SP - Neurology & Neuroscience

Title: Unseen Spine: A Case of Infective Discitis masked by diverticulitis in older patient

Introduction:

Spinal infections include vertebral osteomyelitis, septic discitis, facet joint septic arthritis, and spinal epidural abscesses. The common presentation usually involves back pain, fever, and elevated inflammatory markers, with signs of neurological deficits implying presence of spinal epidural abscess. Spinal infections are infrequent (0.2–3.7 per 100,000 hospital admissions for spondylodiscitis), with relatively higher incidence in elderly patients.

Case presentation:

We present a case of an 80-year-old female patient with a complex past medical history, including chronic back pain, osteoarthritis, bladder cancer, breast cancer, and lymphedema. She presented to the emergency department with a 3-day-history of lower back pain radiating to the abdomen. There was no history of trauma. Examination revealed no signs of intra-abdominal infection. There was a significant elevation of white blood cell count and C-reactive protein (CRP). The initial CT scan identified acute, uncomplicated sigmoid colonic diverticulitis, which was treated under the surgical team conservatively with antibiotics, following which the patient was discharged. Thirteen days later, the patient represented again with the same symptoms with additional pain radiation to the right leg affecting mobility. There was lumbar spinal process tenderness on examination with persistently high inflammatory markers in blood. Blood cultures resulted positive for Streptococcus agalactiae. An MRI spine revealed infective discitis with a right paravertebral abscess, causing thecal sac compression evident on CT scan also with bilateral psoas abscess. Following starting an appropriate antibiotic course guided by the cultures, and CT-guided drainage of the abscess, the patient improved symptomatically and clinically.

Conclusion:

Spinal infections are uncommon, yet significant aetiology of back pain. They should be considered a differential diagnosis in anyone with new or increasing back pain. The investigation and treatment approach must be guided by history taking and clinical examination.

Title: Unseen Spine: A Case of Infective Discitis masked by diverticulitis in older patient

Introduction:

Spinal infections include vertebral osteomyelitis, septic discitis, facet joint septic arthritis, and spinal epidural abscesses. The common presentation usually involves back pain, fever, and elevated inflammatory markers, with signs of neurological deficits implying presence of spinal epidural abscess. Spinal infections are infrequent (0.2–3.7 per 100,000 hospital admissions for spondylodiscitis), with relatively higher incidence in older patients.

Case presentation:

We present a case of an 80-year-old female patient with a complex past medical history, including chronic back pain, osteoarthritis, bladder cancer, breast cancer, and lymphedema. She presented to the emergency department with a 3-day-history of lower back pain radiating to the abdomen. There was no history of trauma. Examination revealed no signs of intra-abdominal infection. There was a significant elevation of white blood cell count and C-reactive protein (CRP). The initial CT scan identified acute, uncomplicated sigmoid colonic diverticulitis, which was treated under the surgical team conservatively with antibiotics, following which the patient was discharged. Thirteen days later, the patient represented again with the same symptoms with additional pain radiation to the right leg affecting mobility. There was lumbar spinal process tenderness on examination with persistently high inflammatory markers in blood. Blood cultures resulted positive for Streptococcus agalactiae. An MRI spine revealed infective discitis with a right paravertebral abscess, causing thecal sac compression evident on CT scan also with bilateral psoas abscess. Following starting an appropriate antibiotic course guided by the cultures, and CT-guided drainage of the abscess, the patient improved symptomatically and clinically.

Conclusion:

Spinal infections are uncommon, yet significant aetiology of back pain. They should be considered a differential diagnosis in anyone with new or increasing back pain. The investigation and treatment approach must be guided by history taking and clinical examination.

Objectives: The objective of this study was to examine participant’s experience with remote delivery during SYNERGIC@Home/SYNERGIE~Chez soi (NCT04997681), a home-based, double-blind, randomized controlled trial targeting older adults at risk for dementia. Metrics included study adherence, adverse events (AEs), participant’s attitudes towards technology, and protocol deviations (PDs) due to technological difficulties. Methods: Participants underwent 16 weeks of physical and cognitive interventions (three sessions/week) remotely administered in their homes via Zoom for Healthcare^TM. Participants used a laptop, webcam, and required email and internet access. Throughout the trial, adherence, AEs, and PDs were recorded. Post- intervention, survey questions about satisfaction with technology were administered and semi-structured interviews were conducted which underwent thematic analysis. Results: Sixty participants, mean age 68.9 and 76.7% female, were randomized to one of four intervention arms, with 52 completing the 16-week intervention. Adherence rate was 87.5% with no significant difference between treatment arms (p=0.656). There were 88 AEs reported in 42 participants. The majority (71.6%) of AEs were unrelated to the intervention, and 69.3% were classified as mild. There was one serious AE, unrelated to the intervention. Most (74.9%) participants reported overall satisfaction with technology, with Zoom being both enjoyable (81.0%) and easy to use (96%). Most enjoyed using the computer (87%), and the majority (87.0%) encountered few difficulties with connectivity. Of the 2496 intervention sessions, 14 (0.56%) were missed due to technical difficulties. Technical difficulties requiring modification to the intervention, such as an unstable internet connection, were reported on 79 occasions (3.0%). Themes from the interviews were: participants built rapport with the research assistants; felt better participating; had fun; and technology helped overcome barriers to participation. Conclusions: Using technology to deliver dementia prevention interventions remotely was well received by participants Participation occurred safely from the comfort of their own home with few technical difficulties.

Introduction: Research suggests that physical and cognitive exercise can have a positive effective on those with dementia, but less is known about such interventions in those at risk for dementia. Understanding the feasibility of administering clinical assessments remotely using Zoom for Healthcare^TM in the context of a dementia prevention trial for at risk older adults is not well understood.

Methods: SYNERGIC@Home/SYNERGIE~Chez soi (NCT04997681) is a home-based, remotely delivered clinical trial targeting older adults at risk for dementia. Participants underwent a screening/baseline assessment and were randomized to one of four physical and cognitive exercise intervention arms for 16 weeks (3 times per week). They were reassessed immediately post-intervention and 6-months later. The standardized assessments of cognition, physical activity, mobility, mental health, nutrition, sleep, and quality of life were done at all three points. A research coordinator completed the assessments on a one-on-one basis via Zoom for Healthcare^TM. The quality of life questionnaire was mailed to the participant.

Results: Forty-eight of 60 participants (80%) (mean age 68.7 ± 5.7 years, 81.3% female) completed the study. Most participants (75.0%) were cognitively intact with at least 2 dementia risk factors. No participants withdrew from the trial because of difficulty with the remote delivery of the assessments. There were no statistically significant changes in any of the assessments of cognition, physical activity, mobility, mental health, nutrition, sleep, or quality of life throughout the study.

Conclusion: This study demonstrates it is possible to administer standardized clinical assessments of cognition, physical activity, mobility, mental health, nutrition, sleep, and quality of life remotely in the context of a clinical trial. The study was not powered to detect meaningful differences in these assessments. Nevertheless, this confirms the feasibility of remotely administering clinical assessments to older adults at risk for dementia

Background and aims

Delirium carries an eightfold risk of future dementia. Small vessel disease (SVD), best seen on MRI, increases delirium risk, yet delirium is understudied in MRI research. We aimed to determine MRI feasibility, tolerability, image usability, and prevalence of acute and chronic SVD lesions in acute delirium.

Methods

This case-control feasibility study performed MRI (3D T1/T2-weighted, FLAIR, Susceptibility-weighted, and Diffusion-weighted imaging (DWI) on 20 medical inpatients >65 years: 10 with delirium ≥3 weeks and 10 without delirium, matched for vascular risk, Clinical Frailty Scale (CFS), and cognitive status. We excluded acute stroke, agitation necessitating sedation, assistance of >2 staff to mobilise, and MRI contraindications. We measured scan duration, tolerability, image usability, acute infarcts on DWI, and chronic SVD features. Six months later, we recorded CFS and cognitive diagnoses.

Results

Mean age was 83.5 years (delirium 78.7 vs non-delirium 88.4); 13/20 were female; 17/20 had premorbid cognitive decline/impairment or dementia. Acquisition took mean 26.8 minutes. MRI was well-tolerated in 16/20 (7/10 in delirium arm; 9/10 in non-delirium arm). 4/20 had early scan termination but 20/20 had clinically interpretable images. We detected DWI-hyperintense lesions in 3/10 (33.3%) with delirium (2/10 small subcortical and 1/10 cortical) and in 3/10 (33.3%) without delirium (2/10 small subcortical; 1/10 cortical). Mean SVD score was 2.4 in delirium vs 3.3 without.

Conclusions

MRI is feasible, usable, and tolerable in delirium, and we detected DWI hyperintense lesions in one third of patients overall. This study indicates acute vascular contributions, including SVD, to delirium, supporting the need for larger studies.

Introduction.

In older adults, dizziness is often experienced as a vague feeling of subjective unsteadiness, where people perceive themselves to be swaying more than they actually are. One factor that potentially drives such distorted perceptions of instability is (hyper)vigilance towards balance. This study aimed to investigate if older adults who report higher levels of trait balance vigilance (i) are more likely to report sensations of general unsteadiness when their balance is acutely threatened, and (ii) if this is accompanied by maladaptive changes in postural control.

Methods.

Forty-eight healthy older adults without vestibular diagnosis (Mean age = 71.0, range = 60–83) completed the recently validated Balance-Vigilance Questionnaire to quantify trait balance vigilance. Participants were fitted a VR headset and completed 60-second, narrow-stance balance trials on a force platform, under conditions designed to create a threatening (standing at a 20-meter virtual height) or non-threatening (virtual ground level) environment. For each condition, we assessed self-reported stability (0-100%) and fear of falling (0-100%), postural control (sway amplitude and frequency), muscular control (tibialis anterior activity), and prefrontal and somatosensory cortical activity using fNIRS.

Results.

Preliminary results are reported. When presented with a postural threat, high-vigilant older adults (Balance Vigilance Score≥18; N=13) reported significantly greater fear of falling (+25%; p=.027) and more reduced perceived stability (-25%; p=.006) compared to low-vigilant older adults – despite there being no differences in actual sway amplitude (p=.157). Only the low-vigilant group showed evidence of an adaptive ‘stiffening’ strategy in response to threat: i.e. increased sway frequency (p=.028) and tibialis anterior activity (p=.027). fNIRS analysis is ongoing.

Conclusions.

These preliminary findings suggest that, in response to a postural threat, older adults with high balance-vigilance are more likely to experience excessive fear of falling and perceptions of instability, and may fail to make adaptive changes to their postural control. Screening for excessive balance vigilance may therefore be recommended.

OBJECTIVE: To assess in Alzheimer’s disease (AD), the treatment impact of donanemab, an amyloid plaque-reducing monoclonal antibody, on readily interpretable item-measures and constructs that matter to patients, care-partners, and clinicians.

BACKGROUND: Positive outcomes were reported from TRAILBLAZER-ALZ2, a randomized, double-blind, placebo-controlled, 18-month, phase 3 study evaluating donanemab as an investigational treatment for mild cognitive impairment (MCI) or mild dementia due to AD. In 1736 participants, donanemab significantly slowed the rate of clinical decline (by 22-36%) as measured by the integrated AD Rating Scale (iADRS) and the Clinical Dementia Rating Scale—Sum-of-Boxes (CDR-SB); both measures of cognition and function as indications of global clinical severity. In these subsequent post-hoc exploratory analyses, the impact of donanemab treatment on individual iADRS cognition and function items, CDR domains, and risks of advancing to greater disease severity were assessed.

METHODS: Mixed model repeated measures and Cox proportional hazard modeling methodology assessed treatment effects on iADRS items and CDR domains.

RESULTS: Donanemab treatment was associated with significant beneficial effects on: 1) iADRS cognitive items related to episodic memory and executive function, and instrumental activities of daily living items related to communication and others (e.g., being left alone, making a meal, using household appliances); 2) all CDR-SB cognitive and functional domains (i.e., memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care); and 3) lowering risk of progression to a more advanced clinical stage of disease.

CONCLUSIONS: These analyses explored the impact of donanemab treatment on constructs that matter to and are considered more readily interpretable by patients, care-partners, and clinicians. These results provide further support that treating those with MCI or mild dementia due to AD with donanemab can meaningfully reduce risk of progression to more severe clinical stages (e.g. moderate stage dementia), and potentially allow greater independence for a longer period of time.

Introduction

Horticultural therapy (HT) is not uncommonly used as non- pharmacological therapy for patients with dementia. However, less is known about its effects on older adults with normal cognition. This systematic review and meta-analysis synthesises available evidence to evaluate the effects of HT on psychosocial and physical function in cognitively intact older adults.

Method

A systematic search in 9 electronic databases for experimental and quasi- experimental studies was performed between January 1, 2001, and July 19, 2021. Studies involving participants above 60 years old with normal cognition, analysing psychosocial and physical effects of HT, were included. Cochrane Risk of Bias 2 (RoB2) tool and Risk Of Bias In Non-randomised Studies- of Interventions (ROBINS-I) were used to assess risk of bias. Meta-analysis was conducted using Stata software. Cochran’s Q test and I2 were used to explore statistical heterogeneity. Narrative synthesis was conducted for trials unsuitable for quantitative pooling.

Results

Nineteen articles (2191 participants) were included. Meta-analyses found that HT showed moderate-large effects on psychosocial outcomes, with improved self- efficacy (Hedges’ g=0.49, 95% Confidence Interval:0.07,0.91, 3 trials, I2 :0.00%) and self-esteem (g=1.01, 95%CI:0.33,1.68, 2 trials, I2 :0.00%), and decreased depressive symptoms (g=-3.33, 95%CI:-6.29,-0.37, 4 trials, I2:98.51%). Narrative synthesis suggested benefits in Health-related Quality of Life. Regarding physical effects, HT improved exercise duration and intensity (g=1.37, 95%CI:0.92,1.82, 2 trials, I2:0.00%). Effects on anxiety, social engagement and fitness did not achieve statistically significance.

Conclusion

The findings support the potential role of HT in promoting psychosocial and physical function among older adults with intact cognition. Given high statistical heterogeneity, more work is needed to explore the effect of possible moderators on treatment effects.

Author names: M Mintun1; C Ritchie2; P Solomon3; JR Sims1; S Salloway4; O Hansson5; LG Apostolova6; JA Zimmer1; CD Evans1; M Lu1; P Ardayfio1; JD Sparks1; AM Wessels1; S Shcherbinin1; H Wang1; ESM Nery1; EC Collins1; EB Dennehy1; DA Brooks1; DM Skovronsky1; TRAILBLAZER-ALZ 2 Investigators; A Farquharson (Non-author presenter)1

Author provenances: 1. Eli Lilly and Company, USA; 2. Scottish Brain Sciences, UK; 3. Boston Center for Memory and Boston University Alzheimer's Disease Center, USA; 4. Departments of Neurology and Psychiatry, Alpert Medical School of Brown University, USA; Butler Hospital, USA; 5. Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden; Memory Clinic, Skåne University Hospital, Sweden; 6. Department of Neurology, Indiana University School of Medicine, USA

Introduction: In TRAILBLAZER-ALZ donanemab (DONA) cleared brain amyloid plaques, significantly slowing disease progression in early symptomatic Alzheimer’s disease (ESAD).

Methods: TRAILBLAZER-ALZ2 enrolled participants with ESAD and amyloid and tau pathology by positron-emission tomography, randomizing (multicenter) those with low/medium-tau (n=1182) and high-tau (n=552) (missing tau n=2). Participants (randomized double-blind,1:1) received DONA (n=860)/placebo (n=876) IV every 4w for 72w. DONA participants meeting amyloid clearance treatment completion criteria at 24/52w had blinded switched to placebo. Primary outcomes: Integrated AD Rating Scale(iADRS) change from baseline at 76w in low/medium-tau or combined (low/medium- and high-tau) populations. Statistical testing allocated most power (80% α spend) to low/medium-tau population outcomes, with the remainder for combined population outcomes, including clinical and biomarker assessments.

Results: In the low/medium-tau population iADRS change at 76w: −6.02 (DONA) and −9.27 (placebo) (difference 3.25; 95%CI, 1.88-4.62; P<.001), 35.1% slowing of disease progression. change in clinical dementia rating scale (cdr)–sum boxes: 1.20 (dona) and 1.88 (placebo) (difference −0.67; 95% ci −0.95 to −0.40; p<0.001), 36.0% slowing. participants receiving dona experienced 38.6% less risk progressing next stage vs placebo over 76w (cdr-global score, hr="0.61;" p<0.001). amyloid clearance at 24 />52/76w: achieved in 34.2%/71.3%/80.1% DONA-treated participants. Significant, positive results were observed in the combined population. Serious AEs: 17.4% (DONA), and 15.8% (placebo), with 3 deaths among DONA patients who experienced serious amyloid-related imaging abnormalities (ARIA). AEs with DONA included ARIA-E (24.0%, 6.1% symptomatic); ARIA-H (31.4%); infusion-related reactions (8.7%).

Conclusion: DONA treatment significantly slowed clinical progression at 76w with a safety profile consistent with earlier studies.

Presented: AAIC2023.

Introduction: The administration of melatonin and melatonin receptor agonists (MRA) may result in a small improvement in sleep quality among middle-aged and older adults living with neurocognitive disorders, but debate remains as to whether effects are clinically meaningful. The purpose of this PROSPERO-registered systematic review and meta-analysis (CRD42022373972) was to synthesise evidence from randomized controlled trials (RCTs) of melatonin or MRA against placebo and other interventions for the treatment of sleep disturbances in adults with neurocognitive disorders.

Method: CENTRAL, MEDLINE, EMBASE, AMED, CINAHL and PsycINFO were systematically searched on November 4th 2022, examining the effect of melatonin and MRA on sleep efficiency: the percentage of time spent asleep while in bed. Results were analysed using Review Manager 5.4. Risk of bias was assessed using RoB 2 and the certainty of evidence was assessed with the GRADE framework.

Results: Among the 1,579 references evaluated, 13 RCTs were selected, corresponding to 16 studies, none including MRA, with a total of 592 patients. Compared with placebo, bright light treatment, or clonazepam, sleep efficiency significantly improved with melatonin administration (MD = 2.85, 95% CI: 0.88 to 4.81, p = 0.004). In subgroup analyses, only low doses of melatonin (< 5 mg) yielded a statistically significant improvement to sleep efficiency (MD = 3.81, 95% CI: 1.13 to 6.49, p = 0.005, I² = 34%), and melatonin administration statistically significantly improved sleep efficiency in patients with Mild Cognitive Impairment, Parkinson's Disease, or Multiple Sclerosis (MD = 3.27, 95% CI: 0.11 to 6.43, p = 0.04, I² = 41%), but not patients with Alzheimer's Disease. We found the overall quality of evidence to be moderate according to GRADE.

Conclusion: Melatonin may modestly ameliorate sleep quality in patients with neurocognitive disorders by improving sleep efficiency, which may be clinically significant to patients and those who care for them.