Résumé
Background: The increasingly appreciated intersection between epilepsy and Alzheimer's disease offers potential therapeutic opportunity. We therefore initiated a pragmatic pilot study to explore whether the anti-seizure medication levetiracetam might offer benefit to people with Alzheimer's disease. Methods: The Investigation of Levetiracetam in Alzheimer's Disease (ILiAD) trial is a randomised, double-blind, placebo-controlled trial. ILiAD recruits people with mild to moderate Alzheimer's disease who have not previously had a seizure and in whom a routine electroencephalogram is normal. The primary outcome is change in a touchscreen memory task. Secondary outcomes include effect on mood, alterations in quality of life and carer-reported outcomes. Results: ILiAD plans to recruit 30 participants. To date, eight people have completed both arms of the study with no withdrawals from those enrolled. The COVID-19 pandemic has had multiple severe impacts on both study recruitment and assessments. The primary outcome measure, in particular, has proved difficult to evaluate during the pandemic owing to many assessments being done remotely. Conclusion: ILiAD is a pilot study that is part of the vanguard of trials exploring the potential role of anti-seizure medications, particularly levetiracetam, in people with Alzheimer's disease. Further work seems important to better understand whether drugs specifically designed to modulate cortical excitability may offer improvement in cognition for those with neurodegenerative disorders.
Résumé
There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations. We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence. 13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n = 15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n = 221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n = 21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n = 13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n = 66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n = 43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n = 64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n = 42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n = 49 326, 19 studies). Heterogeneity for most clinical manifestations was high.Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
Résumé
The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I 2. Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies (n = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14-182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4-34.4%)], followed by fatigue [24.4% (17.5-32.9%)], objective cognitive impairment [20.2% (10.3-35.7%)], anxiety [19.1% (13.3-26.8%)] and post-traumatic stress [15.7% (9.9-24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high (I 2 = 79.6-98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.
Résumé
BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.