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1.
Brain ; 144(8): 2227, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480797
2.
J Neuropsychol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34532963

RESUMO

Apathy is a common, disabling neuropsychiatric syndrome that occurs across many brain disorders and may be associated with diminished motivation in behavioural, cognitive, emotional and social domains. Assessment is complicated by the variability of symptoms across apathy domains and self-report from patients, which can be misleading due to their lack of insight. Independent evaluation by clinicians also has limitations though if it has to be performed with limited time. Caregiver reports are a viable alternative, but current assessments for them either do not distinguish between different apathy domains or are interview-based and take long to administer. In this study, we developed a brief caregiver questionnaire version of the recently developed Apathy Motivation Index (AMI), which is a self-report tool. We confirmed three apathy factors in this new caregiver measure (AMI-CG) that were also present in the AMI: Behavioural Activation, Emotional Sensitivity and Social Motivation. Furthermore, we validated the scores against more extensive caregiver interviews using the established Lillle apathy rating scale as well as patient self-reports of apathy, measures of depression, anhedonia, cognition, activities of daily living and caregiver burden across four different neurological conditions: Parkinson's disease, Alzheimer's disease, subjective cognitive impairment and limbic encephalitis. The AMI-CG showed good internal reliability, external validity and diagnostic accuracy. It also uncovered cases of social apathy overlooked by traditional instruments. Crucially, patients who under-rated their apathy compared to informants were more likely to have difficulties performing everyday activities and to be a greater burden to caregivers. The findings provide evidence for a multidimensional conceptualization of apathy and an instrument for efficient detection of apathy based on caregiver reports for use in clinical practice.

3.
Nat Commun ; 12(1): 5185, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465771

RESUMO

Parkinson's disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21-30 Hz) but not low (13-21 Hz) beta frequency range correlated with 'hyperdirect pathway' fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD.


Assuntos
Vias Neurais , Doença de Parkinson/fisiopatologia , Estudos de Coortes , Globo Pálido/química , Globo Pálido/fisiopatologia , Humanos , Magnetoencefalografia , Córtex Motor/química , Córtex Motor/fisiopatologia , Núcleo Subtalâmico/química , Núcleo Subtalâmico/fisiopatologia
4.
PLoS Med ; 18(9): e1003773, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34582441

RESUMO

BACKGROUND: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. METHODS AND FINDINGS: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score-matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan-Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms. CONCLUSIONS: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.


Assuntos
COVID-19/complicações , Sobreviventes , Adulto , Idoso , COVID-19/epidemiologia , Estudos de Coortes , Dispneia/epidemiologia , Dispneia/etiologia , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Humanos , Incidência , Influenza Humana/complicações , Influenza Humana/epidemiologia , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , Adulto Jovem
5.
Neuropsychologia ; 162: 108028, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34560142

RESUMO

Visual short-term memory (VSTM) deficits including VSTM binding have been associated with Alzheimer's disease (AD) from preclinical to dementia stages, cross-sectionally. Yet, longitudinal investigations are lacking. The objective of this study was to evaluate VSTM function longitudinally and in relation to expected symptom onset in a cohort of familial Alzheimer's disease. Ninety-nine individuals (23 presymptomatic; 9 symptomatic and 67 controls) were included in an extension cross-sectional study and a sub-sample of 48 (23 presymptomatic carriers, 6 symptomatic and 19 controls), attending two to five visits with a median interval of 1.3 years, included in the longitudinal study. Participants completed the "What was where?" relational binding task (which measures memory for object identification, localisation and object-location binding under different conditions of memory load and delay), neuropsychology assessments and genetic testing. Compared to controls, presymptomatic carriers within 8.5 years of estimated symptom onset showed a faster rate of decline in localisation performance in long-delay conditions (4s) and in traditional neuropsychology measures of verbal episodic memory. This study represents the first longitudinal VSTM investigation and shows that changes in memory resolution may be sensitive to tracking cognitive decline in preclinical AD at least as early as changes in the more traditional verbal episodic memory tasks.

6.
Trials ; 22(1): 508, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332638

RESUMO

BACKGROUND: Although Alzheimer's disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer's disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer's disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer's disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer's disease. METHODS: The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer's disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values. DISCUSSION: This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer's disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, the next step will be to rapidly progress to a larger study to establish whether levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03489044 . Registered on April 5, 2018.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Animais , Estudos Cross-Over , Método Duplo-Cego , Humanos , Levetiracetam/efeitos adversos , Camundongos , Estudo de Prova de Conceito , Qualidade de Vida
7.
Nat Commun ; 12(1): 4593, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321478

RESUMO

From a gym workout, to deciding whether to persevere at work, many activities require us to persist in deciding that rewards are 'worth the effort' even as we become fatigued. However, studies examining effort-based decisions typically assume that the willingness to work is static. Here, we use computational modelling on two effort-based tasks, one behavioural and one during fMRI. We show that two hidden states of fatigue fluctuate on a moment-to-moment basis on different timescales but both reduce the willingness to exert effort for reward. The value of one state increases after effort but is 'recoverable' by rests, whereas a second 'unrecoverable' state gradually increases with work. The BOLD response in separate medial and lateral frontal sub-regions covaried with these states when making effort-based decisions, while a distinct fronto-striatal system integrated fatigue with value. These results provide a computational framework for understanding the brain mechanisms of persistence and momentary fatigue.


Assuntos
Encéfalo/fisiologia , Fadiga , Redes Neurais de Computação , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Comportamento de Escolha/fisiologia , Tomada de Decisões/fisiologia , Fadiga/diagnóstico por imagem , Feminino , Lobo Frontal , Humanos , Imageamento por Ressonância Magnética , Masculino , Recompensa , Estriado Ventral , Adulto Jovem
8.
Nat Commun ; 12(1): 4440, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290236

RESUMO

Reinforcement learning is a fundamental mechanism displayed by many species. However, adaptive behaviour depends not only on learning about actions and outcomes that affect ourselves, but also those that affect others. Using computational reinforcement learning models, we tested whether young (age 18-36) and older (age 60-80, total n = 152) adults learn to gain rewards for themselves, another person (prosocial), or neither individual (control). Detailed model comparison showed that a model with separate learning rates for each recipient best explained behaviour. Young adults learned faster when their actions benefitted themselves, compared to others. Compared to young adults, older adults showed reduced self-relevant learning rates but preserved prosocial learning. Moreover, levels of subclinical self-reported psychopathic traits (including lack of concern for others) were lower in older adults and the core affective-interpersonal component of this measure negatively correlated with prosocial learning. These findings suggest learning to benefit others is preserved across the lifespan with implications for reinforcement learning and theories of healthy ageing.


Assuntos
Envelhecimento/psicologia , Comportamento de Ajuda , Reforço Psicológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno da Personalidade Antissocial/psicologia , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Recompensa , Adulto Jovem
13.
Cognition ; 214: 104758, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33984741

RESUMO

There has been surprisingly little examination of how recall performance is affected by processing demands induced by retrieval cues, how manipulations at encoding interact with processing demands during maintenance or due to the retrieval cue, and how these are affected with aging. Here, we investigate these relationships by examining the fidelity of working memory recall across two delayed reproduction tasks with a continuous measure of report across the adult lifespan. Participants were asked to remember and subsequently reproduce from memory the identity and location of a probed item from the encoding display. In Experiment 1, we examined the effect of filtering irrelevant information at encoding and the impact of filtering distracting information at retrieval simultaneously. In Experiment 2, we tested how ignoring distracting information during maintenance or updating current contents with new information during this period affects recall. The results reveal that manipulating processing requirements induced by retrieval cues (by altering the nature of the retrieval foil) had a significant impact on memory recall: the presence of two previously viewed features from the encoding display in the retrieval foil led to a decrease in identification accuracy. Although irrelevant information can be filtered out well at encoding, both ignoring irrelevant information and updating the contents of memory during the maintenance delay had a detrimental effect on recall. These effects were similar across the lifespan, but older individuals were particularly affected by manipulations of processing demands at encoding as well as increasing set size of information to be retained in memory. Finally, analyses revealed that there were no systematic relationships between filtering performance at encoding, maintenance and retrieval suggesting that these processing demands are independent of each other. Rather than filtering being a single, monolithic entity, the data suggest that it is better accounted for as distinctly dissociable cognitive processes that engage and articulate with different phases of working memory.


Assuntos
Memória de Curto Prazo , Rememoração Mental , Adulto , Envelhecimento , Sinais (Psicologia) , Humanos
14.
Nat Hum Behav ; 5(7): 935-946, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34045719

RESUMO

Humans often seek information to minimize the pervasive effect of uncertainty on decisions. Current theories explain how much knowledge people should gather before a decision, based on the cost-benefit structure of the problem at hand. Here, we demonstrate that this framework omits a crucial agent-related factor: the cognitive effort expended while collecting information. Using an active sampling model, we unveil a speed-efficiency trade-off whereby more informative samples take longer to find. Crucially, under sufficient time pressure, humans can break this trade-off, sampling both faster and more efficiently. Computational modelling demonstrates the existence of a cost of cognitive effort which, when incorporated into theoretical models, provides a better account of people's behaviour and also relates to self-reported fatigue accumulated during active sampling. Thus, the way people seek knowledge to guide their decisions is shaped not only by task-related costs and benefits, but also crucially by the quantifiable computational costs incurred.


Assuntos
Cognição , Tomada de Decisões , Comportamento de Busca de Informação , Incerteza , Análise Custo-Benefício , Feminino , Humanos , Masculino , Modelos Teóricos
15.
Alzheimers Dement ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949763

RESUMO

INTRODUCTION: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. METHODS: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. RESULTS: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. DISCUSSION: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.

16.
Psychol Sci ; 32(5): 668-681, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33860711

RESUMO

Social cohesion relies on prosociality in increasingly aging populations. Helping other people requires effort, yet how willing people are to exert effort to benefit themselves and others, and whether such behaviors shift across the life span, is poorly understood. Using computational modeling, we tested the willingness of 95 younger adults (18-36 years old) and 92 older adults (55-84 years old) to put physical effort into self- and other-benefiting acts. Participants chose whether to work and exert force (30%-70% of maximum grip strength) for rewards (2-10 credits) accrued for themselves or, prosocially, for another. Younger adults were somewhat selfish, choosing to work more at higher effort levels for themselves, and exerted less force in prosocial work. Strikingly, compared with younger adults, older people were more willing to put in effort for others and exerted equal force for themselves and others. Increased prosociality in older people has important implications for human behavior and societal structure.


Assuntos
Motivação , Recompensa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Comportamento Cooperativo , Humanos , Pessoa de Meia-Idade , Esforço Físico , Comportamento Social , Adulto Jovem
17.
Sci Rep ; 11(1): 8696, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888739

RESUMO

The basis of visual short-term memory (VSTM) impairments in preclinical Alzheimer's disease (AD) remains unclear. Research suggests that eye movements may serve as indirect surrogates to investigate VSTM. Yet, investigations in preclinical populations are lacking. Fifty-two individuals from a familial Alzheimer's disease (FAD) cohort (9 symptomatic carriers, 17 presymptomatic carriers and 26 controls) completed the "Object-localisation" VSTM task while an eye-tracker recorded eye movements during the stimulus presentation. VSTM function and oculomotor performance were compared between groups and their association during encoding investigated. Compared to controls, symptomatic FAD carriers showed eye movement patterns suggestive of an ineffective encoding and presymptomatic FAD carriers within 6 years of their expected age at symptom onset, were more reliant on the stimuli fixation time to achieve accuracy in the localisation of the target. Consequently, for shorter fixation times on the stimuli, presymptomatic carriers were less accurate at localising the target than controls. By contrast, the only deficits detected on behavioural VSTM function was in symptomatic individuals. Our findings provide novel evidence that encoding processes may be vulnerable and weakened in presymptomatic FAD carriers, most prominently for spatial memory, suggesting a possible explanation for the subtle VSTM impairments observed in the preclinical stages of AD.

18.
19.
Cortex ; 139: 73-85, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33836304

RESUMO

Primary progressive aphasia (PPA) is characterised by predominant language and communication impairment. However, behavioural changes, such as apathy, are increasingly recognised. Apathy is defined as a reduction in motivation and goal-directed behaviour. Recent theoretical models have suggested that apathy can be delineated into multiple dimensions: executive apathy (i.e., deficits in maintaining goals and organisation), emotional apathy (i.e., emotional blunting and indifference) and initiation apathy (i.e., reduced self-initiation). Whether the nature of apathy differs between clinical variants of PPA, and across early and late disease stages, remains to be established. Here, carers/informants of 20 semantic variant PPA (svPPA), 15 non-fluent variant PPA (nfvPPA), 16 logopenic variant PPA (lvPPA) and 25 healthy older controls completed the Dimensional Apathy Scale to quantify executive, emotional and initiation apathy. Voxel-based morphometry was used to identify associations between dimensions of apathy and regions of grey matter intensity decrease. Our behavioural results showed greater executive and initiation apathy in late svPPA than in late nfvPPA patients, while late svPPA had greater emotional apathy than both late nfvPPA and late lvPPA groups. Executive and initiation apathy were significantly higher than premorbid levels in all PPA subtypes, while elevated emotional apathy was only seen in early and late svPPA. Distinct neural correlates were identified across apathy dimensions. Executive apathy correlated with grey matter intensity of the left dorsolateral prefrontal and inferior parietal cortices; emotional apathy with the left medial prefrontal, insular and cerebellar regions; and initiation apathy with right parietal areas. Our findings are the first to reveal evidence of the dimensional nature of apathy in PPA, with different clinical signatures observed for each subtype. From a clinical standpoint, these results will inform the development of targeted interventions for specific aspects of apathy which emerge in PPA.


Assuntos
Apatia , Afasia Primária Progressiva , Transtornos do Desenvolvimento da Linguagem , Afasia Primária Progressiva/diagnóstico por imagem , Emoções , Substância Cinzenta , Humanos
20.
Lancet Psychiatry ; 8(5): 416-427, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33836148

RESUMO

BACKGROUND: Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis. METHODS: For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism. FINDINGS: Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17-34·07), with 12·84% (12·36-13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78-48·09) and for a first diagnosis was 25·79% (23·50-28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50-0·63) for intracranial haemorrhage, 2·10% (1·97-2·23) for ischaemic stroke, 0·11% (0·08-0·14) for parkinsonism, 0·67% (0·59-0·75) for dementia, 17·39% (17·04-17·74) for anxiety disorder, and 1·40% (1·30-1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24-3·16) for intracranial haemorrhage, 6·92% (6·17-7·76) for ischaemic stroke, 0·26% (0·15-0·45) for parkinsonism, 1·74% (1·31-2·30) for dementia, 19·15% (17·90-20·48) for anxiety disorder, and 2·77% (2·31-3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40-1·47, for any diagnosis; 1·78, 1·68-1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14-1·17, for any diagnosis; 1·32, 1·27-1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50-1·67, for any diagnosis; 2·87, 2·45-3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events. INTERPRETATION: Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings. FUNDING: National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.


Assuntos
COVID-19 , Influenza Humana , Transtornos Mentais , Doenças do Sistema Nervoso , Infecções Respiratórias , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/psicologia , Estudos de Coortes , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Saúde Global/estatística & dados numéricos , Humanos , Incidência , Influenza Humana/complicações , Influenza Humana/epidemiologia , Masculino , Transtornos Mentais/classificação , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/classificação , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Modelos de Riscos Proporcionais , Projetos de Pesquisa , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia , Medição de Risco/métodos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
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