Association of oral frailty and gait characteristics in patients with cerebral small vessel disease.

BACKGROUND: The objectives of this study were twofold: (1) to compare gait characteristics between cerebral small vessel disease (CSVD) patients with low-risk oral frailty (OF) and high-risk OF, particularly during dual-task walking (DTW); (2) to investigate the association of OF, the gait characteristics of DTW, and falls among older adults patients with CSVD. METHODS: A total of 126 hospitalized patients diagnosed with CSVD were recruited and classified into a low-risk group (n = 90) and a high-risk group (n = 36) based on OF status in our study. Comprehensive data pertaining to basic parameters (cadence, as well as stride time, velocity and length), variability, asymmetry, and coordination were gathered during both single-task walking (STW) and DTW. Additionally, the number of falls was calculated. Subsequently, t-test or chi-squared test was used for comparison between the two groups. Furthermore, linear regression analysis was employed to elucidate the association of the OF index-8 score and gait parameters during cognitive DTW. Also, logistic regression models were utilized to assess the independent association of OF risk and falls. RESULTS: During cognitive DTW, the high-risk group demonstrated inferior performance in terms of basic parameters (p < 0.01), coefficient of variation (CV) of velocity and stride length (p < 0.05), as well as phase coordination index (PCI) when compared with the low-risk group (p < 0.05). Notably, differences in basic gait parameters were observed in cognitive DTW and STW conditions between the two groups (p < 0.01). However, only the high-risk group evinced significant variations in CV and PCI during cognitive DTW, as opposed to those during STW (p < 0.05). Furthermore, our findings also revealed the association of OF, the gait characteristics of cognitive DTW, (p < 0.01) and falls (p < 0.05). CONCLUSION: CSVD patients with a high risk of OF need to pay more attention to their gait variability or coordination. Also, they are recommended to undergo training involving dual-task activities while walking in daily life, thereby reducing the deterioration and mitigating the risk of falls. Besides, this study has confirmed an association of OF and DTW gait as well as falls in patients with CSVD.

Intensive Care Unit- Acquired Weakness and Hospital Functional Mobility Outcomes Following Invasive Mechanical Ventilation in Patients with COVID-19: A Single-Centre Prospective Cohort Study.

Background: Acute physical function outcomes in ICU survivors of COVID-19 pneumonia has received little attention. Critically ill patients with COVID-19 infection who require invasive mechanical ventilation may undergo greater exposure to some risk factors for ICU-acquired weakness (ICUAW). Purpose: To determine incidence and factors associated with ICUAW at ICU discharge and gait dependence at hospital discharge in mechanically ventilated patients with COVID-19 pneumonia. Methods: Single-centre, prospective cohort study conducted at a tertiary hospital in Madrid, Spain. We evaluated ICUAW with the Medical Research Council Summary Score (MRC-SS). Gait dependence was assessed with the Functional Status Score for the ICU (FSS-ICU) walking subscale. Results: During the pandemic second wave, between 27 July and 15 December, 2020, 70 patients were enrolled. ICUAW incidence was 65.7% and 31.4% at ICU discharge and hospital discharge, respectively. Gait dependence at hospital discharge was observed in 66 (54.3%) patients, including 9 (37.5%) without weakness at ICU discharge. In univariate analysis, ICUAW was associated with the use of neuromuscular blockers (crude odds ratio [OR] 9.059; p = 0.01) and duration of mechanical ventilation (OR 1.201; p = 0.001), but not with the duration of neuromuscular blockade (OR 1.145, p = 0.052). There was no difference in corticosteroid use between patients with and without weakness. Associations with gait dependence were lower MRC-SS at ICU discharge (OR 0.943; p = 0.015), older age (OR 1.126; p = 0.001), greater Charlson Comorbidity Index (OR 1.606; p = 0.011), longer duration of mechanical ventilation (OR 1.128; p = 0.001) and longer duration of neuromuscular blockade (OR 1.150; p = 0.029). Conclusions: In critically ill COVID-19 patients, the incidence of ICUAW and acute gait dependence were high. Our study identifies factors influencing both outcomes. Future studies should investigate optimal COVID-19 ARDS management and impact of dyspnea on acute functional outcomes of COVID-19 ICU survivors.

Falls risk is predictive of dysphagia in Parkinson's disease.

OBJECTIVE: Evaluate the relationship between falls, freezing of gait, and swallowing disturbance in Parkinson's disease (PD). BACKGROUND: Dysphagia is a common symptom in PD, and is often thought of as an axial feature along with falls and gait disturbance. It is of interest to examine the relationship between these symptoms in PD, given the possibility of shared pathophysiology due to non-dopaminergic and extranigral dysfunction. METHODS: We recruited 29 consecutive non-demented patients with idiopathic PD and at least one clinically determined impairment in swallowing, falls, or freezing of gait. Swallow dysfunction was assessed using the Swallowing Disturbance Questionnaire (SDQ). The Falls Efficacy Scale and Freezing-of-gait questionnaire were recorded. Correlation analysis and multiple regression were used to determine the relationship between swallow and gait disturbance. RESULTS: Total SDQ score correlated strongly with the falls efficacy scale (Spearman's rho = 0.594; P = 0.001), but not with the freezing-of-gait score. Linear regression controlling for other factors associated with dysphagia identified falls efficacy score as a significant predictor of swallow dysfunction. CONCLUSIONS: The severity of dysphagia in PD is closely related to severity of falls, but not gait freezing. This may be helpful to more precisely determine the anatomical substrate of levodopa-resistant axial symptoms in PD and provide clues to further management.

Foot ulcer recurrence, plantar pressure and footwear adherence in people with diabetes and Charcot midfoot deformity: A cohort analysis.

AIMS: To investigate people with Charcot midfoot deformity with regard to plantar pressure, footwear adherence and plantar foot ulcer recurrence. METHODS: Twenty people with diabetes, Charcot midfoot deformity, plantar foot ulcer history and custom-made footwear were assessed with regard to barefoot and in-shoe plantar pressures during walking, footwear adherence (% of daily steps over 7-day period) and plantar foot ulcer recurrence over 18 months. In a cohort design, they were compared to 118 people without Charcot foot (non-Charcot foot group) with custom-made footwear and similar ulcer risk factors. RESULTS: Median (interquartile range) barefoot midfoot peak pressures were significantly higher in the Charcot foot group than in the non-Charcot foot group [756 (260-1267) vs 146 (100-208) kPa; P<0.001]. In-shoe midfoot peak pressures were not significantly higher in the Charcot foot group [median (interquartile range) 152 (104-201) vs 119 (94-160) kPa] and significantly lower for all other foot regions. Participants in the Charcot foot group were significantly more adherent, especially at home, than participants in the non-Charcot foot group [median (interquartile range) 94.4 (85.4-95.0)% vs. 64.3 (25.4-85.7)%; P=0.001]. Ulcers recurred in 40% of the Charcot foot group and in 47% of the non-Charcot foot group (P=0.63); midfoot ulcers recurred significantly more in the Charcot foot group (4/8) than in the non-Charcot foot group (1/55; P=0.001). CONCLUSIONS: Effective offloading and very high footwear adherence were found in people with diabetes and Charcot midfoot deformity. While this may help protect against plantar foot ulcer recurrence, a large proportion of such people still experience ulcer recurrence. Further improvements in adherence and custom-made footwear design may be required to improve clinical outcome.

Gait Disorder among Elderly People, Psychomotor Disadaptation Syndrome: Post-Fall Syndrome, Risk Factors and Follow-Up - A Cohort Study of 70 Patients.

INTRODUCTION: Falls among older people are a major health issue and the first cause of accidental death after 75 years of age. Post-fall syndrome (PFS) is commonly known and yet poorly studied. OBJECTIVE: Identify risk factors for PFS and do a follow-up 1 year later. METHODS: We included all patients over 70 years of age hospitalized after suffering a fall in a case-control study, and then followed them in a cohort study. PFS was retained in case of functional mobility decline (transferring, walking) occurring following a fall in the absence of an acute neurological, orthopedic or rheumatic pathology directly responsible for the decline. The data initially collected were: clinical (anamnestic, emergency and departmental/ward evolution, medical history, lifestyle, treatments, clinical examination items); and imaging if the patient had been subjected to brain imaging in the last 3 years prior to inclusion. Regarding the follow-up at 1 year, we collected from the general physician the occurrence and the characteristics of new falls, functional mobility assessment, hospitalization and death. RESULTS: Inclusion took place from March 29, 2016 to June 7, 2016 and follow-up until June 30, 2017. We included 70 patients. A total of 29 patients exhibited a PFS (41.4 %). Risk factors for PFS included age, walking disorder prior to the fall, the use of a walking aid prior to the fall, no unaccompanied outdoor walk in the week before the fall, visual impairment making close reading impossible, stiffness in ankle dorsiflexion, grip strength and the fear of falling. Among patients with PFS, 52.9% could still perform a transfer at 1 year and 64.7% could still walk against 80.7% and 85.2%, respectively, for patients without PFS. CONCLUSION: The study showed the existence of body functions/structure impairments and activity limitations prior to the fall among patients exhibiting a PFS. This suggests the existence of a pre-fall syndrome, i.e., a psychomotor disadaptation syndrome existing prior to the fall. Among the 8 risk factors, fear of falling, vision impairment and muscle strength could be targeted for improvement. The diagnosis of PFS could be a marker of loss of functional mobility at 1 year.

[Association between locomotive syndrome and cognitive decline in community-dwelling older adults].

Objectives　Cognitive function is an important component of health and quality of life in older adults. Locomotive syndrome (LS) is associated with cognitive decline, but this has not been sufficiently shown. Therefore, the purpose of this study was to determine the association between LS and cognitive decline in community-dwelling older adults.Methods　Study participants were 3,751 community-dwelling elderly people (1,914 men and 1,837 women; mean age 71.9±5.7 years) who completed the 25-question Geriatric Locomotive Function Scale (GLFS-25) and the Kihon Checklist administered by the local government in Japan between 2014 and 2016. LS stage was assessed using the total score from the GLFS-25 (non-LS: a score of ≤6, Stage 1: a score of ≥7, and Stage 2: a score of ≥16). The risk of cognitive decline was assessed by the applicable number of 3 cognitive-related items on the Kihon Checklist (mild decline: applicable number ≥1, moderate decline: applicable number ≥2). Multinomial logistic regression analysis adjusted for age, BMI, nutritional status, oral function, and homebound status was used to calculate the odds ratios (ORs) of the LS stage for the risk of cognitive decline.Results　In the multinomial logistic regression model, participants in both stages 1 and 2 of LS had significantly higher ORs for mild cognitive decline than those without LS in men and women. Similar results were observed with moderate cognitive decline. The ORs of LS stages for moderate cognitive decline were as follows: in the multinomial logistic regression model, OR was 1.65 (95% CI, 0.97-2.81) in stage 1 of LS and 2.99 (95% CI, 1.56-5.73) in stage 2 of LS in men (P<0.001), and OR was 1.97 (95%CI, 1.11-3.50) in LS stage 1 and 2.43 (95% CI, 1.14-5.19) in stage 2 of LS in women (P<0.01).Conclusion　This study showed that LS stage had a significant positive association with the decline in cognitive function in older adults and it was more remarkable in cases of increased cognitive decline. Our results suggest that LS might be an independent factor of cognitive decline in community-dwelling elderly people. A longitudinal survey is needed to clarify the association between LS and cognitive function.

Quantitative Gait Impairments in Patients With Stroke or Transient Ischemic Attack: A Population-Based Approach.

BACKGROUND AND PURPOSE: Gait is a complex process involving various cortical and subcortical brain regions. An acute stroke or transient ischemic attack (TIA) may disrupt white and gray matter integrity and, therefore, affect gait in patients without evident neurological signs. We determined whether patients with stroke and TIA experience subtle changes in global gait and several independent gait domains. METHODS: In the population-based Rotterdam Study, 4456 participants (median age, 65 years; 55% women) underwent detailed quantitative gait assessment (GAITRite) between 2009 and 2016. We summarized 30 gait parameters into a global gait score and 7 mutually independent gait domains. First, we assessed the association between prior stroke or TIA and global and domain-specific gait using linear regression models adjusted for age, sex, vascular risk factors, and cognition. Subsequently, we repeated the analysis stratified by the presence of different neurological symptoms in a subgroup of participants with ischemic stroke after study entry. RESULTS: Compared with participants without prior stroke, patients with stroke had a worse global gait (SD, -0.49 [95% CI, -0.64 to -0.34]), especially in the gait domains Pace, Phases, and Turning. The detrimental effect of stroke on gait was amplified in participants with worse cognition. No gait differences were found between participants with and without prior TIA. Ischemic stroke patients without lower limb weakness, loss of coordination, or visuospatial problems still had a worse gait compared with participants without stroke. Stratification by different stroke symptoms showed that different gait domains were affected in each group. CONCLUSIONS: Prior stroke without neurological signs that affect gait is still associated with gait difficulties compared with individuals without stroke. Our study suggests that stroke not only has a direct impact on gait through neurological impairments but also includes an indirect effect possibly through disruption of gray and white matter integrity and accelerated neurodegeneration.

Cholinergic system changes of falls and freezing of gait in Parkinson's disease.

OBJECTIVE: Postural instability and gait difficulties (PIGDs) represent debilitating disturbances in Parkinson's disease (PD). Past acetylcholinesterase positron emission tomography (PET) imaging studies implicate cholinergic changes as significant contributors to PIGD features. These studies were limited in quantification of striatal cholinergic synapse integrity. Vesicular acetylcholine transporter (VAChT) PET ligands are better suited for evaluation of high binding areas. We examined associations between regional VAChT expression and freezing of gait (FoG) and falls. METHODS: Ninety-four PD subjects underwent clinical assessment and VAChT ([18 F]FEOBV) PET. RESULTS: Thirty-five subjects (37.2%) reported a history of falls, and 15 (16%) had observed FoG. Univariate volume-of-interest analyses demonstrated significantly reduced thalamic (p = 0.0016) VAChT expression in fallers compared to nonfallers. VAChT expression was significantly reduced in the striatum (p = 0.0012) and limbic archicortex (p = 0.004) in freezers compared to nonfreezers. Whole-brain voxel-based analyses of FEOBV PET complemented these findings and showed more granular changes associated with falling history, including the right visual thalamus (especially the right lateral geniculate nucleus [LGN]), right caudate nucleus, and bilateral prefrontal regions. Freezers had prominent VAChT expression reductions in the bilateral striatum, temporal, and mesiofrontal limbic regions. INTERPRETATION: Our findings confirm and extend on previous PET findings of thalamic cholinergic deficits associated with falling history and now emphasize right visual thalamus complex changes, including the right LGN. FoG status is associated with reduced VAChT expression in striatal cholinergic interneurons and the limbic archicortex. These observations suggest different cholinergic systems changes underlying falls and FoG in PD. Ann Neurol 2019;85:538-549.

Comparison between deep brain stimulation and magnetic resonance-guided focused ultrasound in the treatment of essential tremor: a systematic review and pooled analysis of functional outcomes.

The current gold standard surgical treatment for medication-resistant essential tremor (ET) is deep brain stimulation (DBS). However, recent advances in technologies have led to the development of incisionless techniques, such as magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy. The authors perform a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to compare unilateral MRgFUS thalamotomy to unilateral and bilateral DBS in the treatment of ET in terms of tremor severity and quality of life improvement. PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and SCOPUS databases were searched. 45 eligible articles, published between 1990 and 2019, were retrieved. 1202 patients were treated with DBS and 477 were treated with MRgFUS thalamotomy. Postoperative tremor improvement was greater following DBS than MRgFUS thalamotomy (p<0.001). A subgroup analysis was carried out stratifying by treatment laterality: bilateral DBS was significantly superior to both MRgFUS and unilateral DBS (p<0.001), but no significant difference was recorded between MRgFUS and unilateral DBS (p<0.198). Postoperative quality of life improvement was significantly greater following MRgFUS thalamotomy than DBS (p<0.001). Complications were differently distributed among the two groups (p<0.001). Persistent complications were significantly more common in the MRgFUS group (p=0.042). While bilateral DBS proves superior to unilateral MRgFUS thalamotomy in the treatment of ET, a subgroup analysis suggests that treatment laterality is the most significant determinant of tremor improvement, thus highlighting the importance of future investigations on bilateral staged MRgFUS thalamotomy.

Pallidal deep brain stimulation in primary Meige syndrome: clinical outcomes and psychiatric features.

OBJECTIVES: To study the efficacy and safety of bilateral globus pallidus internus deep brain stimulation (GPi-DBS) in refractory Meige syndrome (MS) and evaluate the psychiatric disorders before and after surgery. METHODS: Twenty-two patients with MS treated with bilateral GPi-DBS were retrospectively analysed before surgery and after continuous neurostimulation. Before surgery, patients were assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Self-Rating Depression Scale, Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) and Pittsburgh Sleep Quality Index (PQSI), which corresponded to motor symptoms, depressive state, quality of life and sleep quality, respectively. The implantable pulse generator of each patient was activated at 1 month after surgery. At 1 month, 3 months, 6 months and 12 months after continuous neurostimulation, all patients were evaluated by the same scales above. RESULTS: The BFMDRS movement scores decreased from 15.0±5.3 before surgery to 3.5±4.5 at 12 months after neurostimulation, with a mean improvement of 78% (p<0.001). The BFMDRS disability scores improved from 7.4±4.9 before surgery to 4.0±4.6 at 12 months after neurostimulation, with a mean improvement of 56% (p<0.001). The postoperative SF-36 scores had the remarkable improvement compared with baseline scores. Impaired sleep quality was found in 82% of patients and depression in 64% before surgery, which didn't neither obtained amelioration after continuous neurostimulation. CONCLUSIONS: Bilateral pallidal neurostimulation is a beneficial therapeutic option for refractory MS, which could improve the motor symptoms except for depression and sleep quality.

The impact of freezing of gait on functional dependency in Parkinson's disease with regard to motor phenotype.

BACKGROUND AND OBJECTIVE: Freezing of gait (FOG) is a disabling symptom more frequent in Parkinson's disease (PD) patients with postural instability gait difficulty (PIGD) phenotype. The aim of this study was to determine the prevalence of self-reported FOG in a large group of PD patients as well as assess its relationship with functional dependency with regard to motor phenotype. METHODS: The data correspond to the baseline evaluation of the COPPADIS-2015 study. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the freezing of gait questionnaire (FOG-Q). Functional dependency was defined as a Schwab and England (S&E) ADL scale score less than 80%. PIGD and non-PIGD (tremor dominant + indeterminate) groups were considered regarding to motor phenotype. RESULTS: Among the 689 PD patients (62.6 ± 8.9 years old, 59.8% males), 240 reported FOG (34.8%), whereas 63 presented functional dependency (9.1%). A total of 22.1% of patients with FOG presented functional dependency vs. only 2.2% of those without FOG (p < 0.0001). FOG was related to functional dependency (OR = 3.470; 95%CI 1.411-8.530; p = 0.007) after adjustment to age, gender, disease duration, daily equivalent levodopa dose, comorbidity (number of non-antiparkinsonian drugs/day), motor status (UPDRS-III), PIGD phenotype, motor complications (UPDRS-IV), NMS burden (NMSS total score), cognition (PD-CRS), and mood (BDI-II). However, according to motor phenotype, FOG was related to functional dependency only in PIGD patients (OR = 7.163; 95%CI 1.206-42.564; p = 0.030). CONCLUSIONS: Self-reported FOG is associated with functional dependency in PIGD but not in non-PIGD motor phenotype patients.

Cardiac and Neuromuscular Features of Patients With LMNA-Related Cardiomyopathy.

Background: Mutations in the LMNA (lamin A/C) gene have been associated with neuromuscular and cardiac manifestations, but the clinical implications of these signs are not well understood. Objective: To learn more about the natural history of LMNA-related disease. Design: Observational study. Setting: 13 clinical centers in Italy from 2000 through 2018. Patients: 164 carriers of an LMNA mutation. Measurements: Detailed cardiologic and neurologic evaluation at study enrollment and for a median of 10 years of follow-up. Results: The median age at enrollment was 38 years, and 51% of participants were female. Neuromuscular manifestations preceded cardiac signs by a median of 11 years, but by the end of follow-up, 90% of the patients had electrical heart disease followed by structural heart disease. Overall, 10 patients (6%) died, 14 (9%) received a heart transplant, and 32 (20%) had malignant ventricular arrhythmias. Fifteen patients had gait loss, and 6 had respiratory failure. Atrial fibrillation and second- and third-degree atrioventricular block were observed, respectively, in 56% and 51% of patients with combined cardiac and neuromuscular manifestations and 37% and 33% of those with heart disease only. Limitations: Some of the data were collected retrospectively. Neuromuscular manifestations were more frequent in this analysis than in previous studies. Conclusion: Many patients with an LMNA mutation have neurologic symptoms by their 30s and develop progressive cardiac manifestations during the next decade. A substantial proportion of these patients will have life-threatening neurologic or cardiologic conditions. Primary Funding Source: None.

Nonfocal Transient Neurological Attacks Are Associated With Cerebral Small Vessel Disease.

Background and Purpose- Nonfocal transient neurological attacks (TNAs), such as unsteadiness, bilateral weakness, or confusion, are associated with an increased risk of stroke and dementia. Cerebral ischemia plays a role in their pathogenesis, but the precise mechanisms are unknown. We hypothesized that cerebral small vessel disease is involved in the pathogenesis of TNAs and assessed the relation between TNAs and manifestations of cerebral small vessel disease on magnetic resonance imaging. Methods- We included participants from the HBC (Heart-Brain Connection) study. In this study, hemodynamic and cardiovascular contributions to cognitive impairment have been studied in patients with heart failure, carotid artery occlusion, or possible vascular cognitive impairment, as well as in a reference group. We excluded participants with a history of stroke or transient ischemic attacks. The occurrence of the following 8 TNAs was assessed with a standardized interview: unconsciousness, confusion, amnesia, unsteadiness, bilateral leg weakness, blurred vision, nonrotatory dizziness, and paresthesias. The occurrence of TNAs was related to the presence of lacunes or white matter hyperintensities (Fazekas score, ≥2; early confluent or confluent lesions) in logistic regression analysis, adjusted for age, sex, and hypertension. Results- Of 304 participants (60% men; mean age, 67±9 years), 63 participants (21%) experienced ≥1 TNAs. Lacunes and early confluent or confluent white matter hyperintensities were more common in participants with TNAs than in participants without TNAs (35% versus 20%; adjusted odds ratio, 2.32 [95% CI, 1.22-4.40] and 48% versus 27%; adjusted odds ratio, 2.65 [95% CI, 1.44-4.90], respectively). Conclusions- In our study, TNAs are associated with the presence of lacunes and early confluent or confluent white matter hyperintensities of presumed vascular origin, which indicates that cerebral small vessel disease might play a role in the pathogenesis of TNAs.

Identifying the neural correlates of doorway freezing in Parkinson's disease.

Freezing of gait (FOG) in Parkinson's disease (PD) is frequently triggered upon passing through narrow spaces such as doorways. However, despite being common the neural mechanisms underlying this phenomenon are poorly understood. In our study, 19 patients who routinely experience FOG performed a previously validated virtual reality (VR) gait paradigm where they used foot-pedals to navigate a series of doorways. Patients underwent testing randomised between both their "ON" and "OFF" medication states. Task performance in conjunction with blood oxygenation level dependent (BOLD) signal changes between "ON" and "OFF" states were compared within each patient. Specifically, as they passed through a doorway in the VR environment patients demonstrated significantly longer "footstep" latencies in the OFF state compared to the ON state. As seen clinically in FOG this locomotive delay was primarily triggered by narrow doorways rather than wide doorways. Functional magnetic resonance imaging revealed that footstep prolongation on passing through doorways was associated with selective hypoactivation in the presupplementary motor area (pSMA) bilaterally. Task-based functional connectivity analyses revealed that increased latency in response to doorways was inversely correlated with the degree of functional connectivity between the pSMA and the subthalamic nucleus (STN) across both hemispheres. Furthermore, increased frequency of prolonged footstep latency was associated with increased connectivity between the bilateral STN. These findings suggest that the effect of environmental cues on triggering FOG reflects a degree of impaired processing within the pSMA and disrupted signalling between the pSMA and STN, thus implicating the "hyperdirect" pathway in the generation of this phenomenon.

Relationship Between Mood, Thinking, and Walking: A Systematic Review Examining Depressive Symptoms, Executive Function, and Gait.

Prior literature has proposed that the coexistence of late-life depression, executive dysfunction and impaired gait speed may constitute a specific phenotype in older adults with a possible shared brain mechanism. All three conditions are independently associated with negative health outcomes including impaired function, risk of falling, and reduced quality of life. However, the existence, etiology, and implications of having all three conditions as a unitary triad remain unclear. This systematic review examined the literature to assess the consistency of this triad and to explore the possible role of frontal-subcortical circuitry in its etiology. English language literature that assessed mood, executive function, and gait speed using a validated tool in human participants over age 65 were included for this review. Following the PRISMA guidelines, 15 studies including 11,213 participants met criteria for inclusion in this study. The triad's existence was supported by 12 of the 15 studies (80%), including 4 longitudinal studies involving 368 participants. A prevalence of 17% was reported in one population study. The three included intervention studies provided mixed results regarding the benefit of pharmacologic and exercise interventions. Two studies assessed the association between presence of white matter hyperintensities and the triad, with one study finding a significant longitudinal relationship with periventricular white matter hyperintensities. Vascular risk factors were also commonly associated with this triad. Taken together, the relationship between this triad, the vascular depression hypothesis, and frontal-subcortical pathology is suggested. Further longitudinal research is needed to further clarify the etiology and clinical relevance of this concomitant prescence oflate-life depression, executive dysfunction and impaired gait speed.

Factors associated with freezing of gait in patients with Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a common and debilitating problem in patients with Parkinson's disease (PD). The aim of this study was to estimate the prevalence of FOG, and to identify factors that independently contribute to FOG in patients with PD. METHOD: We included 157 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q). Patients with or without FOG were defined as item 3 in the FOG-Q. RESULTS: One hundred eleven (70.7%) out of 157 PD patients presented with FOG. Patients with FOG were older, had long disease duration, were taking higher doses of dopaminergic agents, and had higher motor and non-motor scores than those without FOG. Multivariate linear regression analysis showed that high modified Hoehn and Yahr (mHY) stage, Unified PD Rating Scale (UPDRS) part II score, and non-motor symptom assessment scale for PD (NMSS) total score were significant predictors of a high FOG-Q score. Patients with FOG had significantly higher scores for cardiovascular, gastrointestinal tract, urinary, and miscellaneous NMSS domains than those without FOG. CONCLUSIONS: FOG in PD was associated with higher mHY stage, UPDRS part II score, and total NMSS score. Therefore, clinicians should consider non-motor, motor features and activities of daily living states for the proper management of FOG.

Significance of Nonfocal Symptoms in Patients With Transient Ischemic Attack.

Background and Purpose- Patients with transient ischemic attack (TIA) occasionally show nonfocal symptoms, such as unconsciousness, amnesia, and unsteadiness. The purpose of this study was to clarify the characteristics and prognosis of patients with TIA with nonfocal symptoms, using data from the PROMISE-TIA (Prospective Multicenter Registry to Identify Subsequent Cardiovascular Events After Transient Ischemic Attack). Methods- Patients with TIA within 7 days of onset were consecutively enrolled in the Japanese nationwide registry. Factors associated with nonfocal symptoms and 1-year risks of ischemic stroke and coronary artery diseases were assessed in multivariate-adjusted models. Results- We studied 1362 patients with TIA (879 men; mean age, 69±12 years), including 219 (16%) with nonfocal symptoms. Patients with TIA with nonfocal symptoms were more likely to show acute ischemic lesions in the posterior circulation on diffusion-weighted imaging (multivariate-adjusted odds ratio, 3.07; 95% confidence interval, 1.57-5.82) and arterial stenosis or occlusion in the posterior circulation on vascular examination (odds ratio, 1.94; 95% confidence interval, 1.19-3.09) than those without nonfocal symptoms. Although 1-year risk of ischemic stroke did not differ significantly between groups (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.37), risk of coronary artery disease was higher in patients with TIA with nonfocal symptoms (hazard ratio, 3.37; 95% confidence interval, 1.14-9.03). Conclusions- Both acute ischemic lesions and arterial stenosis and occlusion in the posterior circulation were more frequently observed in patients with TIA with nonfocal symptoms.

What is the Longitudinal Relationship between Gait Abnormalities and Depression in a Cohort of Community-Dwelling Older People? Data From the Irish Longitudinal Study on Ageing (TILDA).

OBJECTIVE: Does baseline gait disturbance predict incident depression in a cohort of community-dwelling older people? METHODS: This is a longitudinal study, embedded within the Irish Longitudinal Study on Ageing (TILDA), examining the association between baseline depression and incident gait abnormalities, as well as between baseline gait abnormalities and incident depression at 2 year follow-up. Depression was defined as a score of ≥16 on the Centre for Epidemiological Studies Depression Scale (CES-D). Gait abnormality was defined as a Timed Up and Go Test (TUG) ≥12 seconds. Assessments were carried out at baseline and at 2 year follow-up. RESULTS: 7% (179/2,638) had baseline depression and 11% (296/2,638) had a gait abnormality at baseline. The incidence of new-onset depression and gait abnormality at Wave 2 was 4% (95/2,364) and 13% (308/2,342) respectively. Logistic regression models demonstrated that baseline gait abnormality was a significant predictor of incident depression with an Incidence Rate Ratio (IRR) of 2.00 (95% CI: 1.18 - 3.40, p =0.010, t =2.57, df =625), which was not attenuated after controlling for covariates. Baseline depression was a predictor of incident gait abnormality at Wave 2 with an IRR of 1.68 (95% CI: 1.16 - 2.43, p =0.006, t =2.75, df =625) but this association was no longer statistically significant when analysis was adjusted for clinical variables. CONCLUSIONS: This study demonstrates that baseline gait disturbance, measured by TUG, predicts incident depression, defined by CES-D, in a population-representative cohort of community-dwelling older people. Possible biological mechanisms for this relationship include white matter disease and executive dysfunction.

Brain comorbidities in normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: This cross-sectional study aims to compare gait changes after the cerebrospinal fluid (CSF) tap test between normal pressure hydrocephalus patients with and without brain comorbidities (NPH+ and NPH- respectively) and then to identify significant contributors to a poor CSF tap test amongst individuals with NPH+. METHODS: Gait changes (during the single task and the dual task of backward counting) were quantified before and 24 h after the CSF tap test with an optoelectronic system in 52 NPH patients (77.4 ± 6.0 years; 34.6% women). Changes after the CSF tap test in stride time variability (STV, %) were our main outcome. CSF Alzheimer's disease biomarkers, cerebrovascular white matter changes assessed with brain imaging and neurodegenerative diseases with parkinsonian syndrome represented the three individual brain comorbidities. RESULTS: Brain comorbidities were frequently identified, NPH+ patients representing 40 patients of our sample (76.9%). NPH- patients improved their STV better in the single task (delta of STV = -58.6% ± 54.3% vs. -14.1% ± 62.0%; P = 0.031) and in the dual task (delta of STV =-32.2% ± 33.7% vs. 6.3% ± 58.4%; P = 0.028) after the CSF tap test than NPH+ patients. Amongst NPH+ individuals, only comorbid Alzheimer's disease was associated with STV increase (i.e. deterioration of gait) in the dual task [ß 38.4; 95% confidence interval (5.64; 71.24); P = 0.023] after the CSF tap test, whilst it was borderline in the single task [ß 35.0; 95% confidence interval (-1.97; 71.90); P = 0.063]. CONCLUSIONS: Brain comorbidities affect gait improvement after the CSF tap test in NPH patients; this influence is driven by Alzheimer's disease-related pathology.

Use of Vitamin K Antagonists and Brain Morphological Changes in Older Adults: An Exposed/Unexposed Voxel-Based Morphometric Study.

BACKGROUND: Vitamin K antagonists (VKAs) are commonly used for their role in haemostasis by interfering with the vitamin K cycle. Since vitamin K also participates in brain physiology, this voxel-based morphometric study aimed to determine whether the duration of exposure to VKAs correlated with focal brain volume reduction in older adults. METHODS: In this exposed/unexposed (1: 2) study nested within the GAIT (Gait and Alzheimer Interactions Tracking) cohort, 18 participants exposed to VKA (mean age 75 ± 5 years; 33.3% female; mean exposure 2,122 ± 1,799 days) and 36 matched participants using no VKA (mean age 75 ± 5 years; 33.3% female) underwent MRI scanning of the brain. Cortical grey and white matter volumes were automatically segmented using statistical parametric mapping. Age, gender, educational level, history of atrial fibrillation, type of MRI, and total intracranial volume were included as covariables. RESULTS: The duration of exposure to VKA correlated inversely across the whole brain with the subvolumes of two clusters in the grey matter (right frontal inferior operculum and right precuneus) and one cluster in the white matter (left middle frontal gyrus). In contrast, the grade of white matter hyperintensities did not differ according to the use of VKA. CONCLUSION: We found focal atrophies in older adults exposed to VKA. These findings provide new insights elucidating the effects of VKAs on brain health and function in older adults.