scholarly journals Effect of prolonged antibiotic treatment on cognition in patients with Lyme borreliosis

Neurology ◽  
2019 ◽  
Vol 92 (13) ◽  
pp. e1447-e1455 ◽  
Author(s):  
Anneleen Berende ◽  
Hadewych J.M. ter Hofstede ◽  
Fidel J. Vos ◽  
Michiel L. Vogelaar ◽  
Henriët van Middendorp ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Antibiotic Treatment ◽  
Lyme Borreliosis ◽  
Additional Treatment ◽  
Controlled Study ◽  
Performance Validity ◽  
Open Label ◽  
Cognitive Domains ◽  
Persistent Symptoms ◽  
Speed Of Information Processing

ObjectiveTo investigate whether longer-term antibiotic treatment improves cognitive performance in patients with persistent symptoms attributed to Lyme borreliosis.MethodsData were collected during the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) trial, a randomized, placebo-controlled study. Study participants passed performance-validity testing (measure for detecting suboptimal effort) and had persistent symptoms attributed to Lyme borreliosis. All patients received a 2-week open-label regimen of intravenous ceftriaxone before the 12-week blinded oral regimen (doxycycline, clarithromycin/hydroxychloroquine, or placebo). Cognitive performance was assessed at baseline and after 14, 26, and 40 weeks with neuropsychological tests covering the cognitive domains of episodic memory, attention/working memory, verbal fluency, speed of information processing, and executive function.ResultsBaseline characteristics of patients enrolled (n = 239) were comparable in all treatment groups. After 14 weeks, performance on none of the cognitive domains differed significantly between the treatment arms (p = 0.49–0.82). At follow-up, no additional treatment effect (p = 0.35–0.98) or difference between groups (p = 0.37–0.93) was found at any time point. Patients performed significantly better in several cognitive domains at weeks 14, 26, and 40 compared to baseline, but this was not specific to a treatment group.ConclusionsA 2-week treatment with ceftriaxone followed by a 12-week regimen of doxycycline or clarithromycin/hydroxychloroquine did not lead to better cognitive performance compared to a 2-week regimen of ceftriaxone in patients with Lyme disease–attributed persistent symptoms.ClinicalTrials.gov identifierNCT01207739.Classification of evidenceThis study provides Class II evidence that longer-term antibiotics in patients with borreliosis-attributed persistent symptoms does not increase cognitive performance compared to shorter-term antibiotics.

scholarly journals Cognitive impairments in patients with persistent symptoms attributed to Lyme disease

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Anneleen Berende ◽  
Joost Agelink van Rentergem ◽  
Andrea W. M. Evers ◽  
Hadewych J. M. ter Hofstede ◽  
Fidel J. Vos ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Lyme Borreliosis ◽  
Cognitive Testing ◽  
Self Report ◽  
Study Cohort ◽  
Performance Validity ◽  
Information Processing Speed ◽  
Persistent Symptoms ◽  
Lower Education Level ◽  
Normative Comparison

Abstract Background Persistent symptoms attributed to Lyme borreliosis often include self-reported cognitive impairment. However, it remains unclear whether these symptoms can be substantiated by objective cognitive testing. Methods For this observational study, cognitive performance was assessed in 280 adults with persistent symptoms attributed to Lyme borreliosis (as part of baseline data collected for the Dutch PLEASE study). Cognitive testing covered the five major domains: episodic memory, working memory / attention, verbal fluency, information-processing speed and executive function. Patients’ profiles of test scores were compared to a large age-, education- and sex-adjusted normative sample using multivariate normative comparison. Performance validity was assessed to detect suboptimal effort, and questionnaires were administered to measure self-reported cognitive complaints, fatigue, anxiety, depressive symptoms and several other psychological factors. Results Of 280 patients, one was excluded as the test battery could not be completed. Of the remaining 279 patients, 239 (85.4%) displayed sufficient performance validity. Patients with insufficient performance validity felt significantly more helpless and physically fatigued, and less orientated. Furthermore, they had a lower education level and less often paid work. Of the total study cohort 5.7% (n = 16) performed in the impaired range. Among the 239 patients who displayed sufficient performance validity, 2.9% (n = 7) were classified as cognitively impaired. No association between subjective cognitive symptoms and objective impairment was found. Conclusions Only a small percentage of patients with borreliosis-attributed persistent symptoms have objective cognitive impairment. Performance validity should be taken into account in neuropsychological examinations of these patients. Self-report questionnaires are insufficiently valid to diagnose cognitive impairment. Trial registration ClinicalTrials.gov NCT01207739. Registered 23 September 2010.

scholarly journals Cognitive impairments in patients with persistent symptoms attributed to Lyme disease

2019 ◽  
Author(s):  
Anneleen Berende ◽  
Joost Agelink van Rentergem ◽  
Andrea W. M. Evers ◽  
Hadewych J. M. ter Hofstede ◽  
Fidel J. Vos ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Lyme Borreliosis ◽  
Cognitive Testing ◽  
Self Report ◽  
Study Cohort ◽  
Performance Validity ◽  
Information Processing Speed ◽  
Persistent Symptoms ◽  
Lower Education Level ◽  
Normative Comparison

Abstract Background: Persistent symptoms attributed to Lyme borreliosis often include self-reported cognitive impairment. However, it remains unclear whether these symptoms can be substantiated by objective cognitive testing. Methods: For this observational study, cognitive performance was assessed in 280 adults with persistent symptoms attributed to Lyme borreliosis (as part of baseline data collected for the Dutch PLEASE study). Cognitive testing covered the five major domains: episodic memory, working memory/attention, verbal fluency, information-processing speed and executive function. Patients’ profiles of test scores were compared to a large age-, education- and sex-adjusted normative sample using multivariate normative comparison. Performance validity was assessed to detect suboptimal effort, and questionnaires were administered to measure self-reported cognitive complaints, fatigue, anxiety, depressive symptoms and several other psychological factors. Results: Of 280 patients, one was excluded as the test battery could not be completed. Of the remaining 279 patients, 239 (85.4%) displayed sufficient performance validity. Patients with insufficient performance validity felt significantly more helpless and physically fatigued, and less orientated. Furthermore, they had a lower education level and less often paid work. Of the total study cohort 5.7% (n=16) performed in the impaired range. Among the 239 patients who displayed sufficient performance validity, 2.9% (n=7) were classified as cognitively impaired. No association between subjective cognitive symptoms and objective impairment was found. Conclusions: Only a small percentage of patients with borreliosis-attributed persistent symptoms have objective cognitive impairment. Performance validity should be taken into account in neuropsychological examinations of these patients. Self-report questionnaires are insufficiently valid to diagnose cognitive impairment.

scholarly journals Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: A randomized, double-blind, placebo-controlled study and a two-period extension study

2020 ◽  
Author(s):  
Gerald Novak ◽  
Johannes Rolf Streffer ◽  
Maarten Timmers ◽  
David Henley ◽  
H Robert Brashear ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Performance ◽  
Oral Treatment ◽  
Controlled Study ◽  
Open Label ◽  
Two Phase ◽  
Double Blind ◽  
Open Label Phase

Abstract Background Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment for Alzheimer’s disease (AD). The long-term safety and effect of atabecestat on cognitive performance in participants with predementia AD in two phase 2 studies were assessed. Methods In the placebo-controlled double-blind parent ALZ2002 study, participants aged 50 to 85 years were randomized (1:1:1) to placebo or atabecestat 10 or 50 mg once-daily (later reduced to 5 and 25 mg) for six months. Participants entered ALZ2004, a 12-month-treatment extension with placebo or atabecestat 10 or 25 mg, followed by an open-label phase. Safety, changes in CSF biomarker levels, brain volume, and effects on cognitive performance were assessed. Results Of 114 participants randomized in ALZ2002, 99 (87%) completed, 90 entered the ALZ2004 double-blind phase, and 77 progressed to open-label phase. CSF Aβ fragments and sAPPβ were reduced dose-proportionately. Decreases in whole brain and hippocampal volumes were greater in participants with mild cognitive impairment (MCI) due to AD, but without apparent relation to treatment. In ALZ2004, change from baseline in RBANS suggested a trend toward worse scores for atabecestat versus placebo. Elevated liver enzyme adverse events reported in 12 participants on atabecestat resulted in dosage modification and increased frequency of safety monitoring. Treatment discontinuation normalized ALT or AST in all except one with pretreatment elevation, which remained mildly elevated. No case met ALT/AST >3X ULN; total bilirubin >2X ULN (Hy’s law). Conclusion Atabecestat was associated with trend toward declines in cognition, and elevation of liver enzymes.

scholarly journals Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: A randomized, double-blind, placebo-controlled study and a two-period extension study

2020 ◽  
Author(s):  
Gerald Novak ◽  
Johannes Rolf Streffer ◽  
Maarten Timmers ◽  
David Henley ◽  
H Robert Brashear ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Performance ◽  
Oral Treatment ◽  
Controlled Study ◽  
Open Label ◽  
Double Blind ◽  
Preclinical Ad ◽  
Open Label Phase

Abstract Background Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment for Alzheimer’s disease (AD). The long-term safety and effect of atabecestat on cognitive performance in participants with predementia AD in two phase 2 studies were assessed. Methods In the placebo-controlled double-blind parent ALZ2002 study, participants aged 50 to 85 years were randomized (1:1:1) to placebo or atabecestat 10 or 50 mg once-daily (later reduced to 5 and 25 mg) for six months. Participants entered ALZ2004, a 12-month-treatment extension with placebo or atabecestat 10 or 25 mg, followed by an open-label phase. Safety, changes in CSF biomarker levels, brain volume, and effects on cognitive performance were assessed. Results Of 114 participants randomized in ALZ2002, 99 (87%) completed, 90 entered the ALZ2004 double-blind phase, and 77 progressed to open-label phase. CSF Aβ fragments and sAPPβ were reduced dose-proportionately. Decreases in whole brain and hippocampal volumes were greater in participants with mild cognitive impairment (MCI) due to AD than in preclinical AD, but were not affected by treatment. In ALZ2004, change from baseline in RBANS trended toward worse scores for atabecestat versus placebo. Elevated liver enzyme adverse events reported in 12 participants on atabecestat resulted in dosage modification and increased frequency of safety monitoring. Treatment discontinuation normalized ALT or AST in all except one with pretreatment elevation, which remained mildly elevated. No case met ALT/AST >3X ULN; total bilirubin >2X ULN (Hy’s law). Conclusion Atabecestat was associated with trend toward declines in cognition, and elevation of liver enzymes.

scholarly journals Cognitive impairments in patients with persistent symptoms attributed to Lyme disease

2019 ◽  
Author(s):  
Anneleen Berende ◽  
Joost Agelink van Rentergem ◽  
Andrea W. M. Evers ◽  
Hadewych J. M. ter Hofstede ◽  
Fidel J. Vos ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Lyme Borreliosis ◽  
Cognitive Testing ◽  
Self Report ◽  
Study Cohort ◽  
Performance Validity ◽  
Information Processing Speed ◽  
Persistent Symptoms ◽  
Lower Education Level ◽  
Normative Comparison

Abstract Background: Persistent symptoms attributed to Lyme borreliosis often include self-reported cognitive impairment. However, it remains unclear whether these symptoms can be substantiated by objective cognitive testing. Methods: For this observational study, cognitive performance was assessed in 280 adults with persistent symptoms attributed to Lyme borreliosis (as part of baseline data collected for the Dutch PLEASE study). Cognitive testing covered the five major domains: episodic memory, attention, verbal fluency, information-processing speed and executive function. Patients’ profiles of test scores were compared to a large age-, education- and sex-adjusted normative sample using multivariate normative comparison. Performance validity was assessed to detect suboptimal effort, and questionnaires were administered to measure self-reported cognitive complaints, fatigue, anxiety, depressive symptoms and several other psychological factors. Results: Of 280 patients, one was excluded as the test battery could not be completed. Of the remaining 279 patients, 239 (85.4%) displayed sufficient performance validity. Patients with insufficient performance validity felt significantly more helpless and physically fatigued, and less orientated. Furthermore, they had a lower education level and less often paid work. Of the total study cohort 5.7% (n=16) performed in the impaired range. Among patients who displayed sufficient performance validity, 2.9% (n=7) were classified as cognitively impaired. No association between subjective cognitive symptoms and objective impairment was found. Conclusions: Only a small percentage of patients with borreliosis-attributed persistent symptoms have objective cognitive impairment. Performance validity should be taken into account in neuropsychological examinations of these patients. Self-report questionnaires are insufficiently valid to diagnose cognitive impairment.

Inconsistent responding on the MMPI-2-RF and uncooperative attitude: Evidence from cognitive performance validity measures.

2018 ◽  
Vol 30 (3) ◽  
pp. 410-415 ◽  
Author(s):  
Roger O. Gervais ◽  
Anthony M. Tarescavage ◽  
Manfred F. Greiffenstein ◽  
Dustin B. Wygant ◽  
Cheryl Deslauriers ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Performance Validity ◽  
Validity Measures ◽  
Performance Validity Measures ◽  
Inconsistent Responding

Evaluating Thrombin Inhibition in Alzheimer’s Disease (The BEACON Trial): Protocol for a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Cláudia Yang Santos ◽  
Christine Getter ◽  
John Stoukides ◽  
Brian Ott ◽  
Stephen Salloway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Cognitive Performance ◽  
Thrombin Inhibitor ◽  
Placebo Control ◽  
Open Label ◽  
Double Blind ◽  
Thrombin Inhibition ◽  
Approved Drugs

BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multicenter, delayed-start, pilot study evaluating thrombin inhibition in people with biomarker-confirmed MCI probably due to AD or mild AD. 40 - 60 participants will be recruited between 50 - 85 years old. In the initial 9-months of study, either dabigatran or placebo will be orally administered to patients at a dose of 150 mg per day. After 9 months of the placebo-control (Phase I), the placebo arm will cross-over to an active, open-label (Phase II) where all patients will be treated with a 150 mg daily dose of dabigatran orally for an additional 12 months. A 3-month non-treatment follow-up period will assess duration of effects. RESULTS Beginning in July 2019, and concluding in August 2022, this study is expected to publish final results in January 2023. CONCLUSIONS BEACON is a first-in-kind randomized clinical trial targeting thrombin activation in AD therapeutics. This trial will stimulate translational investigations of an FDA-approved drugs in a newly defined therapeutic areas. CLINICALTRIAL Clinicaltrials.gov NCT03752294

Cognitive performance in early, treatment-resistant psychosis patients: Could cognitive control play a role in persistent symptoms?

2021 ◽  
Vol 295 ◽  
pp. 113607
Author(s):  
Megan Thomas ◽  
Timea Szentgyorgyi ◽  
Lucy D. Vanes ◽  
Elias Mouchlianitis ◽  
Erica F. Barry ◽  
...  
Keyword(s):  
Cognitive Control ◽  
Cognitive Performance ◽  
Early Treatment ◽  
Treatment Resistant ◽  
Persistent Symptoms

scholarly journals Effectiveness of a digital therapeutic as adjunct to treatment with medication in pediatric ADHD

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Scott H. Kollins ◽  
Ann Childress ◽  
Andrew C. Heusser ◽  
Jacqueline Lutz
Keyword(s):  
Video Game ◽  
Primary Outcome ◽  
Rating Scale ◽  
Stimulant Medication ◽  
Additional Treatment ◽  
Adhd Medication ◽  
Open Label ◽  
Serious Adverse Events ◽  
Treatment Benefit ◽  
Hyperactivity Disorder

AbstractSTARS-Adjunct was a multicenter, open-label effectiveness study of AKL-T01, an app and video-game-based treatment for inattention, as an adjunct to pharmacotherapy in 8–14-year-old children with attention-deficit/hyperactivity disorder (ADHD) on stimulant medication (n = 130) or not on any ADHD medication (n = 76). Children used AKL-T01 for 4 weeks, followed by a 4-week pause and another 4-week treatment. The primary outcome was change in ADHD-related impairment (Impairment Rating Scale (IRS)) after 4 weeks. Secondary outcomes included changes in IRS, ADHD Rating Scale (ADHD-RS). and Clinical Global Impressions Scale—Improvement (CGI-I) on days 28, 56, and 84. IRS significantly improved in both cohorts (On Stimulants: −0.7, p < 0.001; No Stimulants: −0.5, p < 0.001) after 4 weeks. IRS, ADHD-RS, and CGI-I remained stable during the pause and improved with a second treatment period. The treatment was well-tolerated with no serious adverse events. STARS-Adjunct extends AKL-T01’s body of evidence to a medication-treated pediatric ADHD population, and suggests additional treatment benefit.

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