Aging Clin Exp Res DOI 10.1007/s40520-014-0209-z
ORIGINAL ARTICLE
Age-related changes in cognitive function and postural control in Parkinson’s disease Monika Zawadka-Kunikowska • Paweł Zalewski • Jacek J. Klawe • Joanna Pawlak • Małgorzata Tafil-Klawe • Kornelia Ke˛dziora-Kornatowska Julia L. Newton
•
Received: 26 September 2013 / Accepted: 25 February 2014 Ó Springer International Publishing Switzerland 2014
Abstract Background and aims This study objectively analyzed postural instability and cognitive function in patients with Parkinson’s disease (PD) and a group of healthy elderly and middle-aged individuals. Methods The study included ten healthy middle-aged individuals (range 42–57 years), 14 healthy elderly individuals (range 60–90 years) and 15 PD patients (range 58–93 years). Center of pressure (COP) parameters were determined by means of computed static posturography M. Zawadka-Kunikowska and P. Zalewski should be considered as joint first authors. K. Ke˛dziora-Kornatowska and J. L. Newton should be considered as joint senior authors. M. Zawadka-Kunikowska (&) P. Zalewski J. J. Klawe J. Pawlak Department of Hygiene and Epidemiology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, ul. M. SklodowskiejCurie 9, 85-094 Bydgoszcz, Poland e-mail: [email protected] M. Tafil-Klawe Department of Human Physiology, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karłowicza 24, 85-092 Bydgoszcz, Poland K. Ke˛dziora-Kornatowska Department and Clinic of Geriatrics, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, M. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland J. L. Newton Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK
during free standing with open and closed eyes. The level of cognitive functioning was examined with mini mental state examination (MMSE) and counting backwards test (CBT). Results Parkinson’s disease patients showed significantly lower MMSE scores compared to healthy middle-aged (p = 0.004) and elderly individuals (p = 0.03). Mean duration of CBT in PD patients was significantly longer than in healthy subjects. COP parameters correlated with age of subjects and cognitive function (MMSE score). No significant differences in any stabilographic parameters were observed between healthy elderly subjects and PD patients. Conclusions Age is the most significant factor impacting upon the static balance of older individuals during free standing. Compared to middle-aged and elderly individuals without central nervous system impairment, patients with PD present with significant delay in cognitive processes associated with executive function. Keywords Parkinson’s disease Postural stability Cognitive function Aging Elderly
Introduction Understanding the influence of age on postural control is vital in distinguishing between disorders that result from physiological and pathological aging processes [1, 2]. The dopaminergic system of the basal ganglia plays a crucial role in processing sensory information. Physiological aging is associated with degeneration of the nigrostriatal pathway within the dopaminergic system [3]. Our understanding of this is largely based on results from studies of postural control in individuals with Parkinson’s disease
123
Aging Clin Exp Res
(PD) [3–5]. Postural instability in PD is due to dysfunction of postural reflexes, which is generally a manifestation of advanced stages of the disease (Hoehn and Yahr score III to V) [6]. Effects of PD on postural sway characteristics appear to be inconsistent. Some investigators report that PD patients have larger amplitudes of postural sway compared to age-matched controls [7, 8]. However, other researcher found smaller postural sway in PD patients [9] or no difference between the groups at all [4, 10]. Parkinsonian symptoms are an independent attribute of aging, and their presence, although less pronounced, is observed in older individuals without neurological disorders. The prevalence of mild Parkinsonian symptoms increases with age; they are observed in 15–31 % of individuals above 65 years of age, and in more than 50 % of subjects older than 85 years [2, 11]. Clinical signs of PD in older individuals overlap with changes associated with aging and pharmacotherapy, further blurring the clinical manifestation of the disease [7]. Aside from postural control, the dopaminergic system of the basal ganglia is involved in the functional modulation of the prefrontal cortex and the lateral part of the cingulate cortex, both of which participate in the control of attention and executive activities [12, 13]. Previous imaging studies have led to some authors postulating that the impairment in motor function is associated with periventricular lesions in the white matter [14]. As both motor and cognitive functions are prominently controlled by frontal systems, it can be hypothesized that they play a role in geriatric falls [15]. We hypothesize that body sway and cognitive functioning are to some extent related. This preliminary study objectively analyzed postural instability and cognitive function in a group of PD patients compared to groups of healthy elderly and middle-aged individuals.
Materials and methods Overall, 39 individuals were examined, including 24 healthy subjects without neurological impairment (middle-aged, healthy elderly) and 15 patients with confirmed idiopathic PD. The diagnosis of PD was based on the assessment of a neurologist according to the criteria of UK Parkinson’s Disease Society Brain Bank. The participants did not use psychotropic medications or show signs of depression (Geriatric Depression Scale score\10). The protocol of the study was approved by the Bioethical Committee of Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun. All the participants voluntarily provided informed written consent to participate. The clinical stage of PD was graded according to V-item (I–V) Hoehn–Yahr (H–Y) scale. Stage I of this scale corresponds to mild
123
Parkinsonian symptoms, whereas stage V to severe disability and complete dependence on others [16]. The group of middle-aged subjects comprised 10 individuals, among them 6 women and 4 men between 42 and 57 years of age (mean 52.8 ± 5.14 years). The healthy elderly subjects included 14 individuals, 9 women and 5 men, between 60 and 90 years of age (mean 72.36 ± 9.33 years). The group of 15 PD patients comprised 9 women and 6 men between 58 and 93 years of age (mean 73.53 ± 9.72 years). This latter group included PD patients at stage I (n = 5), II (n = 6), and III (n = 4) according to (H–Y) scale. Each patient with PD was examined approximately 2 h after intake of their regular anti-parkinsonian medication. Study group inclusion criteria included confirmed idiopathic PD, disease at stage I–III according to H–Y scale, ability to maintain standing position for at least 96 s, logical verbal contact with the subject, and lack of musculoskeletal disorders that could impair balance during free standing. Individuals with severe dyskinesia or motor fluctuation were excluded. The inclusion criteria for healthy individuals comprised the lack of neurological and orthopedic disorders that could potentially impair balance. Study protocol Postural stability was assessed with a professional diagnostic system comprising posturographic force plate (PROMED) and computer software. The functional status of the balance system was examined in a standing position on the basis of the center of pressure (COP) displacement determined with postural sway recording method. The objective examination of the balance system was based on two sets of posturographic tests: with opened (EO) and closed eyes (EC). The following parameters were analyzed: stabilogram’s area (P) (in mm2), and mean total length (L) covered by the COP (in mm), mean sway velocity (V) (in mm/s), anterior–posterior sway velocity (VA-P) (in mm/s), medio-lateral sway velocity (VM-L) (in mm/s). The sway in coronal and sagittal plane was characterized by medio-lateral (LM-L) (mm) and anterior–posterior (LA-P) (mm) length, respectively. The position of the feet was demarked by lines permanently drawn on the force plate. There was distance of 2 cm between subject’s heels and a 30° forward open angle between their feet. Each subject performed two tests, each lasting for 32 s, with several minutes of rest in between to eliminate potential discomfort associated with standing still for extended period of time. The overall level of cognitive functioning was examined with mini mental state examination (MMSE). The final score of this test includes points for orientation in time and place, repeating three named prompts, attention and
Aging Clin Exp Res
calculation, recall of earlier named prompts after a short period of time, naming two items, performing verbal commands, writing and coping two overlapping pentagrams [17]. Executive function and attention was examined using the counting backwards test (CBT). The participants were asked to count back as quickly as possible, beginning from 20. A longer time interval required to complete the test signifies impaired attention and executive function [18]. Statistical analysis Variable parameters were presented as group size, and mean values for each group together with their standard deviation. Cognitive function was compared between groups. A least significant difference (LSD) post hoc test was used when a significant difference was found in the one-factor ANOVA. The significance of intergroup differences was tested with two-factor ANOVA (group and visual condition) with LSD post hoc test in the case of significant differences. The power and significance of correlations between pairs of selected variables were calculated with the parametric Pearson’s test. The level of significance for all tests was set at p \ 0.05. All calculations were conducted with STATISTICA 10.0 PL statistical package (StatSoft).
Results Assessment of cognitive function MMSE was significantly different between groups: F(2,36) = 5.31 (p = 0.01) PD patients (24.60 ± 5.44) vs middle-aged (29.20 ± 1.03; p = 0.004) or elderly individuals (27.79 ± 2.19; p = 0.03). One-way ANOVA
revealed that PD patients had significantly lower mean score on the test compared to middle-aged and elderly individuals. Also, the CBT differed significantly between the groups: F(2,36) = 4.81 (p = 0.01). Post hoc analysis revealed that PD patients had significantly longer mean time duration of the test (22.07 ± 10.14) compared to middle-aged (12.80 ± 5.47; p = 0.007) and elderly individuals (15.07 ± 6.68; p = 0.02). Postural stability, as measured with COP parameters correlated with the age of subjects and cognitive function (MMSE score). Significant inverse correlations were documented between the weight of subjects and stabilographic parameters (sway velocity, medio-lateral sway velocity and length of stabilogram in medio-lateral direction), Table 1. Furthermore a fair correlation was shown between subject’s age and cognitive function: MMSE (r = 0.51; p = 0.001), CBT (r = 0.54; p \ 0.001). Assessment of postural stability Two-way ANOVA revealed a difference between groups [F(20,126) = 3.24, p \ 0.001] and visual condition [F(5,68) = 5.37, p \ 0.001]. The interaction did not reach significance, (p = 0.71). No significant differences in any stabilographic parameters were observed between healthy elderly subjects and PD patients (p [ 0.05). Two-way ANOVA revealed a difference between groups [F(5,72) = 13.11, p \ 0.001] and visual conditions [F(5,72) = 21.21, p \ 0.001] on area of stabilogram (P). Mean area of stabilogram value in the group of PD patients increased from 716.40 ± 387.32 during open eye testing (EO) to 1,169.47 ± 562.24 during eyes closed testing (EC; p = 0.006). In the group of healthy elderly individuals, closing eyes was reflected by significant increase in mean area of stabilogram value, from
Table 1 Pearson coefficients of correlation in all subjects between stabilographic parameters, demographic characteristics and cognitive function MMSE
CBT
Age
r
p
r
p
r
Area of stabilogram
-0.39*
0.01
0.27
0.10
0.43*
L
-0.36*
0.02
0.22
0.17
0.61*
LM-L
-0.34*
0.04
0.17
0.30
LA-P
-0.30
0.06
0.20
Weight p
Height
r
p
r
p
0.007
-0.26
0.11
-0.11
0.49
0.001
-0.31
0.05
-0.29
0.08
0.43*
0.006
-0.36*
0.02
-0.31
0.05
0.23
0.65*
\0.001
-0.25
0.12
-0.21
0.19 0.08
V
-0.35*
0.03
0.21
0.19
0.59*
\0.001
-0.33*
0.03
-0.28
VM-L
-0.33*
0.04
0.16
0.32
0.40*
0.01
-0.38*
0.02
-0.27
0.01
VA-P
-0.33*
0.04
0.23
0.16
0.61*
\0.001
-0.24
0.134
-0.20
0.22
MMSE mini mental state examination, CBT counting backwards test, L total length, LM-L medio-lateral length of stabilogram, LA-P anterior– posterior length of stabilogram, V mean sway velocity, VM-L medio-lateral sway velocity, VA-P anterior–posterior sway velocity * Statistical significance at p \ 0.05
123
Aging Clin Exp Res
Fig. 1 Group mean values (±SD) of sway velocity in medio-lateral (VM-L) and anterior–posterior (VA-P), length of stabilogram (a, b), medio-lateral length of stabilogram (LM-L) and anterior–posterior (LA-
P) length of stabilogram (c, d), mean sway velocity (V), during eyes open/eyes closed test. Statistically significant differences are indicated with *p \ 0.05, **p \ 0.01 and ***p \ 0.001
526.43 ± 157.82 to 970.21 ± 322.80 (p = 0.001). No significant differences between EO (332.30 ± 143.84) and EC (533.00 ± 147.60) tests were observed in the case of middle-aged subjects (p [ 0.05). Two-way ANOVA showed differences between groups for mean total length (p \ 0.0001), medio-lateral length of stabilogram (p \ 0.001), anterior–posterior length of stabilogram (p \ 0.001) and between visual condition total length (p \ 0.001), medio-lateral length of stabilogram (p = 0.001), anterior–posterior length of stabilogram (p \ 0.001). Eliminating visual information was reflected by a significant increase in total length, anterior–posterior length of the stabilogram value, in all groups, whereas no significant increase was found for the medio-lateral length of stabilogram value in healthy middle-aged subjects and patients with PD (p [ 0.05). No significant differences were observed between healthy elderly and middle-aged subjects for medio-lateral length of stabilogram during EO test Figs. 1c–d, 2a. Two-way ANOVA showed differences between groups for mean sway velocity (p \ 0.001), medio-lateral sway velocity (p = 0.002), anterior–posterior sway velocity (p \ 0.001) and between visual condition for mean sway velocity (p \ 0.001), medio-lateral sway velocity (p = 0.003), anterior–posterior sway velocity (p \ 0.001). Eliminating visual information was reflected by a significant increase in anterior–posterior sway velocity value, both in PD patients and in healthy elderly. No significant
differences between EO and EC tests were observed in case of middle-aged subjects for anterior–posterior sway velocity, and in PD patients for medio-lateral sway velocity, p [ 0.05 Figs. 1a–b, 2b.
123
Discussion Our study revealed a strong correlation between subject’s age and all stabilographic parameters. In addition, our findings indicate that age is the most significant factor impacting upon the static balance of older individuals during free standing. We observed a lack of significant difference in the COP parameters between the results of PD patients and elderly individuals of corresponding age but with no central nervous system impairment. Older persons, both healthy individuals without neurological deficits and PD patients, presented significantly higher values of all stability parameters as compared to healthy middle-aged subjects during EC test. In contrast, during EO test, no significant differences were observed between the healthy elderly subjects and middle-aged subjects for stabilogram’s area, mean sway velocity, sway velocity and length of stabilogram in medio-lateral direction. Similarly, no significant differences were observed between PD patients and healthy elderly subjects for all stability parameters except anterior– posterior sway velocity parameter during EO test. In the
Aging Clin Exp Res
Fig. 2 Group mean values (±SD) of mean sway velocity (V), (a), total length (L), (b) during eyes open/eyes closed test. Statistically significant differences are indicated with *p \ 0.05, **p \ 0.01 and ***p \ 0.001
same condition, no significant differences in anterior– posterior sway velocity parameter were observed between all examined groups (Fig. 1). In all studied groups, significant differences between open and closed eyes’ tests pertained only to several variables: total stabilogram length (L) and the length of stabilogram in sagittal plane (LA-P). This suggests that the length of stabilogram constitutes a sensitive indicator of postural instability. It is postulated that impairment in proprioception cannot be fully compensated for by the unaided availability of visual information [19]. According to other authors, the impairment of postural control takes place as early as at a young age and accelerates at about 60 years of age [20]. Similar findings were previously reported by other authors [4] who did not observe significant differences with regard to the range of sway in PD patients and healthy older individuals, both subjected to tests with eyes opened and closed. Previous studies dealing with the postural stability in PD patients revealed either an increase [7] or a decrease [9] in body sway during free standing. The results of our study suggest that the process of aging exerts different effects on the range of sway in sagittal and coronal plane. In humans, standing position with two-leg support is characterized by greater sagittal sway, suggesting larger involvement of nervous system in postural control of body in this plane of movement [21]. Our findings are consistent with results of a previous study [5] according to which the postural sway of PD patients in sagittal plane is similar compared to age-matched controls. Differences in the range of sagittal and coronal sway between middle-aged and older individuals may result from progressing age-dependent deficit in processing sensory information at various levels of the central nervous system, as well as from using different compensatory mechanisms to restore balance [22]. The lack of differences between elderly individuals and PD patients with regard to postural sway in sagittal and coronal plane may be associated with anti-parkinsonian
medication. PD patients were tested after they had taken their normal doses of Parkinson medication. Some authors have suggested that levodopa can improve postural stability during the ‘‘on’’ phase of this drug [19]. Furthemore, studies with myometry revealed that anti-parkinsonian medication decreases rigidity and rigidity-related stiffness in resting skeletal muscles in PD patients [23]. Our testing of cognitive function revealed that mean MMSE score and CBT of PD patients were significantly worse than in healthy middle-aged or older individuals. This may be due to impaired executive function and cognitive delay associated with PD. Mild cognitive impairment was detected in PD patients. Most authors agree that age-related changes and neurodegenerative processes associated with PD lead to marked cognitive impairment, particularly in older patients [24–26]. Other studies revealed that irrespective of its duration, PD is not associated with dementia in young and middle-aged patients [27]. The MMSE and CBT score correlated with age of all subjects. Moreover, older age, older age at disease onset, and PD stage may constitute prognostic factors with regard to cognitive impairment [26]. Our findings are consistent with the results of previous studies [28] where deficits in attention control and executive function constitute early markers of cognitive impairment. Our findings are consistent with other studies and suggest that control of body sway and cognitive functioning are to some extent related [29, 30]. Postural stability, as measured with COP parameters correlated only with MMSE score. Attention and executive function appear to play an important role in the higher order cognitive control of balance, gait and posture [15]. Lower scores on cognitive tests such as the MMSE have been associated with an increased risk of falls [15, 31]. This study has a number of limitations. First limitation is that the included groups are relatively small and may affect the results of statistical analysis. Moreover, PD patients constitute a heterogeneous group; this heterogeneity can result from complex and incompletely understood pathogenesis, as well as from the overlap of various pathologies specific for
123
Aging Clin Exp Res
advanced age. Another limitation of the study was that only two neuropsychological tests were used to assess cognitive functions. Finally, we did not consider the potential influence of the type and dose of medications used by our patients upon their postural sway and cognitive function.
Conclusion Our study has revealed that body sway and cognitive functioning are to some extent related. PD patients did not differ significantly from individuals of corresponding age without neurological deficits with regard to the range of postural sway during free standing. It would seem that age is the most significant factor impacting upon the static balance of older individuals during free standing. Compared to middle-aged and elderly individuals without central nervous system impairment, patients with PD present with significant delay in cognitive processes associated with executive function. Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
References 1. Du Pasquier RA, Blanc Y, Sinnreich M et al (2003) The effect of aging on postural stability: a cross sectional and longitudinal study. Neurophysiol Clin 33:213–218 2. Bennett DA, Beckett LA, Murray AM et al (1996) Prevalence of parkinsonian signs and associated mortality in a community population of older people. N Engl J Med 334:71–76 3. Cham R, Perera S, Studenski SA et al (2007) Striatal dopamine denervation and sensory integration for balance in middle-aged and older adults. Gait Posture 26:516–525 4. Marchese R, Bove M, Abbruzzese G (2003) Effect of cognitive and motor tasks on postural stability in Parkinson’s disease: a posturographic study. Mov Disord 18:652–658 5. Viitasalo M, Kampman K, Sotaniemi V et al (2002) Analysis of sway in Parkinson’s disease using a new inclinometry-based method. Mov Disord 17:663–669 6. Carpenter MG, Allum JH, Honegger F et al (2004) Postural abnormalities to multidirectional stance perturbations in Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:1245–1254 7. Błaszczyk JW, Orawiec R (2011) Assessment of postural control in patients with Parkinson’s disease: sway ratio analysis. Hum Mov Sci 30:396–404 8. Rocchi L, Chiari L, Horak FB (2002) Effects of deep brain stimulation and levodopa on postural sway in Parkinson’s disease. J Neurol Neurosurg Psychiatry 73:267–274 9. Horak FB, Nutt JG, Nashner LM (1992) Postural inflexibility in parkinsonian subjects. J Neurol Sci 44:46–58 10. Schiepati M, Nardone A (1991) Free and supported stance in Parkinson’s disease. The effect of posture and postural set on leg muscle response to perturbation, and its relation to the severity of the disease. Brain 114:1227–1244
123
11. Wilson RS, Shneider JA, Beckett LA et al (2002) Progression of gait disorder and rigidity and risk of death in older persons. Neurology 58:1815–1819 12. Visser JE, Bloem BR (2005) Role of the basal ganglia in balance control. Neural Plast 12:263–272 13. Zhou S, Chen X, Wang C, Yin C et al (2012) Selective attention deficits in early and moderate stage Parkinson’s disease. Neurosci Lett 509:50–55 14. Onen F, Henry-Feugeas MC, Baron G et al (2004) Leukoaraiosis and mobility decline: a high resolution magnetic resonance imaging study in older people with mild cognitive impairment. Neuroscience 355:185–188 15. Buracchio TJ, Mattek NC, Dodge HH et al (2011) Executive function predicts risk of falls in older adults without balance impairment. BMC Geriatr 9:74 16. Goetz CG, Poewe W, Rascol O et al (2004) Movement disorder society task force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord 19:1892–1898 17. Folstein M, Folstein S, McHugh P (1975) Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198 18. Kanno S, Saito M, Hayashi A et al (2012) Counting-backward test for executive function in idiopathic normal pressure hydrocephalus. Acta Neurol Scand 126:279–286 19. McNeely ME, Duncan RP, Earhart GM (2012) Medication improves balance and complex gait performance in Parkinson disease. Gait Posture 36:144–148 20. Era P, Sainio P, Koskinen S, Haavisto P et al (2006) Postural balance in random sample of 7,979 subjects aged 30 years and over. Gerontology 52:204–213 21. Winter DA, Patla AE, Prince F et al (1998) Stiffness control of balance in quiet standing. J Neurophysiol 80:1211–1221 22. Nashner LM. (1989) Sensory, neuromuscular and biomechanical contributions to human balance. In: Proceedings of the Forum of the American Physical Therapy Association. Nashville, pp 5–12 23. Marusiak J, Jasko´lska A, Koszewicz M et al (2012) Myometry revealed medication-induced decrease in resting skeletal muscle stiffness in Parkinson’s disease patients. Clin Biomech 27:632–635 24. Levy G, Schupf N, Tang MX et al (2002) Combined effect of age and severity on the risk of dementia in Parkinson’s disease. Ann Neurol 51:722–729 25. Zakharov VV, Iakhno NN (2005) Cognitive dysfunction in patients with Parkinson’s disease. Zh Nevrol Psikhiatr Im S S Korsakova 105:13–19 26. Stepkina DA, Zakharov VV, Yakhno NN (2010) Cognitive impairments in progression of Parkinson’s disease. Neurosci Behav Physiol 40:61–67 27. Antonenko LM, Damulin IV (2003) Characteristics of impairments to balance and gain in elderly patients with Parkinson’s disease, progressive supranuclear palsy, and multisystem atrophy. Klin Gerontol 9:51–52 28. Perry RJ, Hodges JR (1999) Attention and executive deficits in Alzheimer’s disease: a critical review. Brain 122:383–404 29. Andersson G, Hagman J, Talianzadeh R et al (2002) Effect of cognitive load on postural control. Brain Res Bull 58:135–139 30. Caixeta GC, Dona´ F, Gazzola JM (2012) Cognitive processing and body balance in elderly subjects with vestibular dysfunction. Braz J Otorhinolaryngol 78:87–95 31. Gleason CE, Gangnon RE, Fischer BL et al (2009) Increased risk for falling associated with subtle cognitive impairment: secondary analysis of a randomized clinical trial. Dement Geriatr Cogn Disord 27:557–563
ORIGINAL ARTICLE
Age-related changes in cognitive function and postural control in Parkinson’s disease Monika Zawadka-Kunikowska • Paweł Zalewski • Jacek J. Klawe • Joanna Pawlak • Małgorzata Tafil-Klawe • Kornelia Ke˛dziora-Kornatowska Julia L. Newton
•
Received: 26 September 2013 / Accepted: 25 February 2014 Ó Springer International Publishing Switzerland 2014
Abstract Background and aims This study objectively analyzed postural instability and cognitive function in patients with Parkinson’s disease (PD) and a group of healthy elderly and middle-aged individuals. Methods The study included ten healthy middle-aged individuals (range 42–57 years), 14 healthy elderly individuals (range 60–90 years) and 15 PD patients (range 58–93 years). Center of pressure (COP) parameters were determined by means of computed static posturography M. Zawadka-Kunikowska and P. Zalewski should be considered as joint first authors. K. Ke˛dziora-Kornatowska and J. L. Newton should be considered as joint senior authors. M. Zawadka-Kunikowska (&) P. Zalewski J. J. Klawe J. Pawlak Department of Hygiene and Epidemiology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, ul. M. SklodowskiejCurie 9, 85-094 Bydgoszcz, Poland e-mail: [email protected] M. Tafil-Klawe Department of Human Physiology, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Karłowicza 24, 85-092 Bydgoszcz, Poland K. Ke˛dziora-Kornatowska Department and Clinic of Geriatrics, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, M. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland J. L. Newton Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK
during free standing with open and closed eyes. The level of cognitive functioning was examined with mini mental state examination (MMSE) and counting backwards test (CBT). Results Parkinson’s disease patients showed significantly lower MMSE scores compared to healthy middle-aged (p = 0.004) and elderly individuals (p = 0.03). Mean duration of CBT in PD patients was significantly longer than in healthy subjects. COP parameters correlated with age of subjects and cognitive function (MMSE score). No significant differences in any stabilographic parameters were observed between healthy elderly subjects and PD patients. Conclusions Age is the most significant factor impacting upon the static balance of older individuals during free standing. Compared to middle-aged and elderly individuals without central nervous system impairment, patients with PD present with significant delay in cognitive processes associated with executive function. Keywords Parkinson’s disease Postural stability Cognitive function Aging Elderly
Introduction Understanding the influence of age on postural control is vital in distinguishing between disorders that result from physiological and pathological aging processes [1, 2]. The dopaminergic system of the basal ganglia plays a crucial role in processing sensory information. Physiological aging is associated with degeneration of the nigrostriatal pathway within the dopaminergic system [3]. Our understanding of this is largely based on results from studies of postural control in individuals with Parkinson’s disease
123
Aging Clin Exp Res
(PD) [3–5]. Postural instability in PD is due to dysfunction of postural reflexes, which is generally a manifestation of advanced stages of the disease (Hoehn and Yahr score III to V) [6]. Effects of PD on postural sway characteristics appear to be inconsistent. Some investigators report that PD patients have larger amplitudes of postural sway compared to age-matched controls [7, 8]. However, other researcher found smaller postural sway in PD patients [9] or no difference between the groups at all [4, 10]. Parkinsonian symptoms are an independent attribute of aging, and their presence, although less pronounced, is observed in older individuals without neurological disorders. The prevalence of mild Parkinsonian symptoms increases with age; they are observed in 15–31 % of individuals above 65 years of age, and in more than 50 % of subjects older than 85 years [2, 11]. Clinical signs of PD in older individuals overlap with changes associated with aging and pharmacotherapy, further blurring the clinical manifestation of the disease [7]. Aside from postural control, the dopaminergic system of the basal ganglia is involved in the functional modulation of the prefrontal cortex and the lateral part of the cingulate cortex, both of which participate in the control of attention and executive activities [12, 13]. Previous imaging studies have led to some authors postulating that the impairment in motor function is associated with periventricular lesions in the white matter [14]. As both motor and cognitive functions are prominently controlled by frontal systems, it can be hypothesized that they play a role in geriatric falls [15]. We hypothesize that body sway and cognitive functioning are to some extent related. This preliminary study objectively analyzed postural instability and cognitive function in a group of PD patients compared to groups of healthy elderly and middle-aged individuals.
Materials and methods Overall, 39 individuals were examined, including 24 healthy subjects without neurological impairment (middle-aged, healthy elderly) and 15 patients with confirmed idiopathic PD. The diagnosis of PD was based on the assessment of a neurologist according to the criteria of UK Parkinson’s Disease Society Brain Bank. The participants did not use psychotropic medications or show signs of depression (Geriatric Depression Scale score\10). The protocol of the study was approved by the Bioethical Committee of Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun. All the participants voluntarily provided informed written consent to participate. The clinical stage of PD was graded according to V-item (I–V) Hoehn–Yahr (H–Y) scale. Stage I of this scale corresponds to mild
123
Parkinsonian symptoms, whereas stage V to severe disability and complete dependence on others [16]. The group of middle-aged subjects comprised 10 individuals, among them 6 women and 4 men between 42 and 57 years of age (mean 52.8 ± 5.14 years). The healthy elderly subjects included 14 individuals, 9 women and 5 men, between 60 and 90 years of age (mean 72.36 ± 9.33 years). The group of 15 PD patients comprised 9 women and 6 men between 58 and 93 years of age (mean 73.53 ± 9.72 years). This latter group included PD patients at stage I (n = 5), II (n = 6), and III (n = 4) according to (H–Y) scale. Each patient with PD was examined approximately 2 h after intake of their regular anti-parkinsonian medication. Study group inclusion criteria included confirmed idiopathic PD, disease at stage I–III according to H–Y scale, ability to maintain standing position for at least 96 s, logical verbal contact with the subject, and lack of musculoskeletal disorders that could impair balance during free standing. Individuals with severe dyskinesia or motor fluctuation were excluded. The inclusion criteria for healthy individuals comprised the lack of neurological and orthopedic disorders that could potentially impair balance. Study protocol Postural stability was assessed with a professional diagnostic system comprising posturographic force plate (PROMED) and computer software. The functional status of the balance system was examined in a standing position on the basis of the center of pressure (COP) displacement determined with postural sway recording method. The objective examination of the balance system was based on two sets of posturographic tests: with opened (EO) and closed eyes (EC). The following parameters were analyzed: stabilogram’s area (P) (in mm2), and mean total length (L) covered by the COP (in mm), mean sway velocity (V) (in mm/s), anterior–posterior sway velocity (VA-P) (in mm/s), medio-lateral sway velocity (VM-L) (in mm/s). The sway in coronal and sagittal plane was characterized by medio-lateral (LM-L) (mm) and anterior–posterior (LA-P) (mm) length, respectively. The position of the feet was demarked by lines permanently drawn on the force plate. There was distance of 2 cm between subject’s heels and a 30° forward open angle between their feet. Each subject performed two tests, each lasting for 32 s, with several minutes of rest in between to eliminate potential discomfort associated with standing still for extended period of time. The overall level of cognitive functioning was examined with mini mental state examination (MMSE). The final score of this test includes points for orientation in time and place, repeating three named prompts, attention and
Aging Clin Exp Res
calculation, recall of earlier named prompts after a short period of time, naming two items, performing verbal commands, writing and coping two overlapping pentagrams [17]. Executive function and attention was examined using the counting backwards test (CBT). The participants were asked to count back as quickly as possible, beginning from 20. A longer time interval required to complete the test signifies impaired attention and executive function [18]. Statistical analysis Variable parameters were presented as group size, and mean values for each group together with their standard deviation. Cognitive function was compared between groups. A least significant difference (LSD) post hoc test was used when a significant difference was found in the one-factor ANOVA. The significance of intergroup differences was tested with two-factor ANOVA (group and visual condition) with LSD post hoc test in the case of significant differences. The power and significance of correlations between pairs of selected variables were calculated with the parametric Pearson’s test. The level of significance for all tests was set at p \ 0.05. All calculations were conducted with STATISTICA 10.0 PL statistical package (StatSoft).
Results Assessment of cognitive function MMSE was significantly different between groups: F(2,36) = 5.31 (p = 0.01) PD patients (24.60 ± 5.44) vs middle-aged (29.20 ± 1.03; p = 0.004) or elderly individuals (27.79 ± 2.19; p = 0.03). One-way ANOVA
revealed that PD patients had significantly lower mean score on the test compared to middle-aged and elderly individuals. Also, the CBT differed significantly between the groups: F(2,36) = 4.81 (p = 0.01). Post hoc analysis revealed that PD patients had significantly longer mean time duration of the test (22.07 ± 10.14) compared to middle-aged (12.80 ± 5.47; p = 0.007) and elderly individuals (15.07 ± 6.68; p = 0.02). Postural stability, as measured with COP parameters correlated with the age of subjects and cognitive function (MMSE score). Significant inverse correlations were documented between the weight of subjects and stabilographic parameters (sway velocity, medio-lateral sway velocity and length of stabilogram in medio-lateral direction), Table 1. Furthermore a fair correlation was shown between subject’s age and cognitive function: MMSE (r = 0.51; p = 0.001), CBT (r = 0.54; p \ 0.001). Assessment of postural stability Two-way ANOVA revealed a difference between groups [F(20,126) = 3.24, p \ 0.001] and visual condition [F(5,68) = 5.37, p \ 0.001]. The interaction did not reach significance, (p = 0.71). No significant differences in any stabilographic parameters were observed between healthy elderly subjects and PD patients (p [ 0.05). Two-way ANOVA revealed a difference between groups [F(5,72) = 13.11, p \ 0.001] and visual conditions [F(5,72) = 21.21, p \ 0.001] on area of stabilogram (P). Mean area of stabilogram value in the group of PD patients increased from 716.40 ± 387.32 during open eye testing (EO) to 1,169.47 ± 562.24 during eyes closed testing (EC; p = 0.006). In the group of healthy elderly individuals, closing eyes was reflected by significant increase in mean area of stabilogram value, from
Table 1 Pearson coefficients of correlation in all subjects between stabilographic parameters, demographic characteristics and cognitive function MMSE
CBT
Age
r
p
r
p
r
Area of stabilogram
-0.39*
0.01
0.27
0.10
0.43*
L
-0.36*
0.02
0.22
0.17
0.61*
LM-L
-0.34*
0.04
0.17
0.30
LA-P
-0.30
0.06
0.20
Weight p
Height
r
p
r
p
0.007
-0.26
0.11
-0.11
0.49
0.001
-0.31
0.05
-0.29
0.08
0.43*
0.006
-0.36*
0.02
-0.31
0.05
0.23
0.65*
\0.001
-0.25
0.12
-0.21
0.19 0.08
V
-0.35*
0.03
0.21
0.19
0.59*
\0.001
-0.33*
0.03
-0.28
VM-L
-0.33*
0.04
0.16
0.32
0.40*
0.01
-0.38*
0.02
-0.27
0.01
VA-P
-0.33*
0.04
0.23
0.16
0.61*
\0.001
-0.24
0.134
-0.20
0.22
MMSE mini mental state examination, CBT counting backwards test, L total length, LM-L medio-lateral length of stabilogram, LA-P anterior– posterior length of stabilogram, V mean sway velocity, VM-L medio-lateral sway velocity, VA-P anterior–posterior sway velocity * Statistical significance at p \ 0.05
123
Aging Clin Exp Res
Fig. 1 Group mean values (±SD) of sway velocity in medio-lateral (VM-L) and anterior–posterior (VA-P), length of stabilogram (a, b), medio-lateral length of stabilogram (LM-L) and anterior–posterior (LA-
P) length of stabilogram (c, d), mean sway velocity (V), during eyes open/eyes closed test. Statistically significant differences are indicated with *p \ 0.05, **p \ 0.01 and ***p \ 0.001
526.43 ± 157.82 to 970.21 ± 322.80 (p = 0.001). No significant differences between EO (332.30 ± 143.84) and EC (533.00 ± 147.60) tests were observed in the case of middle-aged subjects (p [ 0.05). Two-way ANOVA showed differences between groups for mean total length (p \ 0.0001), medio-lateral length of stabilogram (p \ 0.001), anterior–posterior length of stabilogram (p \ 0.001) and between visual condition total length (p \ 0.001), medio-lateral length of stabilogram (p = 0.001), anterior–posterior length of stabilogram (p \ 0.001). Eliminating visual information was reflected by a significant increase in total length, anterior–posterior length of the stabilogram value, in all groups, whereas no significant increase was found for the medio-lateral length of stabilogram value in healthy middle-aged subjects and patients with PD (p [ 0.05). No significant differences were observed between healthy elderly and middle-aged subjects for medio-lateral length of stabilogram during EO test Figs. 1c–d, 2a. Two-way ANOVA showed differences between groups for mean sway velocity (p \ 0.001), medio-lateral sway velocity (p = 0.002), anterior–posterior sway velocity (p \ 0.001) and between visual condition for mean sway velocity (p \ 0.001), medio-lateral sway velocity (p = 0.003), anterior–posterior sway velocity (p \ 0.001). Eliminating visual information was reflected by a significant increase in anterior–posterior sway velocity value, both in PD patients and in healthy elderly. No significant
differences between EO and EC tests were observed in case of middle-aged subjects for anterior–posterior sway velocity, and in PD patients for medio-lateral sway velocity, p [ 0.05 Figs. 1a–b, 2b.
123
Discussion Our study revealed a strong correlation between subject’s age and all stabilographic parameters. In addition, our findings indicate that age is the most significant factor impacting upon the static balance of older individuals during free standing. We observed a lack of significant difference in the COP parameters between the results of PD patients and elderly individuals of corresponding age but with no central nervous system impairment. Older persons, both healthy individuals without neurological deficits and PD patients, presented significantly higher values of all stability parameters as compared to healthy middle-aged subjects during EC test. In contrast, during EO test, no significant differences were observed between the healthy elderly subjects and middle-aged subjects for stabilogram’s area, mean sway velocity, sway velocity and length of stabilogram in medio-lateral direction. Similarly, no significant differences were observed between PD patients and healthy elderly subjects for all stability parameters except anterior– posterior sway velocity parameter during EO test. In the
Aging Clin Exp Res
Fig. 2 Group mean values (±SD) of mean sway velocity (V), (a), total length (L), (b) during eyes open/eyes closed test. Statistically significant differences are indicated with *p \ 0.05, **p \ 0.01 and ***p \ 0.001
same condition, no significant differences in anterior– posterior sway velocity parameter were observed between all examined groups (Fig. 1). In all studied groups, significant differences between open and closed eyes’ tests pertained only to several variables: total stabilogram length (L) and the length of stabilogram in sagittal plane (LA-P). This suggests that the length of stabilogram constitutes a sensitive indicator of postural instability. It is postulated that impairment in proprioception cannot be fully compensated for by the unaided availability of visual information [19]. According to other authors, the impairment of postural control takes place as early as at a young age and accelerates at about 60 years of age [20]. Similar findings were previously reported by other authors [4] who did not observe significant differences with regard to the range of sway in PD patients and healthy older individuals, both subjected to tests with eyes opened and closed. Previous studies dealing with the postural stability in PD patients revealed either an increase [7] or a decrease [9] in body sway during free standing. The results of our study suggest that the process of aging exerts different effects on the range of sway in sagittal and coronal plane. In humans, standing position with two-leg support is characterized by greater sagittal sway, suggesting larger involvement of nervous system in postural control of body in this plane of movement [21]. Our findings are consistent with results of a previous study [5] according to which the postural sway of PD patients in sagittal plane is similar compared to age-matched controls. Differences in the range of sagittal and coronal sway between middle-aged and older individuals may result from progressing age-dependent deficit in processing sensory information at various levels of the central nervous system, as well as from using different compensatory mechanisms to restore balance [22]. The lack of differences between elderly individuals and PD patients with regard to postural sway in sagittal and coronal plane may be associated with anti-parkinsonian
medication. PD patients were tested after they had taken their normal doses of Parkinson medication. Some authors have suggested that levodopa can improve postural stability during the ‘‘on’’ phase of this drug [19]. Furthemore, studies with myometry revealed that anti-parkinsonian medication decreases rigidity and rigidity-related stiffness in resting skeletal muscles in PD patients [23]. Our testing of cognitive function revealed that mean MMSE score and CBT of PD patients were significantly worse than in healthy middle-aged or older individuals. This may be due to impaired executive function and cognitive delay associated with PD. Mild cognitive impairment was detected in PD patients. Most authors agree that age-related changes and neurodegenerative processes associated with PD lead to marked cognitive impairment, particularly in older patients [24–26]. Other studies revealed that irrespective of its duration, PD is not associated with dementia in young and middle-aged patients [27]. The MMSE and CBT score correlated with age of all subjects. Moreover, older age, older age at disease onset, and PD stage may constitute prognostic factors with regard to cognitive impairment [26]. Our findings are consistent with the results of previous studies [28] where deficits in attention control and executive function constitute early markers of cognitive impairment. Our findings are consistent with other studies and suggest that control of body sway and cognitive functioning are to some extent related [29, 30]. Postural stability, as measured with COP parameters correlated only with MMSE score. Attention and executive function appear to play an important role in the higher order cognitive control of balance, gait and posture [15]. Lower scores on cognitive tests such as the MMSE have been associated with an increased risk of falls [15, 31]. This study has a number of limitations. First limitation is that the included groups are relatively small and may affect the results of statistical analysis. Moreover, PD patients constitute a heterogeneous group; this heterogeneity can result from complex and incompletely understood pathogenesis, as well as from the overlap of various pathologies specific for
123
Aging Clin Exp Res
advanced age. Another limitation of the study was that only two neuropsychological tests were used to assess cognitive functions. Finally, we did not consider the potential influence of the type and dose of medications used by our patients upon their postural sway and cognitive function.
Conclusion Our study has revealed that body sway and cognitive functioning are to some extent related. PD patients did not differ significantly from individuals of corresponding age without neurological deficits with regard to the range of postural sway during free standing. It would seem that age is the most significant factor impacting upon the static balance of older individuals during free standing. Compared to middle-aged and elderly individuals without central nervous system impairment, patients with PD present with significant delay in cognitive processes associated with executive function. Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
References 1. Du Pasquier RA, Blanc Y, Sinnreich M et al (2003) The effect of aging on postural stability: a cross sectional and longitudinal study. Neurophysiol Clin 33:213–218 2. Bennett DA, Beckett LA, Murray AM et al (1996) Prevalence of parkinsonian signs and associated mortality in a community population of older people. N Engl J Med 334:71–76 3. Cham R, Perera S, Studenski SA et al (2007) Striatal dopamine denervation and sensory integration for balance in middle-aged and older adults. Gait Posture 26:516–525 4. Marchese R, Bove M, Abbruzzese G (2003) Effect of cognitive and motor tasks on postural stability in Parkinson’s disease: a posturographic study. Mov Disord 18:652–658 5. Viitasalo M, Kampman K, Sotaniemi V et al (2002) Analysis of sway in Parkinson’s disease using a new inclinometry-based method. Mov Disord 17:663–669 6. Carpenter MG, Allum JH, Honegger F et al (2004) Postural abnormalities to multidirectional stance perturbations in Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:1245–1254 7. Błaszczyk JW, Orawiec R (2011) Assessment of postural control in patients with Parkinson’s disease: sway ratio analysis. Hum Mov Sci 30:396–404 8. Rocchi L, Chiari L, Horak FB (2002) Effects of deep brain stimulation and levodopa on postural sway in Parkinson’s disease. J Neurol Neurosurg Psychiatry 73:267–274 9. Horak FB, Nutt JG, Nashner LM (1992) Postural inflexibility in parkinsonian subjects. J Neurol Sci 44:46–58 10. Schiepati M, Nardone A (1991) Free and supported stance in Parkinson’s disease. The effect of posture and postural set on leg muscle response to perturbation, and its relation to the severity of the disease. Brain 114:1227–1244
123
11. Wilson RS, Shneider JA, Beckett LA et al (2002) Progression of gait disorder and rigidity and risk of death in older persons. Neurology 58:1815–1819 12. Visser JE, Bloem BR (2005) Role of the basal ganglia in balance control. Neural Plast 12:263–272 13. Zhou S, Chen X, Wang C, Yin C et al (2012) Selective attention deficits in early and moderate stage Parkinson’s disease. Neurosci Lett 509:50–55 14. Onen F, Henry-Feugeas MC, Baron G et al (2004) Leukoaraiosis and mobility decline: a high resolution magnetic resonance imaging study in older people with mild cognitive impairment. Neuroscience 355:185–188 15. Buracchio TJ, Mattek NC, Dodge HH et al (2011) Executive function predicts risk of falls in older adults without balance impairment. BMC Geriatr 9:74 16. Goetz CG, Poewe W, Rascol O et al (2004) Movement disorder society task force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord 19:1892–1898 17. Folstein M, Folstein S, McHugh P (1975) Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198 18. Kanno S, Saito M, Hayashi A et al (2012) Counting-backward test for executive function in idiopathic normal pressure hydrocephalus. Acta Neurol Scand 126:279–286 19. McNeely ME, Duncan RP, Earhart GM (2012) Medication improves balance and complex gait performance in Parkinson disease. Gait Posture 36:144–148 20. Era P, Sainio P, Koskinen S, Haavisto P et al (2006) Postural balance in random sample of 7,979 subjects aged 30 years and over. Gerontology 52:204–213 21. Winter DA, Patla AE, Prince F et al (1998) Stiffness control of balance in quiet standing. J Neurophysiol 80:1211–1221 22. Nashner LM. (1989) Sensory, neuromuscular and biomechanical contributions to human balance. In: Proceedings of the Forum of the American Physical Therapy Association. Nashville, pp 5–12 23. Marusiak J, Jasko´lska A, Koszewicz M et al (2012) Myometry revealed medication-induced decrease in resting skeletal muscle stiffness in Parkinson’s disease patients. Clin Biomech 27:632–635 24. Levy G, Schupf N, Tang MX et al (2002) Combined effect of age and severity on the risk of dementia in Parkinson’s disease. Ann Neurol 51:722–729 25. Zakharov VV, Iakhno NN (2005) Cognitive dysfunction in patients with Parkinson’s disease. Zh Nevrol Psikhiatr Im S S Korsakova 105:13–19 26. Stepkina DA, Zakharov VV, Yakhno NN (2010) Cognitive impairments in progression of Parkinson’s disease. Neurosci Behav Physiol 40:61–67 27. Antonenko LM, Damulin IV (2003) Characteristics of impairments to balance and gain in elderly patients with Parkinson’s disease, progressive supranuclear palsy, and multisystem atrophy. Klin Gerontol 9:51–52 28. Perry RJ, Hodges JR (1999) Attention and executive deficits in Alzheimer’s disease: a critical review. Brain 122:383–404 29. Andersson G, Hagman J, Talianzadeh R et al (2002) Effect of cognitive load on postural control. Brain Res Bull 58:135–139 30. Caixeta GC, Dona´ F, Gazzola JM (2012) Cognitive processing and body balance in elderly subjects with vestibular dysfunction. Braz J Otorhinolaryngol 78:87–95 31. Gleason CE, Gangnon RE, Fischer BL et al (2009) Increased risk for falling associated with subtle cognitive impairment: secondary analysis of a randomized clinical trial. Dement Geriatr Cogn Disord 27:557–563
