Comparing balance using the BESTest in Alzheimer, Huntington and Parkinson disease

Abstract

Aim: Individuals with Alzheimer disease (AD), Huntington disease (HD) and Parkinson disease (PD) have impaired balance, and comparing these deficits could improve management of neurological diseases.

Methods: Scores on the Balance Evaluation Systems Test (BESTest) were compared across three groups, consisting of individuals with AD, HD and PD in early stages of their respective disease.

Results: Individuals with PD had significantly higher scores on the BESTest than individuals with AD (95% CI [4.30, 21.37], p < 0.01) or HD (95% CI [6.53, 24.18], p < 0.001). Individuals with AD and HD were not significantly different on the overall BESTest or any of its subsections.

Conclusion: AD and HD may have overlapping pathologies resulting in early and similar balance impairments in these groups.

Tweetable Abstract

Balance impairment differs among individuals with Alzheimer disease, Huntington disease and Parkinson disease, with individuals with Parkinson disease demonstrating significantly better balance when compared in early stages of each disease.

Plain language summary

Article highlights.

Background

• Neurodegenerative diseases including Alzheimer, Huntington, and Parkinson disease have overlapping signs and symptoms.

• Understanding how overlapping symptoms, like balance impairment, differ in each of these conditions could help guide treatment.

Methods

• The Balance Evaluation Systems Test (BESTest) breaks balance down into six subsections, allowing for better identification of specific balance impairments.

Results

• Individuals with Parkinson disease have significantly better balance, as measured by the BESTest, than individuals with Alzheimer disease and Huntington disease at a similar early disease stage.

• Individuals with Alzheimer disease and Huntington disease had lowest scores on dynamic balance subsections of the BESTest (III, IV and VI).

• Individuals with Alzheimer disease and Huntington disease were not significantly different on any of the subsections of the BESTest.

Discussion

• Cognitive impairment may contribute to the balance impairments in individuals with Alzheimer disease and Huntington disease.

Conclusions

• Future research should focus on how balance changes over time in these diseases, and how cognitive impairment may relate to these changes.

1. Introduction

Neurodegenerative diseases are a group of disorders characterized by progressive neuronal loss [1]. They are often categorized by their clinical features or the location of the neuronal loss in the brain [1], but there is significant overlap in the signs and symptoms across these diseases. The two most common neurodegenerative diseases are Alzheimer disease (AD) and Parkinson disease (PD) [2,3]. While AD is characterized by dementia [4], individuals with this disease can also experience motor symptoms [5]. Conversely, PD is characterized by the four cardinal motor symptoms of bradykinesia, rigidity, postural instability and tremor [6], but individuals with PD can also experience cognitive impairment and dementia [7]. Huntington disease (HD), another neurodegenerative condition, is characterized by motor, cognitive and psychiatric symptoms [8]. While these diseases have distinct pathologies and progressions, their overlapping manifestations lead to questions about whether the similar signs and symptoms manifest differently among this group of diseases.

Although AD and PD are common diseases, with a combined total of nearly 8 million patients in the United States [2,3], HD is rare, affecting only approximately 30,000 individuals in the US [9]. Because of this, research is more limited in HD. There is evidence to suggest that AD and HD share some common neural pathologies that eventually lead to neuronal death, including impaired protein processing that causes synapse loss [10]. Additionally, basal ganglia degeneration and dopamine dysfunction are present in both HD and PD [11,12] with late stage HD mirroring the dopamine depletion seen in PD [12]. These related pathologies could lead to similar symptoms, allowing for treatments that are effective in AD or PD to be similarly effective in HD. However, without directly comparing among the three diseases it is unclear if the similar pathologies lead to similar symptoms.

Consistent measurement of motor and mobility deficits in neurological conditions is important for both research and clinical care. In 2018, the Academy of Neurologic Physical Therapy recommended a core set of measures to be used in all neurological populations across the continuum of care in order to streamline assessment [13]. The Academy is currently in the process of revising this core set [14], but the principle remains important. By understanding how movement is impacted as measured by the same core assessments, researchers and clinicians can more easily compare issues across disorders. Additionally, knowledge gathered using standardized outcomes could inform assessment and intervention for more rare diseases, like HD, which may not have a large body of literature to document their deficits.

A common deficit among these three neurodegenerative diseases is impaired balance. Individuals with AD, PD, and HD have impaired postural control [15–21]. These impairments can lead to falls and injuries [22–25], which in turn lead to increased disease burden [26]. While many studies have explored balance deficits and interventions for these deficits in PD [27–29] and AD [30,31], less is known about HD. Directly comparing balance in AD, PD, and HD would allow for better understanding of these neurodegenerative diseases and inform future research directions, particularly in HD. To our knowledge, no study to date directly compares balance among individuals with AD, HD, and PD. Therefore, the purpose of the present study is to explore differences in balance in individuals with AD, HD, and PD.

2. Methods

2.1. Study Design

This is a secondary analysis of data collected for three separate and distinct cohort studies [32–34].

2.2. Participants

Data were originally collected between 2011 and 2023 at Washington University School of Medicine in St. Louis School. Detailed inclusion and exclusion criteria can be found in the original publications [32–34], but briefly, all participants had to be diagnosed with their respective neurodegenerative disease (AD, HD, or PD), be able to walk independently with or without an assistive device, and could not be diagnosed with other neurological conditions besides the disease of interest. All individuals with PD were tested in the on state of medication to reflect real-world performance. Data included in the present analysis included 25 individuals with AD, 22 individuals with HD, and 27 individuals with PD. All participants were considered to be in the early stage of their respective disease progression according to their disease-specific measure (Table 1). Each study was approved by the institutional review board (IRB) of Washington University School of Medicine in St. Louis and written informed consent was obtained from participants and/or their caregivers at the time of original data collection. The current analysis was also approved (IRB ID #202312036).

Table 1.

Participant characteristics.

	AD (n = 25)	HD (n = 22)	PD (n = 27)
Age	76.6 (5.4)	54.0 (12.2)	65.7 (9.4)
Sex	M = 16, F = 9	M = 10, F = 12	M = 18, F = 9
Disease Severity	CDR of 0.5: n = 14 CDR of 1: n = 11	UHDRS-TMS = 22.6 (16.4)	MDS-UPDRS-III = 32.8 (10.0)

Mean (SD).

2.3. Protocol

Data were extracted from the original databases, taking only the minimal information needed for the present analysis. All data were de-identified to maintain participant confidentiality. In order to perform the present analysis, all data were combined into a single file, with variable names made consistent for analysis. The measures extracted were as follows: Balance Evaluation Systems Test (BESTest), MiniBESTest, BriefBESTest, Timed Up and Go Test (TUG), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Scale (CDR), Unified Huntington Disease Rating Scale Total Motor Score (UHDRS-TMS), and Movement Disorders Society Unified Parkinson Disease Rating Scale Part III Motor Severity (MDS-UPDRS-III). These measures are described below in detail.

Balance was assessed using the Balance Evaluation Systems Test (BESTest) [35]. The BESTest divides balance into six domains, namely I. Biomechanical Constraints, II. Stability Limits / Verticality, III. Anticipatory Postural Adjustments, IV. Postural Responses, V. Sensory Orientation, and VI. Stability in Gait. The BESTest is a validated measure [36] and has been used in various neurologic populations including PD [37], stroke [38], and multiple sclerosis [39]. Items on the BESTest are scored on a 0 to 3 scale, with total scores ranging from 0 to 108. Lower scores indicate greater balance impairment [35]. All ratings were done in the same lab, with all assessors undergoing the same training to administer the BESTest. While administering the BESTest, the MiniBESTest and BriefBESTest were also scored. Because the BESTest takes 35–45 min to administer [35], the shortened versions offer better clinical utility [40,41] and may be more useful to practicing clinicians.

The MiniBESTest was developed as a shortened version of the BESTest to allow for better clinical utility [40]. It uses items from subsections III-VI of the BESTest, focusing on dynamic balance [40]. Unlike the BESTest, the MiniBESTest items are scored on a 0 to 2 scale, with a total possible score of 28 [40,42]. The MiniBESTest has been validated in balance disorders [43], chronic stroke [44], and PD [37].

The BriefBESTest uses one item from each of the six subsections of the BESTest [41]. Like the MiniBESTest, the BriefBESTest was created to improve clinical utility and has been validated for both construct validity and internal consistence [41]. Although the BriefBESTest was not scored during the original data collection for the AD or PD groups, the scores were calculated by taking the scores from the items on the BESTest, as item scoring for the BriefBESTest is the same as the BESTest. Total scores range from 0 to 24 [41].

Given the clinical utility of the Timed Up and Go Test (TUG), single and dual task TUG times were extracted from the BESTest. While the TUG is the last item of the BESTest, it is also a stand-alone clinical measure [45] that has been used in clinical and non-clinical populations to assess mobility and fall risk [46–48]. The test involves the individual rising from a chair, walking 3 meters, turning, walking back to the chair and sitting back down [45]. The dual task TUG involves participants subtracting by 3's from a randomly selected number between 20 and 100 while performing the standard TUG walking task [46]. The TUG and dual task TUG are quick and easy to perform clinically, so the times for each of them are reported herein.

In addition to the balance assessments, participants were assessed with disease-specific rating scales. Prior to enrollment, all individuals with AD were assessed using the Clinical Dementia Rating Scale (CDR) [49]. CDR is a validated measure of dementia [50] and is rated on a 0 to 3 scale, with 0 indicating “Normal” cognition, 0.5 “Very Mild Dementia”, 1 “Mild Dementia”, 2 “Moderate Dementia”, and 3 “Severe Dementia” [49]. The CDR has been used to track dementia progression in individuals with AD [51].

All individuals with HD were assessed with the Unified Huntington's Disease Rating Scale – Total Motor Score (UHDRS-TMS) [52]. The UHDRS-TMS is a 15-item measure used to evaluate motor symptoms of HD, such as dysarthria, chorea, and dystonia [52]. Each item is scored on a 0 to 4 scale, with a total possible score of 124. Higher scores indicate greater motor impairment [52]. Additionally, individuals with HD were assessed using the Montreal Cognitive Assessment (MoCA) [53]. Cognitive impairment is common in HD, and may present prior to motor symptoms [54]. The MoCA has been validated in the HD population and shown to be sensitive for detecting mild cognitive impairment and dementia in HD [55,56]. The measure assesses eight domains of cognition and has a total possible score of 30 [53], with scores of 25 or below indicating impairment in HD [55].

Individuals with PD were assessed in the on-state of medication with the Movement Disorder Society Unified Parkinson Disease Rating Scale Part III Motor Severity (MDS-UPDRS-III) [57]. Similar to the UHDRS-TMS, the MDS-UPDRS-III was designed to assess motor symptoms and includes 18 items rated on a 0 to 4 scale, with higher scores indicating greater motor impairment [57]. At the end of the MDS-UPDRS-III, individuals are staged on the Hoehn and Yahr scale [57]. All participants with PD included in the present analysis were in Hoehn and Yahr Stage 2, indicating mild disease severity [58]. This was chosen to allow for comparison among the three groups of patients who were all in the early stages of their respective diseases.

2.4. Statistical analysis

All data were analyzed using R statistical software [59]. Means and standard deviations were calculated for all measures by group. BESTest, MiniBESTest and BriefBESTest overall percentage scores as well as BESTest subsection percentage score were compared using 3 × 1 ANOVAs. If there was a significant effect of group, secondary Tukey Multiple Comparison tests were run to determine which groups were different from each other. Significance for all ANOVA analyses was set at p < 0.01 due to the number of tests being run. Tukey Multiple Comparison Tests utilized adjusted p values.

TUG times were compared using a 3 × 2 ANOVA with effects of group (AD, HD, and PD) and condition (single task vs dual task). If significant effects of group, condition, or the interaction were found, then Tukey Multiple Comparison Tests were utilized to further understand these effects.

An exploratory analysis of the effect of age on BESTest score was also performed. Age was expected to be significantly different between groups due to the age of onset of each disease [4,6,8]. Correlations were calculated between BESTest total percent score and age for the entire sample as well as separately for each group. This was done to ensure that differences on the BESTest among the groups were not solely driven by age. Correlations from 0.3 to 0.49 were considered weak, 0.5 to 0.69 moderate and 0.7 or higher strong [60].

3. Results

Participant characteristics are presented in Table 1. Individuals with HD were the youngest on average (54.0 ± 12.2 years), with individuals with AD being oldest (76.6 ± 5.4 years). Age was significantly different for all groups (F = 30.8, p < 0.001; HD vs AD 95% CI [-29.53, -15.70], p < 0.001; PD vs AD 95% CI [-17.49, -4.19], p < 0.001; PD vs. HD 95% CI [5.21, 18.3], p < 0.001) (Table 1). Based upon the average MoCA score, individuals with HD would be considered to have mild cognitive impairment (22.3 ± 5.1). While cognition was not formally assessed for individuals with PD, all participants scored at least 24 on the Mini Mental State Examination [61] during screening for the study and self-reported that they had not been diagnosed with dementia prior to enrollment. All participants were in the early stages of their respective diseases as measured by their disease-specific rating scale (Table 1).

Average BESTest, MiniBESTest, and BriefBESTest total percentage scores are presented in Figure 1. Percentage scores were calculated by dividing the score achieved on each subsection by the total possible score on that subsection and multiplying by 100. Percentages, rather than raw scores, are presented due to previous cutoff scores being established with percentages [62]. There was a main effect of group on the overall scores on the BESTest, MiniBESTest, and BriefBESTest (F = 10.44, p < 0.001, Cohen's f = 0.54; F = 8.64, p < 0.001, Cohen's f = 0.49; and F = 6.39, p < 0.01, Cohen's f = 0.42 respectively). The Tukey Multiple Comparisons Tests showed that on the BESTest, scores for individuals with HD vs. AD were not significantly different (95% CI [-11.51, 6.46], p = 0.78), while scores were significantly different for PD vs. AD (95% CI [4.30, 21.37], p < 0.01) and PD vs. HD (95% CI [6.53, 24.18], p < 0.001). Likewise, MiniBESTest scores for individuals with HD vs. AD were not significantly different (95% CI [-15.18, 9.10], p = .82), while scores again were significantly different for PD vs. AD (95% CI [4.28, 27.33], p < 0.01) and PD vs. HD (95% CI [6.92, 30.77], p < 0.001). The BriefBESTest scores mirrored this pattern, with no significant difference for HD vs. AD (95% CI [-14.93, 12.26], p = 0.97) and significant differences for PD vs AD (95% CI [3.20, 29.01], p = 0.01) and PD vs. HD (95% CI [4.08, 30.80], p < 0.01).

Figure 1.

BESTest, MiniBESTest and BriefBESTest total scores by group. ***p < 0.001. Error bars indicate ± 1 SD.

Average percentage scores for the BESTest subsections are presented in Figure 2. For BESTest subsections, there was no effect of group on sections I. Biomechanical Constraints (F = 3.51, p = 0.04, Cohen's f = .31), II. Stability Limits / Verticality (F = 2.80, p = 0.07, Cohen's f = .28), or V. Sensory Orientation (F = 3.67, p = 0.03, Cohen's f = .32). There was a main effect of group on sections III. Anticipatory Postural Adjustments (F = 12.56, p < 0.001, Cohen's f = .59), IV. Postural Responses (F = 15.89, p < 0.001, Cohen's f = .67), and VI. Stability in Gait (F = 6.39, p < 0.01, Cohen's f = .73). Results of the Tukey Multiple Comparisons test indicated no significant difference between individuals with HD vs. AD on sections III (95% CI [-11.25, 8.34], p = .93), IV (95% CI [-14.92, 13.06], p = .99), or VI (95% CI [-10.58, 13.65], p = .95). As with the overall BESTest scores, there were significant differences for PD vs. AD for sections III (95% CI [6.92, 25.53], p < 0.001), IV (95% CI [13.49, 40.06], p < 0.001), and VI (95% CI [15.00, 38.01], p < 0.001). These differences were also seen for PD vs. HD in sections III (95% CI [8.04, 27.30], p < 0.001) IV (95% CI [13.96, 41.45], p < 0.001), and VI (95% CI [13.07, 36.87], p < 0.001) (Figure 2). All values for BESTest, MiniBESTest, BriefBESTest and BESTest subsections by group are available in Supplementary Table S1 as percentages and Supplementary Table S2 as raw scores.

Figure 2.

BESTest subsection scores by group. ***p < 0.001. Error bars indicate ± 1 SD.

Due to the significant difference of age among the groups, an exploratory analysis of the effect of age on BESTest total score was performed. When ignoring group and considering the sample as a whole, there was a weak but significant correlation between BESTest total score and age (r = -.45, p < 0.001). When separating into groups, there were strong and significant correlations between BESTest score and age for the AD and HD groups (AD: r = -.70, p < 0.001, HD: r = -.74, p < 0.001, respectively) and a moderate, significant correlation for the PD group (PD: r = -.59, p = 0.001) (Figure 3).

Figure 3.

BESTest total score vs age by group.

Finally, average single task and dual task TUG times are presented in Table 2. There was a significant main effect of group (F = 12.58, p < 0.001, Cohen's f = .42) and of condition (F = 18.06, p < 0.001, Cohen's f = .36), but no interaction (F = 2.26, p = .11, Cohen's f = .18). For the main effect of group, HD vs. AD was not significantly different (95% CI [-5.35, 0.26], p = 0.08). Again, there was a significant difference for PD vs. HD (95% CI [-5.71, -0.35], p = 0.02) and PD vs. AD (95% CI [-8.15, -2.91], p < 0.001). For the main effect of condition, single task times were significantly less (i.e., faster) than dual task times.

Table 2.

Single task TUG and dual task TUG times.

	AD (n = 25)	HD (n = 22)	PD (n = 27)
Single Task Time (sec)	12.62 (4.03)	11.71 (3.94)	9.24 (2.00)b
Dual Task Time (sec)	19.27 (10.77)a	14.92 (5.51)	11.32 (3.61)b

^aTwo participants with AD did not complete the DT-TUG condition.

^bSignificantly different from AD and HD.

Mean (SD).

4. Discussion

The present analysis demonstrates that individuals in the early stages of PD have significantly better balance than individuals with AD or HD in similarly early disease stages as measured by the BESTest. On the overall BESTest, as well as in subsections III, IV and VI, individuals with early-stage PD have significantly higher scores than both individuals with AD and HD, indicating better balance function (Figure 1,2). Subsections III, IV and VI encompass dynamic balance, including tasks like transitioning from sit to stand and dual task walking [35]. Impaired dynamic balance is associated with future falls [37,63] and is a target of exercise interventions in older adults [64–66]. Falls are prevalent in AD and HD, with previous studies showing up to 80% of individuals experiencing a fall every year [19,24]. Dynamic balance is used in everyday life, and the greater deficits seen in AD and HD are important to note. No significant differences were noted in subsections I and V, which encompass strength and static balance, respectively (Figure 2). All groups demonstrated similar deficits in these areas (Figure 2), indicating that the differences in global balance deficits seen across groups are likely driven by the impairments in dynamic balance. This is further supported by the significant differences in TUG times between the PD and HD groups and PD and AD groups. The TUG has been used to assess functional mobility and fall risk [46,47], and the impairments noted here demonstrate the impaired TUG times may relate to impaired dynamic balance as a whole.

It is unclear why individuals with PD performed better on the BESTest than their AD and HD counterparts. One possible explanation could be age. Age was expected to be significantly different among the groups, as each of these disorders have different ages of onset [4,6,8]. Age and BESTest score were weakly correlated when group was not considered, but the correlations were much stronger within group. This indicates that age is impacting balance differently within each disorder. Age alone could explain the differences in balance between the AD and PD groups, as the individuals with AD are significantly older than those in the PD group, and balance is known to be impaired in older adults [67]. However, this would not explain why the HD group is worse than the PD group, given that individuals with HD are significantly younger than those with PD (Table 1), nor would it explain why individuals with AD and HD perform similarly on the BESTest (Figure 1). These results suggest that age may not be the main underlying cause of the differences seen in balance performance.

Another possible explanation of the superior performance by the PD group could be cognitive status. Both the AD group and the HD group demonstrated cognitive impairment as measured by CDR and MoCA, respectively. Previous research suggested that cognitive impairment is related to impaired gait and balance [68]. While the present dataset does not contain a cognitive measure for the PD group, the deficits seen in the AD and HD groups align with previous findings [15,16,68,69], and bolster evidence for the connection between cognitive impairment and motor deficits.

The similar performance between individuals with AD and HD is promising for future research and useful for clinicians to understand. As mentioned previously, HD is a rare disease. Knowing that individuals with AD and HD have similar balance deficits in early stages of the disease allows future researchers to focus their efforts on testing exercise interventions shown to be effective in AD to address balance deficits in HD. It is difficult to study many different interventions in HD due to the rarity of the disease, so having a narrower focus may allow researchers to find interventions that are effective in HD more quickly. For clinicians, the evidence for similarities in balance deficits in AD and HD shown here may help inform their choice of exercise and balance interventions. The current recommendations for exercise intervention in HD are broad [70] due to the limited research in HD, so clinicians may be able to explore the more prolific AD literature to help inform clinical decision making.

It is important to note the limitations of the present study. First, the groups were relatively small and the individuals are in the early stages of their respective diseases, so the results may not be generalizable to all patients with these conditions. Second, the lack of cognitive measure for the PD group makes it difficult to draw conclusions about the influence of cognitive status on balance. Related to this, the AD and HD groups were assessed using different cognitive assessments, so it is difficult to directly compare the two groups. Future work should utilize consistent measures of cognitive status to improve understanding of the relationship of cognitive impairment and motor deficits in neurodegenerative diseases. Finally, the BESTest was rated by different raters for the three groups. Although all raters were trained in the same lab to perform this assessment, it is possible that bias occurred due to individual differences. Previous work has shown that the BESTest has excellent interrater reliability [35], and the quantitative nature of many of the items, including the TUG, help reduce these concerns.

Future work should continue to explore the balance deficits present in neurodegenerative diseases, and how these deficits relate to other symptoms, particularly cognitive impairment. Utilizing consistent measures across diseases, as suggested by the Academy of Neurologic Physical Therapy [13,14], will improve both research and clinical practice. Researchers should continue to assess various neurologic populations with consistent motor assessments so that researchers and clinicians can have a better understanding of the similarities and differences that exist across diagnoses and across time. This will improve management of these disorders, and help fill in gaps for more rare disorders that do not have extensive studies in the rehabilitation realm.

Overall, these results demonstrate the importance of early screening for balance impairment in all three of these neurodegenerative diseases. All groups demonstrated impairments, showing the need for balance interventions in all of these diseases. Future research should explore how balance impairments progress over the disease span and if these changes differ among the conditions. Additionally, future work could measure cognition and balance concurrently to help elucidate this relationship.

5. Conclusion

Balance impairments differ in individuals with AD, HD, and PD. Individuals with AD and HD demonstrated similar balance impairments, particularly in dynamic balance tasks. These deficits highlight the importance of early screening for balance, and also highlight the added influence of cognitive impairment on motor performance. Future research should focus on how individuals with these conditions respond to both balance and cognitive interventions for motor performance.

Funding Statement

This study was funded by the Program in Physical Therapy at Washington University School of Medicine in St. Louis.

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17582024.2024.2388507

Financial disclosure

This study was funded by the Program in Physical Therapy at Washington University School of Medicine in St. Louis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Author RD would like to acknowledge the K23 Researcher Development Award he received through NIH-NICHD (award number 1K23HD100569-01).

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval (Institutional Review Board at Washington University School of Medicine in St. Louis) and/or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.