimate the influence of motor laterality on cognition in PD patients.


We enrolled 67 patients with PD, and they were divided into two groups according to side of symptom onset or predominant motor symptom presentation (right and left). Right-sided PD (RPD, 40) and left-sided PD (LPD, 27) patients underwent a neuropsychological battery exploring memory, attention/working memory, frontal/executive, visuospatial, and language functions. Student's t-test and Chi-square test have been carried out to compare the clinical and neuropsychological data between two groups.


There were no significant differences in any neuropsychological test between the RPD and LPD groups, except for digit forward span test. RPD patients scored lower on the digit forward span test than LPD patients (5.43±9.49 vs. 6.15±1.38, p=0.045).


RPD patients seem to experience more difficulties in attention and working memory than did LPD patients. The laterality of motor symptoms is not a major determinant for cognitive impairment in PD patients but, we should consider differences of cognitive deficits depending on the side of motor symptoms to treat patients with PD.

Keywords: Parkinson’s disease; cognitive impairment; motor asymmetry; laterality; working memory


Parkinson’s disease (PD) is a neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, and postural instability.1 According to the supportive positive feature of PD according to UK brain bank criteria, the symptom of PD starts on one side of the body. In addition, even if the symptoms spread to the other side later, there is a persistent asymmetry affecting the side of onset and asymmetric tendencies are reported to be 47% to 85%.2, 3 There is no study explaining the precise pathophysiology of asymmetric occurrence. However, hypotheses such as an asymmetry of neuronal loss in both sides of the substantia nigra, one-sided weakness of the blood brain barrier of the midbrain, and an asymmetric neuroprotective effect caused by enhanced unilateral physical activity have been suggested as possible pathological theories.4, 5, 6, 7 Our previous study revealed a significant thinning of motor-related cortical areas in the contralateral hemisphere occurs to the symptomatic side only in left-sided PD (LPD) patients.8 If different cortical thinning areas according to side of symptom dominance and asymmetric dopaminergic depletion are exist, there would presumably be differences in cortical functioning-including cognitive functioning-depending on which side is symptomatic. Our study aimed to investigate whether asymmetric motor laterality could predict specific measures of cognitive functioning.



We recruited early PD patients with right-handed who visited Soonchunghyang University Hospital and Samsung Medical Center from March 2011 to December 2012. Inclusion criteria were: 1) the clinical diagnosis of PD was based on the UK Brain Bank Criteria;1 2) a Hoehn and Yahr (H&Y) stage of less than 2.5. Exclusion criteria were the presence of either: 1) secondary or atypical parkinsonism; 2) a serious medical condition such as an infection or malignancy; 3) present or past medication which might influence cognitive functioning within the past 6 months; or 4) severe cognitive impairment as judged by scores on clinical dementia rating (3, 4, 5). We enrolled 78 patients with early PD. Among these patients, Unified Parkinson’s Disease Rating Scale (UPDRS) data was not present in the records of 4 patients. Additionally, 7 patients did not have lateralized PD symptoms. Finally, 67 patients were analyzed and divided into two groups in accordance with the side of symptom onset or motor laterality. These groups comprised 40 right-sided PD (RPD) patients and 27 LPD patients. The methods for obtaining information were approved by the Institutional Review Board of the Soonchunhyang University School of Medicine.


The patients’ motor functions and clinical stages were assessed by UPDRS part III and H&Y score. Motor laterality was defined as follows: 1) side of symptom onset, 2) opposite side of dominantly-decreased dopamine uptake in positron emission tomography using 18F-fluorinated N-3-fluoropropyl-2-beta-carbonethoxy-3-beta-(4-iodophenyl) nortropane, and 3) a conjunctive point of high composite scores summing the individual motor items of UPDRS part III (rigidity, bradykinesia, and tremor). If no differences were found between right and left side scores, we defined the side of symptom onset as motor laterality. The status of overall cognitive functioning was measured using the Korean version of the Montreal Cognitive Assessment (K-MoCA) and the Seoul Neuropsychological Screening Battery (SNSB). The SNSB is composed of five cognitive domains: attention, memory, language, visuospatial function, and frontal/executive function.9 The scoring of UPDRS part III, H&Y, and cognitive performance were conducted during the ‘on’ state of PD.

Statistical analysis

Statistical analyses were performed with SPSS 18.0 (IBM, Chicago, IL, USA), and the significance threshold was set at 0.05. The independent t-test was used to compare the means of variables and the chi-square test was used to compare the gender ratio.


Demographic and clinical features

The demographic characteristics of each group are described in Table 1. There were no significant differences in terms of age, gender, duration of education, duration of disease, UPDRS-III, and H&Y stage. General cognitive functioning was assessed by Korean version of the Mini-Mental State Examination and K-MoCA-neither of which showed differences between RPD and LPD.

Table 1
Demographic and clinical characteristics
Click for larger image

Comparison of neuropsychological procedures between RPD and LPD

The neuropsychological data of each group are presented in Table 2. The digit forward score was lower in subjects with RPD than in those with LPD (5.43±9.49 vs. 6.15±1.38). There were no significant differences in the digit backward test, memory, language, visuospatial function and frontal/executive function between these patient groups.

Table 2
Comparison of neuropsychological tests between the right and left groups
Click for larger image


Motor symptoms such as bradykinesia, rigidity, and resting tremor usually have a tendency to develop unilaterally (in one side of the body) in patients with PD. Although the parkinsonism gradually becomes bilateral, the initial side commonly remains more affected than does the side involved later on in the progression of the disease-and this distinction is called laterality.10 The each cerebral hemisphere has its own distinct functions. For instance, the left cerebral hemisphere is dominant in language ability, whereas the right cerebral hemisphere is dominant in visual and spatial ability.11 Supposing that motor laterality reflects an asymmetric degeneration, the predominant involvement of one-sided hemisphere would affect related cognitive dysfunction according to the lateralized side.

The results of our study showed that only digit span forward was lower in RPD than LPD. Most previous studies revealed no significant differences between LPD and RPD group performance of the digit span test;12, 13 whereas two studies found results similar to ours.14, 15 The ‘digit span forward’ task has been suggested as being a task of working memory and simple verbal fluency.16 In RPD, the left hemisphere would presumably be affected more than the right hemisphere would be, given that the cognitive battery weighted on language might be influenced. The digit span forward test was significant, but the p-value was close to 0.05. There were no significant differences in the demographic characteristics of each group. However, data including age, duration of disease, UPDRS-III, and H&Y stage were comparatively more likely to affect cognitive impairment in RPD. If the sample size increases, and if the above cofactors are corrected, the digit span forward might not be significant either.

There were a few studies reporting the association between motor laterality and cognitive profiles, and the results varied. Some studies revealed that side of onset does not influence cognition.17, 18 Cooper et al.19 observed a significant association between RPD and verbal memory, visuospatial function, and verbal fluency; and LPD was not related to any composite cognitive domain. In previous studies, the sample size was too small to generalize from the results; and those studies did not explain the differences in cognitive functioning, depending on the side of hand dominance because the dominant hand was not set.13 Furthermore, the patients who had severe cognitive impairment in late-stage PD were also included; and neither H&Y stage nor the severity of motor symptoms were considered.19, 20 In order to overcome these limitations, we compared the differences and characteristics of cognitive functioning according to motor laterality in early PD patients (H&Y stage ≤2.5) who were right-handed.

The pathophysiology of the relationship between motor laterality and cognition in PD patients has not been clearly defined. Several studies have claimed that decreased dopamine secretion caused by asymmetric neuronal degeneration in the substantia nigra is related to motor laterality. Neurodegenerative change of the substantia nigra controls the corpus striatum asymmetrically, and it influences circuits-including basal ganglia and the cerebral cortex-which are related to cognitive functions.4, 21 A previous study, which had shown that similar cognitive impairments had been caused by ventral pallidotomy and by prefrontal injury, support the aforementioned hypothesis.22 Furthermore, relationship between working memory and the prefrontal lobe cortex was reported in a study using positron emission tomography and functional magnetic resonance imaging.23, 24 Additionally, an animal study found that working memory was found to be related to dopamine release into the prefrontal lobe and to the stimulation of the dopamine D1 receptor of the dorsolateral prefrontal lobe. These findings support the hypothesis that cognitive deficits are caused by an interruption of the circuit connecting the basal ganglia and the frontal cortex. Based on these findings, our result implied a greater influence on verbal fluency and working memory in RPD than in LPD.

This study had several limitations. Firstly, the sample size was relatively small, making the results of this study difficult to be generalized. Secondly, clinical data was collected retrospectively, and selection bias could exist. Thirdly, although medication such as an anticholinergic agent could influence cognitive functioning in patients, we did not check precise medications.

In conclusions, our study demonstrated that there were no differences in overall cognitive domains depending on the side of motor laterality. However, RPD patients had significantly lower scores in the digit span forward than did LPD patients. These data implied that patients with RPD had more impaired verbal fluency and working memory than did those with LPD. We need to consider motor function laterality as well as cognitive impairment in the treatment of PD patients. To confirm this, further studies are needed for exploring the possibility that directly-related factors may influence the cognitive functioning of PD patients.


Conflicts of Interest:The authors have no financial conflicts of interest.


This work was supported by Soonchunhyang research fund.

1. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–184.
2. Yust-Katz S, Tesler D, Treves TA, Melamed E, Djaldetti R. Handedness as a predictor of side of onset of Parkinson’s disease. Parkinsonism Relat Disord 2008;14:633–635.
3. Uitti RJ, Baba Y, Whaley NR, Wszolek ZK, Putzke JD. Parkinson disease: handedness predicts asymmetry. Neurology 2005;64:1925–1930.
4. Kempster PA, Gibb WR, Stern GM, Lees AJ. Asymmetry of substantia nigra neuronal loss in Parkinson’s disease and its relevance to the mechanism of levodopa related motor fluctuations. J Neurol Neurosurg Psychiatry 1989;52:72–76.
5. Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, et al. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol 2005;57:176–179.
6. Tillerson JL, Cohen AD, Philhower J, Miller GW, Zigmond MJ, Schallert T. Forced limb-use effects on the behavioral and neurochemical effects of 6-hydroxydopamine. J Neurosci 2001;21:4427–4435.
7. Cohen AD, Tillerson JL, Smith AD, Schallert T, Zigmond MJ. Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: possible role of GDNF. J Neurochem 2003;85:299–305.
8. Kim JS, Yang JJ, Lee JM, Youn J, Kim JM, Cho JW. Topographic pattern of cortical thinning with consideration of motor laterality in Parkinson disease. Parkinsonism Relat Disord 2014;20:1186–1190.
9. Kang Y, Jang S, Na DL. In: Seoul Neuropsychological Screening Battery (SNSB-II). 2nd ed. Seoul: Human Brain Research & Consulting Co.; 2012.
10. Cronin-Golomb A. Parkinson’s disease as a disconnection syndrome. Neuropsychol Rev 2010;20:191–208.
11. Chapman LF, Wolff HG. The cerebral hemispheres and the highest integrative functions of man. Arch Neurol 1959;1:357–424.
12. Agniel A, Celsis P, Viallard G, Montastruc JL, Rascol O, Demonet JF, et al. Cognition and cerebral blood flow in lateralised parkinsonism: lack of functional lateral asymmetries. J Neurol Neurosurg Psychiatry 1991;54:783–786.
13. St Clair J, Borod JC, Sliwinski M, Cote LJ, Stern Y. Cognitive and affective functioning in Parkinson’s disease patients with lateralized motor signs. J Clin Exp Neuropsychol 1998;20:320–327.
14. Huber SJ, Miller H, Bohaska L, Christy JA, Bornstein RA. Asymmetrical cognitive differences associated with hemiparkinsonism. Arch Clin Neuropsychol 1992;7:471–480.
15. Starkstein S, Leiguarda R, Gershanik O, Berthier M. Neuropsychological disturbances in hemiparkinson’s disease. Neurology 1987;37:1762–1764.
16. Hale JB, Hoeppner JAB, Fiorello CA. Analyzing digit span components for assessment of attention processes. J Psychoeduc Assess 2002;20:128–143.
17. Erro R, Santangelo G, Picillo M, Vitale C, Amboni M, Longo K, et al. Side of onset does not influence cognition in newly diagnosed untreated Parkinson’s disease patients. Parkinsonism Relat Disord 2013;19:256–259.
18. Oyebode JR, Barker WA, Blessed G, Dick DJ, Britton PG. Cognitive functioning in Parkinson’s disease: in relation to prevalence of dementia and psychiatric diagnosis. Br J Psychiatry 1986;149:720–725.
19. Cooper CA, Mikos AE, Wood MF, Kirsch-Darrow L, Jacobson CE, Okun MS, et al. Does laterality of motor impairment tell us something about cognition in Parkinson disease? Parkinsonism Relat Disord 2009;15:315–317.
20. Kim JS, Lee KH, Lee SJ, Song IU, Kim YI, Lee KS. The pattern of cognitive impairment associated with the motor subtype in Parkinson’s disease. J Korean Geriatr Soc 2008;12:227–234.
21. Middleton FA, Strick PL. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Brain Res Rev 2000;31:236–250.
22. Trépanier LL, Saint-Cyr JA, Lozano AM, Lang AE. Neuropsychological consequences of posteroventral pallidotomy for the treatment of Parkinson’s disease. Neurology 1998;51:207–215.
23. Cohen JD, Forman SD, Braver TS, Casey BJ, Servan-Schreiber D, Noll DC. Activation of the prefrontal cortex in a nonspatial working memory task with functional MRI. Hum Brain Mapp 1994;1:293–304.
24. Fiez JA, Raife EA, Balota DA, Schwarz JP, Raichle ME, Petersen SE. A positron emission tomography study of the short-term maintenance of verbal information. J Neurosci 1996;16:808–822.