Few geriatric heart failure patients investigated according to clinical guidelines: a retrospective review of patient records.

BACKGROUND: Research on heart failure (HF) has often focused on younger patients. The aim of this study was to analyze extent of investigation and treatment among older patients prior to referral to inpatient geriatric care for worsening of HF. METHODS: Data on etiology, ejection fraction (EF) by echocardiography (ECHO), level of functioning according to New York Heart Association (NYHA), analysis of N-terminal-pro-brain natriuretic peptide (NT-Pro-BNP), ongoing treatment, adherence to guidelines, and information from previous caregiver were collected from patient records prior to admission from a sample of 134 patients. RESULTS: Few patients had been examined by a cardiologist (14%) during the year prior to referral. EF assessment had been performed in 78% (n = 105). The patients were categorized as having HF with reduced (HFrEF 28%), preserved (HFpEF 53%) or mid-range (HFmrEF 19%) EF. HFpEF patients had older EF assessments (mean 517 days) than those with HFrEF (385 days). In 61% (n = 82) at least one assessment with NT-Pro-BNP had been performed, being older among patients with HFpEF (290 days vs 16 days). There was a strong positive correlation (OR 4.9, p = 0.001) between having recent assessments of EF and NT-Pro-BNP (n = 30, 21%) and being presented with etiology in the referral, adjusted for EF, age, sex, and comorbidity. Among the HFrEF patients, 78% were treated with ACEI/ARB and BB according to ESC guidelines but reaching only half of target doses. In the HFpEF group the corresponding treatment was 46%. Among patients with EF ≤ 35% only 14% were treated with mineral receptor antagonists, ie low adherence to guidelines. CONCLUSIONS: HF care in this population of older individuals showed deficiencies. There was little contact with cardiologists, lack of information of etiology in referrals and low adherence to treatment guidelines. Improving adherence to HF guidelines regarding investigation and treatment for HF in older people is therefore urgent and calls for more collaboration between specialists in cardiology and geriatric medicine.

White matter abnormalities mediate the association between masticatory dysfunction and cognition among older adults.

BACKGROUND: Masticatory parameters, such as reduced number of teeth and posterior contacts, have been shown to be associated with reduced cognitive status. The underlying mechanisms that affect these associations, are however, not well understood. OBJECTIVES: The study aims to investigate the association between masticatory dysfunction and cognition and explore the mediating effect of brain structure. METHODS: In this cross-sectional study, 45 older adults with subjective masticatory dysfunction (mean age 72.3 ± 4.0 years) were included. Mini-Mental State Examination score <25, brain trauma, neurological disease, neurodegenerative disorders, depression or poor Swedish language skills were criteria for exclusion. Cognitive functions (executive function and episodic memory) and masticatory dysfunction defined by functional occluding status (FOS; the number of occluding units and number of remaining teeth) were analysed with partial correlation models. Structural magnetic resonance imaging was performed on 28 feasible participants. Multiple regression analyses were performed to evaluate the predictive value of brain structure and white matter hypointensities (WM-hypo) on cognitive functions. A mediation analysis was applied to assess significant predictor/s of the association between FOS and cognition. RESULTS: Both episodic memory and executive functions were positively correlated with FOS. WM-hypo predicted cognitive status (executive function, p ≤ .01). WM-hypo mediated 66.6% (p = 0.06) of the association between FOS and executive functions. CONCLUSION: Associations between FOS and cognitive functions are reported, where FOS, a potential modifiable risk factor, was related to both episodic memory and executive functions. The mediating effect of WM-hypo on the association between FOS and executive functions highlights the impact of the vascularisation of the brain on the link between mastication and cognition. The present study provides increased knowledge that bridges the gap between masticatory dysfunction and cognition.

Orofacial dysfunction after stroke-A multidisciplinary approach.

OBJECTIVE: This paper describes the study protocol in an ongoing clinical trial evaluating oral screen training as part of a post-stroke rehabilitation programme. Baseline data were related to four domains: dysphagia, lip function, masticatory performance and patient-related outcome measures (PROM). BACKGROUND: Stroke is one of the most common causes of disability-adjusted life years, and dysphagia is a common remaining problem after stroke. Rehabilitation using oral screen training has been suggested to improve swallowing, but evidence is still insufficient. MATERIALS AND METHODS: Patients diagnosed with stroke with persisting objective and/or subjective swallowing dysfunction after primary rehabilitation were assessed for eligibility. In total, 25 patients were included. Objective function was assessed by swallowing capacity test (SCT), lip force and masticatory performance, subjective function by EAT-10 and NOT-S and PROM by LiSat-11 and ESAS. RESULTS: Baseline data presented a heterogeneous pattern with no significant association between objective and subjective dysfunction. Most of the participants (20/25) showed impaired swallowing capacity in SCT, and 23/24 revealed orofacial dysfunction according to NOT-S. The most common subjective item reported was chewing and swallowing problems (19/24). CONCLUSION: The heterogenous findings in the included tests and the lack of correlations emphasise the importance of multidisciplinary approaches to identify objective and subjective orofacial post-stroke dysfunction in clinical practice to be able to offer evidence-based individualised care. The included participants were representative of stroke patients with dysphagia, which supports proceeding with the planned intervention.

Adults with spina bifida: ambulatory performance and cognitive capacity in relation to muscle function.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: Describe and compare ambulatory performance and cognitive capacity in relation to muscle function in an adult cohort with spina bifida. Also, explore factors associated with ambulation in participants with muscle function level 3. SETTING: Specialist clinic for adults with spinal cord disorders in Stockholm, Sweden. METHODS: A total regional cohort of adults (n = 219) with spina bifida was invited, 196 (104 women, mean age 35 years, SD 13 years) participated. Mode of mobility, cognitive capacity and muscle function were investigated. For participants with muscle function level 3, factors associated with ambulation were investigated using multivariate logistic regression analysis. RESULTS: In all, 84 participants (42%) were community ambulators, 22 (12%) household ambulators and 90 (46%) wheelchair users. There was a linear association between the lower degree of muscle function and scoliosis (P < 0.001). Mode of mobility varied despite similar muscle prerequisites in participants with muscle function level 3 (n = 58). Factors associated with ambulation in participants with muscle function level 3 were the absence of scoliosis, lower BMI and higher cognitive capacity. CONCLUSIONS: Cognitive capacity and mode of mobility varied widely across the cohort. However, in participants with muscle function level 3, despite similar muscular prerequisites, a large variation in the mode of mobility was found, suggesting that other factors were involved. It is important to prevent scoliosis, support a healthy lifestyle, as well as offer cognitive screening and support to promote ambulatory function and optimise independence in the everyday lives of adults with spina bifida.

Cognitive changes and neural correlates after oral rehabilitation procedures in older adults: a protocol for an interventional study.

BACKGROUND: Epidemiological studies show an association between masticatory function and cognitive impairment. This has further strengthened the notion that tooth loss and impaired masticatory function may be risk factors for dementia and cognitive decline. Animal experiments have indicated a causal relationship and several possible mechanisms have been discussed. This evidence is, however, lacking in humans. Therefore, in the current interventional study, we aim to investigate the effect of rehabilitation of masticatory function on cognition in older adults. METHODS: Eighty patients indicated for prosthodontic rehabilitation will be randomly assigned to an experimental or a control group. Participants will conduct neuropsychological assessments, masticatory performance tests, saliva tests, optional magnetic resonance imaging, and answer questionnaires on oral health impact profiles and hospital anxiety and depression scale before, 3 months, and 1 year after oral rehabilitation. The difference between the two groups is that the control group will be tested an additional time, (at an interval of about 3 months) before the onset of the oral rehabilitation procedure. The primary outcome is a change in measures of episodic memory performance. DISCUSSION: Although tooth loss and masticatory function are widespread in older people, it is still an underexplored modifiable risk factor potentially contributing to the development of cognitive impairment. If rehabilitation of masticatory function shows positive effects on the neurocognitive function, this will have great implications on future health care for patients with impaired masticatory status. The present project may provide a new avenue for the prevention of cognitive decline in older individuals. TRIAL REGISTRATION: The protocol for the study was retrospectively registered in ClinicalTrials.gov Identifier: NCT04458207, dated 02-07-2020.

Cognitive challenges in persons with spina bifida: Bearing on urological dysfunctions?

AIM: To evaluate if adult persons with spina bifida (SB) who have urinary tract complications have cognitive difficulties that can be identified by neuropsychological tests. METHODS: All individuals with SB ≥ 18 years of age registered at a regional outpatient clinic (n = 219) were invited, of which, 154 persons were included. Neuropsychological assessment of their cognitive status was performed with Wechsler Adult Intelligence Scale®-Fourth Edition: Coding, Block design, Arithmetic's, FAS (word generation), Rey Auditory Verbal Test for learning, and delayed recall 30 min. Bladder and bowel function were assessed with questions used by the Nordic Spinal Cord Injury Registry (NSCIR) in structured interviews, by questionnaires, and by chart reviews. RESULTS: Average neuropsychological test results for this SB population was shown to be approximately 1 SD under the median for the general population. The Coding test showed significantly lower test results as compared with the whole SB group in persons with urinary tract complications, especially urinary tract infections, reduced kidney function, dependent emptying of the bladder, and the bowel and accidental bowel leakage. The Arithmetic's test showed a significant difference between subgroups in all parameters except reduced kidney function whereas the other neuropsychological tests were significantly correlated with some but not all urological parameters. CONCLUSION: We propose neuropsychological testing with primarily two tests to find those persons with SB who, due to cognitive challenges, might need extra support to minimize urological complications.

Voiding conditions, renal and bowel function in a cohort of adults with spina bifida.

AIM: To map voiding patterns, degree of continence, use of drugs for voiding disorders, kidney function and surgical interventions but also the bowel function in a near-total regional cohort of adults with spina bifida aged more than or equal to 18 years. METHODS: All individuals more than or equal to 18 years of age with spina bifida registered at a regional outpatient clinic (n = 219) were invited to participate, of which 196 persons were included. Bladder and bowel function were assessed according to questions used by the Nordic Spinal Cord Injury Registry by structured interviews and questionnaires in combination with review of patient charts including kidney function. RESULTS: Twenty percent of the patients voided spontaneously. Fifty-four percent used clean intermittent catherization (CIC) and of these, 14% had also undergone augmentation of the bladder and/or implantation of an artificial sphincter or sling, 23% had undergone major urological surgery, and 3% had an indwelling catheter. Seventeen percent of patients voiding spontaneously or using CIC reported total continence but as many as 36% reported daily leakage. Anticholinergics was the most common drug, used by 21% in the total cohort. About 13% of the patients had a reduced kidney function but only 1.5% had end stage renal failure. Seventy-three percent had problems emptying the bowel and 18% experienced fecal leakage weekly or even daily. CONCLUSION: We found a large variation in problems with bladder and bowel function in this adult group of persons with spina bifida. A structured customized program for follow-up seems necessary to optimize their health status in these areas.

Factors associated with self-rated health in a Norwegian population of older people participating in a preventive home visit program: a cross-sectional study.

BACKGROUND: Assessing self-rated health by preventive home visits of older people can provide information about the person's well-being, quality of life and risk of developing illness. The aim of this study was to examine associations between self-rated health and factors related to demographics, lifestyle, health conditions and medical diagnoses by older people participating in a preventive home visit program. METHODS: A cross-sectional study including 233 participants (age 75-79) from three municipalities of Western Norway was conducted. Data were collected through preventive home visits performed by six nurses, using a questionnaire including self-rated health assessment and questions and tests related to demographics (e.g. education and housing), lifestyle (e.g. social activities, alcohol and smoking), health conditions (e.g. sensory impairment, pain and limited by disease) and medical diagnoses. Descriptive and inferential statistics including linear block-wise regression model were applied. RESULTS: The block-wise regression model showed that the variables Limited by disease and Pain were negatively associated with self-rated health and Use internet was positively associated. The model had a R2 0.432. The variable that contributed to largest change in the model was Limited by disease (R2 Change; 0.297, p-value< 0.001). CONCLUSIONS: In the present study, being limited by disease and pain were strongly associated with poor self-rated health, indicating that these are important factors to assess during a preventive home visit. Also, digital competence (Use internet) was associated with a better self-rated health, suggesting that it could be useful to ask, inform and motivate for the use of digital tools that may compensate for or improve social support, social contact and access to health -related information.

A health concept with a social potential: an interview study with nursing home residents.

BACKGROUND: A qualitative, interview-based study was embedded in a randomized intervention trial, the Older People Exercise and Nutrition (OPEN) study. Participants in the OPEN study were encouraged to conduct sessions of sit-to-stand (STS) exercises combined with Oral Nutritional Supplements (ONS) intake. The aim was to describe the older persons' perceptions and experiences of being given the daily opportunity to perform the STS exercise and drink ONS. METHODS: In-depth interviews were conducted in six nursing homes with the participants using a semi-structured interview guide. One or two individual interviews were performed with each included participant. Twenty-three NH residents (16 women and 7 men) participated in the qualitative study. Their ages ranged between 76 and 96 years, and their Mini Mental State Examination (MMSE) scored between 8 and 29. The transcribed interviews and field notes written during the visits were analyzed inductively following a constant comparative method described in Grounded Theory. RESULTS: The exercise and nutritional intervention was described as highly practical by the NH residents, who claimed it also had a social aspect as they felt acknowledged and empowered to engage others in the combined intervention. Experiences of the intervention ranged from neutral to mainly positive and could be sorted into 5 categories: 1. Perceived hopes and expectations, 2. Health-related driving forces, 3. Appreciated daily activities, 4. A concept easy to perform and integrate into daily life, 5. A beneficial health concept for all. The intervention created perceived benefits on various health aspects due to participants feeling energized and stronger. An overall theme was identified as A health concept with a social potential, as participants feel acknowledged and strong enough to help others. CONCLUSIONS: The intervention was described by participants as a health concept that could potentially be beneficial for a broader spectrum of NH residents. The findings indicate that health concepts, such as STS/ONS, might contribute to a more meaningful day for older people, even vulnerable NH residents approaching the end of life. TRIAL REGISTRATION: ClinicalTrials.govIdentifier: NCT02702037 . Date of trial registration February 26, 2016.

Fetal CD103+ IL-17-Producing Group 3 Innate Lymphoid Cells Represent the Dominant Lymphocyte Subset in Human Amniotic Fluid.

Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45+ cells in AF is represented by a subset of fetal CD103+ group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF. Fetal CD103+ ILC3s could also be detected at high frequency in second-trimester mucosal tissues (e.g., the intestine and lung). Taken together, our data indicate that CD103+ ILC3s accumulate with gestation in the fetal intestine and subsequently egress to the AF. The dominance of ILC3s producing IL-17 and TNF in AF suggests that they could be involved in controlling intra-amniotic infections and inflammation and as such could be important players in regulating subsequent premature birth.

A study protocol of Older Person's Exercise and Nutrition Study (OPEN) - a sit-to-stand activity combined with oral protein supplement - effects on physical function and independence: a cluster randomized clinical trial.

BACKGROUND: Poor nutrition and age per see add to the development of sarcopenia, i.e. loss of muscle mass and strength, which contributes to increased risk of impaired activities of daily living (ADL) and reduced independence. Protein deficiency plays an important role in the development of sarcopenia. In order to increase the muscle mass protein intake should be combined with physical exercise. A daily physical activity, the sit-to-stand exercise, has been proven to decrease older persons' dependence in ADL. Our study aims to evaluate the effects of the sit-to-stand exercise in combination with a protein-rich nutritional supplement, on physical function and independence in frail nursing home residents. The resident's perceptions and experiences of the intervention and the staff's experiences of supporting the resident to complete the intervention will also be explored. METHODS: The study is a two-arm cluster-randomized controlled trial which will be performed in nursing homes at two municipalities in Sweden. We will recruit 120 residents, age 75 or older and able to stand up from a seated position. Residents (n = 60) randomized to the intervention group will perform the sit-to-stand exercise at four occasions daily and will be offered a protein-rich oral supplement, twice a day. The intervention period will last for 12 weeks and measures of physical function, nutritional status, quality of life and health economy will be performed at baseline and at 12-weeks follow-up. The primary outcome will be the number of chair rises performed in 30 s. The control group will receive standard care. Data will be analysed by intention-to-treat analysis and with mixed effect models. During the last part of the intervention period individual interviews with the residents, on the topic of feasibility with the OPEN concept will be held. Likewise, focus-group-interviews with staff will be performed. DISCUSSION: The residents' physical and mental health could be expected to improve. Even the work situation for staff could be positively affected. One innovative feature of the OPEN study is the simple intervention consisting of a basic daily activity that can be performed by several nursing home residents with the support of existing staff and available resources. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02702037.

Assessment of voice, speech and communication changes associated with cervical spinal cord injury.

BACKGROUND: Respiratory muscle impairment following cervical spinal cord injury (CSCI) may lead to reduced voice function, although the individual variation is large. Voice problems in this population may not always receive attention since individuals with CSCI face other, more acute and life-threatening issues that need/receive attention. Currently there is no consensus on the tasks suitable to identify the specific voice impairments and functional voice changes experienced by individuals with CSCI. AIMS: To examine which voice/speech tasks identify the specific voice and communication changes associated with CSCI, habitual and maximum speech performance of a group with CSCI was compared with that of a healthy control group (CG), and the findings were related to respiratory function and to self-reported voice problems. METHODS & PROCEDURES: Respiratory, aerodynamic, acoustic and self-reported voice data from 19 individuals (nine women and 10 men, aged 23-59 years, heights = 153-192 cm) with CSCI (levels C3-C7) were compared with data from a CG consisting of 19 carefully matched non-injured people (nine women and 10 men, aged 19-59 years, heights = 152-187 cm). OUTCOMES & RESULTS: Despite considerable variability of performance, highly significant differences between the group with CSCI and the CG were found in maximum phonation time, maximum duration of breath phrases, maximum sound pressure level and maximum voice area in voice-range profiles (all p = .000). Subglottal pressure was lower and phonatory stability was reduced in some of the individuals with CSCI, but differences between the groups were not statistically significant. Six of 19 had voice handicap index (VHI) scores above 20 (the cut-off for voice disorder). Individuals with a vital capacity below 50% of the expected for an equivalent reference individual performed significantly worse than participants with more normal vital capacity. Completeness and level of injury seemed to impact vocal function in some individuals. CONCLUSIONS & IMPLICATIONS: A combination of maximum performance speech tasks, respiratory tasks and self-reported information on voice problems help to identify individuals with reduced voice function following CSCI. Early identification of individuals with voice changes post-CSCI, and introducing appropriate rehabilitation strategies, may help to minimize development of maladaptive voice behaviours such as vocal strain, which can lead to further impairments and limitations to communication participation.

Factors Associated With Recurrent Falls in Individuals With Traumatic Spinal Cord Injury: A Multicenter Study.

OBJECTIVE: To identify factors associated with recurrent falls in individuals with traumatic spinal cord injury (SCI). DESIGN: Cross-sectional multicenter study. SETTING: Two specialized rehabilitation centers. PARTICIPANTS: Included: individuals with traumatic SCI ≥1 year postinjury who were aged ≥18 years. Excluded: individuals with motor complete injuries above C5 or below L5. The study sample comprised participants (N=224; 151 wheelchair users, 73 ambulatory; 77% men; mean age ± SD, 50±15y; median time since injury, 15y [range, 1-56y]) who were consecutively recruited at regular follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Primary outcome was factors associated with recurrent falls (defined as low frequent [0-2] or recurrent [>2]) the previous year. Independent variables were demographic data, wheelchair user or ambulatory, work, health-related quality of life, risk willingness, alcohol consumption, ability to get up from the ground, and exercise habits. RESULTS: Fifty percent reported recurrent falls. In the final multiple logistic regression model, ambulation (odds ratio [OR]=2.67; 95% confidence interval [CI], 1.33-5.37), ability to get up from the ground (OR=2.22; 95% CI, 1.21-4.10), and regular exercise (OR=1.86; 95% CI, 1.05-3.31) were associated with recurrent falls (P≤.05), and with increasing age the OR decreased (OR=.97; 95% CI, .95-.99). CONCLUSIONS: Individuals with SCI should be considered at risk of recurrent falls, and thereby at risk of fall-related injuries. Fall prevention programs should be focused on ambulatory, younger, and more active individuals who had the highest risks for recurrent falls.

Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease.

INTRODUCTION: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. METHOD: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. RESULTS: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-ß, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. DISCUSSION: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.

A Protocol for Comprehensive Analysis of Gait in Individuals with Incomplete Spinal Cord Injury.

This is a protocol for comprehensive analysis of gait and affecting factors in individuals with incomplete paraplegia due to spinal cord injury (SCI). A SCI is a devastating event affecting both sensory and motor functions. Due to better care, the SCI population is changing, with a greater proportion retaining impaired ambulatory function. Optimizing ambulatory function after SCI remains challenging. To investigate factors influencing optimal ambulation, a multi-professional research project was grounded with expertise from clinical rehabilitation, neurophysiology, and biomechanical engineering from Karolinska Institutet, the Spinalis Unit at Aleris Rehab Station (Sweden's largest center for specialized neurorehabilitation), and the Promobilia MoveAbility Lab at KTH Royal Institute of Technology. Ambulatory adults with paraplegia will be consecutively invited to participate. Muscle strength, sensitivity, and spasticity will be assessed, and energy expenditure, 3D movements, and muscle function (EMG) during gait and submaximal contractions will be analyzed. Innovative computational modeling and data-driven analyses will be performed, including the identification of clusters of similar movement patterns among the heterogeneous population and analyses that study the link between complex sensorimotor function and movement performance. These results may help optimize ambulatory function for persons with SCI and decrease the risk of secondary conditions during gait with a life-long perspective.

Träning och protein för funktion och självtillit.

Exercise and protein for function and self-confidence - The OPEN model for community care of older persons Experiences from the COVID-19 pandemic indicate the need to introduce care routines for health promotion among recipients of care for older persons. A treatment model with daily repeated sit-to-stand exercises in combination with oral protein supplements twice daily has been evaluated in community care for older persons in the Stockholm Region; the Older Person's Exercise and Nutrition (OPEN) Study. The 3-month controlled study included 102 residents. A substantial part of the residents were able to follow the intervention, and to maintain or improve their chair-rising capacity, while also increasing their weight and muscle mass. Interview studies showed that the participants found the OPEN concept was easy to adopt, gave increased self-confidence and an increased sense of hope. The staff perceived the intervention as a potentially positive concept. The OPEN model is a method that may contribute to a health-promoting way of working in the care of older persons.

Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.

BACKGROUND/AIMS: Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability. METHODS: This was an open-label, 12-month study in 6 AD patients. Patients were implanted stereotactically with EC-NGF biodelivery devices targeting the basal forebrain. Patients were monitored with respect to safety, tolerability, disease progression and implant functionality. RESULTS: All patients were implanted successfully with bilateral single or double implants without complications or signs of toxicity. No adverse events were related to NGF or the device. All patients completed the study, including removal of implants at 12 months. Positive findings in cognition, EEG and nicotinic receptor binding in 2 of 6 patients were detected. CONCLUSIONS: This study demonstrates that surgical implantation and removal of EC-NGF biodelivery to the basal forebrain in AD patients is safe, well tolerated and feasible.

Gait and dynamic balance in adults with spina bifida.

BACKGROUND: Spina bifida (SB) is a complex congenital malformation, often causing impaired gait performance depending on the level and extent of malformation. Research regarding gait and balance performance in adults with SB, has not been sufficiently described yet. RESEARCH QUESTION: What are the characteristics of spatiotemporal gait parameters and balance performance in adults with SB? Further, do persons with muscle function (MF) level 3 differ regarding gait and balance performance from those with MF level 1-2? METHODS: Cross-sectional observational study at an outpatient clinic. 41 adults with SB (18-65 years), who walked regularly. Spatiotemporal parameters of gait was assessed with the APDM system and balance performance with the Mini Balance Evaluation Systems Test (Mini-BESTest). Muscle strength in the legs was assessed with 0-5 manual muscle test, and participants were classified according to level of MF into groups MF1, MF2, and MF3. Two-sided t-test was used for parametric independent variables, and Cohen's d was used for effect sizes. The Mann-Whitney U test was used for non-parametric independent data and effect size was calculated by the z value (r = z/√n). RESULTS: Mean gait speed was 0.96 (SD 0.20) m/s and mean stride length 1.08 m (SD 0.17), individuals with MF3 showed significantly slower gaitspeed and shorter stride length (p < 0.05). Lumbar rotation was 21° (SD 11), and thoracic lateral sway 15° (IQR 15) with significantley difference (p < 0.001 and p < 0.05) for individuals in MF3. Mini-BESTest showed a mean score of 11.3 (SD 6.9), and individuals with MF3 showed significantly lower scores (p ≤ 0.001). SIGNIFICANCE: Gait and balance performance was reduced compared to normative data in almost all parameters, especially in persons with less muscle function. Increased knowledge from advanced gait analysis may help healthcare professionals to design rehabilitation programmes, in order to achieve and maintain a sustainable gait and balance performance.

Fast Alpha Activity in EEG of Patients With Alzheimer's Disease Is Paralleled by Changes in Cognition and Cholinergic Markers During Encapsulated Cell Biodelivery of Nerve Growth Factor.

Background: Basal forebrain cholinergic neurons are dependent on nerve growth factor (NGF) for growth and survival and these cells are among the first to degenerate in Alzheimer's disease (AD). Targeted delivery of NGF has been suggested as a potential therapy for AD. This hypothesis was tested in a clinical trial with encapsulated cell biodelivery of NGF (NGF-ECB) in AD patients. Three of six patients showed improved biomarkers for cognition by the end of the study. Here, we report on the effects of targeted delivery of NGF on human resting EEG. Materials and methods: NGF-ECB implants were implanted bilaterally in the basal forebrain of six AD patients for 12 months. EEG recordings and quantitative analysis were performed at baseline, 3 and 12 months of NGF delivery, and analyzed for correlation with changes in Mini-mental state examination (MMSE) and levels of the cholinergic marker choline acetyltransferase (ChAT) in cerebrospinal fluid (CSF). Results: We found significant correlations between the topographic variance of EEG spectral power at the three study points (baseline, 3 and 12 months) and changes in MMSE and CSF ChAT. This possible effect of NGF was identified in a narrow window of alpha frequency 10-11.5 Hz, where a stabilization in MMSE score during treatment was related to an increase in EEG alpha power. A similar relation was observed between the alpha power and ChAT. More theta power at 6.5 Hz was on the contrary associated with a decrease in CSF ChAT during the trial period. Conclusion: In this exploratory study, there was a positive correlative pattern between physiological high-frequency alpha activity and stabilization in MMSE and increase in CSF ChAT in AD patients receiving targeted delivery of NGF to the cholinergic basal forebrain.