BODY COMPOSITION, FALLS, AND FREEZING OF GAIT IN PARKINSON’S DISEASE: GENDER-SPECIFIC EFFECTS

 

C. Pongmala^1-3, C. Stonsaovapak⁴, M. van Emde Boas^1-3,5, H. Bhanderi^1,2, A. Luker^1,2, F. Michalakis^1,2, P. Kanel^1-3,5, R.L. Albin^3,5,6,7,*, J.M. Haus^8,*, N.I. Bohnen^1-3,5-7,*

 

1. Department of Radiology, University of Michigan, Ann Arbor, MI, USA; 2. Functional Neuroimaging, Cognitive, and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan, Ann Arbor, MI, USA; 3. Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, MI, USA; 4. Department of Rehabilitation Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 5. Parkinson’s Foundation Research Center of Excellence, University of Michigan, Ann Arbor, MI, USA; 6. Neurology Service and GRECC, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; 7. Department of Neurology, University of Michigan, Ann Arbor, MI, USA; 8. School of Kinesiology, University of Michigan, Ann Arbor, MI, USA; *Senior author

Corresponding Author: Chatkaew Pongmala, Ph.D., Functional Neuroimaging, Cognitive and Mobility Laboratory, Department of Radiology, University of Michigan, 24 Frank Lloyd Wright Drive, Box 362, Ann Arbor, MI 48105-9755, USA. TEL: (1) 734 998 8400. E-mail: pchatkae@umich.edu

J Frailty Aging 2024;in press
Published online April 2, 2024, http://dx.doi.org/10.14283/jfa.2024.31

 

---

Abstract

BACKGROUND: Postural instability and gait difficulties (PIGD) are a significant cause of mobility loss and lower quality of life in Parkinson’s disease (PD). When PD progresses, patients may experience falls and freezing of gait (FoG) resulting in fear of falling and increasing sedentariness. Sedentary behavior results in sarcopenia associated with other changes in body composition, especially in older patients becoming frail. Previous studies have shown gender-specific changes in body composition with aging as well as gender disparities in symptoms and progression of PD, yet the association between gender-specific body composition and PIGD symptoms such as FoG along with falls, remains unexplored.
OBECTIVE: This study aimed to investigate the association between gender-specific changes in body composition, FoG and falls assessment.
Methods: 136 PD subjects underwent detailed clinical test batteries and had whole-body composition assessed using dual-energy X-ray absorptiometry (DXA). Multivariate logistic forward stepwise regression was performed to define body composition associations for FoG and falls.
RESULTS: Multivariate regression analysis revealed that in males with PD, lower leg lean mass was significantly associated with the presence of FoG (OR, 0.429; 95% CI, 0.219-0.839; p=0.013) but not with falls. In females with PD, higher leg adipose mass was significantly associated with falls (OR, 4.780; 95% CI, 1.506-15.174; p=0.008) but not with FoG.
CONCLUSION: These observations suggest gender specific associations between body composition and FoG vs. falls in PD. Future research should explore the impact of interventions on body composition in individuals with PD by paying specific attention to gender differences.

Key words: Fat mass, risk factors, gender differences, muscle weakness, ALMI.

---

 

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disorder that becomes more prevalent with aging and results in dependency (1). It is characterized by motor and non-motor features. Among the motor features, postural instability and gait difficulties (PIGD) stand out as significant contributors to falls and decreased quality of life in advanced PD (2,3). PIGD features encompass problems such as balance impairments and altered walking patterns (slow walking and Freezing of Gait (FoG)) which often result in falls. Multiple other factors contribute to falls, including older age, more severe bradykinesia, and non-motor features (4).
As PD advances, patients experience increasingly severe motor symptoms, which often lead to falls and heightened fear of falling, ultimately resulting in a sedentary lifestyle. Sedentary behavior has the potential to further diminish mobility and hinder physical performance, ultimately contributing to the development of immobilization syndrome and declines in musculoskeletal function. These declines may include the onset of osteoporosis and sarcopenia (5, 6). Individuals suffering from PD exhibit diminished bone mineral density (BMD) compared to control individuals of similar ages. Decline in bone mass, coupled with higher incidence of falls, accounts for elevated susceptibility to fractures in the PD population (7). Sarcopenia is a condition characterized by decreased muscle strength, muscle mass, and physical function, associated with falls, disability, hospitalization, and mortality (8). A meta-analysis revealed that the pooled prevalence rate of sarcopenia in individuals with PD was 29%, surpassing that of elderly non-PD control groups. The suggested reasons behind this phenomenon, other than immobility, include the potential impact of neuroinflammation and brain dysfunctions (1). Declines in structures and functions of bones and muscles make it crucial to consider both osteoporosis and sarcopenia to prevent falls and loss of independent living (9).
Biological sex is acknowledged as a contributing factor not only to different symptoms—both motor and non-motor—and disease progression, but also to differences in the pathogenesis of dopaminergic neuron degeneration in PD (10). Previous research showed that females with PD exhibited milder motor symptoms in comparison to their male counterparts with PD (11) and PIGD symptoms were found to be more prevalent among males with PD (12).
Among the elderly, recent investigations have identified that body composition was different between males and females with frailty. Furthermore, recent research has demonstrated that alterations in body composition, such as decreased bone mineral density (BMD) and muscle mass, are linked to issues like falls, gait problems, and balance impairment in normal elderly individuals (13-16). Additionally, recent studies have highlighted the association between sarcopenia and gait impairments (17).
In patients with PD, numerous studies examined risk factors for PIGD motor features using clinical motor assessments. Few assessed potential contributions of bone and muscle deficits to falls and FoG and how this relates to gender (18, 19).
In this study, our primary aim was to investigate associations between gender-specific changes in body composition, including variations in bone, lean mass, and adipose mass, and PIGD motor features. Our rationale for conducting this study was to establish the link between indices of body composition and motor symptoms given the clinical known incidence of sarcopenia and loss of muscle quality in PD patients. We hypothesized that gender differences in body composition associate differentially with FoG or falls in PD.

 

Methods

Study participants

This study was conducted as a cross-sectional investigation. Male and female PD patients who sought medical care at the University of Michigan and VA Ann Arbor Health System were included. The study protocol was reviewed and approved by the institutional review boards from the University of Michigan and VA Ann Arbor Health System. Written informed consent was obtained from all patients.
Subjects underwent a comprehensive multidimensional clinical assessment with whole-body composition assessed using dual-energy X-ray absorptiometry (DXA) Hologic Discovery W (Hologic Inc., Bedford, MA, USA). This DXA assessment included measurements of whole body lean and adipose mass (g), as well as BMD (g/cm2) for the lumbar spine, femoral neck, and hip.
Demographic information, clinical data, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), levodopa equivalent dose (LED), duration of disease, gait velocity, the short Activity-specific Balance Confidence (sABC) scale, and history of falls, was collected during subjects’ visit. Motor assessment was collected during “OFF” medication to observe the motor severity of the disease; however, other assessments were collected during “ON” state.

Outcome measures

We conducted a cross-sectional analysis to explore potential associations for two primary PIGD motor features: FoG and falls. FoG status was determined during the off-state following an overnight medication withdrawal, using MDS-UPDRS item 3.11, where a score greater than 0 indicated the presence of FoG. Fall status was established by assessing whether participants had falls within the past year (20).
Automatically calculated T-scores were used to determine osteopenia and osteoporosis classification in lumbar and hip based on guidelines from the World Health Organization (WHO), with T-scores between -1 and -2.5 indicating osteopenia and scores below -2.5 indicating osteoporosis (21).

Statistical analysis

We compared groups using the Chi-square test for categorical data and the Mann-Whitney U test for continuous variables. Subsequently, we conducted univariate logistic regression models with FoG and falls as dependent variables and body composition variables (bone, lean mass, and adipose mass) as independent variables. We calculated unadjusted odds ratios (OR), Wald statistics, and 95% confidence intervals (CI).
For a more comprehensive analysis, we implemented multivariate logistic forward stepwise regression models, including bone, muscle, and adipose mass variables that exhibited p-values less than 0.05 in the univariate linear regression analyses. These models were adjusted for age, disease duration, and LED, yielding adjusted ORs, Wald statistics, and 95% CIs to account for potential confounding effects. Before conducting the multivariate regression analysis, we assessed multicollinearity to understand correlations between variables. These analyses were carried out for both the entire PD population and separately for each gender. All tests were two-tailed with a P-value < 0.05. Statistical analyses were performed using SPSS (version 29) statistical software.

 

Results

136 subjects (102 males and 34 females) with PD (mean age 67.45+6.77 years, mean disease duration 6.6+4.4 years, mean MDS-UPDRS II 7.85±5.83, mean MDS-UPDRS III 37.95±14.0, and median Hoehn and Yahr stage of 2.5) were included. See more details in Table S1.

FoG analysis

Of the 136 PD subjects, 23 experienced FoG (18 males and 5 females). See more details in table S1. When stratified subject based on FoG, we observed that PD in the FoG group exhibited a significantly longer disease duration (p=0.023), higher LED (p=0.007), and elevated scores in the MDS-UPDRS II (p=0.001) and MDS-UPDRS III (p<0.001) assessments. In the FoG group, gait speed and sABC were lower when compared to individuals with PD who did not experience FoG (p <0.001 and p=0.024 respectively). No distinctions in body composition were evident between these two groups (p>0.05).
When examining each gender separately (Table 1), males with PD and FoG had lower lean mass in the arms (p=0.014), trunk (p=0.019), legs (p=0.005), and a lower total lumbar T-score (p=0.037; within normal range) compared to males with PD and no FoG. Females with PD and FoG exhibited higher leg lean mass (p=0.04) than females with PD and no FoG. Both males and females with PD and histories of FoG exhibited a lower gait speed than those without history of FoG (p<0.001, p=0.007 respectively). Only males with PD and histories of FoG had lower sABC score than those without histories of FoG (p=0.020). Conversely, no differences in body composition were noted between the two groups of females with PD (Table 1), except females with PD and FoG had greater leg lean mass than females with PD and no FoG (p=0.04).

PwPD: Patients with Parkinson’s disease; FoG: freezing of gait; PD: Parkinson’s disease; LED: Levodopa equivalent dose; MDS-UPDRS: International Parkinson and Movement Disorder Society – Unified Parkinson’s Disease Rating Scale; H&Y: Hoehn and Yahr; sABC: the short Activity-specific Balance Confidence scale; ALM: Appendicular lean mass; BMI: Body mass index

 

Univariate logistic regression analyses revealed associations between lower arm lean mass (adjusted OR, 0.374; 95% CI, 0.145-0.963; p=0.042), trunk lean mass (adjusted OR, 0.479; 95% CI, 0.244-0.940; p=0.032), and leg lean mass (adjusted OR, 0.429; 95% CI, 0.219-0.839; p=0.013) and the presence of FoG in males with PD (Figure 1; Table 2).

LED: Levodopa equivalent dose; FoG: freezing of gait; PD: Parkinson’s disease; ALM: Appendicular lean mass; BMI: Body mass index. Total males PD were 102 which 18 experienced FoG and 30 experienced falls, while total females PD were 34 which 5 experienced FoG and 13 experienced falls.

 

In the multivariate logistic forward stepwise regression analysis, adjusting for age, disease duration, and LED, leg lean mass (adjusted OR, 0.430; 95% CI, 0.206-0.897; p=0.024) was associated with FoG in males with PD. No association between body composition and the presence of FoG in females with PD was observed (Figure 1; Table 2).

Falls analysis

Among the 134 PD subjects, 43 reported experiencing falls at least once in the past year (30 males and 13 females). See more details in Table S2. Individuals who experienced falls had higher MDS-UPDRS II scores (p=0.03), and lower gait speed (p=0.033) compared to those who did not experience falls, but there were no differences in body composition between these two groups (p>0.05).
When examining genders separately, females with PD and histories of falls had greater waist circumference (p=0.033), total percent adipose mass (p=0.006), body mass index (BMI) (p=0.011), arm adipose mass (p=0.025), trunk adipose mass (p=0.036) and leg adipose mass (p<0.001), but lower ALM/BMI ratio (p = 0.005), compared to females with PD who did not experience falls (Table 3). Females with PD and histories of falls exhibited lower gait speeds (p=0.001) than those who had no history of falls. No differences in body composition were noted between the two groups of males with PD (Table 3).

PwPD: Patients with Parkinson’s disease; FoG: freezing of gait; PD: Parkinson’s disease; LED: Levodopa equivalent dose; MDS-UPDRS: International Parkinson and Movement Disorder Society – Unified Parkinson’s Disease Rating Scale; H&Y: Hoehn and Yahr; sABC: the short Activity-specific Balance Confidence scale; ALM: Appendicular lean mass; BMI: Body mass index

 

Univariate logistic regression analyses demonstrated associations between total percent body adipose mass (adjusted OR, 3.092; 95% CI, 1.141-8.377; p=0.026), BMI (adjusted OR, 3.491; 95% CI, 1.124-10.837; p=0.031), ALM/BMI (adjusted OR, 0.273; 95% CI, 0.081-0.918; p=0.036), arm adipose mass (adjusted OR, 2.824; 95% CI, 1.099-7.261; p=0.031), and leg adipose mass (adjusted OR, 4.780; 95% CI, 1.506-15.174; p=0.008) with the presence of falls in females with PD (Figure 2; Table 2).

In a multivariate logistic forward stepwise regression analysis, adjusted for age, disease duration, and LED, leg adipose mass was associated with the presence of falls in females with PD (adjusted OR, 4.780; 95% CI, 1.506-15.174; p=0.008). No associations between body composition and the presence of falls were identified in males with PD (Table 2).

 

Discussion

This is the first study to examine associations between gender-specific changes in body composition, including variations in bone, lean mass, and adipose mass, and PIGD motor features of FoG and falls. Lower lean mass was more prevalent in males with PD compared to their female counterparts. Among males with PD, a significant correlation was observed between diminished lean mass in the legs and presence of FoG. Among female PD subjects, increased leg adipose mass was associated with a history of falls.
FoG is a condition characterized by inability to complete steps effectively, irrespective of the intention to move. It is commonly observed in advanced stages of PD (22). In PD patients experiencing FoG, impaired mobility and increasing fear of falling lead to more sedentary behaviors. Our results showed lower sABC scores-fear of falling in the FoG group compared to non-FoG group. Sedentary behaviors in PD patients can result in a reduction in muscle mass and muscle strength (1). We observed gender differences, specifically an association between leg lean mass and FoG in male PD subjects, but not in female PD subjects. One possible explanation could be relatively higher fear of falling in male PD subjects with FoG, leading to more sedentary lifestyle and relative leg muscle atrophy. Another possible explanation is gender specific features of advancing degeneration in PD, as suggested by some recent peripheral biomarker studies (23, 24). These could include direct effects on neuromuscular junctions, as seen in one preclinical model (25). While plasma levels of α-synuclein are lower in the advanced stages of PD, α-synuclein aggregates have been found to accumulate in the brain, heart, skin, intestine, spinal cord, autonomic ganglia, and motor nerve terminal in animal models (25, 26). Further research is needed to explore the possible role of primary disease mechanisms in the development of PD-associated sarcopenia.
One recent study investigated the connection between the thickness of the temporalis muscle (TMT), measured during baseline MRI brain scans as a proxy for sarcopenia, and various clinical motor outcomes, including FoG (27). This study indicated that baseline TMT was not linked to an increased risk of developing FoG, but it did show a correlation with the long-term need for dopaminergic medications in male PD. Our identification of an association between reduced in leg lean mass and FoG occurrence in male PD patients may be a more useful measure of sarcopenia-related phenomena in PD.
Among females with PD who experienced falls, higher leg adipose mass was observed compared to those who did not fall. Many studies indicated that obesity, particularly in elderly females, is associated with a higher risk of falling (28-30). Recent research proposed that obesity in elderly females may impair joint responsiveness in supporting body weight during a fall (31). Das et al. found that obese females have reduced knee proprioception compared to obese males and Wu et al (32). suggested that obesity might contribute to falls by impairing balance due to diminished plantar sensitivity on the soles of the feet. Moreover, a recent study has uncovered that obese individuals with normal blood sugar levels display a noteworthy incidence of neuropathy. This implies that obesity alone may be a primary factor contributing to the development of neuropathy (33). Apart from impairing sensory input, obesity could also shift the center of mass away from the base of support, increasing fall risk.
There is also evidence that an increase in fatty degeneration in hip muscles may contribute to an elevated risk of falls by increasing the instability of hip joints (34). Among female individuals with PD who experienced falls, we observed a trend toward developing sarcopenia, although it did not meet the FNIH diagnosis criteria. Additionally, this group exhibited higher levels of obesity compared to the non-falling group. These findings suggest that females with PD in the falling group are inclined towards sarcopenic obesity, associated with a heightened risk of falls (35) and that examination of muscle quality, not simply muscle quantity, might be an important component of the sarcopenic phenotype observed in PD.
While elderly females are more prone to falling and sustaining fall-related injuries than elderly males (36, 37), the mortality rate resulting from falls is higher among males (37). This difference might be attributed to the additional adipose mass present in females, which could serve as a protective cushion during falls.

Significant outcomes

Our results suggest possible gender specific therapy approaches to reduce the risk of falls in individuals with PD. For male PD patients targeted nutritional and exercise management aiming to increase muscle mass by promoting higher protein intake and implementing strengthening exercises, especially for the lower limbs. For female PD patients, the focus could be on reducing adipose tissue through aerobic exercises and calorie control to facilitate weight loss. Encouraging a reduction in sedentary behavior and the promotion of increased physical activity should be the primary goals for managing PD patients (38).

Study limitations

We identified several limitations in our study. Firstly, there exist multiple tools and tests for assessing sarcopenia; we exclusively employed DXA for evaluating body composition. For a more comprehensive assessment, future studies should consider incorporating functional motor tests, such as grip strength and gait speed. Secondly, there are varying criteria for diagnosing sarcopenia, and in our study, we utilized the FNIH criteria. Thirdly, as our study was designed as an observational cross-sectional study, it is possible that extenuating factors may have influenced both body composition and PIGD outcomes. Prospective, longitudinal analysis would be useful in clarifying the potential causal relationships between leg lean mass and adiposity, sedentism, and primary disease mechanism. Lastly, our results showed that the sex distribution in our study targeting FoG in PD was skewed towards males than females PD. There are several explanations for this observed difference. PD is slightly more prevalent in men compared to women with the approximated ratio 2:1 (39), however, the gender ratio (3:1) in our study was much higher. In addition, males PD have been associated with later development of freezing of gait, while females PD have been associated with the progression of falls and have tremor symptom than PIGD (10). Finally, we recruited in part from a Veteran’s hospital (VA Ann Arbor Health System). We recommend conducting a prospective cohort study with a more balanced gender sample size to gain a more comprehensive understanding of these relationships.

Future recommendations

Given that leg lean mass and leg adipose mass appear to associate with development of FoG and falls in PD, further research is warranted to evaluate interventions aimed at increasing leg lean mass and the skeletal muscle quality, while reducing leg adipose mass in individuals with PD and pursue gender-specific assessments. Future research should also investigate the role of α-synuclein plasma levels or aggregation in motor nerve terminal in predicting the development of FoG.

 

Conclusion

In summary, our study revealed gender-specific associations between body composition and PIGD motor features, FoG, and falls in PD. Future studies should explore the effects of interventions on the body composition of individuals with PD, with a particular focus on gender-based variations.

 

Author Roles: 1. Research Project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing the First Draft, B. Review and Critique. C.P:1A,1B,1C,2A,2B,3A,3B; C.S: 3A,3B; M.v.E.B: 3A,3B; H.B: 1B, 1C; A.L: 1B, 1C; F.M: 1B, 1C; P.K: 3A, 3B; R.L.A: 3A, 3B; J.M.H: 3A, 3B; N.I.B: 1A, 2C, 3A, 3B.

Data Availability Statement: Data available on request due to privacy/ethical restrictions.

Ethical Compliance Statement: We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The study protocol was reviewed and approved by the institutional review boards from University of Michigan and Ann Arbor VA medical center. The study was conducted in accordance with the declaration of Helsinki and written informed consent was obtained from all patients.

Funding Sources and Conflicts of Interest: This work was funded by National Institutes of Health (R01AG073100, RO1NS070856, P50NS091856, P50NS123067), Department of Veterans Affairs grant (I01 RX001631), the Michael J. Fox Foundation, and the Parkinson’s Foundation. Financial Disclosures for Previous 12 Months: C.P. has no conflict of interest to report. C.S. has no conflict of interest to report. M.v.E.B has no conflict of interest to report. H.B. has no conflict of interest to report. A.L. has no conflict of interest to report. F.M. has no conflict of interest to report. P.K. has no conflict of interest to report. R.L.A. is funded by NIH grants (R25NS089450, P50NS123067, R01AG070897, R01AG058724, U24NS107158, R21NS114749, and P301P30AG053760), and the Parkinson’s Foundation. He is Data Safety & Monitoring Boards for the SIGNAL-AD trial (Vaccinex), the CELIA trial (Icon/Biogen), the Zilgenersen trial (Ionis), and the TOPAS-MSA trial (Icon/Teva). J.M.H. is funded by NIH grants (R01DK109948, U01NS113851 and R21AG081916). N.I.B. is funded by NIH grants (R01AG073100, RO1NS070856, P50NS091856, P50NS123067), Department of Veterans Affairs grant (I01 RX001631), the Michael J. Fox Foundation, and the Parkinson’s Foundation.

 

SUPPLEMENTARY MATERIAL

 

References

1. Cai Y, Feng F, Wei Q, Jiang Z, Ou R, Shang H. Sarcopenia in Patients With Parkinson’s Disease: A Systematic Review and Meta-Analysis. Front Neurol. 2021;12:598035. doi:10.3389/fneur.2021.598035
2. Factor SA, Steenland NK, Higgins DS, et al. Postural instability/gait disturbance in Parkinson’s disease has distinct subtypes: an exploratory analysis. J Neurol Neurosurg Psychiatry. May 2011;82(5):564-8. doi:10.1136/jnnp.2010.222042
3. Bohnen NI, Costa RM, Dauer WT, et al. Discussion of Research Priorities for Gait Disorders in Parkinson’s Disease. Mov Disord. Feb 2022;37(2):253-263. doi:10.1002/mds.28883
4. Giladi N, Horak FB, Hausdorff JM. Classification of gait disturbances: distinguishing between continuous and episodic changes. Mov Disord. Sep 15 2013;28(11):1469-73. doi:10.1002/mds.25672
5. Yazar T, Yazar HO, Zayimoglu E, Cankaya S. Incidence of sarcopenia and dynapenia according to stage in patients with idiopathic Parkinson’s disease. Neurol Sci. Aug 2018;39(8):1415-1421. doi:10.1007/s10072-018-3439-6
6. Pinheiro MB, Oliveira J, Bauman A, Fairhall N, Kwok W, Sherrington C. Evidence on physical activity and osteoporosis prevention for people aged 65+ years: a systematic review to inform the WHO guidelines on physical activity and sedentary behaviour. Int J Behav Nutr Phys Act. Nov 26 2020;17(1):150. doi:10.1186/s12966-020-01040-4
7. van den Bos F, Speelman AD, Samson M, Munneke M, Bloem BR, Verhaar HJ. Parkinson’s disease and osteoporosis. Age Ageing. Mar 2013;42(2):156-62. doi:10.1093/ageing/afs161
8. Cruz-Jentoft AJ, Sayer AA. Sarcopenia. Lancet. Jun 29 2019;393(10191):2636-2646. doi:10.1016/S0140-6736(19)31138-9
9. Inoue T, Maeda K, Satake S, Matsui Y, Arai H. Osteosarcopenia, the co-existence of osteoporosis and sarcopenia, is associated with social frailty in older adults. Aging Clin Exp Res. Mar 2022;34(3):535-543. doi:10.1007/s40520-021-01968-y
10. Cerri S, Mus L, Blandini F. Parkinson’s Disease in Women and Men: What’s the Difference? J Parkinsons Dis. 2019;9(3):501-515. doi:10.3233/JPD-191683
11. Kang KW, Choi SM, Kim BC. Gender differences in motor and non-motor symptoms in early Parkinson disease. Medicine (Baltimore). Jan 21 2022;101(3):e28643. doi:10.1097/MD.0000000000028643
12. Haaxma CA, Bloem BR, Borm GF, et al. Gender differences in Parkinson’s disease. J Neurol Neurosurg Psychiatry. Aug 2007;78(8):819-24. doi:10.1136/jnnp.2006.103788
13. Waters DL, Qualls CR, Cesari M, Rolland Y, Vlietstra L, Vellas B. Relationship of Incident Falls with Balance Deficits and Body Composition in Male and Female Community-Dwelling Elders. J Nutr Health Aging. 2019;23(1):9-13. doi:10.1007/s12603-018-1087-4
14. Roh E, Choi KM. Health Consequences of Sarcopenic Obesity: A Narrative Review. Front Endocrinol (Lausanne). 2020;11:332. doi:10.3389/fendo.2020.00332
15. Kim S, Won CW. Sex-different changes of body composition in aging: a systemic review. Arch Gerontol Geriatr. Sep-Oct 2022;102:104711. doi:10.1016/j.archger.2022.104711
16. Lee Y, Shin S. The Effect of Body Composition on Gait Variability Varies with Age: Interaction by Hierarchical Moderated Regression Analysis. Int J Environ Res Public Health. Jan 21 2022;19(3)doi:10.3390/ijerph19031171
17. Fan Y, Zhang B, Huang G, et al. Sarcopenia: Body Composition and Gait Analysis. Front Aging Neurosci. 2022;14:909551. doi:10.3389/fnagi.2022.909551
18. Wang F, Pan Y, Zhang M, Hu K. Predicting the onset of freezing of gait in Parkinson’s disease. BMC Neurol. Jun 7 2022;22(1):213. doi:10.1186/s12883-022-02713-2
19. Ehgoetz Martens KA, Lukasik EL, Georgiades MJ, et al. Predicting the onset of freezing of gait: A longitudinal study. Mov Disord. Jan 2018;33(1):128-135. doi:10.1002/mds.27208
20. Pongmala C, Roytman S, van Emde Boas M, Dickinson O, Kanel P, Bohnen NI. Composite measures of motor performance and self-efficacy are better determinants of postural instability and gait difficulties than individual clinical measures in Parkinson’s disease. Parkinsonism Relat Disord. Feb 2023;107:105251. doi:10.1016/j.parkreldis.2022.105251
21. Kanis JA, Johnell O, Oden A, Jonsson B, De Laet C, Dawson A. Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis. Bone. Nov 2000;27(5):585-90. doi:10.1016/s8756-3282(00)00381-1
22. Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. Aug 2011;10(8):734-44. doi:10.1016/S1474-4422(11)70143-0
23. Wang XY, Kang WY, Yang Q, Zhang LY, Chen SD, Liu J. Using gastrocnemius sEMG and plasma alpha-synuclein for the prediction of freezing of gait in Parkinson’s disease patients. PLoS One. 2014;9(2):e89353. doi:10.1371/journal.pone.0089353
24. Caranci G, Piscopo P, Rivabene R, et al. Gender differences in Parkinson’s disease: focus on plasma alpha-synuclein. J Neural Transm (Vienna). Aug 2013;120(8):1209-15. doi:10.1007/s00702-013-0972-6
25. Yang Q, Wang Y, Zhao C, Pang S, Lu J, Chan P. alpha-Synuclein aggregation causes muscle atrophy through neuromuscular junction degeneration. J Cachexia Sarcopenia Muscle. Feb 2023;14(1):226-242. doi:10.1002/jcsm.13123
26. Van Den Berge N, Ferreira N, Mikkelsen TW, et al. Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats. Brain. Jul 28 2021;144(6):1853-1868. doi:10.1093/brain/awab061
27. Chung SJ, Kim YJ, Yoo HS, et al. Temporalis Muscle Thickness as an Indicator of Sarcopenia Is Associated With Long-term Motor Outcomes in Parkinson’s Disease. J Gerontol A Biol Sci Med Sci. Nov 15 2021;76(12):2242-2248. doi:10.1093/gerona/glab082
28. Dutil M, Handrigan GA, Corbeil P, et al. The impact of obesity on balance control in community-dwelling older women. Age (Dordr). Jun 2013;35(3):883-90. doi:10.1007/s11357-012-9386-x
29. Lockhart TE, Frames CW, Soangra R, Lieberman A. Effects of Obesity and Fall Risk on Gait and Posture of Community-Dwelling Older Adults. Int J Progn Health Manag. 2019;10(1)doi:10.36001/ijphm.2019.v10i1.2750
30. Sotiriadi-Vlachou S. Obesity and its relationship with falls, fracture site and bone mineral density in postmenopausal women. J Frailty Sarcopenia Falls. 2017;2(2):28-32.
31. Das PR, Yadav, S., Rijwi, M. R., Saini, P., & Sharma, D. . Gender specific effect of obesity on knee proprioception in weight bearing and non-weight bearing position. JK Practitioner. 2020;(25)
32. Wu X, Madigan ML. Impaired plantar sensitivity among the obese is associated with increased postural sway. Neurosci Lett. Nov 7 2014;583:49-54. doi:10.1016/j.neulet.2014.09.029
33. Callaghan BC, Gao L, Li Y, et al. Diabetes and obesity are the main metabolic drivers of peripheral neuropathy. Ann Clin Transl Neurol. Apr 2018;5(4):397-405. doi:10.1002/acn3.531
34. Kiyoshige Y, Watanabe E. Fatty degeneration of gluteus minimus muscle as a predictor of falls. Arch Gerontol Geriatr. Jan-Feb 2015;60(1):59-61. doi:10.1016/j.archger.2014.07.013
35. Öztürk ZA, Türkbeyler İ H, Abiyev A, et al. Health-related quality of life and fall risk associated with age-related body composition changes; sarcopenia, obesity and sarcopenic obesity. Intern Med J. Aug 2018;48(8):973-981. doi:10.1111/imj.13935
36. Chang VC, Do MT. Risk factors for falls among seniors: implications of gender. Am J Epidemiol. Apr 1 2015;181(7):521-31. doi:10.1093/aje/kwu268
37. Stevens JA, Corso PS, Finkelstein EA, Miller TR. The costs of fatal and non-fatal falls among older adults. Inj Prev. Oct 2006;12(5):290-5. doi:10.1136/ip.2005.011015
38. Zhang X, Molsberry SA, Schwarzschild MA, Ascherio A, Gao X. Association of Diet and Physical Activity With All-Cause Mortality Among Adults With Parkinson Disease. JAMA Netw Open. Aug 1 2022;5(8):e2227738. doi:10.1001/jamanetworkopen.2022.27738
39. Miller IN, Cronin-Golomb A. Gender differences in Parkinson’s disease: clinical characteristics and cognition. Mov Disord. Dec 15 2010;25(16):2695-703. doi:10.1002/mds.23388

© Serdi 2024