Neurology
APA workgroup update maintains skepticism on pharmacogenomic tools for depression – Am J Psychiatry
25 May, 2024 | 19:47h | UTCA recent review by the American Psychiatric Association (APA) Council of Research Workgroup on Biomarkers and Novel Treatments revisits the use of pharmacogenomic (PGx) tools for selecting depression treatments. The review assesses new clinical trials and meta-analyses conducted from 2017 to 2022. Of the studies analyzed, few demonstrated significant efficacy in treatment response using PGx tools, with many suffering from methodological flaws such as lack of full blinding and insufficient control measures. Despite some trials showing promise, the overall evidence remains insufficient to support the widespread clinical application of PGx tools in managing major depressive disorder. The Workgroup reaffirms the 2018 conclusions and aligns with the U.S. Food and Drug Administration’s stance, recommending that future research should focus on more rigorous study designs and explore other potential benefits of pharmacogenomics, such as predicting rare adverse drug reactions.
Reference (link to abstract – $ for full-text)
Cohort Study: Thick liquids not linked to better outcomes in hospitalized patients with dementia—further studies required – JAMA Intern Med
25 May, 2024 | 19:41h | UTC– This matched cohort study evaluated the impact of thick vs. thin liquids on clinical outcomes in 8916 hospitalized patients aged 65 and older with Alzheimer Disease and Related Dementias (ADRD) and oropharyngeal dysphagia. Conducted across 11 diverse hospitals in New York from January 2017 to September 2022, the study utilized propensity score matching to ensure comparability between the two diet groups based on demographic and clinical characteristics.
– The study found no significant difference in mortality rates between the thick and thin liquid groups (hazard ratio, 0.92; 95% CI, 0.75-1.14; P = .46). Patients on a thick liquid diet were less likely to require intubation (odds ratio [OR], 0.66; 95% CI, 0.54-0.80) but exhibited a higher incidence of respiratory complications such as pneumonia (OR, 1.73; 95% CI, 1.56-1.91).
– The findings suggest that while thick liquids may reduce the need for intubation, they may increase the risk of respiratory complications. These results underscore the necessity for future prospective studies to more definitively ascertain the effectiveness of thick liquids in improving clinical outcomes for this patient population.
Reference (link to abstract – $ for full-text):
Makhnevich, A. et al. (2024). Thick Liquids and Clinical Outcomes in Hospitalized Patients With Alzheimer Disease and Related Dementias and Dysphagia. JAMA Intern Med. Published online May 6, 2024. doi:10.1001/jamainternmed.2024.0736
Cohort Study: Efficacy of first-line color doppler ultrasound in diagnosing giant cell arteritis – Ann Intern Med
25 May, 2024 | 19:39h | UTCThis prospective multicenter study aimed to evaluate the efficacy of using color Doppler ultrasound of the temporal arteries as the first-line diagnostic tool for Giant Cell Arteritis (GCA) in 165 elderly patients with high clinical suspicion of the disease. The study followed participants over two years, comparing ultrasound results with temporal artery biopsy (TAB) and physician-based clinical diagnosis including other imaging tests. Key findings indicate that ultrasound confirmed GCA in 44% of cases, which was higher compared to TAB (17%) and clinical expertise (21%). The study showed that using ultrasound first can avoid the need for further invasive tests like TAB in patients with positive ultrasound results. The limitations of the study include its small sample size, unblinded test results, and the absence of a universally accepted objective diagnostic standard. However, it highlights the potential of ultrasound in the early and non-invasive diagnosis of GCA, potentially reducing the risk of severe complications by expediting treatment initiation.
Reference (link to abstract – $ for full-text):
RCT: Thrombectomy improves outcomes in acute stroke with large infarcts – N Engl J Med
25 May, 2024 | 19:35h | UTCStudy Design and Population: This randomized clinical trial investigated the efficacy of thrombectomy in combination with standard medical care versus medical care alone in patients with acute stroke and large infarcts. Participants included 333 patients with proximal cerebral vessel occlusion in the anterior circulation, presenting within 6.5 hours of symptom onset. They were randomized in a 1:1 ratio to either undergo thrombectomy or receive only medical care. An Alberta Stroke Program Early Computed Tomographic Score of ≤5 was used to define large infarcts.
Main Findings: The primary outcome, assessed by the modified Rankin scale score at 90 days, showed a median score of 4 in the thrombectomy group compared to 6 in the control group, indicating better functional outcomes with thrombectomy (generalized odds ratio, 1.63; 95% CI, 1.29 to 2.06; P<0.001). Mortality at 90 days was significantly lower in the thrombectomy group (36.1%) compared to the control group (55.5%) with an adjusted relative risk of 0.65. However, thrombectomy was associated with a higher rate of symptomatic intracerebral hemorrhage (9.6% vs. 5.7% in the control group).
Implications for Practice: The findings suggest that thrombectomy, when added to standard medical care, can significantly improve functional outcomes and reduce mortality in patients with large infarct strokes. However, the increased risk of symptomatic intracerebral hemorrhage must be considered when deciding on this intervention. These results support the broader use of thrombectomy in clinical settings with similar patient profiles but underscore the need for careful risk-benefit analysis due to the potential for serious hemorrhagic complications.
Reference (link to abstract – $ for full-text):
Cohort Study: APOE4 Homozygosity as a Distinct Genetic Form of Alzheimer’s Disease with Early Biomarker Changes – Nat Med
25 May, 2024 | 18:55h | UTCThis cohort study investigated the impact of APOE4 homozygosity on Alzheimer’s disease (AD) by analyzing clinical, pathological, and biomarker data. The study utilized data from the National Alzheimer’s Coordinating Center and five additional large cohorts, comprising a total of 3,297 individuals for the pathological study and 10,039 for the clinical study. Results demonstrated that APOE4 homozygotes exhibited almost universal AD pathology and had significantly higher levels of AD biomarkers from age 55, compared to APOE3 homozygotes. By age 65, nearly all APOE4 homozygotes showed abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans, indicating a high biological penetrance of AD. These individuals also exhibited an earlier onset of symptoms, around age 65.1, and the progression and predictability of biomarker changes paralleled those observed in autosomal dominant AD and Down syndrome. However, in the dementia stage, amyloid and tau positron emission tomography scans showed no differences across haplotypes. The study concludes that APOE4 homozygosity represents a genetically distinct form of AD, underscoring the importance of tailored prevention strategies and treatments.
Reference (link to abstract – $ for full-text):
RCT: KarXT (xanomeline–trospium) demonstrates significant symptom reduction in schizophrenia compared to placebo – The Lancet
11 May, 2024 | 13:42h | UTCStudy Design and Population: The EMERGENT-2 study was a randomized, double-blind, placebo-controlled, flexible-dose, 5-week phase 3 trial conducted across 22 inpatient sites in the USA. It targeted adults aged 18–65 years diagnosed with schizophrenia, exhibiting a recent exacerbation in psychotic symptoms. A total of 252 participants, each with a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher and a Clinical Global Impression-Severity score of 4 or more, were enrolled and randomized equally into two groups to receive either the muscarinic receptor agonist KarXT (xanomeline–trospium) or a placebo.
Main Findings: KarXT significantly reduced the PANSS total scores from baseline to week 5, with a mean decrease of 21.2 points compared to 11.6 points in the placebo group (least squares mean difference -9.6; 95% CI -13.9 to -5.2; p<0.0001; Cohen’s d=0.61). All secondary endpoints were also met favorably for KarXT. Common adverse events for KarXT included constipation, dyspepsia, and nausea, but rates of extrapyramidal symptoms were similar between the two groups. The treatment was generally well tolerated with comparable discontinuation rates due to adverse events.
Implications for Practice: These results indicate that KarXT could represent a new class of antipsychotic treatment, diverging from traditional D2 dopamine receptor antagonists and instead leveraging muscarinic receptor activation. The promising outcomes observed in EMERGENT-2 suggest that KarXT has the potential to improve both positive and negative symptoms of schizophrenia while maintaining a favorable safety profile. Ongoing and future studies (EMERGENT-3, EMERGENT-4, and EMERGENT-5) will further elucidate the long-term efficacy and safety of KarXT.
Reference (link to abstract – $ for full-text):
Meta-Analysis: Acute adverse effects of therapeutic psilocybin doses in treating depression and anxiety – JAMA Netw Open
7 May, 2024 | 15:29h | UTCThis meta-analysis examined the acute adverse effects of psilocybin when used in therapeutic doses for treating depression and anxiety. The study analyzed data from six randomized, double-blind clinical trials involving a total of 528 participants. Significant adverse effects identified included headaches, nausea, anxiety, dizziness, and elevated blood pressure, compared to controls. No significant risks of paranoia or transient thought disorder were associated with psilocybin use. Overall, the adverse effects were tolerable and typically resolved within 48 hours, although the study calls for further research into their management.
Reference (link to free full-text):
M-A: Psilocybin significantly reduces depression symptoms across diverse populations – The BMJ
4 May, 2024 | 12:51h | UTCStudy Design and Population:
This systematic review and meta-analysis synthesized data from randomized trials assessing the efficacy of psilocybin as a treatment for depression in adults. Researchers utilized five electronic databases for published literature and four databases for unpublished and international studies. The analysis included 436 participants, aged 36 to 60 years, from seven randomized trials, with both genders represented and varying comorbidities such as cancer.
Main Findings:
The meta-analysis revealed a significant reduction in depression scores among participants treated with psilocybin, with a Hedges’ g value of 1.64, indicating a large effect size. Notably, the improvement was more pronounced among those with secondary depression and those assessed using self-report depression scales. Subgroup analyses and metaregression also highlighted that older age and previous use of psychedelics correlated with greater symptom improvement. Despite the robust findings, high heterogeneity and a risk of small study bias led to a low certainty of evidence.
Implications for Practice:
The findings support psilocybin’s potential as an effective antidepressant, particularly among specific subgroups such as those with secondary depression. However, the presence of high heterogeneity and small study biases suggests that further research is needed to explore the impact of expectancy effects, moderating factors, and treatment modalities. Clinicians should consider these elements when discussing psilocybin as a treatment option with patients, and further high-quality studies are necessary to solidify its role in clinical practice.
Reference (link to free full-text):
Phase 2 RCT: Lixisenatide slows progression of motor disability in early Parkinson’s disease, but with notable gastrointestinal side effects
30 Apr, 2024 | 13:00h | UTCIn a phase 2, double-blind, randomized, placebo-controlled trial, the effect of lixisenatide, a glucagon-like peptide-1 receptor agonist, was evaluated for its potential to slow the progression of motor disability in patients with early Parkinson’s disease. A total of 156 patients, diagnosed within the past three years and stable on symptom-managing medications, were enrolled and equally divided into lixisenatide and placebo groups. After 12 months, the lixisenatide group showed a slight improvement in motor disability (−0.04 point change) compared to a worsening in the placebo group (3.04 point change) on the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III. This difference was statistically significant (p=0.007). However, after a 2-month washout period, improvements were less distinct. Notably, 46% of lixisenatide-treated patients experienced nausea, and 13% reported vomiting. These findings suggest potential benefits of lixisenatide for motor symptoms in Parkinson’s disease, though further research is necessary to fully assess its efficacy and tolerability.
Commentary on X:
Original Article: Trial of Lixisenatide in Early Parkinson’s Disease (LIXIPARK phase 2 trial) https://t.co/2ancdAqO9i
Editorial: GLP-1, Parkinson’s Disease, and Neuroprotection https://t.co/ZaFfYyvEP9 #Neurology pic.twitter.com/h6Ds5wVSHu
— NEJM (@NEJM) April 5, 2024
Reference (link to abstract – $ for full-text):
Observational Study: Synergistic effects of early menopause and vascular risk on cognitive decline in postmenopausal women
27 Apr, 2024 | 18:20h | UTCStudy Design and Population:
This study analyzed data from 8,360 postmenopausal women and an equal number of age-matched male participants from the Canadian Longitudinal Study on Aging. Researchers assessed the independent and combined effects of age at menopause, vascular risk factors, and history of hormone therapy on cognitive outcomes. Participants’ cognitive function was measured using a global cognitive composite at baseline and again at a 3-year follow-up.
Main Findings:
The study found a synergistic interaction between early menopause (ages 35-48) and high vascular risk, significantly associated with lower cognitive scores at follow-up. Specifically, earlier menopause combined with higher vascular risk resulted in greater cognitive decline, compared to their individual effects. Notably, hormone therapy did not modify this association. This pattern was not observed in female participants with average or later menopause ages, nor in the age-matched male cohort.
Implications for Practice:
The findings underscore the importance of considering both endocrine and vascular health as predictive markers in dementia prevention strategies, particularly for women. These results suggest that women with early menopause and vascular risk factors should be closely monitored to mitigate their higher risk of cognitive impairment.
Reference (link to abstract – $ for full-text):
Retrospective Cohort Study: Delirium associated with increased risk of subsequent dementia and higher mortality in older adults
27 Apr, 2024 | 15:54h | UTCStudy Design and Population:
This retrospective cohort study utilized hospital administrative data from both public and private hospitals in New South Wales, Australia, spanning from July 2001 to March 2020. The study examined data from 650,590 patients aged 65 years or older, who did not have dementia at baseline. Diagnoses of dementia and delirium were identified using ICD-10 codes. The cohort was carefully matched into 55,211 pairs based on personal and clinical characteristics, focusing on those who developed delirium and their outcomes over a follow-up period exceeding five years.
Main Findings:
The analysis found that patients who experienced delirium had a 39% increased risk of mortality (hazard ratio: 1.39, 95% CI: 1.37-1.41) and a threefold increase in the risk of developing dementia (subdistribution hazard ratio: 3.00, 95% CI: 2.91-3.10) compared to those without delirium. The risk associated with dementia was notably stronger among men. Furthermore, each additional episode of delirium was linked to a 20% increased risk of subsequent dementia (subdistribution hazard ratio: 1.20, 95% CI: 1.18-1.23).
Implications for Practice:
The strong association between delirium and increased risks of death and incident dementia in older adults highlights the importance of delirium as a clinical marker that warrants significant attention. These findings suggest that enhanced monitoring and management of delirium in hospital settings could be crucial for identifying patients at higher risk of adverse outcomes, including dementia. Efforts to improve delirium management might not only address immediate clinical needs but also assist in stratifying risk and tailoring post-discharge care plans to better support the long-term health of these patients. Further research is needed to explore effective strategies for delirium intervention and to determine how these approaches can impact long-term cognitive outcomes and overall mortality.
Reference (free full-text):
Cohort Study: Elevated autism spectrum disorder risk in children exposed to valproate during pregnancy
21 Mar, 2024 | 13:16h | UTCStudy Design and Population: This cohort study utilized two health care utilization databases in the United States, covering the period from 2000 to 2020, to investigate the association between prenatal exposure to antiseizure medications and the risk of autism spectrum disorder (ASD) in children. The study compared children exposed to topiramate, valproate, or lamotrigine during the second half of pregnancy to those unexposed to any antiseizure medication, specifically focusing on a population-based cohort of pregnant women and their offspring.
Main Findings: The cumulative incidence of ASD at 8 years of age was found to be higher in children exposed to these medications compared to the general population. Notably, the incidence was 6.2% for children exposed to topiramate, 10.5% for valproate, and 4.1% for lamotrigine among children born to mothers with epilepsy. However, after adjusting for potential confounders, the increased risk of ASD remained significant only for valproate exposure, with a hazard ratio of 2.67, indicating a substantial risk compared to unexposed children. Topiramate and lamotrigine showed no significant increase in risk after adjustment.
Implications for Practice: The findings underscore the importance of carefully considering the risks and benefits of using antiseizure medications during pregnancy. Specifically, valproate should be used with caution, if at all, given its significant association with an increased risk of ASD in offspring. This study supports the need for targeted counseling and monitoring of pregnant women with epilepsy and highlights the necessity for further research to fully understand the neurodevelopmental impact of prenatal exposure to antiseizure medications.
Reference: Sonia Hernández-Díaz et al. (2024). Cohort Study: Assessing Autism Spectrum Disorder Risk in Children Exposed to Antiseizure Medications During Pregnancy. N Engl J Med, 390(13), 1069-1079. DOI: 10.1056/NEJMoa2309359. Access the study here: [Link]
Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021
21 Mar, 2024 | 11:10h | UTCStudy Design and Population
This study, a systematic analysis conducted by the Global Burden of Disease Study 2021, aimed to estimate the global, regional, and national health loss attributable to 37 unique nervous system conditions from 1990 to 2021. The researchers estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) across 204 countries. The analysis included morbidity and deaths directly resulting from damage to the central or peripheral nervous system, as well as neurological health loss from conditions where nervous system morbidity is a secondary outcome.
Main Findings
The collective global burden of these nervous system conditions emerged as the leading cause of DALYs in 2021, affecting approximately 3.40 billion individuals (43.1% of the global population) and resulting in 443 million DALYs. Although global DALY counts for these conditions increased by 18.2% from 1990 to 2021, there was a notable decrease in the age-standardised rates of deaths and DALYs by 33.6% and 27.0%, respectively. The conditions contributing most significantly to the age-standardised DALYs were stroke, neonatal encephalopathy, migraine, and Alzheimer’s disease among others.
Implications for Practice
This analysis underscores the critical need for effective prevention, treatment, and rehabilitation strategies for nervous system disorders, which now lead the global disease burden. Highlighting an 18.2% increase in DALY counts over the study period, it calls for heightened public health attention and resource allocation towards these conditions. The findings support the prioritization of nervous system health on the global health agenda and stress the importance of further research into modifiable risk factors and equitable access to care.
Reference
GBD 2021 Nervous System Disorders Collaborators (2024). Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021. The Lancet Neurology, Volume(issue), Pages. DOI: https://doi.org/10.1016/S1474-4422(24)00038-3. Access the study here: Link
Perspective | Will unpredictable side effects dim the promise of new Alzheimer’s drugs?
8 Aug, 2023 | 13:30h | UTCWill unpredictable side effects dim the promise of new Alzheimer’s drugs? – Science (a few articles per month are free)
Related:
RCT | Donanemab slows early symptomatic Alzheimer’s progression, but raises serious safety concerns
RCT | Lecanemab slows cognitive decline in early Alzheimer’s disease but raises safety concerns
Review | Treatment of pediatric convulsive status epilepticus
4 Aug, 2023 | 11:42h | UTCTreatment of pediatric convulsive status epilepticus – Frontiers in Neurology
RCT | Recombinant human prourokinase demonstrates noninferiority to alteplase in acute ischemic stroke treatment
3 Aug, 2023 | 13:46h | UTCSee also: Visual Abstract
Study | Frequent soccer heading linked to cognitive impairment risk in retired players
3 Aug, 2023 | 13:12h | UTCInvited Commentary: Heading Frequency and Risk of Cognitive Impairment in Retired Male Professional Soccer Players – JAMA Network Open
Related:
Dementia risk in former professional footballers is related to player position and career length.
Study: Neurodegenerative Disease Mortality Increased Among Former Professional Soccer Players
Commentary on Twitter
In retired professional UK soccer players, repetitive heading was linked to an increased risk of cognitive impairment later in life by >2x (6-15/match) and >3x (>15x/match). https://t.co/lV2xNa1TTR
— JAMA Network Open (@JAMANetworkOpen) July 17, 2023
Review | Diagnosing delirium in perioperative and intensive care medicine
3 Aug, 2023 | 13:09h | UTCDiagnosing delirium in perioperative and intensive care medicine – Current Opinion in Anesthesiology
RCT | Multiple sclerosis disease-modifying therapy continuation versus discontinuation in older individuals
2 Aug, 2023 | 14:00h | UTCRisk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial – The Lancet Neurology (link to abstract – $ for full-text)
Commentaries:
Discontinuing Multiple Sclerosis Therapies at Age 55 or Older – NEJM Journal Watch
RCT | Atogepant outperforms placebo in reducing migraines over 12 weeks
2 Aug, 2023 | 13:56h | UTCAtogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial – The Lancet (link to abstract – $ for full-text)
Cohort Study | Depression at any life stage linked to increased dementia incidence
2 Aug, 2023 | 13:49h | UTCAssociation of Early-, Middle-, and Late-Life Depression With Incident Dementia in a Danish Cohort – JAMA Neurology (link to abstract – $ for full-text)
Commentary: Depression Over Adulthood May Increase Risk of Dementia – Psychiatric News Alert
Review | First-line immunosuppression in neuromuscular diseases
1 Aug, 2023 | 14:09h | UTCFirst-line immunosuppression in neuromuscular diseases – Practical Neurology
Review | Multiple system atrophy
1 Aug, 2023 | 14:08h | UTCMultiple system atrophy – Practical Neurology
Review | Clinical assessment of parietal lobe function
1 Aug, 2023 | 14:03h | UTCClinical assessment of parietal lobe function – Practical Neurology
Review | Antiamyloid monoclonal antibody therapy for Alzheimer disease: emerging issues in neurology
31 Jul, 2023 | 14:07h | UTCNews Release: AAN issues guidance on new treatments for early Alzheimer’s disease – American Academy of Neurology