BACKGROUND: The management of neurodegenerative diseases (NDDs) in older populations is usually demanding and involves care provision by various health care services, resulting in a greater burden on health care systems in terms of costs and resources. The convergence of various health services within integrated health care models, which are enabled and adopted jointly with information and communication technologies (ICTs), has been identified as an effective alternative health care solution. However, its widespread implementation faces formidable challenges. Both the development and implementation of integrated ICTs are linked to the collaboration and acceptance of different groups of stakeholders beyond patients and health care professionals, with reported discrepancies in the needs and preferences among these groups.
OBJECTIVE: Complementing a previous publication, which reported on the needs and requirements of end users in the development of the European Union-funded project PROCare4Life (Personalized Integrated Care Promoting Quality of Life for Older People), this paper aimed to report on the opinions of other key stakeholders from various fields, including academia, media, market, and decision making, for improving the acceptability and implementation of an integrated ICT-based health care platform supporting the management of NDDs.
METHODS: The study included 30 individual semistructured interviews that took place between June and August 2020 in 5 European countries (Germany, Italy, Portugal, Romania, and Spain). Interviews were mostly conducted online, except in cases where participants requested to be interviewed in person. In these cases, COVID-19 PROCare4Life safety procedures were applied.
RESULTS: This study identified 2 themes and 5 subthemes. User engagement, providing training and education, and the role played by the media were identified as strategic measures to ensure the acceptability of ICT-based health care platforms. Sustainable funding and cooperation with authorities were foreseen as additional points to be considered in the implementation process.
CONCLUSIONS: The importance of the user-centered design approach in ensuring the involvement of users in the development of ICT-based platforms has been highlighted. The most common challenges that hinder the acceptability and implementation of ICT-based health care platforms can be addressed by creating synergies among the efforts of users, academic stakeholders, developers, policy makers, and decision makers. To support future projects in developing ICT-based health care platforms, this study outlined the following recommendations that can be integrated when conducting research on users\' needs: (1) properly identify the particular challenges faced by future user groups without neglecting their social and clinical contexts; (2) iteratively assess the digital skills of future users and their acceptance of the proposed platform; (3) align the functionalities of the ICT platform with the real needs of future users; and (4) involve key stakeholders to guide the reflection on how to implement the platform in the future.
UNASSIGNED: RR2-10.2196/22463.

The development of anti-AD drugs has attracted much attention as the number of AD patients is increasing year by year. Five diosmetin derivatives (1-5) were designed and synthesized by introducing carbamate groups. The crystal structure of 1 was analyzed by X-ray diffraction, which showed a large conjugated coplanar structure and might be favorable for the insertion into the Aβ folding. Meanwhile, in vitro experiments were carried out to investigate the anticholinesterase activity, metal chelating property, antioxidant activity, and anti-Aβ aggregation ability of 1-5. The results showed that 1-5 had good cholinesterase inhibitory activities. Compound 4 showed the highest inhibitory activities against butyrylcholinesterase (IC50 = 0.0760 μM). Further kinetic experiments and molecular docking studies showed that 4 could bind well to butyrylcholinesterase. The molecular dynamics simulations also signified that compared with diosmetin, 4 could reduce the flexibility of the butyrylcholinesterase protein skeleton to a greater extent, and thus had a better inhibitory effect. In addition, 1-5 could selectively chelate copper ions and all of them had good antioxidant activity as well as anti-Aβ aggregation ability. Among them, 4 had the strongest activity to inhibit Cu2+-induced Aβ aggregation (51.09%) and had low cytotoxicity. In addition, in vivo ROS activity assay (Caenorhabditis elegans) showed that 4 had the ability to scavenge ROS. Besides, the in vivo Aβ aggregation assay showed that 4 could reduce Aβ aggregation. In conclusion, 4 has the potential to be developed into a multifunctional anti-AD drug.

OBJECTIVE: Parkinson disease (PD) is a common progressive neurodegenerative disorder in our ageing society. Early-stage PD biomarkers are desired for timely clinical intervention and understanding of pathophysiology. Since one of the characteristics of PD is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, we propose a feature extraction method for analysing the differences in the substantia nigra between PD and non-PD patients.
METHODS: We propose a feature-extraction method for volumetric images based on a rank-1 tensor decomposition. Furthermore, we apply a feature selection method that excludes common features between PD and non-PD. We collect neuromelanin images of 263 patients: 124 PD and 139 non-PD patients and divide them into training and testing datasets for experiments. We then experimentally evaluate the classification accuracy of the substantia nigra between PD and non-PD patients using the proposed feature extraction method and linear discriminant analysis.
RESULTS: The proposed method achieves a sensitivity of 0.72 and a specificity of 0.64 for our testing dataset of 66 non-PD and 42 PD patients. Furthermore, we visualise the important patterns in the substantia nigra by a linear combination of rank-1 tensors with selected features. The visualised patterns include the ventrolateral tier, where the severe loss of neurons can be observed in PD.
CONCLUSIONS: We develop a new feature-extraction method for the analysis of the substantia nigra towards PD diagnosis. In the experiments, even though the classification accuracy with the proposed feature extraction method and linear discriminant analysis is lower than that of expert physicians, the results suggest the potential of tensorial feature extraction.

BACKGROUND: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset.
METHODS: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use.
RESULTS: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)].
CONCLUSIONS: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.

BACKGROUND: We aimed to clarify the predictive value of cerebral small-vessel disease and intracranial large artery disease (LAD) observed in magnetic resonance imaging of the brain and magnetic resonance angiography on future vascular events and cognitive impairment.
RESULTS: Data were derived from a Japanese cohort with evidence of cerebral vessel disease on magnetic resonance imaging. This study included 862 participants who underwent magnetic resonance angiography after excluding patients with a modified Rankin Scale score >1 and Mini-Mental State Examination score <24. We evaluated small-vessel disease such as white matter hyperintensities and lacunes in magnetic resonance imaging and LAD with magnetic resonance angiography. Outcomes were incident stroke, dementia, acute coronary syndrome, and all-cause death. Over a median follow-up period of 4.5 years, 54 incident stroke, 39 cases of dementia, and 27 cases of acute coronary syndrome were documented. Both small-vessel disease (white matter hyperintensities and lacunes) and LAD were associated with stroke; however, only white matter hyperintensities were related to dementia. In contrast, only LAD was associated with acute coronary syndrome. Among the 357 patients with no prior history of stroke, coronary or peripheral artery disease, or atrial fibrillation, white matter hyperintensities emerged as the sole predictor of future stroke and dementia, while LAD was the sole predictor of acute coronary syndrome.
CONCLUSIONS: Among cerebral vessels, small-vessel disease could underlie the cognitive impairment while LAD was associated with coronary artery disease as atherosclerotic vessel disease.

BACKGROUND: Chronic headache greatly affects the quality of life and also constitutes a significant burden on the health system.
OBJECTIVE: The objective of this study was to evaluate the feasibility of telephone-based follow-up in a cohort of headache patients in India.
METHODS: This was a longitudinal cohort study of patients with episodic headache with one physical visit in the neurology outpatient services in the last year. Two neurologists conducted the telephone follow up (TFU) of included patients 12 weeks apart. We evaluated the following: (1) objective characterization of headache, (2) coexistent depression and anxiety, (3) patient satisfaction, (4) treatment adherence, and (5) changes in medications.
RESULTS: A total of 214 out of 274 eligible patients were included in the cohort. The mean age was 31.74 ± 7.77 years (18-45), and 164 (77%) were females. Migraine without aura was the most common diagnosis in 159 (74%). The mean disease duration was 78.01 ± 70.15 months (8-360). Concurrent depression and anxiety were noted in 87 (40.6%) and 45 (21%) of the patients, respectively. There was a significant improvement in the headache frequency (23.82 vs. 1.06, P < 0.001), severity (7.21 vs. 2.62, P = 0.032), and Headache Impact 6-item score (58.12 vs. 38.01, P = 0.014) at baseline and second follow-up. The satisfaction level to TFU in the first and second interviews was 94.4% and 97.2%, respectively.
CONCLUSIONS: Telephone-based follow-up is a feasible alternative for repeat outpatient consultation of headache patients.

OBJECTIVE: To evaluate the effectiveness of a multidisciplinary program, including Cognitive behavioral therapy (CBT), in the treatment of patients with chronic migraine (CM) and concomitant chronic insomnia (CI).
METHODS: The study included 96 patients with CM and CI, average age 35.7±8.6. All patients underwent clinical interviews and testing using clinical and psychological techniques. Patients were randomized into two groups: group 1 received study treatment (an multudisciplinary program including CBT for pain and insomnia, combined with standard treatment for migraine), group 2 received standard treatment for migraine (preventive and acute pharmacotherapy for migraine, recommendations about lifestyle and sleep hygiene). All patients were assessed for clinical and psychological parameters before treatment and at 3, 6, 12 and 18 months follow-up.
RESULTS: At 3 month follow-up a statistically significant improvement was observed in group 1: a decrease in the frequency of headaches and the use of painkillers, parameters on the Insomnia Severity Index (ITI), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory, and the Migraine Disability Assessment (MIDAS) (p<0.05). At 6, 12 and 18 months follow-up the achieved improvements were maintained. At 3 month follow-up, group 2 showed a statistically significant improvement in only 4 parameters: a decrease in the frequency of headaches and painkiller use, and parameters for ITI and MIDAS. These parameters increased to values that were not statistically significantly different from the parameters before treatment in group 2 at 6 month follow-up. At 3 month follow-up in group 165% of patients achieved clinical effect (CE) according to CM (headache frequency decreased by 50% or more), in group 2 - 40%, which was not statistically significantly different (p>0.001); in group 1, 76% of patients achieved CE according to CI (ITI decreased by 8 points or more), which is statistically significantly more than in group 2 with 45% of patients with CE (p<0.001). At 18 month follow-up, in group 1, 81.5% of patients achieved CE according to CM, which is statistically significantly more than in group 2 with 33% of patients with CE (p<0.001); in group 1, 85% of patients achieved CE according to CI, which is statistically significantly more than in group 2, where 38% of patients had CE (p<0.001).
CONCLUSIONS: High effectiveness of CBT in patients with CM and combined CI was noted.
UNASSIGNED: Оценить эффективность междисциплинарной программы, включающей когнитивно-поведенческую терапию (КПТ), в лечении пациентов с хронической мигренью (ХМ) и сочетанной хронической инсомнией (ХИ).
UNASSIGNED: В исследование включены 96 пациентов с ХМ и ХИ, средний возраст 35,7±8,6 года. Со всеми пациентами проводились клиническая беседа и тестирование с помощью клинико-психологических методик. Пациенты были рандомизированы в две группы: 1-я группа получала стандартное лечение (фармакотерапию профилактическую и для купирования мигрени, рекомендации по образу жизни и гигиене сна) и КПТ, 2-я группа — только стандартное лечение. У всех пациентов оценивались клинико-психологические показатели до лечения и на 3, 6, 12 и 18-й месяцы после лечения.
UNASSIGNED: Через 3 мес терапии в 1-й группе наблюдалось статистически значимое улучшение: снижение частоты приступов головной боли и приема обезболивающих, показателей по Индексу тяжести инсомнии (ИТИ), шкале личностной и ситуативной тревоги Спилбергера—Ханина, шкале депрессии Бека, шкале оценки влияния мигрени на повседневную активность (ШОВМА) (p<0,05). Через 6, 12 и 18 мес терапии достигнутые улучшения сохранились. Через 3 мес терапии во 2-й группе наблюдалось статистически значимое (p<0,05) улучшение только по 4 параметрам: снижение частоты приступов головной боли и приема обезболивающих, показателей по ИТИ и ШОВМА. С 6 мес терапии во 2-й группе эти показатели статистически значимо не отличались от показателей до лечения. Через 3 мес терапии клинического эффекта (КЭ) по ХМ (снижение частоты головной боли на 50% и более) в 1-й группе достигли 65% пациентов, во 2-й группе — 40%; КЭ по ХИ (ИТИ уменьшился на 8 баллов и более) в 1-й группе — 76% пациентов, во 2-й группе — 45% (p<0,001). Через 18 мес терапии КЭ по ХМ в 1-й группе достигли 81,5% пациентов, во 2-й группе — 33% (p<0,001); КЭ по ХИ в 1-й группе — 85% пациентов, во 2-й группе — 38% (p<0,001).
UNASSIGNED: Отмечена высокая эффективность КПТ у пациентов с ХМ и сочетанной ХИ.

UNASSIGNED: Seizure is one of the neurologic manifestations of coronavirus disease 2019 (COVID-19) infection. There are few studies focused on the outcome of hospitalized patients with COVID-19 and seizure.
UNASSIGNED: This was a subgroup analysis of patients with seizure based on a nationwide, multicenter, retrospective study of COVID-19 patients admitted in 37 hospitals in the Philippines.
UNASSIGNED: A total of 10,881 patients with COVID-19 infection were included. Among these, 27 (0.2 %) patients had pre-existing seizure/epilepsy and 125 (1.1 %) had new-onset seizure. The patients with pre-existing seizure/epilepsy had a mean age of 49 years and majority were males (63.0 %). The patients with new-onset seizure had a mean age of 57 years and majority were males (60.5 %). Among patients with pre-existing seizure/epilepsy, there were no significant differences in the proportion of severe/critical COVID-19 (p = 0.131), all-cause mortality (p = 0.177), full/partial neurologic recovery (p = 0.190), ventilator use (p = 0.106), length of intensive care unit stay (p = 0.276), and length of hospitalization (p = 0.591). Patients with new-onset seizure were 2.65 times more likely to have severe/critical COVID-19 infection (p < 0.001), 3.12 times more likely to die (p < 0.001), and 3.51 times more likely to require a ventilator (p < 0.001) than those without new-onset seizure. New-onset seizure, however, was not significantly associated with full/partial neurologic recovery (p = 0.184) and prolonged length of hospitalization (p = 0.050).
UNASSIGNED: Severe/critical COVID-19 infection, higher mortality rate, and use of a ventilator were significantly higher among patients with new-onset seizure but not among patients with pre-existing seizure/epilepsy.

Objectives: We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has only been used in cadaver and non-recovery studies. This is the first study to test the robot-driven laser tool in an in vivo recovery animal study. Methods: A preoperative computed tomography (CT) scan was conducted to plan trajectories in sheep specimens. Burr hole craniotomies were performed using a frameless, navigated, robot-driven laser tool. Depth electrodes were implanted after cut-through detection was confirmed. The electrodes were cut at the skin level postoperatively. Postoperative imaging was performed to verify accuracy. Histopathological analysis was performed on the bone, dura, and cortex samples. Results: Fourteen depth electrodes were implanted in two sheep specimens. Anesthetic protocols did not show any intraoperative irregularities. One sheep was euthanized on the same day of the procedure while the other sheep remained alive for 1 week without neurological deficits. Postoperative MRI and CT showed no intracerebral bleeding, infarction, or unintended damage. The average bone thickness was 6.2 mm (range 4.1-8.0 mm). The angulation of the planned trajectories varied from 65.5° to 87.4°. The deviation of the entry point performed by the frameless laser beam ranged from 0.27 mm to 2.24 mm. The histopathological analysis did not reveal any damage associated with the laser beam. Conclusion: The novel robot-driven laser craniotomy tool showed promising results in this first in vivo recovery study. These findings indicate that laser craniotomies can be performed safely and that cut-through detection is reliable.

Alzheimer\'s disease (AD) is a devastating neurodegenerative condition with unknown etiology and no cure. Therefore, it is imperative to learn more about the underlying risk factors. Since AD is an age-related disease, one approach is to look at factors associated with aging. One example is sleep disruption, which increases with age and accelerates the progression of cognitive decline. However, some people with sleep loss experience little or no cognitive impairment and are considered resilient. The concept that resilience to sleep disruption increases resistance to AD can be modeled in aging mice with or without cognitive impairment to determine resistance or susceptibility to AD. Given that sleep disruption is a relevant and rising health concern, it is essential to gain a better understanding of resilience, and factors associated with resistance to AD, in order to develop successful intervention strategies.