Review Article

Relationship between Freezing of Gait and Anxiety in Parkinson’s Disease Patients: A Systemic Literature Review

Table 2

Summary of studies included in literature review.

AuthorsPurpose and designDemographic characteristicsPD measuresAnxiety measuresFOG measuresNotable results

Zhang et al. [18](i) A 3-year prospective longitudinal study where suspected risk factors for FOG in patients with early-stage PD are tabulated
(ii) Incidence of FOG assessed at one, two, and three years following study initiation to evaluate suspected risk factors (including anxiety) associated with future development of FOG
(iii) Participants recruited from the Third People’s Hospital of Huzhou, Zhejiang Province of China
(i) Chinese population
(ii) 248 PD patients
 (a) 112 males; 136 females
 (b) <65 years old (n = 78) mean age: 58.22 ± 5.43
 (c) >65 years old (n = 170) mean age: 69.42 ± 3.41
(iii) Inclusion criteria: early-stage PD patients, never experienced FOG prior to study initiation, and never taken anti-Parkinson drugs
(iv) Exclusion criteria: presence of atypical or secondary parkinsonism
(i) All participants diagnosed in accordance with the UK Brain Bank clinical criteria
(ii) UPDRS-III and H&Y stage used to assess severity of PD motor symptoms
(iii) UPDRS-III score
 (a) All 248 patients met the criteria
 (b) Mean: 19.22 ± 2.61
(iv) H&Y stage:
 (a) Stage 1 (n = 56)
 (b) Stage 1.5 (n = 135)
 (c) Stage 2 (n = 55)
 (d) Stage 2.5 (n = 2)
(i) Patients diagnosed by at least one trained psychiatrist and who had completed both the HAMA and HAMD Anxiety subscale
(ii) At baseline, 51 PD patients were diagnosed with anxiety, and 3 years later,
 (a) 27 of these individuals developed FOG
 (b) 24 of these individuals did not develop FOG
(iii) PD patients with FOG 3 years later (n = 128)
 (a) Overall HAMA: 11.35 ± 7.12
 (b) HAMA-Somatic Anxiety: 4.81 ± 3.28
 (c) HAMA-Psychic anxiety: 6.54 ± 3.96
 (d) HAMD-Anxiety/Somatic: 2.79 ± 1.75
(iv) PD patients without FOG 3 years later (n = 120)
 (a) Overall HAMA: 10.23 ± 7.77
 (b) HAMA-Somatic Anxiety: 4.44 ± 3.50
 (c) HAMA-Psychic Anxiety: 5.79 ± 3.49
 (d) HAMD-Anxiety/Somatic: 2.26 ± 1.43
(v) The paper mentions some patients were on anxiolytics but does not report numbers
(i) A convincing subjective report of FOG in addition to patient’s recognition of FOG phenomenon when demonstrated by an experienced clinician.
OR
(ii) Answered yes to FOG-Q3OR
(iii) Reported by patients, their family members, or caregivers when occurring at home.
 (a) FOG after 1 year = 40
 (b) FOG after 2 years = 98
 (c) FOG after 3 years = 128
Following age-adjusted ANCOVA:
(i) No significant association with HAMA scores at baseline and FOG 3 years later
(ii) Significantly higher HAMD anxiety scores in FOG compared with non-FOG patients 3 years later ()
Following binary logistic regression analysis:
(i) Baseline HAMD Anxiety significantly associated with future development of FOG 2 years later () but not 1 year later ()

Martens et al. [19](i) To compare anxiety levels of PD patients with FOG directly with PD patients without FOG, as well as how anxiety contributes to FOG
(ii) Participants recruited from a larger cohort of cases prospectively evaluated between 2008 and 2015 and divided into groups based on presence and severity of FOG and various clinical variables tabulated and compared including anxiety
(i) Australian population
(ii) 461 PD patients at the University of Sydney-affiliated PD Research Clinic recruited and split into 3 groups:
(iii) PD without FOG (PDNF) (n = 231)
 (a) 150 males; 81 females
 (b) Mean age: 67.8 ± 0.64
 (c) Mean PD duration: 3.8 ± 0.56 years
(ii) PD with mild FOG (PDmFOG) (n = 50)
 (a) 34 males; 16 females
 (b) Mean age: 69.3 ± 1.09
 (c) Mean PD duration: 6.3 ± 0.87 years
(iii) PD with FOG (PDFOG) (n = 180)
 (a) 109 males; 71 females
 (b) Mean age: 69.2 ± 0.77
 (c) Mean PD duration: 8.7 ± 0.6 years
(iv) Exclusion criteria: presence of neurological disease other than PD, psychiatric disorders other than affective disorder, and MMSE <24
(i) All participants had confirmed diagnosis of idiopathic PD by a trained neurologist based on UK Brain Bank clinical criteria
(ii) PDNF
 (a) Mean UPDRS-III: 28.3 ± 1.1
(iii) PDmFOG
 (a) Mean UPDRS-III: 33.5 ± 2.5
(iv) PDFOG
 (a) Mean UPDRS-III: 41.55 ± 1.3
(v) Significant group differences in above scores observed in ANOVA (), further covariate analysis performed to factor UPDRS-III score out of outcome measures analysis (in addition to MMSE score and age)
(i) Anxiety subscale of HADS (HADS-A) subtotalled and compared between groups with scores ≥ 8 meeting criteria for anxiety disorder
(ii) PDNF
 (a) Mean HADS-A: 3.5 ± 0.22
(iii) PDmFOG
 (a) Mean HADS-A: 4.7 ± 0.55
(iv) PDFOG
 (a) Mean HADS-A: 5.8 ± 0.31
(v) To determine whether or not HADS-A could predict FOG, PDmFOG group combined with the PDFOG group and HADS-A and HADS-D scores between the two groups compared:
 (a) PDNF (231 total): 14 patients with anxiety and 10 patients with anxiety and depression
 (b) PDFOG combined (230 total): 26 patients with anxiety and 39 patients with anxiety and depression
(vi) 129 patients in this study taking anxiolytics and/or antidepressants
 (a) 62/231 PDNF
 (b) 13/50 PDmFOG
 (c) 54/180 PDFOG
(i) FOG-Q3 score used to differentiate participants into 3 groups:
(ii) PDNF
 (a) FOG-Q3: 0
(iii) PDmFOG
 (a) FOG-Q3: 1
(iv) PDFOG
 (a) FOG-Q3: 2–4
(i) An ANCOVA conducted across groups demonstrated that, compared to PDNF, PDFOG patients had significantly greater anxiety (); PDmFOG was not significantly different from PDFOG
(ii) Pearson’s correlations with stepwise multiple regression analyses demonstrated that, in all groups, severity of anxiety symptoms was significantly correlated with FOG-Q3 scores ()
(iii) In PDFOG combined compared with PDNF, a significant odds ratio of 3.40 () when anxiety was exposure outcome and FOG was the variable
(ii) HADS-A score PPV of 28.26% (95% CI 22.26%–34.35%) for identifying patients with FOG
(iii) HADS-A score NPV of 89.61% (95% CI: 84.94%–93.23%) for identifying patients without FOG

Walton et al. [20](i) To examine the impact of FOG on the Health-Related Quality of Life scale in PD patients
(ii) Additionally, other factors that are known to impact patient well-being were assessed (including anxiety)
(iii) Data collected from baseline assessment of a group of PD patients from December 2008 and November 2013 patients at the University of Sydney-affiliated PD Research Clinic
(i) Australian population
(ii) 203 PD patients
 (a) 139 males; 64 females
 (b) Mean age: 66.77 ± 8.9
 (c) Mean PD duration: 61.30 ± 61.3 months
(iii) Excluded if MMSE <24
(i) All participants had confirmed diagnosis of idiopathic PD based on United Kingdom Brain Bank clinical criteria by a trained neurologist
(ii) Mean UPDRS-III score: 27.60 ± 15.1
(iii) H&Y stage
 (a) Stage 1: 39 (19.21%)
 (b) Stage 1.5: 7 (3.45%)
 (c) Stage 2: 98 (48.28%)
 (d) Stage 2.5: 39 (19.21%)
 (e) Stage 3: 20 (9.85%)
HADS-A score quantified:
 (a) Mean: 3.95 ± 3.4
(i) FOG-Q3 score used to identify patients that had experienced FOG:
 (a) 86 patients ≥1 (43% FOG)
(ii) Full 6-Item FOG-Q used to assess severity of FOG:
 (b) Mean score: 5.34 ± 5.7
(i) Pearson’s bivariate correlation indicated HADS-A score significantly associated with severity of FOG ()

Ehgoetz Martens et al. [32](i) To induce anxiety via virtual reality and measure presence/severity of FOG in a controlled experimental setting
(ii) 10 randomized walking trials across a 6-metre long plank positioned between two platforms in one of the two different virtual 3-D environments: a low condition wherein the plank was positioned on the floor of the virtual environment, and a high condition wherein the plank was positioned over a pit 8 metres in depth of the virtual environment
(iii) Patients recruited through a Wilfrid Laurier University affiliated Research and Rehabilitation Centre in Waterloo, Canada
(i) Canadian population
(ii) 31 PD patients divided into freezers and nonfreezers:
(iii) 14 freezers:
 (a) 11 males; 3 females
 (b) Mean age: 71 ± 7.8
(iv) 17 nonfreezers:
 (a) 14 males; 3 females
 (b) Mean age: 66 ± 8.7
Exclusion criteria: unable to walk 10 m unassisted, severe vertigo, motion sickness, severe kyphosis, other neurological disorders, severe head tremor, or dyskinesias
(i) Previous diagnosis of idiopathic PD by a neurologist
(ii) Mean UPDRS-III score:
 (a) Freezers: 34 ± 10.1
 (b) Nonfreezers: 20 ± 10.4
(i) State and Trait Anxiety Inventory Scale assessed baseline levels of anxiety prior to completing experiment:
(ii) Freezers
 (a) Average STAI-Trait: 33 ± 6.9
 (b) Average STAI-State: 34 ± 8.7
(iii) Nonfreezers
 (a) Average STAI-Trait: 32 ± 6.6
 (b) Average STAI-State: 30 ± 5.9
(iii) Participants additionally completed a 9-point self-assessment manikin scale after each walking trial to quantify anxiety experienced during the experiment
(i) Previous history of FOG and self-reported FOG using the UPDRS-II and FOG confirmed by movement disorder specialist prior to participation in study differentiated freezers from nonfreezers
(ii) Freezers vs. nonfreezers
 (a) Low condition: % of each trial frozen = 11.03 ± 23 seconds
 (b) High condition:
% of each trail frozen = 23.1 ± 28.7
(i) Freezers spent a significantly greater portion of time frozen in the high condition compared to the low condition (F(1,13) = 11.35, )
(ii) Freezers exhibited significantly higher numbers of freezing episodes in the high condition relative to the low condition (F(1,13) = 8.29, ), but no significant differences in duration of freezing episodes (F(1,13) = 2.48, )
(iii) Freezers self-reported significantly higher levels of anxiety during the experiment than nonfreezers (F(1,29) = 16.96, ), with both groups reporting significantly higher levels of anxiety in the high condition compared to the low condition (F(1,29) = 29.83, )
(iv) No significant differences between freezers and nonfreezers in terms of STAI-Trait () and STAI-state scores ()

Ou et al. [21](i) To explore the prevalence and clinical correlates of FOG
(ii) A cross-sectional observational study and participants were recruited from Department of Neurology, West China Hospital of Sichuan University between May 2011 and April 2014
(i) Chinese population
(ii) 474 PD patients
(iii) 221 with FOG
 (a) 117 males; 104 females
 (b) 108 ≤ 65 years old
 (c) 113 ≥ 65 years old
 (d) Mean age: 64.36 ± 10.16
 (e) Mean PD duration: 5.97 ± 4.24 years
(iv) 252 without FOG
 (a) 140 males; 113 females
 (b) 155 ≤ 65 years old
 (c) 98 ≥ 65 years old
 (d) Mean age: 60.11 ± 10.50
 (e) Mean PD duration: 3.73 ± 3.55 years
(v) Atypical or secondary parkinsonism excluded
(i) Patients previously diagnosed with UK Brain Bank criteria for PD
(ii) H&Y stage and UPDRS-III used to assess severity
(iii) Freezer H&Y stage
 (a) Stage 1–2.5: 115
 (b) Stage 3: 74
 (c) Stage 4-5: 32
 (d) Median: 2.5 (1.0)
(iv) Nonfreezer H&Y stage
 (a) Stage 1–2.5: 228
 (b) Stage 3: 20
 (c) Stage 4-5: 3
 (d) Median: 2.0 (0.5)
(v) Mean UPDRS-III score:
 (a) Freezers: 35.90 ± 14.48
 (b) Nonfreezers: 24.10 ± 10.45
(i) HAMA scores quantified for freezers vs. nonfreezers:
 (a) Mean HAMA freezers: 9.64 ± 7.50
 (b) Mean HAMA nonfreezers: 6.21 ± 5.92
(i) Freezing episodes observed by the neurologist during visit or reported by patient/family/caregiver if happened at home
(ii) FOG-Q3 is used to assess
(i) 46.62 % prevalence of FOG in this population of PD patients
(ii) ANCOVA adjusted for age, disease duration, and H&Y stage total HAMA scores significantly higher in freezers than nonfreezers ()
(iii) Binary logistic regression model indicated no significant correlation between HAMA anxiety score and FOG ()

Perez-Loret et al. [34](i) To determine prevalence of FOG and assess its relationship with quality of life and other clinical factors (including anxiety)
(ii) Cross-sectional study
(iii) Patients included prospectively as outpatients of public or private practicing neurologists in 32 centres from 4 different regions of France
(i) French population
(ii) 672 patients:
 (a) 381 males; 291 females
 (b) Age ≥ 68: 341
 (c) PD duration ≥ 5 years: 341
(iii) Exclusion criteria: patient’s <18 years old, MMSE <24, undergoing deep brain stimulation, and having serious disease affecting life expectancy in the short term
(i) Each PD patient examined by the neurologist with standardized/structured interview(i) Anxiety subscale of HADS (HADS-A) subtotalled, with a number of PD patients with scores ≥ 7 totalled and compared between freezers and nonfreezers
(ii) Freezers
 (a) Number of PD patients with HADS-A ≥ 7: 136
(iii) Nonfreezers
 (a) Number of PD patients with HADS-A ≥7: 194
(i) FOG identified by scores ≥1 on Item 14 of UPDRS-II
(ii) Nonfreezers: 415
(iii) Freezers: 257
(i) 38.2% FOG point prevalence reflecting a mixed population of patients with early and advanced disease who were still ambulatory, with or without motor fluctuations
(ii) No significant differences between HADS-A anxiety in freezers vs nonfreezers

Burn et al. [22](i) To identify associations between phenotypic variants of motor and mood subtypes of PD
(ii) Cross-sectional study
(iii) Participants were recruited over a period of 12 months from specialist PD or movement disorder outpatient clinics as part of the PROMS-PD longitudinal study
(i) UK population
(ii) 513 PD patients
(iii) Phenomenological data relating to depression and anxiety collected by trained staff using the Geriatric Mental State semi-structured interview and sorted into 4 groups:
 (a) Anxious-depressed (8.6%)
 (b) Depressed (9.0%)
 (c) Anxious (22%)
 (d) Low-level psychiatric symptomatology (60.4%)
Inclusion criteria: able to provide informed consent and resided within 2 hours travel time of a study research centre
Exclusion criteria: the presence of communication difficulty or sensory deficits that interfered with assessment. Cognitive impairment and severe psychiatric disorders only met exclusion criteria if they were severe enough to affect capacity to consent
(i) Patients with a previous diagnosis of PD recruited from specialist movement disorder and care of the elderly clinics
(ii) Freezer H&Y stage
 (a) Stage 1–2.5: 115
 (b) Stage 3: 74
 (c) Stage 4-5: 32
 (d) Median: 2.5 (1.0)
(iii) Nonfreezer H&Y stage
 (a) Stage 1–2.5: 228
 (b) Stage 3: 20
 (c) Stage 4-5: 3
 (d) Median: 2.0 (0.5)
(iv) Mean UPDRS-III score:
 (a) Freezers: 35.90 ± 14.48
 (b) Nonfreezers: 24.10 ± 10.4
(i) Anxiety subscale of HADS (HADS-A) subtotalled with scores ≥ 11 meeting criteria for significant anxiety symptoms (22.0%)
(ii) Number of PD patients with HADS ≥ 11
 (a) Freezers: 25 (33%)
 (b) Nonfreezers: 87 (20%)
(iii) Mean total HADS-A Score
 (a) Freezers: 8.8 ± 4.6
 (b) Nonfreezers: 6.9 ± 4.4
(i) FOG identified by scores >1 on Item 14 of UPDRS-II
 (a) FOG present: 75 patients (14.62%)
 (b) FOG not present: 438 patients (85.38%)
(i) The mean total HADS-A scores in freezers was significantly higher than in nonfreezers (), with a significantly higher proportion of freezers meeting the HADS-A ≥ 11 criteria for anxiety than nonfreezers ()
(ii) Presence of FOG did not predict membership in the anxious-depressed, depressed, or anxious mood subtypes

Lieberman [23](i) To study the association between anxiety, depression, and panic with FOG in Parkinson’s patients(i) US population
(ii) 109 patients:
 (a) 72 males; 37 females
 (b) Mean age: 69.0 ± 11.4
 (c) PD duration: 7.6 ± 5.7
(iii) Patient’s completed the Activities of Daily Living section of the UPDRS which contains a question about freezing
(i) Patients previously diagnosed with PD(i) HAMA scores quantified with score ranges of 18–54 meeting criteria for anxiety
 (a) 18/29 with FOG (62%)
 (b) 14/80 without FOG (18%)
(ii) DSM-IV criteria for panic attacks used to identify presence of panic attacks
 (a) 14/29 with FOG (48%)
 (b) 6/80 without FOG (80%)
(i) Those that answered yes to the initial freezing question (item 14 of UPDRS-II) further questioned and evaluated using 6 Item FOG-Q to calculate FOG severity(i) FOG was significantly associated with anxiety () and panic attacks ()

Hall et al. [35](i) Evaluate domains of motor, cognitive, affective, autonomic, and REM sleep behaviour disorder in early-stage PD and their respective associations with FOG
(ii) Data collected from baseline assessment of a group of PD patients from December 2008 and November 2013 at the University of Sydney-affiliated PD Research Clinic
(i) Australian population
(ii) 91 PD patients
(iii) Freezers (n = 38)
 (a) 27 males; 11 females
 (b) Mean age: 65.20 ± 9.00
 (c) Mean PD duration: 1.91 ± 1.40 years
(iv) Nonfreezers (n = 53)
 (a) 35 males; 18 females
 (b) Mean age: 64.58 ± 8.63
 (c) Mean PD duration: 1.69 ± 1.26 years
(v) Included if a H&Y stage <3 and a disease duration of 5 years or less
(vi) Excluded on the presence of other neurological diseases, conditions that would impair gait, or presence of dementia as rated by Movement Disorder Task Force criteria
(vii) No significant differences in age, years of education, and disease duration between freezers and nonfreezers
(i) All participants had confirmed diagnosis of idiopathic PD based on United Kingdom Brain Bank clinical criteria by a trained neurologist
(ii) Freezers
 (a) Mean H&Y stage: 2.00 ± 0.42
 (b) Mean UPDRS-III: 25.66 ± 14.11
(iii) Nonfreezers
 (a) Mean H&Y stage: 1.85 ± 0.44
 (b) Mean UPDRS-III: 20.85 ± 10.70
(i) HADS-A scores quantified for freezers vs. nonfreezers:
 (a) Mean HADS-A freezers: 4.92 ± 4.58
 (b) Mean HADS-A nonfreezers: 3.42 ± 2.49
(i) FOG-Q3 used to separate freezers from nonfreezers
(a) ≥1: 38 freezers (41.76%)
(b) 0: 53 nonfreezers (58.24%)
(i) Despite higher mean scores on the HADS-A scale, no significant differences were noted between anxiety scores of freezers compared with nonfreezers ()

Yao et al. [24](i) Exploring whether cognitive impairment is correlated with occurrence of FOG in PD neuropsychological assessments utilized to evaluate cognitive functioning: SCOPA-COG, UPDRS, MMSE, HAMA, and HAMD.
(ii) Data collected from PD patients diagnosed and treated in YangPu, Nanjing Drum Tower and Huashan hospitals
(iii) Case-control study
(i) Chinese population
(ii) 186 patients with PD
(iii) FOG PD patients (n = 104)
 (a) 55 males; 49 females
 (b) Mean age: 65.72 ± 7.34
 (c) Mean PD duration: 9.52 ± 1.54 years
 (d) Years of education: 13.51 ± 4.24
(iv) Non-FOG PD patients (n = 82)
 (a) 44 males; 32 females
 (b) Mean age: 66.35 ± 8.67
 (c) Mean PD duration: 9.16 ± 1.27 years
 (d) Years of education: 12.82 ± 3.67
(v) 125 health controls
 (a) 66 males; 59 females
 (b) Mean age: 65.91 ± 6.86
 (c) Years of education: 13.32 ± 2.93
(vi) Inclusion criteria: disease duration <10 years, MMSE ≥24, H&Y stage ≤2.5, signs of stabilization with antiparkinsonism treatment prior to study
(vii) Exclusion criteria: significant comorbidities exhibit signs of depression/anxiety, patients diagnosed with cardiovascular and/or cerebrovascular disease, anticholinergic treatments, orthopaedic or additional neurological disorders
(PD and control group subjects matched for gender, age, year of education, and course of disease)
(i) After diagnosis by the neurologist, a total of 186 PD patients were selected for the study
(ii) FOG PD patients (n = 104)
 (a) UPDRS-I: 4.53 ± 1.24
 (b) UPDRS-II: 10.64 ± 3.42
 (c) UPDRS-III: 13.71 ± 4.16
 (d) H&Y rating: 2.01 ± 0.26
 (e) Levodopa therapy, n: 62 (59.62%)
 (f) Dopamine agonist therapy, n: 42 (40.38%)
(iii) Non-FOG PD patients (n = 82)
 (a) UPDRS-I: 3.32 ± 1.54
 (b) UPDRS-II: 6.85 ± 3.32
 (c) UPDRS-III: 9.27 ± 3.81
 (d) H&Y rating: 1.92 ± 0.31
 (e) Levodopa therapy, n: 51 (62.2%)
 (f) Dopamine agonist therapy, n: 31 (37.8%)
(i) Mean HAMA scores (including somatic/psychic anxiety subdomains) and the HAMD-anxiety/somatic subdomain were quantified and compared between FOG and non-FOG PD patients
(ii) FOG PD patients:
 (a) Overall HAMA: 11.14 ± 3.71
 (b) HAMA-Somatic Anxiety: 5.20 ± 2.51
 (c) HAMA-Psychic Anxiety: 7.14 ± 3.12
 (d) HAMD-Anxiety/Somatic: 3.12 ± 1.12
(iii) Non-FOG PD patients:
 (a) HAMA: 9.96 ± 3.21
 (b) HAMA-Somatic Anxiety: 4.93 ± 2.60
 (c) HAMA-Psychic Anxiety: 6.23 ± 3.43
 (d) HAMD-anxiety/somatic: 2.67 ± 1.03
(iv) HAMD-Anxiety scale score compared with severity of FOG within FOG patients
(v) The paper does not document incidence of anxiolytic treatment
(i) FOG identified by 2/3 criteria used by Snijders et al. (2011):
 (a) Convincing subjective reports of FOG
 (b) Patient’s subjective recognition of FOG when demonstrated by an experienced clinician
 (c) Scores ≥1 on nFOG-Q
(ii) nFOG-Q used to assess severity of FOG
(i) Two-tailed t-test comparing HAMA scores between FOG and non-FOG PD patients showed higher mean scores for the FOG group but no statistically significant differences between groups.
(ii) Higher mean scores and significant differences between the HAMD-Anxiety/Somatic scale were observed between groups: overall HAMA (), HAMA-Somatic Anxiety (), HAMA-Psychic Anxiety (), and HAMD-Anxiety ()
(iii) Spearman’s rho correlation between HAMD-Anxiety and FOG questionnaire demonstrated severity of FOG positively correlated with anxiety within the FOG group:
 (a) r = 0.79 ()

Rahimi et al. [25](i) A pilot study wherein optimally medicated PD patients with intractable FOG were treated with a 90-day course of 1 mg rasagiline, with FOG and cognitive/motor measures assessed prior to and following treatment
(ii) UPDRS motor section (Items 18–31), MoCA, BAI, BDI, FOG-Q, 6 scripted gait tasks, and free walking task administered pre- and posttreatment. Gait tasks were video-recorded with subsequent analysis by two independent examiners
(iii) Prospective, experimental, pre-/posttreatment design, uncontrolled design
(iv) Participants recruited from a movement disorders clinic in London, on using the convenience-sampling method
(i) Canadian population
(ii) 14 participants completed entire study protocol (out of 18 total); PD patients separated into 3 groups upon completion of rasagiline therapy and subsequent analysis: improved, worsened, and no change
(iii) Improved (n = 6)
 (a) 5 males; 1 females
 (b) Mean age: 69.7 ± 3.88
 (c) Mean PD duration: 9.8 ± 3.13 years
 (d) Mean FOG duration: 5.2 ± 2.64 years
(iv) Worsened (n = 5)
 (a) 4 males; 1 females
 (b) Mean age: 67.8 ± 7.40
 (c) Mean PD duration: 12.0 ± 5.34 years
 (d) Mean FOG duration: 4.0 ± 2.00 years
(ii) No change (n = 3)
 (a) 3 males, 0 females
 (b) Mean age: 67.8 ± 7.40
 (c) Mean PD duration: 15.67 ± 7.02 years
 (d) Mean FOG duration: 5.0 ± 2.00 years
(v) No significant differences among groups for any of the demographic or baseline variables between the 3 groups ( values ≥0.10)
(vi) Inclusion criteria: H&Y scores between 2 and 4, experienced intractable FOG even with optimal dopaminergic treatment, on stable clinically optimated medications for 3 months prior and were clinically determined to require adjunct therapy with rasagiline
(vii) Exclusion criteria: history of neurological procedures, other neurological disorders, untreated clinical depression, diagnosed GAD, dementia, and use of a gait aid
(i) A movement disorders neurologist enrolled all participants during routine clinic visits. All enrolled patients met UK Brain Bank criteria for PD.(i) BAI scale used to assess anxiety
(ii) Improved
 (a) Mean pretreatment BAI score: 13.0 ± 7.43
 (b) Mean posttreatment BAI score: 15.7 ± 8.69,
(ii) Worsened (n = 5)
 (a) Mean pretreatment BAI score: 18.2 ± 9.15
 (b) Mean posttreatment BAI score: 16.2 ± 10.59
(iii) No change (n = 3)
 (a) Mean pretreatment BAI score: 12.7 ± 9.24
 (b) Mean posttreatment BAI score: 13.7 ± 15.18
(i) FOG diagnosed by movement disorders neurologist through gait analysis in clinic, patient report corroborated by a family member, and clinical history, UPDRS scores, and FOG-Q scores administered at the first visit(i) No significant differences in pre-/posttreatment BAI scores (t(13) = 0.26, ), or overall count and duration of FOG episodes (F(1,13) = 0.96, ; F(1,13) = 1.00, , respectively)
(ii) Higher BAI anxiety scores predicted FOG worsening following rasagiline therapy ()
(iii) Final predictive model explained 99% of the variance between the improved and worsened groups as a function of treatment with rasagiline

Huh et al. [36](i) Case control cross-sectional design
(ii) Examined postural sensory deficits linked to FOG severity through a computerized dynamic posturography system
(iii) Participants evaluated with a sensory organization test and several clinical measures (including anxiety)
(iv) Participants recruited through Samsung Medical Centre
(v) Clinical, neurological exams, and posturography were performed during the morning off-medication, at least 12 hours after holding Parkinson’s medications
(i) South Korean population
(ii) 47 patients with PD
(iii) FOG PD patients (n = 25)
 (a) 13 males; 12 females
 (b) Median age: 64.0 (58.5–69.5)
 (c) Median PD duration: 10.0 (8.0–12.0)
 (d) Median years of education: 12.0 (12.0–16.0)
(iv) Non-FOG PD patients (n = 22)
 (a) 13 males; 9 females
 (b) Median age: 64.5 (61.0–67.8)
 (c) Median PD duration: 9.0 (7.8–10.3)
 (d) Median years of education: 12.0 (9.0–16.0)
(v) 26 healthy controls
 (a) 13M, 13F
 (b) Median age: 64.0 (62.0–66.0)
 (c) Median years of education: 12.0 (12.0–16.0)
(vi) No significant differences between gender, age, and years of education between the 3 groups
(vii) No significant different between years of PD duration between FOG PD patients and non-FOG PD patients
Exclusion criteria: unable to stand safely unaided, history of falls in the last 12 months, dementia, visual disturbances, clinical signs of disorders affecting proprioception, musculoskeletal problems, orthostatic hypotension, neurosurgical interventions, history, or clinical signs of vestibular disease
(data are shown as median (25th–75th quartile))
(i) A diagnosis of idiopathic PD made by a specialist experienced in movement disorders based on UK Brain Bank Criteria.
(ii) Median UPDRS-III score:
 (a) Freezers: 35.0 (33.0–38.3)
 (b) Nonfreezers: 36.0 (31.5–37.3)
 (c) Controls: 0 (0–2.0)
(iii) Median H&Y stage:
 (a) Freezers: 2.5 (2.5–3.0)
 (b) Nonfreezers: 2.5 (2.0–3.0)
(data are shown as median (25th–75th quartile)
(i) BAI used to assess anxiety
(ii) FOG PD patients:
 (a) Median: 7.0 (3.0–14.0)
(iii) Non-FOG PD patients:
 (a) Median: 5.0 (3.0–12.3)
(iv) Controls:
 (a) Median: 1.0 (0–2.0)
(data are shown as median (25th–75th quartile)
(i) nFOG-Q used to assign participants to the FOG group based on item 1 of the questionnaire (if they had experienced FOG during the past month), and if ≥ 1, FOG episodes were elicited and detected by 2 movement specialists using a 2-minute tight and rapid turning-in-place protocol
(ii) FOG PD patients:
 (a) Median nFOG-Q: 12.0 (10.5–18.5)
(iii) Non-FOG PD patients:
 (a) Median: 0
(data are shown as median (25th–75th quartile)
(i) FOG patients and non-FOG patients had significantly higher BAI scores than the control group () with no significant difference between groups ()

Ehgoetz Martens et al. [28](i) Prospective longitudinal study design
(ii) PD patients were separated into 3 groups based on their responses to FOG-Q3 at baseline and a follow-up point 6–24 months later, with measures of anxiety and FOG severity taken at both of these time points
(iii) Participants recruited from University of Sydney’s PD Research Clinic at the Brain and Mind Centre from 2008 to 2016
(i) Australian population
(ii) 221 PD patients
(iii) Continuing freezer (n = 92)
 (a) 56 males; 36 females
 (b) Mean age: 70.24 ± 10.85
 (c) Mean PD duration: 9.66 ± 7.50 years
(iv) Transitional freezer (n = 41)
 (a) 26 males; 15 females
 (b) Mean age: 70.75 ± 9.39
 (c) Mean PD duration: 5.97 ± 4.14 years
(v) Nonfreezers (n = 88)
 (a) 52 males; 36 females
 (b) Mean age: 65.37 ± 9.84
 (c) Mean PD duration: 3.16 ± 4.32 years
(vi) Significant group effects for age () and disease duration () found and therefore entered as covariates in subsequent analysis
(i) A diagnosis of idiopathic PD made by a specialist experienced in movement disorders based on UK Brain Bank Criteria.
(ii) Mean baseline UPDRS-III scores:
 (a) Continuing freezers: 48.64 ± 20.68
 (b) Transitional freezers: 35.14 ± 17.07
 (c) Nonfreezers: 24.51 ± 13.62
(iii) Mean follow-up UPDRS-III scores:
 (a) Continuing freezers: 49.81 ± 21.06
 (b) Transitional freezers: 38.42 ± 15.33
 (c) Nonfreezers: 25.51 ± 14.40
(i) HADS-A used to assess anxiety
(ii) Mean baseline HADS-A scores:
 (a) Continuing freezers: 2.94 ± 3.89
 (b) Transitional freezers: 3.65 ± 3.08
 (c) Nonfreezers: 1.18 ± 2.31
(iii) Mean follow-up HADS-A scores:
 (a) Continuing freezers: 5.38 ± 4.19
 (b) Transitional freezers: 5.18 ± 4.68
 (c) Nonfreezers: 3.62 ± 2.93
(i) FOG-Q3 used to assign participants to groups based on scores, FOG-Q total used to assess severity (with Item 3 removed)
(ii) Mean FOG-Q total scores:
 (a) Continuing freezers: 10.23 ± 4.19
 (b) Transitional freezers: 2.68 ± 1.74
 (c) Nonfreezers: 1.41 ± 1.37
(iii) Mean follow-up FOG-Q total scores:
 (a) Continuing freezers: 10.79 ± 4.02
 (b) Transitional freezers: 6.17 ± 2.39
 (c) Nonfreezers: 1.68 ± 1.60
(i) HADS-A scores increased significantly from baseline to follow-up across all 3 groups, and both continuing and transitional freezers had significantly greater mean HADS-A scores than nonfreezers at baseline and follow-up
(ii) Correlational analysis revealed HADS-A scores were significantly associated with FOG-Q total scores (0.206, )—predictive model constructed with HADS-A and FOG-Q total score as variables with the overall predictive success of 82.1%

Ou et al. [27](i) Prospective longitudinal study design
(ii) PD patients were assessed at baseline and at follow-up 2.5–3 years later to investigate potential clinical predictors of FOG, which included anxiety
(iii) Participants
recruited from West China Hospital of Sichuan’s Department of Neurology between March 2012 and May 2013
(i) Chinese population
(ii) 225 PD patients
(iii) 85 developed FOG after 3 years
 (a) 44 males; 41 females
 (b) Mean age: 62.5 ± 11.1
 (c) Mean PD duration: 6.8 ± 3.3 years
(iv) 140 did not develop FOG after 3 years
 (a) 85 males; 55 females
 (b) Mean age: 58.1 ± 12.6
 (c) Mean PD duration: 4.5 ± 2.4 years
(v) Inclusion criteria: between H&Y stages I-III, no prior FOG
(vi) Exclusion criteria: atypical or secondary Parkinsonism, unstable disease, participants who declined follow-up
(vii) Freezers significantly older () and had significantly longer PD duration () than nonfreezers on average and further analysis done with ANCOVA adjusted for age and disease duration
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) Mean baseline UPDRS-III scores:
 (a) Freezers: 32.9 ± 12.8
 (b) Nonfreezers: 21.4 ± 10.5
(iii) Mean follow-up UPDRS-III scores:
 (a) Freezers: 44.3 ± 14.8
 (b) Nonfreezers: 29.8 ± 11.2
(iv) Average change in UPDRS-III score
 (a) Freezers: 3.7 ± 3.4
 (b) Nonfreezers: 3.2 ± 3.0
(v) Mean baseline H&Y stages:
 (a) Freezers: 2.4 ± 0.6
 (b) Nonfreezers: 1.5 ± 0.6
(vi) Mean follow-up H&Y stages:
 (a) Freezers: 2.9 ± 0.8
 (b) Nonfreezers: 2.2 ± 0.5
(i) HAMA used to assess anxiety
(ii) Mean baseline HAMA scores:
 (a) Freezers: 10.3 ± 6.8
 (b) Nonfreezers: 7.2 ± 5.8
(iii) Mean follow-up HAMA scores:
 (a) Freezers: 11.0 ± 6.9
 (b) Nonfreezers: 7.7 ± 6.0
(iv) Average change in HAMA score
 (a) Freezers: −0.2 ± 1.9
 (b) Nonfreezers: −0.2 ± 1.7
(i) FOG-Q3 ≥ 1 used to separate freezers from nonfreezers
(ii) Freezing episodes observed by the neurologist during visit or reported by patient/family/caregiver if happened at home
(i) Higher mean HAMA scores in freezers than nonfreezers at both baseline and follow-up ()
(ii) Annual change in HAMA did not differ significantly between groups
()

Ehgoetz Martens et al. [26] (fMRI study)(i) An experimental task-based fMRI study
(ii) PD patients with FOG completed virtual reality gait paradigm while in 3T MRI scanner
(iii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(vi) Gait observed during the virtual reality task (foot tapping) was compared between freezing episodes and normal foot-tapping using fMRI
(v) Participants recruited from University of Sydney’s Brain and Mind Centre
(i) Australian population
(ii) 41 PD patients with FOG, 5 freezing episodes were required in the MRI scanner for effective modelling of freezing events: 20 met this criteria (MRI + group), while 21 did not (MRI group)
(iii) MRI+
 (a) 17M, 3F
 (b) Mean age: 66.45 ± 5.34
(iii) MRI−
 (a) 15 males; 16 females
 (b) Mean age: 68.75 ± 7.26
(iv) Inclusion criteria: FOG-Q3 ≥ 1, clinically evident FOG confirmed by a neurologist, ability to complete virtual reality task in MRI scanner after a minimum of 12 hours following intake of dopaminergic medication (off state)
(v) Exclusion criteria: neurological comorbidities and presence of pathological lesions/abnormalities on structural imaging
(vi) Notably MRI+ and − groups were matched in age, symptom severity, FOG-Q3, and anxiety
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) MRI+
 (a) Mean UPDRS-III: 34.15 ± 12.19
 (b) MRI−
 (c) Mean UPDRS-III: 33.62 ± 15.84
(i) HADS-A used to assess anxiety
(ii) MRI+
 (a) Mean HADS-A: 6.3 ± 3.25
(iii) MRI−
 (a) Mean HADS-A: 5.29 ± 3.98
(i) FOG-Q3 ≥ 1 an inclusion criteria for the study used to identify PD patients with FOG in this study, which was additionally confirmed by a neurologist
(ii) Objective measures of FOG collected through virtual gait paradigm
(iii) MRI +
 (a) Mean step time variability: 24.99 ± 7.04 s
 (b) Modal foot step latency: 0.38 ± 0.17 s
 (c) Overall time spent frozen: 0.14 ± 0.08%
(iv) MRI−
 (a) Mean step time variability: 21.27 ± 8.32 s
 (b) Modal foot step latency: 0.64 ± 0.29 s
 (c) Overall time spent frozen: 0.07 ± 0.14%
(v) HADS-total one of three variables used to calculate the Freezing Component Index which was compared to the freezing network signature collected via fMRI
(i) Higher HADS-A scores associated with increased coupling between limbic network and ventral striatum + cognitive control network during gait freezing compared to normal foot tapping

Gilat et al. [42](i) A resting state MRI study investigating functional connectivity differences in PD patients with and without FOG
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants recruited through Oregon Health and Science University’s Parkinson’s Centre of Oregon clinic
(i) American population
(ii) Data from 40 PD participants included in study
(iii) 19 freezers
 (a) Gender demographics not documented
 (b) Mean age: 68.4 ± 7.2
 (c) Mean PD duration: 9.31 ± 6.6 years
(iv) 21 Nonfreezers
 (a) Gender demographics not documented
 (b) Mean age: 66.9 ± 7.6
 (c) Mean PD duration: 6.01 ± 4.6 years
(v) Inclusion criteria: participants able to stop taking all dopaminergic medication for 12 hours prior to the experiment
(vi) Exclusion criteria were as follows: unable to safely walk 20 feet without an aid, previous joint replacement, musculoskeletal or vestibular disorder, claustrophobia, severe tremor, and presence of metal implants
(vii) No significant differences were
found between freezers and nonfreezers in terms of age (t = 0.645, ), disease duration (t = 0.019, ), and UPDRS-III (t = 1.63, )
(i) A diagnosis of idiopathic PD by both a neurologist and movement disorders specialist
(ii) Freezers
 (a) Mean UPDRS-III: 42.7 ± 14
 (b) Mean H&Y stage: 2 ± 2 − 4
(iii) Nonfreezers
 (a) Mean UPDRS-III: 36.1 ± 11
 (b) Mean H&Y stage: 2 ± − 3
(i) Items 21 and 9 of PDQ-39 administered for anxiety outcome measure
(ii) Freezers mean PDQ-39:
 (a) Item 21: 1 ± 0 − 2
 (b) Item 9: 1 ± 0 − 2
(iii) Nonfreezers mean PDQ-39:
 (a) Item 21: 1 ± − 0 − 3
 (b) Item 9: 0 ± 0 − 2
(i) FOG-Q3 ≥ 1 used to separate freezers from nonfreezers
(ii) FOG was objectively quantified through a turning-in-place task with inertial sensors, allowing the FOG ratio to be calculated for each participant
(iii) Mean FOG ratio
 (a) Freezers: 3.21 ± 2.9
 (b) Nonfreezers: 1.04 ± 0.73
(i) No significant differences were observed between freezers and nonfreezers for Item 21 of the PDQ-39
(Z = −0.520, )
(ii) A trend towards significance was exhibited for freezers compared to nonfreezers in terms of higher PDQ Item 9 scores (z = −1.79, ), but this ultimately was not significant
(iii) Freezers had significantly higher FOG-ratios than nonfreezers (t(38) = 3.12, ), and worsening FOG severity was associated with greater degrees of anticoupling between the amygdala and the frontoparietal attention control network

Ehgoetz Martens et al. [28](i) An experimental study to characterize subtypes of freezing of gait with a newly generated FOG questionnaire: the C-FOG
(ii) Participants subdivided into 3 categories based on C-FOG results: asymmetric-motor, anxious, and sensory-attention
(iii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(i) Australian population
(ii) 41 participants
(iii) Anxious subgroup (n = 15)
 (a) 11 males; 4 females
 (b) Mean age: 66.8 ± 8
 (c) Mean PD duration: 12.3 ± 3.6 years
(iv) Asymmetric-motor subgroup (n = 13)
 (a) 8 males; 5 females
 (b) Mean age: 68.2 ± 9.3
 (c) Mean PD duration: 8.6 ± 4.8 years
(v) Sensory attention subgroups (n = 13)
 (a) 10 males; 3 females
 (b) Mean age: 70.5 ± 7.8
 (c) Mean PD duration: 8.7 ± 4.1 years
(vi) No inclusion or exclusion criteria directly specified by paper
(vii) Apart from significantly higher mean UPDRS-III scores in the off state compared with the asymmetric-motor group (F2,35 = 3.64, ), no other statistically significant differences in baseline demographic information between the anxiety and remaining subgroups emerged.
(i) PD patients with confirmed FOG participated in the study
(ii) Anxious subgroup
(a) Mean H&Y stage: 2.8 ± 0.7
(b) Mean UPDRS-III ON: 38.7 ± 10.1
(c) Mean UPDRS-III OFF: 44.9 ± 9.6
(iii) Asymmetric-motor subgroup
 (a) Mean H&Y stage: 2.5 ± 0.9
 (b) Mean UPDRS-III ON: 30.9 ± 16.6
 (c) Mean UPDRS-III OFF: 34.6 ± 11.9
(iv) Sensory attention subgroup
 (a) Mean H&Y Stage: 2.7 ± 0.4
 (b) Mean UPDRS-III ON: 37.7 ± 12.0
 (c) Mean UPDRS-III OFF: 43.1 ± 8.7
(i) PAS used to assess anxiety
(ii) Anxious subgroup
 (a) Mean PAS: 15.5 ± 6.8
(iii) Asymmetric-motor subgroup
 (a) Mean PAS: 9.9
(iv) Sensory attention subgroup
(a) Mean PAS: 13.2 ± 9.6
(i) FOG was assessed with the C-FOG as well as the FOG-Q total
(ii) Each participant’s gait was assessed over the course of 8 walking trials, both ON and OFF dopaminergic medication, with testing order counterbalanced across patients. The percentage of freezing time (%FOG) was also calculated.
(iii) Anxious subgroup
 (a) Mean FOG total: 11.7 ± 3.0 min
(vi) Asymmetric-motor subgroup
(a) Mean FOG total: 10.7 ± 3.3 min
(v) Sensory attention subgroup
 (a) Mean FOG total: 11.8 ± 5.3 min
(vi) %FOG was significantly positively related to the anxiety subgroup data cluster (r = 0.43)—this result formed the basis of delineating an anxiety subgroup
(i) Mean PAS scores were significantly higher in the anxious subgroup compared to the asymmetric-motor (t26 = −2.19, ) and sensory attention (13.2 ± 9.6, t26 = −1.81, ) subgroups
(ii) Significantly higher degrees of freezing
on anxiety-related items of the C-FOG compared to the motor-related
(t14 = −3.91, ) and set shifting-
related items (t14 = 4.34, )
within the anxious subgroup

Lagravinese et al. [43](i) An experimental study to examine the effect of emotional stimuli on gait in PD patients with and without FOG
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(iii) Participants were recruited from the University of Genova’s Department of Neuroscience
(i) Italian population
(ii) 30 patients with PD
(iii) PD FOG+ (n = 15)
 (a) No gender demographics
 (b) Mean age: 71.87 ± 4.75
 (c) Mean PD duration: 11.20 ± 5.22 years
(iv) PD FOG− (n = 15)
 (a) No gender demographics
 (b) Mean age: 73 ± 6.31
 (c) Mean PD duration: 10.42 ± 5.34 years
(v) 14 healthy age-matched controls (ELD)
 (a) No gender demographics
 (b) Mean age: 66.58 ± 6
(vi) Inclusion criteria: an H&Y stage of ≤3 and ability to walk unassisted
(vii) Exclusion criteria: MMSE <24, history of additional neurological disorders, and any visual/vestibular/orthopaedic
impairment that would negatively affect task performance
(viii) There were no statistically significant differences between groups for age (), disease duration (), H&Y stage (), or UPDRS-III score ().
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) PD FOG+
 (a) Mean H&Y stage: 2.43 ± 0.58
 (b) Mean UPDRS-III: 27.18 ± 13.13
(iii) PD FOG−
 (a) Mean H&Y stage: 2.05 ± 0.64
 (b) Mean UPDRS-III: 20.37 ± 10.27
(i) BAI used to assess anxiety
(ii) PD FOG+
 (a) Mean BAI: 9.35 ± 4.82
(iii) PD FOG−
 (a) Mean BAI: 9.87 ± 7.41
(iv) ELD
Mean BAI: 5.42 ± 3.73
(i) The nFOG was used to delineate the PD FOG+ and PD FOG− groups, as well as a measure of FOG severity in the PD FOG+ group
(ii) PD FOG+
 (a) nFOG-Q total: 15.28 ± 4.50
(i) No statistically significant differences in BAI scores between PD FOG+, PD FOG−, and ELD groups ()

Stefanova et al. [41](i) An experimental study performed in to explore whether attentional set shifting and inhibitory control were associated with FOG in PD
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(iii) Participants were recruited from the University of Belgrade’s Institute of Neurology
(i) Serbian population
(ii) 66 patients with PD
(iii) Freezers (n = 30)
 (a) No gender demographics
 (b) Mean age: 64.90 ± 8.29
 (c) Mean PD duration: 11.61 ± 4.42 years
(iv) Nonfreezers (n = 36)
 (a) No gender demographics
 (b) Mean age: 64.67 ± 7.16
 (c) Mean PD duration: 10.09 ± 5.94
(v) Healthy age and sex-matched controls (n = 22)
 (a) No gender demographics
 (b) Mean age: 65.04 ± 7.64
(vi) Inclusion criteria: ≥ 45 years old, an H&Y stage of <4, stable and optimized on antiparkinsonism treatment during the 4 weeks prior to study initiation and an MMSE ≥25
(vii) Exclusion criteria: significant comorbidities limiting gait, major depression according to DSM-IV criteria, and treatment with anticholinergic medications
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) Freezers
(a) Mean H&Y stage: 2.77 ± 0.50
(b) Mean UPDRS-III: 37.50 ± 11.44
(iii) Nonfreezers
(a) Mean H&Y stage: 2.29 ± 0.64
(b) Mean UPDRS-III: 32.33 ± 9.84
(i) HAMA used to assess anxiety
(ii) Freezers
(a) Mean HAMA: 10.07 ± 6.10
(iii) Nonfreezers
(a) Mean HAMA:
8.18 ± 6.10
(iv) Control group
Mean HAMA:
6.45 ± 4.41
(i) A score of ≥1 on FOG-Q3 used to separate freezers and nonfreezers
(ii) Two of the following criteria required for FOG confirmation
(a) Direct observation of FOG by 2 experienced neurologists
(b) Self-reported FOG by the participant
(c) Recognition of past episodes of FOG occurrence when the phenomena was described by a physician
(iii) Mean FOG-Q total score
(a) Freezers: 12.85 ± 4.88
(b) Nonfreezers: 6.28 ± 5.50
(i) HAMA differences between the groups were not statistically significant ()

Raffo De Ferrari et al. [15](i) An experimental study examining the relationship between Theory of Mind and FOG presence in PD patients
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(iii) Participants recruited from the University of Genoa’s Department of Neuroscience
(i) Italian population
(ii) 29 patients with PD
(iii) PD FOG+ (n = 15)
 (a) No gender demographics
 (b) Mean age: 72 ± 4.5
 (c) Mean PD duration: 10.2 ± 6.3 years
(iv) PD FOG− (n = 14)
 (a) No gender demographics
 (b) Mean age: 71 ± 4.3
 (c) Mean PD duration: 7.9 ± 3.5 years
(v) Healthy age-matched controls (n = 19)
 (a) No gender demographics
 (b) Mean age: 71 ± 6.8
(vi) Inclusion criteria: a H&Y stage ≤3, and an MMSE >24
(vii) PD group exclusion criteria: met DSM-IV criteria for major depression or were undergoing treatment via deep brain stimulation
(viii) Healthy control exclusion criteria: a diagnosis of PD or other neurological disorder, major depression, or an MMSE <24
(ix) There were no statistically significant differences present between age or gender between groups ( always >0.05)
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) PD FOG+
 (a) Mean H&Y stage: 2.6 ± 0.5
 (b) Mean UPDRS-III: 31 ± 9.5 s
(iii) PD FOG−
 (a) Mean H&Y stage: 2.4 ± 0.5
 (b) Mean UPDRS-III: 30.8 ± 9.5
(i) BAI used to assess anxiety
PD FOG+
 (a) Mean BAI: 11.9 ± 10.7
(ii) PD FOG−
 (a) Mean BAI: 7.5 ± 6.8
(iii) Control group
Mean BAI: 7.8 ± 6.4
(i) nFOG was used to separate PD participants into freezers and nonfreezers
(ii) FOG presence confirmed via direct observation by a movement disorders neurologist in clinic using 360° turning tasks
(iii) PD FOG+
 (a) nFOG-Q total: 11.3 ± 3.9
(i) No significant main effect for group was found for the BAI (F(2.47 = 1.39, )

Vandenbossche et al. [30](i) An experimental study investigating executive functioning and attention in PD patients with FOG with participants assessed in their home environment
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(i) Belgian population
(ii) 22 patients with PD
(iii) Freezers (n = 11)
 (a) 9 males; 2 females
 (b) Mean age: 67.32 ± 2.72
 (c) Mean PD duration: 10.45 ± 0.70 years
(iv) Nonfreezers (n = 11)
 (a) 9 males; 2 females
 (b) Mean age: 68.20 ± 1.74
 (c) Mean PD duration: 8.55 ± 1.09 years
(v) Healthy age-, gender-, and education-matched controls (n = 10)
 (a) 8 males; 2 females
 (b) Mean age: 66.10 ± 2.27
(vi) Inclusion criteria: no additional neurological or orthopaedic disorders
(vii) Exclusion criteria: MMSE <24
(viii) No significant differences were present between age and gender, with values consistently >0.45
(i) Confirmed diagnosis of idiopathic PD by a specialist neurologist (who administered both neurological and neuropsychological examinations)
(ii) Freezers
 (a) Mean H&Y stage: 2.5 ± 0.39
 (b) Mean UPDRS-III: 38.91 ± 3.08
(iii) Nonfreezers
 (a) Mean H&Y stage: 2.23 ± 0.26
 (b) Mean UPDRS-III: 34.18 ± 2.46
(i) HADS-A used to assess anxiety
(ii) Mean HADS-A scores
 (a) Freezers: 7.36 ± 0.90
 (b) Nonfreezers: 6.09 ± 1.16
 (c) Healthy controls: 5.50 ± 1.63
(i) nFOG used to separate freezers and nonfreezers with scores >0 meeting criteria for the freezer group(i) Group-to-group comparisons of mean HADS-A scores were not statistically significant ( values consistently >0.33)
(ii) A correlational analysis revealed HADS-A score was significantly associated with nFOG-Q total score (Spearman ρ = 0.81, )

Heremans et al. [40](i) An experimental study exploring handwriting differences in PD patients with FOG
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(i) Belgian population
(ii) 30 patients with PD
(iii) Freezers (n = 15)
 (a) 12 males; 3 females
 (b) Mean age: 65 ± 9
 (c) Mean PD duration: 9 ± 5 years
(iv) Nonfreezers (n = 15)
 (a) 10 males; 5 females
 (b) Mean age: 65 ± 9
 (c) Mean PD duration: 8 ± 5 years
(v) Healthy age-matched controls (n = 15)
 (a) 5 males; 10 females
 (b) Mean age: 64.3 ± 15
(vi) Inclusion criteria: between H&Y stages 1–3 during the ON state, experiencing writing problems as indexed by an UPDRS-II item 2.7 score of >1 and had no additional neurological disorders or history of depression
(vii) Exclusion criteria: MMSE ≤24, disease or surgery involving the upper limb, deep brain stimulation, and vision problems which impacted performance on the writing tasks
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) Freezers
 (a) Mean H&Y stage: 2 ± 0
 (b) Mean UPDRS-III: 40 ± 16
(iii) Nonfreezers
 (a) Mean H&Y stage: 2 ± 0
 (b) Mean UPDRS-III: 29 ± 9
(i) HADS-A was used to assess anxiety
(ii) Mean HADS-A scores
 (a) Freezers: 7 ± 4
 (b) Nonfreezers: 4 ± 4
(i) A nFOG-Q score of ≥1 was used to delineate the freezer and nonfreezer groups within PD patients
(ii) Mean FOG-Q total scores
 (a) Freezers: 14 ± 8
 (b) Nonfreezers: 0 ± 0
(i) Higher mean HADS-A score evidenced by the freezers compared to the nonfreezers was not statistically significant ()

Kostić et al. [31](i) An experimental MRI study exploring patterns of grey matter tissue loss in PD patients with FOG
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(iii) Participants were recruited from outpatient clinics in the University of Belgrade’s Department of Neurology
(i) Serbian population
(ii) 37 patients with PD
(iii) PD-FOG (n = 17)
 (a) 10 males; 7 females
 (b) Mean age: 64 ± 8
 (c) Mean PD duration: 12 ± 5 years
(iv) PD-noFOG− (n = 20)
 (a) 12 males; 8 females
 (b) Mean age: 63 ± 6
 (c) Mean PD duration: 11 ± 4 years
(v) Healthy controls (n = 34)
 (a) 20 males; 14 females
 (b) Mean age: 64 ± 7
(v) Inclusion criteria: ≥ 45 years old, had an H&Y stage of <4 during the OFF state, had undergone stable and optimized antiparkinsonism treatment during the 4 weeks prior to study initiation, and had an MMSE ≥25
(vi) Exclusion criteria: significant comorbidities limiting gait, major depression according to DSM-IV criteria, treatment with anticholinergic medications, and underlying focal or diffuse brain damage
(vii) No significant differences in age (), gender (), and disease duration () between groups
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) PD-FOG
 (a) Mean H&Y stage: 2.7 ± 0.5
 (b) Mean UPDRS-III: 39 ± 12
(iii) PD-noFOG
 (a) Mean H&Y stage: 2.4 ± 0.6
 (b) Mean UPDRS-III: 29 ± 12
(i) HAMA was used to assess anxiety
(ii) Mean HAMA scores
 (a) PD-FOGs: 14 ± 11
 (b) PD-noFOG: 7 ± 6
 (c) Healthy controls: 6 ± 4
(i) A score of ≥1 on FOG-Q3 used to separate freezers and nonfreezers
(ii) Two of the following criteria required for FOG confirmation
 (a) Direct observation of FOG by 2 experienced neurologists
 (b) Self-reported FOG by the participant
 (c) Recognition of past episodes of FOG occurrence when the phenomena was described by a physician
(i) FOG-Q total scores were quantified
 (a) Mean FOG-Q total scores
 (b) PD-FOG: 16 ± 3
 (c) PD-noFOG: 5 ± 3
(i) Mean HAMA scores were higher in PD-FOG compared to PD-noFOG () and healthy controls ()

Vanden bossche et al. [39](i) An experimental study that investigated whether sequence learning was diminished in PD patients with FOG, with participants completing a serial reaction time task with random or sequenced block conditions
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(i) Belgian population
(ii) 28 patients with PD
(iii) Freezers (n = 14)
 (a) 11 males; 3 females
 (b) Mean age: 65.72 ± 7.91
 (c) Mean PD duration: 10.21 ± 2.97 years
(iv) Nonfreezers (n = 14)
 (a) 11 males; 3 females
 (b) Mean age: 68.03 ± 5.11
 (c) Mean PD duration: 8.21 ± 3.40 years
(v) Healthy age-, gender-, and education-matched controls (n = 14)
 (a) 11 males; 3 females
 (b) Mean age: 67.07 ± 6.64
(vi) Inclusion criteria: no additional neurological or orthopaedic disorders and normal or corrected-to-normal vision
(vii) Exclusion criteria: MMSE <24
(i) Confirmed diagnosis of idiopathic PD by a specialist neurologist (who administered both neurological and neuropsychological examinations)
(ii) Freezers
 (a) Mean H&Y stage: 2.43 ± 0.416
 (b) Mean UPDRS-III: 37.21 ± 15.99
(iii) Nonfreezers
 (a) Mean H&Y stage: 2.43 ± 0.319
 (b) Mean UPDRS-III: 35.64 ± 9.10
(i) HADS-A used to assess anxiety
(ii) Mean HADS-A scores
 (a) Freezers: 6.57 ± 3.13
 (b) Nonfreezers: 5.64 ± 3.56
 (c) Healthy controls: 5.29 ± 5.54
(i) nFOG used to separate freezers and nonfreezers with scores >0 meeting criteria for the freezer group(i) HADS-A scores were not significantly different between groups (, )

Rubino et al. [38](i) An experimental MRI study examining differences in grey matter volume between PD patients with and without FOG
(ii) Baseline assessment data, including anxiety outcome measures, performed on all participants
(i) Italian population
(ii) 26 patients with PD
(iii) FOG+ (n = 13)
 (a) 10 males; 3 females
 (b) Mean age: 68.077 ± 8.221
 (c) Mean PD duration: 8.154 ± 4.180 years
(iv) FOG− (n = 13)
 (a) 9 males; 4 females
 (b) Mean age: 68.692 ± 7.664
 (c) Mean PD duration: 7.077 ± 2.985 years
(v) Inclusion criteria: treatment with stable dopaminergic medications, had appropriate visual acuity and hearing for the testing procedure, an MMSE >26, absence of dementia as per Movement Disorder Society clinical criteria, and no contraindications to MRI scan
(vi) Exclusion criteria: additional neurological disorders, uncertain history of chronic dopaminergic medication responsiveness, unstable medical illness, history of alcoholism/drug abuse/head trauma/mental disorders, and presence of brain lesions, tumour, or marked cortical atrophy MRI
(vii) No significant differences in gender, age, and disease duration between groups ( values consistently > 0.42)
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) FOG+
 (a) Mean H&Y stage: 2.423 ± 0.400
 (b) Mean UPDRS-III: 17.846 ± 6.22
(iii) FOG−
 (a) Mean H&Y stage: 2.307 ± 0.325
 (b) Mean UPDRS-III: 17.230 ± 2.77
(i) HAMA used to quantify anxiety
(ii) Mean HAMA scores
 (a) FOG+: 6.154 ± 3.95
 (b) FOG−: 6.385 ± 4.46
(i) Participants were classified as FOG+ if they had a score of ≥1 on the FOG-Q3 and direct observation of FOG by 2 experienced neurologists or self-report of FOG by participant and/or the recognition of past episodes of FOG when the phenomena was described by a physician(i) Mean HAMA scores were not significantly different in FOG+ vs. FOG− ()

Pimenta et al. [33](i) An observational cross-sectional study examining the relationship between anxiety and FOG in PD
(ii) Several self-report measures were administered to PD patients with and without FOG, including anxiety outcome measures
(iii) Participants were recruited from a movement disorders clinic the State of Bahia Health Attention for the Elderly in Brazil
(i) Brazilian population
(ii) 78 patients with PD
(iii) Freezers (n = 27)
 (a) 16 males; 11 females
 (b) Median age: 71 (61–85)
 (c) Median PD duration: 9.0 (2–20)
(iv) Nonfreezers (n = 51)
 (a) 26 males; 25 females
 (b) Median age: 68 (60–89)
 (c) Median PD duration: 4.0 (1–14)
(v) Inclusion criteria: able to walk without the assistance of another person (with or without a gait aid)
(vi) Exclusion criteria: atypical parkinsonism, dementia, severe visual or auditory disturbance, and presence of comorbidities that affected balance and gait.
(vii)Freezers were significantly older than nonfreezers (), had significantly longer disease durations than nonfreezers (), and the gender composition of each group was not significantly different ()
(data are shown as median (range))
(i) A diagnosis of idiopathic PD made by a trained neurologist based on UK Brain Bank Criteria
(ii) Freezers
 (a) Median H&Y stage: 3.0 (2–4)
 (b) Mean UPDRS-III: 39.8 ± 9.9
(ii) Nonfreezers
 (a) Median H&Y stage: 2.5 (1.5–3)
 (b) Mean UPDRS-III: 28.4 ± 11.7
(i) Anxiety subscale of HADS (HADS-A) subtotalled and compared between groups with scores ≥ 8 meeting criteria for anxiety disorder
(ii) Freezers
 (a) Number of PD patients with HADS-A ≥ 8: 19 (70% of freezers)
(iii) Nonfreezers
 (a) Number of PD patients with HADS-A ≥ 8: 16 (31% of nonfreezers)
(i) Freezers were classified based on a FOG-Q3 score of ≥1
(ii) FOG items 3–6 score used to assess FOG severity
(i) Significantly higher proportions of freezers had a HADS-A score ≥ 8 than nonfreezers ()
(ii) Correlation analysis demonstrated a significant relationship between HADS-A and FOG-Q3 (rho = 0.44, ) and FOG severity (rho = 0.36, )
(iii) Univariate regression analysis showed a significant association between HADS-A and FOG severity (B = 2.92, 95% CI: 1.24–4.59, )
(iv) Multivariate linear regression analysis also indicated a significant relationship between HADS-A ≥8 and FOG severity (B = 1.89, 95% CI: 0.47–3.31, adjusted R2 = 0.385, ) with a HADS-A score of ≥8 accounting for 38% of the variance in FOG severity scores