Category: Nevin Manimala

Alzheimers Dement. 2021 Dec;17 Suppl 2:e058565. doi: 10.1002/alz.058565.

ABSTRACT

BACKGROUND: Sensorineural hearing loss is treated using cochlear implants. The electrodes in the implants directly stimulate spiral ganglion neurons (SGNs). However, SGNs continually degenerate and are difficult to access behind the bony modiolar wall of the cochlea. The electrode-tissue interface needs to be improved to enhance hearing for users. Implanting the electrode closer to the SGNs, requires a greater insertion depth and increases the amount of scar tissue that forms around the electrode. The introduction of neurotrophic factors has the potential to improve neural regeneration. However, currently there are a lack of methods to deliver neurotrophic factors locally and sustainably into the cochlea. We propose a neural electrode system utilising electrical stimulation (ES) to increase the expression of brain-derived neurotrophic factor (BDNF) and guide SGNs and their neurites towards the electrode. Additionally, the electrode system would utilise an electrospun nanofiber scaffold surrounding the electrode to act as a mechanical support to the cells and their projections.

METHOD: Nanofiber scaffolds were electrospun onto wires and glass coverslips and cultured with human SH-SY5Y neuroblastoma and rat Schwann cells. Immunohistochemistry and scanning electron microscopy were used to characterise the scaffolds and biocompatibility. Platinum electrodes were used to stimulate both rat Schwann cells and SH-SY5Y cells for 3 hours using a 100mV/mm DC electric field. Following 20 hours of incubation, the cells were immunostained to measure changes in BDNF expression.

RESULT: We discovered that not only were the scaffolds biocompatible, but the cells aligned along the nanofibers, forming networks on the scaffolds. We observed statistically significant increases in BDNF expression in Schwann cells, as well as a limited BDNF increase in SH-SY5Y cells that may be a result of the incubation period used in our experiment and is currently under investigation.

CONCLUSION: These results suggest the feasibility of the system and have the potential to improve cochlear implants.

PMID:34971154 | DOI:10.1002/alz.058565

Alzheimers Dement. 2021 Dec;17 Suppl 12:e058131. doi: 10.1002/alz.058131.

ABSTRACT

BACKGROUND: Dementia and type 2 diabetes mellitus (T2D) are prevalent disorders in older adults, and increasingly T2D is recognized as a robust predictor of cognitive impairment, decline and dementia. Older adults with T2D experience global cognitive decline at a rate that is double those without T2D over a 5-year period. With regard to specific cognitive domains, associations between T2D and pre-diabetic levels of insulin resistance are most commonly reported with both episodic memory and decreased executive function, including verbal fluency, working memory, processing speed, cognitive flexibility, and cognitive control. Identification of those living with diabetes at risk for cognitive decline is critically important for early intervention.

METHOD: We used the EPAD LCS vIMI baseline dataset (n=1324, excluding participants with missing data). Our primary outcome measure was performance on the Four Mountains Test (4MT), a measure of allocentric processing. Diabetes was recorded in the medical history. Covariates were age, sex, years of education, family history, APOE status, pTau and Aβ1-42. Our statistical analysis approach was linear regression.

RESULT: There were 90 participants with diabetes included in the sample. Their mean score on the 4MT was 8.32 (±2.32) correct (out of 15) compared to 9.24 (±2.60) for participants without diabetes. In uncorrected models, diabetes was significantly associated with worse 4MT total scores (β=-0.92, p=0.001). This relationship remained significant in a fully adjusted model including sex, age, education, family history of dementia and APOE status (β=-0.71, p=0.0017). There was no significant interaction between diabetes and APOE status. pTau was significantly higher in participants with diabetes compared to those without. Including pTau and Aβ1-42 in the fully adjusted model further attenuated it but it remained significant (β: -0.62, p=0.02) CONCLUSION: Individuals with diabetes performed worse on the 4MT compared to those without diabetes in the EPAD LCS v.IMI dataset. Novel cognitive tests, such as the 4MT, may be appropriate to identify early cognitive changes in this high-risk group. Future research will investigate longitudinal associations between diabetes and 4MT performance over multiple visits.

PMID:34971092 | DOI:10.1002/alz.058131

Am J Med Genet A. 2021 Dec 31. doi: 10.1002/ajmg.a.62629. Online ahead of print.

ABSTRACT

Congenital myasthenic syndromes (CMS) is a group of diseases that causes abnormalities at the neuromuscular junction owing to genetic anomalies. The pathogenic variant in ALG14 results in a severe pathological form of CMS causing end-plate acetylcholine receptor deficiency. Here, we report the cases of two siblings with CMS associated with a novel variant in ALG14. Immediately after birth, they showed hypotonia and multiple joint contractures with low Apgar scores. Ptosis, low-set ears, and high-arched palate were noted. Deep tendon reflexes were symmetrical. They showed worsening swallowing and respiratory problems; hence, nasal feeding and tracheotomy were performed. Cranial magnetic resonance imaging scans revealed delayed myelination and cerebral atrophy. Exome sequencing indicated that the siblings had novel compound heterozygous missense variants, c.590T>G (p.Val197Gly) and c.433G>A (p.Gly145Arg), in exon 4 of ALG14. Repetitive nerve stimulation test showed an abnormal decrease in compound muscle action potential. After treatment with pyridostigmine, the time off the respirator increased. Their epileptic seizures were well controlled by anti-epileptic drugs. Their clinical course is stable even now at the ages of 5 and 2 years, making them the longest reported survivors of a severe form of CMS with the ALG14 variant thus far.

PMID:34971077 | DOI:10.1002/ajmg.a.62629

Am J Med Genet B Neuropsychiatr Genet. 2021 Dec 31. doi: 10.1002/ajmg.b.32884. Online ahead of print.

ABSTRACT

The world learned of the heated dispute about the methodology of the early works by Davenport and Rosanoff claiming Mendelian transmission patterns for mental handicap and psychiatric illness in a bold headline in the New York Times on Sunday, November 9, 1913: ENGLISH EXPERT ATTACKS AMERICAN EUGENIC WORK. I here focus on the debate surrounding Rosanoff’s 1911 study where he presented evidence that the neuropathic constitution, including, among its manifestations, dementia praecox, and manic-depressive illness, was an autosomal recessive trait. The “English expert,” David Heron, a student of Pearson’s, launched the debate in his 1913 paper which argued that Rosanoff’s field work methods were biased, his clinical assessments sloppy, his phenotype far too broad, and his statistical approach flawed. Both Davenport, Rosanoff’s mentor, and Rosanoff vigorously defended their methods. Behind this sometimes personal debate was the long simmering controversy about the relative validity of Biometrical genetic (represented by Heron and Pearson) and Mendelian genetic (represented by Rosanoff and Davenport) models for genetic transmission in plants, animals and, especially, humans. A review suggests that most of Heron’s criticisms were valid. This episode presages later controversies within psychiatric genetics, for example between twin and linkage researchers in the 1980s and 1990s.

PMID:34971081 | DOI:10.1002/ajmg.b.32884

Alzheimers Dement. 2021 Dec;17 Suppl 11:e051128. doi: 10.1002/alz.051128.

ABSTRACT

BACKGROUND: COVID-19 has placed an extraordinary and disproportionate level of responsibility and risk on certified nursing assistants (CNAs) caring for persons with dementia (PWD) relative to their training, resources, and compensation levels. Nearly one-quarter of COVID-19 deaths in the United States have been nursing home residents and staff. Despite providing the majority of direct care, CNAs are amongst the most under-resourced and under-trained frontline workers. Given their essentiality, it is critical to support CNAs during the COVID-19 pandemic. The purpose of this work is to provide CNAs with a space to strengthen their knowledge and confidence in caring for PWD. This pilot study applies a virtual reality (VR) curriculum to train CNAs regarding the lived experiences of PWD and their loved ones. The VR vignette portrays a Latinx woman, Beatriz, through progressive stages of Alzheimer’s disease.

METHOD: Chicago Methodist Senior Services (CMSS) CNAs were recruited (N=7; 86% female, 86% Black) for a seven-week online training program consisting of 1.5 hours per week. Each class included a didactic lecture and an Embodied Labs VR module depicting a first-person experience of dementia through a distributive model approach. The program concluded with two recorded focus groups. Participants completed the UCLA Geriatric Attitudes Scale, a dementia knowledge assessment, the Interpersonal Reactivity Index surveys, and a COVID-19 Impact questionnaire. Current analyses include qualitative content analysis for focus group data and descriptive, quantitative statistics for pre-and post-VR intervention surveys.

RESULT: Preliminary results demonstrate that CNAs endorsed a positive change in attitudes toward older adults (p=0.069), a deepened understanding of dementia, and increased confidence in caregiving skills. Focus groups allowed CNAs to discuss changes in resident behavior and support one another through a virtual platform during a global pandemic.

CONCLUSION: Combining traditional didactic lectures with VR-based curricula provided CNAs with foundational knowledge and first-hand experience of dementia pathology. Participants reported greater levels of insight and empathy for PWD. Future aims include expansion of training content to include end-of-life conversations, LGBTQIA aging, and Lewy body dementia.

PMID:34971052 | DOI:10.1002/alz.051128

J Esthet Restor Dent. 2021 Dec 31. doi: 10.1111/jerd.12863. Online ahead of print.

ABSTRACT

OBJECTIVE: This study was aimed at comparing the bleaching efficacy and bleaching sensitivity (BS) of two higher-concentration in-office bleaching gels (37% carbamide peroxide [CP] and 38% hydrogen peroxide [HP]) applied under two conditions: alone or in association with sonic activation.

METHODS: Fifty-six volunteers were randomly assigned in the split-mouth design into the following groups: CP, CP with sonic activation (CPS), HP, and HP with sonic activation (HPS). Two in-office bleaching sessions were performed. Color was evaluated using Vita Classical, Vita Bleachedguide, and digital spectrophotometer at baseline and at 30 days post-bleaching. Absolute risk and intensity of BS were recorded using two pain scales. All data were evaluated statistically (color changes [t test], BS [Chi-square and McNemar test], and BS intensity [VAS; t test; NRS; Wilcoxon; α = 0.05]).

RESULTS: Significant and higher whitening was observed for HP when compared with CP (p < 0.04). However, higher BS intensity was observed in the former (p < 0.001). No significant difference was observed in whitening effect or BS when the HP or CP bleaching gels were agitated (sonic application) compared with when they were not (p > 0.05).

CONCLUSION: The 37% CP gel demonstrated lower bleaching efficacy and lower BS compared with the 38% HP bleaching gel. The whitening effect was not influenced by the use of sonic activation.

CLINICAL SIGNIFICANCE: The use of 37% CP gel did not achieve the same whitening effect when compared to 38% HP gel used for in-office bleaching. The use of sonic activation offers no benefit for in-office bleaching.

PMID:34971074 | DOI:10.1111/jerd.12863

Alzheimers Dement. 2021 Dec;17 Suppl 11:e052988. doi: 10.1002/alz.052988.

ABSTRACT

BACKGROUND: Conventional means for dementia diagnosis rely on qualitative tests usually administered after significant pathogenesis. Past studies suggest the utility of more quantitative analytical approaches such as handwriting/drawing tasks (Impedevo et al., 2018). Such tools would provide low-cost, portable, and instantaneous quantitative diagnostics for more efficient patient screening. However, efforts to realize these methods have faced challenges such as low sample size, incomplete feature extraction, and lack of task diversity. We attempted to create a tablet application that uses pen-tracking technology to surmount these challenges.

METHOD: As fine motor control provides fundamental markers of neurological health (Bisio et al., 2017; Thomas et al., 2017), rigorous statistical analysis of simple drawing tasks on a tablet permitted differentiation between neuronormative patients and dementia patients with high fidelity. We have started testing our data analysis pipeline with open access datasets: PaHaW (Drotár et al., 2016), Isuniba (Impedovo et al, 2013), ParkinsonHW (Isenkul et al., 2014). These datasets contain drawing data for healthy individuals and those with both dementia and other neurodegenerative diseases. They contain similar raw data that the in-house iPad app collects. From that raw data, we extracted predictive features, including velocity, acceleration, jerk, curvature, and measures of variation.

RESULT: We have successfully created an iPad app that is able to record the dynamic handwriting process with an Apple Pencil. Our platform has the potential to generate more standardized datasets with improved documentation compared to existing archives. Patients trace complex figures such as spirals and infinity symbols at varying speeds over multiple trials. Additionally, the subjects are asked to remember and draw a shape that was presented to them at the beginning of the test. The app collects key data such as the position of the pen tip, velocity of pen movement, pen angle relative to the surface, and pressure exerted on the surface.

CONCLUSION: We plan to deploy our in-house iPad app in clinical trials to collect pen-tracking data with which to facilitate differential diagnoses for neurodegenerative diseases afflicting Alzheimer’s and Parkinson’s patients. The validation of such a platform would improve upon existing diagnostic datasets and lower major barriers to dementia screening.

PMID:34971031 | DOI:10.1002/alz.052988

Alzheimers Dement. 2021 Dec;17 Suppl 11:e052585. doi: 10.1002/alz.052585.

ABSTRACT

BACKGROUND: An estimated 44 million people worldwide live with Alzheimer’s disease and related dementias (ADRD). There is increasing interest in using emerging technologies such as robotics and artificial intelligence to provide assistance to people living with ADRD and their caregivers.

METHOD: We conducted an anonymous, online survey to study the public’s attitude and acceptance of using a human-like robot to assist people with ADRD. The survey was distributed via social media (e.g., Facebook, Twitter, LinkedIn), emails, and Listservs. Participants above age 18 were recruited to complete the survey. After informed consent, participants watched a brief (3 minute) video, which provided examples of how humanoid robots could be used to help people with ADRD. This was followed by questions, which took approximately 10 minutes to complete and assessed perceptions of the robot’s appearance and functions (e.g., companion, communication, providing entertainment, medication, emergence call). The participant could skip any questions that they do not wish to answer.

RESULT: Inputs to the survey were collected between November 13, 2020 and January 15, 2021. During that time, 1,004 people viewed the survey. The survey was started by 249 people from 16 different countries and districts (7 in Asia, 5 in Europe, 2 in North America, 1 in Oceania, and 1 in Africa). Ninety-seven people dropped out before finishing all the questions and 152 people completed the survey. Among the complete responses, 11 persons reported to have dementia and 79 people had experience in providing care to ADRD patients. Among a list of robot’s functions, reminding to take medicine, making emergency call, and helping to contact medical services were rated as the most important by participants with dementia. Monitoring medication and making emergency communication/alert were rated as the most important by participants with experience in dementia caregiving.

CONCLUSION: The study presents statistical results from an anonymous online survey that collect international inputs on the use of social robots in Alzheimer’s care. Results of the survey show an overall positive attitude towards using humanoid robots for people with ADRD. Results may shed insight for design and development of assistive technology in robotics and AI for ADRD.

PMID:34971041 | DOI:10.1002/alz.052585

Alzheimers Dement. 2021 Dec;17 Suppl 11:e050149. doi: 10.1002/alz.050149.

ABSTRACT

BACKGROUND: People with dementia (PwD) often become lost, which is commonly attributed to spatial disorientation, one of the earliest symptoms of dementia, particularly of the Alzheimer’s disease type. Spatial disorientation can limit a person’s ability to navigate in an outdoor environment. As a result, PwD experience outdoor mobility decline, which, in turn, can have a negative impact on their cognitive functions. Thus, enabling safe outdoor mobility is important for dementia research. Artificial Intelligence (AI) methods in conjunction with Global Positioning System (GPS) data show great potential for supporting the outdoor mobility needs of PwD. The objective of this work is to evaluate the extent to which we can predict future destinations of PwD by learning from their past mobility habits.

METHOD: Eight cognitively-intact older adults (CTL) and seven older adults with dementia completed four weeks of GPS recording. Each participant’s stops and trips were extracted from their trajectories. We determined the predictability of each participant’s mobility patterns using three approaches. First, we assumed each stop is visited with equal probability, thus, disregarding temporal aspects of travel. Next, we built on the previous approach by including stop visitation probability, thus, capturing the heterogeneity of visitations. Finally, to capture the full spatiotemporal characteristics of mobility, we added in-depth temporal characteristics including the visitation frequency, the order in which the stops were visited, and the time spent at each stop.

RESULT: Relying solely on the spatial dimension of mobility yielded no predictive power across the two groups. Adding the heterogeneity of visitation patterns, we observed an increase in the predictability power; PwD displayed a trend toward higher predictability compared to the CTLs, but the student’s t-test did not reach statistical significance (0.833±0.085vs.0.768±0.029, t(13)=-2.06, p=0.06; d=-1.07). Finally, relying on full spatiotemporal characteristics, a 4-week record of mobility patterns displayed 95% (SD=2%) and 92% (SD=1%) predictability among PwD and CTLs, respectively. This value was significantly higher among PwD, t(13) = -3.39, p<.01; d=-1.75.

CONCLUSION: Our findings offer new perspectives on the predictive mobility models based on GPS data and AI that can be used to provide personalized assistance for outdoor navigation of people with dementia.

PMID:34971030 | DOI:10.1002/alz.050149

Neuro Endocrinol Lett. 2021 Nov 30;42(7). Online ahead of print.

ABSTRACT

OBJECTIVES: The main aim of this study was to analyse selected biomechanical aspects of the asymmetrical loading of the human postural system when riding the C1 speed canoe and their influence on the development of muscular imbalances.

METHODS: 3D kinematic analysis of a simulated forward stroke of the canoeist in a pool with a counter-current (N = 9) and analysis of MRI data with selected individuals (N = 5), videoanalysis of actual paddling top athletes (N = 12), the kinesiological analysis of movement.

RESULTS: Can be stated that when riding a C1 speed canoe the postural system is exposed to two types of asymmetric loading. In the first place, there is lateral asymmetry, which stems from the very nature of the one-sided paddling on this type of vessel. The canoeist has to compensate for the consequent instability by shifting the body’s centre of gravity higher above the kneeling lower limb. This effect is achieved by the so-called pelvic lateralisation from the paddling side and by this side’s skewing to the kneeling lower limb. Another asymmetry is connected to the forward-backward body movement and its time-dependent deviation from the neutral posture. A significant disproportion between generally fixation movements of the lower part of the body and phasic movements of the upper part of the body has been confirmed. These asymmetrical positions result in a significant unilateral overloading of the quadratus lumborum on the side of the supporting lower limb (side without the paddle), as well as an overloading of the spine straighteners in the lumbar area, in particular on the part of a supporting lower limb, and bilateral yet asymmetric overloading of m. iliopsoas, which in addition takes place in different isometries. The analysis of MRI data indicates that, during longitudinal training, lateral disproportion in the volume and intensity of postural system loading is the cause of different cross sections of the iliopsoas muscle and quadratus lumborum muscle on the side of the kneeling and supporting lower limbs. With both muscles, larger cross sections with a statistical significance level α = 0.05 and thus also strength on the side of the supporting lower limb can be expected.

CONCLUSION: When canoeing on the C1, a significant unilateral overloading occurs with m. quadratus lumborum on the part of the supporting lower limb (side without paddle). Furthermore, spine straighteners in the lumbar area are overloaded, in particular in the part of the supporting lower limb. Last but not least however, the bilateral asymmetric overloading of m. iliopsoas occurs.

PMID:34969187