Changes in postural stability after cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus.

Introduction: In patients with idiopathic normal pressure hydrocephalus (iNPH), the characteristics of balance disturbance are not as well understood as those related to gait. This study examined changes in postural stability in quiet standing after the cerebrospinal fluid tap test (CSFTT) in these patients. Furthermore, the study explored the relationship between the amount of spontaneous body sway and both gait and executive function. Materials and methods: All patients diagnosed with iNPH underwent CSFTT. We evaluated their center of pressure (COP) measurements on a force plate during quiet standing, both pre- and post-CSFTT. Following the COP measurements, we calculated COP parameters using time and frequency domain analysis and assessed changes in these parameters after CSFTT. At pre-CSFTT, we assessed the Timed Up and Go (TUG) and the Frontal Assessment Battery (FAB). We investigated the relationship between COP parameters and the TUG and FAB scores at pre-CSFTT. Results: A total of 72 patients with iNPH were initially enrolled, and 56 patients who responded positively to CSFTT were finally included. Post-CSFTT, significant improvements were observed in COP parameters through time domain analysis. These included the velocity of COP (vCOP), root-mean-square of COP (rmsCOP), turn index, torque, and base of support (BOS), compared to the pre-CSFTT values (p < 0.05). In the frequency domain analysis of COP parameters post-CSFTT, there was a decrease in both the peak and average of power spectral density (PSD) values in both the anteroposterior (AP) and mediolateral (ML) directions below 0.5 Hz (p < 0.05). In addition, the TUG scores showed a positive correlation with vCOP, rmsCOP, turn index, torque, BOS, and both the peak and average PSD values in the AP and ML directions below 0.5 Hz (p < 0.05). The FAB scores demonstrated a negative correlation with vCOP, rmsCOP, turns index, BOS, and both peak and average PSD values in the AP direction below 0.5 Hz (p < 0.05). Conclusion: In patients with iNPH who responded to CSFTT, there was an improvement in spontaneous body sway during quiet standing after CSFTT. Increased spontaneous sway is associated with impaired gait and frontal lobe function. This may be linked to impaired cortico-cortical and cortico-subcortical circuits in patients with iNPH.

Distinct cerebral cortical perfusion patterns in idiopathic normal-pressure hydrocephalus.

The aims of the study are to evaluate idiopathic normal-pressure hydrocephalus (INPH)-related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH patients. We investigated cortical CBF utilizing surface-based early-phase 18 F-florbetaben (E-FBB) PET analysis in two groups: INPH patients and healthy controls. All 39 INPH patients and 20 healthy controls were imaged with MRI, including three-dimensional volumetric images, for automated surface-based cortical thickness analysis across the entire brain. A subgroup with 37 participants (22 INPH patients and 15 healthy controls) that also underwent 18 F-fluorodeoxyglucose (FDG) PET imaging was further analyzed. Compared with age- and gender-matched healthy controls, INPH patients showed statistically significant hyperperfusion in the high convexity of the frontal and parietal cortical regions. Importantly, within the INPH group, increased perfusion correlated with cortical thickening in these regions. Additionally, significant hypoperfusion mainly in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions was observed in the INPH group relative to the control group. However, this hypoperfusion was not associated with cortical thinning. A subgroup analysis of participants that also underwent FDG PET imaging showed that increased (or decreased) cerebral perfusion was associated with increased (or decreased) glucose metabolism in INPH. A distinctive regional relationship between cerebral cortical perfusion and cortical thickness was shown in INPH patients. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.

Distinct volumetric features of cerebrospinal fluid distribution in idiopathic normal-pressure hydrocephalus and Alzheimer's disease.

OBJECTIVE: The aims of the study were to measure the cerebrospinal fluid (CSF) volumes in the lateral ventricle, high-convexity subarachnoid space, and Sylvian fissure region in patients with idiopathic normal-pressure hydrocephalus (INPH) and Alzheimer's disease (AD), and to evaluate differences in these volumes between INPH and AD groups and healthy controls. METHODS: Forty-nine INPH patients, 59 AD patients, and 26 healthy controls were imaged with automated three-dimensional volumetric MRI. RESULTS: INPH patients had larger lateral ventricles and CSF spaces of the Sylvian fissure region and smaller high-convexity subarachnoid spaces than other groups, and AD patients had larger lateral ventricles and CSF spaces of the Sylvian fissure region than the control group. The INPH group showed a negative correlation between lateral ventricle and high-convexity subarachnoid space volumes, while the AD group showed a positive correlation between lateral ventricle volume and volume for CSF spaces of the Sylvian fissure region. The ratio of lateral ventricle to high-convexity subarachnoid space volumes yielded an area under the curve of 0.990, differentiating INPH from AD. CONCLUSIONS: Associations between CSF volumes suggest that there might be different mechanisms between INPH and AD to explain their respective lateral ventricular dilations. The ratio of lateral ventricle to high-convexity subarachnoid space volumes distinguishes INPH from AD with good diagnostic sensitivity and specificity. We propose to refer to this ratio as the VOSS (ventricle over subarachnoid space) index.

Impact of an Education Program for Caregivers of Patients with Alzheimer's Disease on Treatment Discontinuation and Compliance in Korea.

BACKGROUND AND PURPOSE: Reportedly 30-50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer's disease patients who had newly been prescribed donepezil. METHODS: This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer's disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. RESULTS: The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. CONCLUSIONS: Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer's Disease Patients in Asia.

BACKGROUND AND PURPOSE: The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer's disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. METHODS: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50-90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation, treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). RESULTS: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test-Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. CONCLUSIONS: In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Quantitative gait analysis of idiopathic normal pressure hydrocephalus using deep learning algorithms on monocular videos.

A vision-based gait analysis method using monocular videos was proposed to estimate temporo-spatial gait parameters by leveraging deep learning algorithms. This study aimed to validate vision-based gait analysis using GAITRite as the reference system and analyze relationships between Frontal Assessment Battery (FAB) scores and gait variability measured by vision-based gait analysis in idiopathic normal pressure hydrocephalus (INPH) patients. Gait data from 46 patients were simultaneously collected from the vision-based system utilizing deep learning algorithms and the GAITRite system. There was a strong correlation in 11 gait parameters between our vision-based gait analysis method and the GAITRite gait analysis system. Our results also demonstrated excellent agreement between the two measurement systems for all parameters except stride time variability after the cerebrospinal fluid tap test. Our data showed that stride time and stride length variability measured by the vision-based gait analysis system were correlated with FAB scores. Vision-based gait analysis utilizing deep learning algorithms can provide comparable data to GAITRite when assessing gait dysfunction in INPH. Frontal lobe functions may be associated with gait variability measurements using vision-based gait analysis for INPH patients.

Transversus abdominis plane block for lumboperitoneal shunt surgery in idiopathic normal pressure hydrocephalus: a case report.

The transversus abdominis plane (TAP) block is an ideal pain control method used in surgeries that require abdominal wall incisions through the injection of an anesthetic solution into the plane between the internal oblique muscle and transversus abdominis muscle. Herein, we report an 83-year-old man who was diagnosed with idiopathic normal pressure hydrocephalus (iNPH) and underwent lumboperitoneal shunt surgery (LPS). The TAP block was performed before LPS, and the numerical rating scale for pain was 0 at day 1 after the surgery. The patient was discharged early at day 3 after surgery despite the patient being extremely old, as he reported quick relief from the postoperative abdominal pain. The TAP block can hence be considered for use before LPS in elderly patients with iNPH.

Human Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Cerebellar Ataxia: A Case Report.

To date, there is no curable treatment option for non-hereditary degenerative cerebellar ataxia. Here we report the case of a patient with sporadic adult-onset ataxia (SAOA) who underwent allogeneic bone marrow-derived mesenchymal stem cell (MSC) therapy via the intrathecal route. A 60-year-old male patient visited our clinic complaining of progressive gait disturbance that commenced two years ago. Upon neurologic examination, the patient exhibited limb dysmetria and gait ataxia. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy whereas the autonomic function test was normal. The patient was diagnosed with SAOA. The medications that were initially prescribed had no significant effects on the course of this disease and the symptoms deteriorated progressively. At the age of 64, the patient was treated with allogeneic bone marrow-derived MSC therapy. The subsequent K-SARA (Korean version of the Scale for the Assessment and Rating of Ataxia) scores demonstrated a distinct improvement up until 10 months post-administration. No adverse events were reported. The improved post-treatment K-SARA scores may suggest that the MSC therapy can have a neuroprotective effect and that stem cell therapy may serve as a potential therapeutic option for degenerative cerebellar ataxia.

Clinical significance of vitamin D in idiopathic normal pressure hydrocephalus.

BACKGROUND: Although recent studies show vitamin D deficiency is associated with cognitive decline, urinary incontinence, and gait instability, there has been no study on the effect of vitamin D on idiopathic normal pressure hydrocephalus (iNPH) characterized by the classic symptom triad of cognitive decline, urinary incontinence, and gait instability. We investigated the clinical significance of vitamin D in patients with iNPH. METHODS: Between 2017 and 2020, 44 patients who underwent ventriculoperitoneal shunt surgery were divided into low (< 15 ng/mL) and high (≥ 15 ng/mL) vitamin D groups according to the concentration of 25(OH)D, an effective indicator of vitamin D status. They were respectively evaluated according to clinical and radiological findings. RESULTS: The low vitamin D group (n = 24) showed lower preoperative cognition compared to the high vitamin D group (n = 20) in terms of Korean-Mini Mental Status Examination (K-MMSE) and iNPH grading scale (iNPHGS) (K-MMSE: 20.5 ± 5.4 versus 24.0 ± 4.5, p = 0.041; iNPHGS cognitive score: 2 ± 0.9 versus 1 ± 0.6, p = 0.025). And the low vitamin D group showed pre- and postoperatively more severe urinary incontinence (preoperative iNPHGS urinary score: 1 ± 1.0 versus 0 ± 0.9, p = 0.012; postoperative iNPHGS urinary score:1 ± 1.0 versus 0 ± 0.9, p = 0.014). The score of narrow high-convexity sulci for the low vitamin D group was lower (low vitamin D group: 1 ± 0.7 versus high vitamin D group: 2 ± 0.4, p = 0.031). CONCLUSION: Lower concentration of vitamin D in iNPH may be related to lower preoperative cognition, pre- and postoperative urinary incontinence, and brain morphological change.

Caregiving, care burden and awareness of caregivers and patients with dementia in Asian locations: a secondary analysis.

BACKGROUND: This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer's disease (AD) across different Asian locations. METHODS: This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients' awareness of their dementia diagnosis was assessed by asking the following yes/no question: "Do you have dementia?" Caregivers' awareness of the patient's dementia diagnosis was assessed by asking the following yes/no question: "Does your patient have dementia?" RESULTS: In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p < 0.001 and p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p < 0.001). CONCLUSIONS: Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02262975 . Registered 13 October 2014.

Gait in Benign Paroxysmal Positional Vertigo.

Purpose: Patients with benign paroxysmal positional vertigo (BPPV) experience gait unsteadiness not only during the attacks but also between the spells. This study aimed to measure gait changes in BPPV and determine whether these changes are associated with the involved canal or lesion side. Methods: We recruited 33 patients with a diagnosis of unilateral BPPV. Patients with other vestibular or central nervous system disorders were excluded. Gait was assessed using the GAITRite™ system before and after canalith repositioning treatment (CRT). Results: After CRT, improvements were observed in various gait parameters including velocity (p < 0.001), cadence (p < 0.001), functional ambulation profile (p = 0.011), and the coefficient of variation of stride time (p = 0.004). Exploration of the center of pressure (COP) distribution also revealed improved stabilization during locomotion after CRT. The spatiotemporal gait variables did not differ between the patients with horizontal- and posterior-canal BPPV, or between the ipsilesional and contralesional sides before CRT. Conclusions: The gait parameters reflecting velocity and rhythmicity along with stability of COP distribution improved after the resolution of BPPV. Episodic overexcitation of semicircular canal may impair the vestibular information that is integrated with the other reference afferent systems and lead to impaired gait performance.

Increased plasma levels of chitinase 3-like 1 (CHI3L1) protein in patients with idiopathic normal-pressure hydrocephalus.

Idiopathic normal-pressure hydrocephalus (iNPH) is an uncommon neurological disorder with no known pathological hallmarks. INPH may share common degenerative pathways with other neurological diseases, such as Alzheimer's disease (AD). However, the reversible properties of iNPH may share differing pathophysiological mechanisms with other diseases. This study aimed at assessing the diagnostic value of plasma chitinase 3-like 1 (CHI3L1) protein levels as a disease-specific biomarker for iNPH. We selected both iNPH and AD patients as well as normal and disease control subjects from an enrolled dementia registry. A total of 121 AD, 80 iNPH, 13 idiopathic Parkinson's disease, and 23 mild cognitive impairment patients with 83 healthy controls were included in the final analysis. The Aß42, total tau, and phosphorylated tau levels within the cerebrospinal fluid, as well as plasma levels of CHI3L1, were measured using commercially available enzyme-linked immunosorbent assay kits. CHI3L1 levels for iNPH patients were higher than those of the other groups. Analysis of covariance adjusting for age showed significantly increased plasma CHI3L1 levels in iNPH patients than in the controls (p < 0.001). CHI3L1 plasma levels may be useful in differentiating iNPH patients from healthy individuals.

Clinical application of the experimental ADL test for patients with cognitive impairment: pilot study.

We employed a hospital-based Internet of Things (IoT) platform to validate the role of real-time activities of daily living (ADL) measurement as a digital biomarker for cognitive impairment in a hospital setting. Observational study. 12 patients with dementia, 11 patients with mild cognitive impairment (MCI), and 15 cognitively normal older adults. The results of 13 experimental ADL tasks were categorized into success or fail. The total number of successful task and the average success proportion of each group was calculated. Time to complete the total tasks was also measured. Patients with dementia, patients with MCI, and cognitively normal older adults performed 13 experimental ADL tasks in a hospital setting. Significant differences in the average success rate of 13 tasks were found among groups. Dementia group showed the lowest success proportion (49.3%) compared with MCI group (78.3%) and normal group (97.4%). Correlation between classical ADL scales and the number of completed ADL tasks was statistically significant. In particular, instrumental ADL (I-ADL) had stronger relationship with the number of completed ADL tasks than Barthel's ADL (B-ADL). Dementia group required more time to accomplish the tasks when compared to MCI and normal groups. This study demonstrated that there is a clear relationship between the performance of experimental ADL tasks and the severity of cognitive impairment. The evaluation of ADLs involving the IoTs platform in an ecological setting allows accurate assessment and quantification of the patient's functional level.

Abnormal cortical thickening and thinning in idiopathic normal-pressure hydrocephalus.

We investigated differences in cortical thickness between idiopathic normal-pressure hydrocephalus (INPH) patients and healthy controls. We also explored whether a relationship exists between cortical thinning and gait disturbance in INPH patients. Forty-nine INPH patients and 26 healthy controls were imaged with MRI, including 3-dimensional volumetric images, for automated surface-based cortical thickness analysis across the entire brain. Compared with age- and gender-matched healthy controls, unexpectedly, INPH patients showed statistically significant cortical thickening mainly in areas located in the high convexity of the frontal, parietal, and occipital regions. Additionally, cortical thinning mainly in temporal and orbitofrontal regions was observed in the INPH group relative to the control group. The Gait Status Scale (GSS) scores were negatively correlated with cortical thickness in the medial orbital part of the superior frontal gyrus, gyrus rectus, superior temporal gyrus, temporal pole, and insula. A distinctive pattern of cortical thickness changes was found in INPH patients. We cautiously suggest that cortical thickening in INPH can result from reactive gliosis. Further, our results support the hypothesis that cortical thinning in INPH can result from neuronal degeneration. In addition, cortical thinning can play an important role in gait disturbances in INPH patients.