GRAPHICAL ABSTRACT

INTRODUCTION

Huntington’s disease (HD) is an autosomal dominant inherited disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene, which encodes an abnormally long polyglutamine stretch in the huntingtin protein. The disease is characterized by a triad of signs and symptoms, including motor, cognitive, and psychiatric features [1]. Patients have progressively deteriorating conditions and usually die 15 to 20 years after onset [2]. The structural changes in the brain in HD patients occur mainly in the striatum, and other regions, such as the globus pallidus, thalamus, and hippocampus, also undergo atrophy [3]. Although chorea is the most prominent motor symptom and is used to determine the onset of HD, previous studies have demonstrated that several more subtle motor changes may also occur early, such as gait ataxia [4] and slowed ocular movements [5].

There are many subtle changes in the brains of HTT mutation carriers, resulting in various impairments early before the disease manifests. A large part of the brain contributes to the vestibular system, which senses the position of the head and the acceleration of movement, so abnormalities in the vestibular system in HD may help in identifying the earliest disease-related changes [6]. The visual system detects the images of objects of interest and provides a subjective sense of self-motion and orientation to keep the image of the target object on the fovea. By combining multimodal signals in visual pathways, the brain effectively shapes behaviors, such as a coordinated sequence of eye and head movements, to voluntarily redirect our visual axis to a target of interest. The impulse to make decisions at a relatively high level in the brain is transmitted to regulate trunkand limb-related muscles to maintain body balance [7].

The clinical assessment of HD covers multiple domains of motor disability, including eye movement functions and gait variabilities [8]. A series of eye movement impairments have been demonstrated in HD patients and are considered potential markers for tracking disease progression [9,10]. The earliest oculomotor abnormality is the increased latency of voluntary saccades, sometimes requiring blink or head movement for saccadic initiation. Saccade impairments can be observed early in premanifest HD (pre-HD) individuals. Additionally, fixation is impaired because HD patients are unable to suppress reflexive saccades toward stimuli within the visual field [11], and smooth pursuit movements are affected later in the disease [12]. Spatiotemporal gait changes also begin early, and previous studies have revealed that there are slower walking velocities, shorter step lengths, and changes in the gait cycle in HD patients [13,14]. Even in pre-HD, previous studies revealed decreased gait velocity and greater variability in stride length [15], and stride-to-stride variability and first step duration under self-triggered conditions may be used to differentiate pre-HD early from healthy controls (HCs) [16]. Although oculomotor examination and gait variability are essential in HD and can be potential markers, previous studies have focused on these factors separately. There is a lack of systematic evaluations that combine both eye movements and gait.

In this study, we performed multiple eye movement and gait variability examinations in HTT mutation carriers and then analyzed the correlations between eye movement or gait parameters in HD patients and the clinical severity of disease. We also examined the associations between oculomotor impairments and gait deficits.

MATERIALS & METHODS

Participants

Between January 2021 and June 2022, 37 HTT mutation carriers, including 30 HD patients and 7 pre-HD individuals from 28 families, were consecutively recruited from the Department of Neurology at the Second Affiliated Hospital of Jiaxing University. Genetic testing of the HTT gene was performed via a previously described method4 at the Second Affiliated Hospital of Zhejiang University School of Medicine. HTT mutation carriers were diagnosed based on a positive HTT genetic test result (CAG repeat ≥36). Pre-HD individuals had a total motor score (TMS) on the Unified Huntington’s Disease Rating Scale (UHDRS) of 5 or less points, indicating that no substantial motor signs were present [17]. Moreover, 30 age-matched HCs without a family history of hereditary diseases or neuropsychiatric diseases were recruited from the community. The study was approved by the Ethical Committees of the Second Affiliated Hospital of Zhejiang University School of Medicine and the Second Affiliated Hospital of Jiaxing University, and each participant signed written informed consent before enrollment with the ethics approval number 2017-059 and 2022SW064.

Clinical assessments

The UHDRS [17] was used to assess the clinical severity of HD patients and pre-HD individuals. The UHDRS is a universal scale for assessing the disease severity of HD and consists of four sections (motor function, cognitive, behavior, and functional capacity). The UHDRS-TMS subscale involves 15 items assessing various features of the motor domain, including chorea, dystonia, parkinsonism, motor performance, oculomotor function, and balance. Scores from items 1 (ocular pursuit), 2 (saccade initiation), and 3 (saccade velocity) are added for oculomotor symptoms, allowing a more comprehensive evaluation of eye movements. The score from item 13 reflects both the speed and base of gait. The scale assessment showed reliability and validity and was able to quickly reflect the disease severity of the patients [18].

Eye movement recording

Eye movement data were acquired and analyzed by EyeSee-Cam (Interacoustics A/S, Middelfart, Denmark), and we recorded the data only in the horizontal direction. Briefly, three types of eye movement tasks were used: saccades, smooth pursuit, and the optokinetic reflex. The participants were seated in front of a screen on which a series of moving stimuli was presented, and their heads were fixed in the median position. The distance between the eyes and the visual target was approximately 1.2 meters. During the examination, the participants were required to cooperate and avoid head movement. Detailed descriptions of the eye movement parameters are provided in the Supplementary Material (in the online-only Data Supplement).

Gait analysis

Gait parameters, including stride length, walking velocity, step length, step deviation, and gait phase, were collected from HCs and pre-HD and HD patients via a gaitwatch (Jumho, Guangzhou, China) by a professional neurologist who was unaware of the participants’ diagnosis to the grouping of the participants in the study. Detailed descriptions of the gait analysis methods are provided in the Supplementary Material (in the online-only Data Supplement).

Statistical analysis

The statistical analysis was performed via SPSS (version 20.0; IBM Cop., Armonk, NY, USA). The average results of the left and right sides were used in the analysis of each test. Two-sample t tests were used for continuous variables, and χ² tests were used for comparisons of categorical variables. The multiple sample rank sum test was used for comparisons among three groups. The Kruskal‒Wallis test followed by Dunn’s multiple comparisons test was used for statistical analysis between subgroups, and the results were characterized as the mean and standard deviation. A p value of less than 0.05 indicated a significant difference. The correlations between UHDRS scores and eye movement or gait parameters were determined via Spearman correlation coefficient analysis. Receiver operating characteristic (ROC) analysis was used to examine the ability of oculomotor or gait examinations to correctly distinguish HD patients from controls. The area under the curve (AUC) represents the overall sensitivity and specificity of each test.

RESULTS

Participant characteristics

In this cohort, there were 30 HCs, 7 pre-HD patients, and 30 HD patients. The mean ages of the three groups were 48.8±17.2 years, 26.7±5.2 years, and 48.5±11.4 years, respectively. There were significant differences in age between the HC and pre-HD groups and between the pre-HD and HD groups (both p=0.001), while there were no differences in the gender ratio. There was no difference in the number of CAG repeats between the pre-HD and HD groups. The detailed demographic and clinical characteristics of the participants are shown in Supplementary Table 1 (in the online-only Data Supplement).

Comparisons of eye movement features among HCs, pre-HD patients, and HD patients

First, we compared the saccade test results among controls, pre-HD, and HD patients. There was one pre-HD individual with an injury to the left eye, so the actual eye movements of the six pre-HD individuals were examined, as shown in Figure 1A. There was no significant difference in the latency of saccades between pre-HD and control individuals. However, the latency of saccades in HD patients was significantly greater than that in controls or pre-HD patients. Interestingly, the speed of saccades was significantly different between pre-HD patients and controls (Figure 1B). Compared with that of controls, the speed of saccades in HD patients decreased significantly but was similar to that in pre-HD patients. The detailed results of the saccade test are shown in Table 1. To analyze the accuracy of saccades in distinguishing HD patients from controls, we conducted ROC analysis of latency and speed, as shown in Supplementary Figure 1A and B (in the online-only Data Supplement). The latency (p<0.001) and speed (p<0.001) of saccades have statistically significantly high discriminative capacities.

We subsequently analyzed the gain and slow phase velocity (SPV) of smooth pursuit (Table 1). As shown in Figure 1C, there was no significant difference in gain of smooth pursuit between pre-HD patients and controls. However, the gain of smooth pursuit in HD patients was significantly lower than that in controls or pre-HD patients. There was no significant difference in the SPV of smooth pursuit among the control, pre-HD, and HD groups (Figure 1D). As shown in Supplementary Figure 1C and D (in the online-only Data Supplement), gain (p<0.001) of smooth pursuit significantly distinguished HD patients from controls, but SPV was not significant (p=0.294).

To further explore oculomotor impairments, we analyzed the gain and SPV of the optokinetic (OPK) test, which represents a comprehensive response of the smooth tracking and scanning eye movement systems (Table 1). As shown in Figure 1E, there was no significant difference in the gain of OPK 20 between pre-HD patients and normal controls, but the gain of OPK 20 in HD patients was significantly lower than that in controls or pre-HD patients. Similar results were found in the comparison of the SPV of OPK 20, as well as the gain and SPV of OPK 35, between the groups (Figure 1F-H). As shown in Supplementary Figure 1E-H (in the online-only Data Supplement), the gain and SPV of OPK 20 or OPK 35 can also significantly distinguish HD patients from controls.

The consistency between eye movement examinations and UHDRS scores

The UHDRS is the most widely used method for assessing disease severity and progression. To explore the consistency between eye movement parameters and UHDRS scores, we performed

correlation analysis. As shown in Figure 2A, the latency of the saccade test was significantly positively correlated with the UHDRS-TMS score. There was a statistically significant negative correlation between the speed of the saccade test and UHDRS-TMS (Figure 2B) and between the gain of smooth pursuit and UHDRS-TMS (Figure 2C). However, there was no significant correlation between the smooth pursuit SPV and UHDRS-TMS (Figure 2D). Because the subset of oculomotor symptoms in UHDRS is important for assessing eye movement abnormalities, we also conducted a correlation analysis between the above parameters and the oculomotor subset of UHDRS. As shown in Figure 2E-H, the results of the correlation between eye movement parameters and the oculomotor subscale of the UHDRS were similar to those of the UHDRS-TMS.

Comparisons of gait parameters among HC, pre-HD, and HD

There were no significant differences in stride length, walking velocity, or step deviation between pre-HD patients and controls (Figure 3A-C), but there were significant differences in step length, single-support phase, or double-support phase (Figure 3D-F). However, the stride length, walking velocity and step length in the HD group were significantly lower than those in the control or pre-HD groups, whereas the step deviation, single or double support phase and swing phase in the HD group were significantly greater than those in the other two groups (Figure 3A-G). As shown in Supplementary Figure 2A-C (in the online-only Data Supplement), stride length, walking velocity, and step deviation significantly (all p<0.001) distinguished HD patients from controls (Supplementary Table 2 in the online-only Data Supplement). The representative results of gait analysis among the three groups are shown in Table 2.

The consistency between gait parameters and UHDRS scores

Correlation analysis suggested that stride length and walking velocity were significantly negatively correlated with UHDRSTMS (Figure 4A, B, and D), whereas step deviation was significantly positively correlated with UHDRS-TMS (Figure 4C). We also analyzed the consistency between gait parameters and the gait score on the UHDRS. Stride length and walking velocity were significantly negatively correlated with gait score on the UHDRS (Supplementary Figure 2D and E in the online-only Data Supplement), whereas step deviation was significantly positively correlated with gait score (Supplementary Figure 2F in the online-only Data Supplement).

The association between eye movement and gait variability

We subsequently analyzed the correlations between eye movement and gait variability parameters in HD patients (Supplementary Figure 3 in the online-only Data Supplement) and between age and the effects of covariates through partial correlation analysis (Figure 5). We found that the latency of saccades was significantly negatively correlated with stride length (Figure 5A and Supplementary Figure 3A in the online-only Data Supplement), step deviation (Figure 5C and Supplementary Figure 3B in the online-only Data Supplement), and swing phases (Figure 5F and Supplementary Figure 3K in the online-only Data Supplement). The speed of saccades was significantly positively correlated with stride length (Supplementary Figure 3C in the online-only Data Supplement) and walking velocity (Figure 5D and Supplementary Figure 3D in the online-only Data Supplement). The gain of smooth pursuit only showed a significant positive correlation with walking velocity (Supplementary Figure 3E in the online-only Data Supplement). The gain and SPV of OPK 20 and OPK 35 were significantly correlated with stride length or step length (Figure 5B and Supplementary Figure 3F, G, J in the online-only Data Supplement), walking velocity, step length, and swing phase (Figure 5E, G and Supplementary Figure 3H, I in the online-only Data Supplement).

DISCUSSION

This study systematically compared the results of eye movement examinations and gait variability between normal controls, pre-HD individuals, and manifest HD patients. We found that there were significant differences in saccades, smooth pursuit, OPK tests, stride length, walking velocity, and step deviation between the HD group and the other two groups. These examinations can significantly distinguish HD patients from controls. However, the results between pre-HD and controls are similar, and only the speed of saccades significantly differs. The parameters of eye movement and gait variability in HD patients were also consistent with the scores of the UHDRS-TMS and the corresponding subscales.

As an important part of HD assessment, oculomotor function in HD patients has been less investigated than other motor symptoms, such as chorea and dystonia. Our study revealed significant and extensive impairments in saccades, smooth pursuit, and OPK tests in HD patients. The former two tests reflect the functions of gaze shifting (voluntary) and gaze holding (involuntary), respectively, whereas the OPK test requires intact smooth pursuit and saccadic systems, and the relative pathways involve both direct retinal and indirect cortical signals [6]. The abnormalities in these tests reflect impairments in neural pathways that control head and eye movements, such as cortical centers and brainstem reticular formation; it also indicates the deficiency of patients in analyzing the interactions between the visual eye system and the vestibular system and in suppressing interference signals [11,19]. Compared with that in normal controls, the velocity of saccades is significantly impaired in pre-HD individuals, which reflects early abnormalities in the neurons that control pulse types of activity, such as burst neurons in the brainstem reticular formation [6]. This finding also suggests that in pre-HD individuals, we may use the saccade test to detect early changes in brain structure before any obvious motor symptoms arise. Owing to the limited number and cooperation of participants, we were not able to carefully analyze eye movement function in pre-HD individuals or HD patients at different stages. In addition, owing to the absence of disease control, such as other forms of chorea or parkinsonism, the diagnostic accuracy in our study should be interpreted with caution in regard to clinical application. Further research that includes appropriate disease controls would be beneficial to strengthen the diagnostic accuracy and enhance the practical utility of these outcomes in a clinical setting.

In addition, HD patients usually present several changes in gait features, which may be associated with damage to the basal ganglia nuclei and vestibular system [20]. Our study revealed significant impairments in stride length, walking velocity, and step deviation in HD patients and revealed correlations between gait parameters and UHDRS scores. Like previous analyses from other studies, our findings confirmed the existence of gait changes in Chinese HD patients [14,21,22], and these footstep parameters may act as more accurate biomarkers to reflect the severity of motor decline. However, we did not find any significant alterations in footstep patterns before HD, which may be due to an insufficient sample size, and further studies with larger samples are needed.

This study also revealed significant associations between eye movement examinations and gait variability parameters in HD patients. The central nervous system integrates afferent nerve information from vision, the vestibule, and proprioception and then outputs bioelectrical signals to regulate muscle tension and coordinate random movements [7]. Therefore, when visual sensory systems are abnormal, the ability to regulate postural stability and maintain balance may be influenced. The core of the joint analysis mechanism of eye movement and gait is the eye‒gait coordination mechanism, which reflects the comprehensive regulation of vision, attention, spatial cognition, and motor coordination of individuals during walking [23]. The frontal, parietal, and basal ganglia and the cerebellum collectively participate in the coordinated control of eye movement and gait. In the process of walking, the frontal lobe is responsible for executive function and visual information integration, the parietal lobe is involved in spatial positioning and visual attention, and the basal ganglia and cerebellum regulate the rhythm and coordination of movement [24]. Damage to any region may lead to abnormal eye movement and gait. Thus, the abnormalities found in eye movement may also be related to impairments in maintaining balance and gait ataxia in HD patients, resulting in correlations between eye movement and gait parameters. Joint analysis can provide comprehensive information about the pathological characteristics of these diseases, reveal individual neural control and cognitive behavioral characteristics, and provide a strong basis for clinical diagnosis and intervention.

In conclusion, we assessed various eye movement parameters and gait parameters in HTT mutation carriers. Our results revealed significant impairments in these examinations in HD patients, and the velocity of saccades was impaired early in pre-HD individuals. We also found that these eye movement and gait abnormalities in HD patients were significantly correlated with clinical disease severity and that eye movement impairments were significantly correlated with gait variability deficits. A limitation of our study is that we analyzed horizontal eye movements, vertical eye movements can be further investigated in future studies.

Supplementary Materials

Notes

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

This work was supported by the grants from the Medical and Health Science and Technology Plan of Zhejiang Provincial Health Commission (2022 KY1249) and the Key Research and Development project of Zhejiang Province (2019C03039).

Author Contributions

Conceptualization: Zhi-Ying Wu. Data curation: Shu-Xia Qian. Formal analysis: Shu-Xia Qian, Yu-Feng Bao. Funding acquisition: Shu-Xia Qian, Zhi-Ying Wu. Investigation: Zhi-Ying Wu. Methodology: Shu-Xia Qian. Project administration: Shu-Xia Qian, Zhi-Ying Wu. Resources: Yu-Feng Bao. Software: Shu-Xia Qian. Supervision: Zhi-Ying Wu. Validation: Xiao-Yan Li. Visualization: Yi Dong. Writing—original draft: Shu-Xia Qian, Yu-Feng Bao. Writing—review & editing: all authors.

Acknowledgments

We would like to thank all the individuals for their support and willingness to participate in this study. Ai-ping Huang performed the eye movement examinations. Ya Sun performed the gait analysis. We greatly appreciate all the patients and their families for volunteering their time and offering information.

Figure 1.

Results for saccades, smooth pursuit, and optokinetic tests in premanifest and manifest patient groups as well as a matched HC group. Latency of saccades (A), speed of saccades (B), gain of smooth pursuit (C), SPV of smooth pursuit (D), gain of OPK 20 (E), SPV of OPK 20 (F), gain of OPK 35 (G), and SPV of OPK 35 (H) in HCs, pre-HD patients, and HDs. The data are shown as the means±standard deviations. HC, healthy control; pre-HD, premanifest HD; HD, Huntington’s disease; SPV, slow phase velocity; OPK, optokinetic.

Figure 2.

Results of the correlations between eye movement parameters and UHDRS-TMS or oculomotor subscale scores in HD patients. Correlation analyses of the latency of saccades (A), speed of saccades (B), gain of smooth pursuit (C), and SPV of smooth pursuit (D) with UHDRS-TMS. Correlation analyses of the latency of saccades (E), speed of saccades (F), gain of smooth pursuit (G), and SPV of smooth pursuit (H) with the UHDRS-oculomotor subscale. UHDRS, Unified Huntington’s Disease Rating Scale; TMS, total motor score; SPV, slow phase velocity; HD, Huntington’s disease.

Figure 3.

Results for gait variability in three groups. Stride length (A), walking velocity (B), step deviation (C), step length (D), single support phase (E), double-support phase (F), swing phase (G) in HCs, pre-HDs, and HDs. HC, healthy control; pre-HD, premanifest HD; HD, Huntington’s disease.

Figure 4.

Correlations between gait parameters and UHDRS-TMS scores in HD patients. Correlations between stride length (A), walking velocity (B), step deviation (C), step length (D), single support phase (E), double support phase (F), swing phase (G), and UHDRS-TMS scores in HD patients. UHDRS, Unified Huntington’s Disease Rating Scale; TMS, total motor score; HD, Huntington’s disease.

Figure 5.

Results for correlations between ocular motor and gait variables while controlling for age as a covariate through partial correlation analysis. A: The correlation between the latency of saccades and stride length. B: The correlation between gain of OPK 20 and stride length. C: The correlation between the latency of saccades and step deviation. D: The correlation between the speed of saccades and the walking velocity. E: The correlation between the SPV of OPK 35 and step length. F: The correlation between the latency of saccades and the swing phase. G: The correlation between the gain of OPK 20 and the swing phase. OPK, optokinetic; SPV, slow phase velocity.

REFERENCES

• 1. Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, et al. Huntington disease. Nat Rev Dis Primers 2015;1:15005.ArticlePubMedPDF
• 2. Ross CA, Tabrizi SJ. Huntington’s disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 2011;10:83–98.ArticlePubMed
• 3. Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol 2014;10:204–216.ArticlePubMedPDF
• 4. Dong Y, Sun YM, Liu ZJ, Ni W, Shi SS, Wu ZY. Chinese patients with Huntington’s disease initially presenting with spinocerebellar ataxia. Clin Genet 2013;83:380–383.ArticlePubMed
• 5. Walker FO. Huntington’s disease. Lancet 2007;369:218–228.ArticlePubMed
• 6. Lal V, Truong D. Eye movement abnormalities in movement disorders. Clin Park Relat Disord 2019;1:54–63.ArticlePubMedPMC
• 7. Cullen KE. The vestibular system: multimodal integration and encoding of self-motion for motor control. Trends Neurosci 2012;35:185–196.ArticlePubMedPMC
• 8. Reilmann R, Schubert R. Motor outcome measures in Huntington disease clinical trials. Handb Clin Neurol 2017;144:209–225.ArticlePubMed
• 9. Antoniades CA, Xu Z, Mason SL, Carpenter RH, Barker RA. Huntington’s disease: changes in saccades and hand-tapping over 3 years. J Neurol 2010;257:1890–1898.ArticlePubMedPDF
• 10. Patel SS, Jankovic J, Hood AJ, Jeter CB, Sereno AB. Reflexive and volitional saccades: biomarkers of Huntington disease severity and progression. J Neurol Sci 2012;313:35–41.ArticlePubMed
• 11. Kassavetis P, Kaski D, Anderson T, Hallett M. Eye movement disorders in movement disorders. Mov Disord Clin Pract 2022;9:284–295.ArticlePubMedPMCPDF
• 12. Henderson T, Georgiou-Karistianis N, White O, Millist L, Williams DR, Churchyard A, et al. Inhibitory control during smooth pursuit in Parkinson’s disease and Huntington’s disease. Mov Disord 2011;26:1893–1899.ArticlePubMedPDF
• 13. Browning S, Holland S, Wellwood I, Bilney B. Spatiotemporal gait parameters in adults with premanifest and manifest Huntington’s disease: a systematic review. J Mov Disord 2023;16:307–320.ArticlePubMedPMCPDF
• 14. Pyo SJ, Kim H, Kim IS, Park YM, Kim MJ, Lee HM, et al. Quantitative gait analysis in patients with Huntington’s disease. J Mov Disord 2017;10:140–144.ArticlePubMedPMCPDF
• 15. Rao AK, Muratori L, Louis ED, Moskowitz CB, Marder KS. Spectrum of gait impairments in presymptomatic and symptomatic Huntington’s disease. Mov Disord 2008;23:1100–1107.ArticlePubMed
• 16. Delval A, Bleuse S, Simonin C, Delliaux M, Rolland B, Destee A, et al. Are gait initiation parameters early markers of Huntington’s disease in pre-manifest mutation carriers? Gait Posture 2011;34:202–207.ArticlePubMed
• 17. Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D, et al. Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 2009;8:791–801.ArticlePubMedPMC
• 18. Li XY, Bao YF, Xie JJ, Qian SX, Gao B, Xu M, et al. The Chinese version of UHDRS in Huntington’s disease: reliability and validity assessment. J Huntingtons Dis 2022;11:407–413.ArticlePubMed
• 19. Vaca-Palomares I, Brien DC, Coe BC, Ochoa-Morales A, Martínez-Ruano L, Munoz DP, et al. Implicit learning impairment identified via predictive saccades in Huntington’s disease correlates with extended corticostriatal atrophy. Cortex 2019;121:89–103.ArticlePubMed
• 20. Coppen EM, Jacobs M, van den Berg-Huysmans AA, van der Grond J, Roos RAC. Grey matter volume loss is associated with specific clinical motor signs in Huntington’s disease. Parkinsonism Relat Disord 2018;46:56–61.ArticlePubMed
• 21. Desai R, Blacutt M, Youdan G, Fritz NE, Muratori LM, Hausdorff JM, et al. Postural control and gait measures derived from wearable inertial measurement unit devices in Huntington’s disease: recommendations for clinical outcomes. Clin Biomech (Bristol) 2022;96:105658.ArticlePubMed
• 22. Gaßner H, Jensen D, Marxreiter F, Kletsch A, Bohlen S, Schubert R, et al. Gait variability as digital biomarker of disease severity in Huntington’s disease. J Neurol 2020;267:1594–1601.ArticlePubMedPMCPDF
• 23. Hausdorff JM. Gait variability: methods, modeling and meaning. J Neuroeng Rehabil 2005;2:19.ArticlePubMedPMCPDF
• 24. Lin J, Xu T, Yang X, Yang Q, Zhu Y, Wan M, et al. A detection model of cognitive impairment via the integrated gait and eye movement analysis from a large Chinese community cohort. Alzheimers Dement 2024;20:1089–1101.ArticlePubMed

Figure & Data

References

Citations

Citations to this article as recorded by  

Comments on this article