The Association Between Somatic Symptom Disorders and Neurocognitive Disorders: A Systematic Review.

OBJECTIVE: Onset of neuropsychiatric symptoms in older adults may represent prodromal manifestations of neurodegenerative disorders. The association between the onset of somatic symptom and related disorders (SSRD) and the subsequent development of neurodegenerative disorders remains unclear. A critical review of studies describing the association between SSRD and neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Lewy body dementia was performed. OBJECTIVE: To critically review studies describing the association between SSRD and neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Lewy body dementia. METHODS: A systematic review of Web of Science Core databases was carried out from inception of databases up to May 2021 to identify observational studies pertaining to both SSRD and neurodegenerative disorders. Data was extracted and compiled regarding subjects enrolled, age at onset of the SSRD and at onset of the neurodegenerative disorders, and specific SSRD manifestations and underlying neuropathologies reported. RESULTS: Thirteen articles were included. Of the 123 identified subjects with SSRD at baseline, 34.1% developed a neurodegenerative disorder, with 80.9% of these being a Lewy body spectrum disorder. The interval between onset of SSRD manifestations and subsequent development of a neurodegenerative disorder was less than 3 years for half of the cases. Of the 1,494 subjects with a neurodegenerative disorder at baseline retrieved, SSRD manifestations were reported in 33.4% of Lewy body spectrum disorders cases. Onset of SSRD manifestations antedated or was concomitant to the diagnosis of the Lewy body spectrum disorder in 65.6% of cases. CONCLUSION: While limited, current evidence suggests a possible association between late-onset SSRD and the subsequent development of neurodegenerative disorders, notably Lewy body spectrum disorders.

Systematic review of research barriers, facilitators, and stakeholders in long-term care and geriatric settings, and a conceptual mapping framework to build research capacity.

BACKGROUND: Older adults are underrepresented in research. Heterogeneity of research processes in this population, specifically in long-term care (LTC) and geriatric acute care (GAC), is not well described and may impede the design, planning, and conduct of research. In this study, we identified, quantified, and mapped stakeholders, research stages, and transversal themes of research processes, to develop a mapping framework to improve research capacity by better characterizing this heterogeneity. METHODS: Multicomponent mixed methods study. An environmental scan was used to initiate a preliminary framework. We conducted a systematic literature search on processes, barriers, and methods for clinical research in GAC and LTC to extract and update stakeholders, research stages, and themes. Importance and interactions of elements were synthesized via heatmaps by number of articles, mentions, and content intersections. RESULTS: For our initial framework and environmental scan, we surveyed 24 stakeholders. Of 9277 records, 68 articles were included in our systematic review and allowed us to identify 12 stakeholders, 13 research stages, 17 transversal themes (either barriers, facilitators, general themes, or recommendations), and 1868 intersections. Differences in relative importance between LTC and GAC emerged for stakeholders (staff, managers vs. caregivers, ethics committees), and for research stages (funding, facility recruitment vs. ethics, individual recruitment). Crucial themes according to specific stakeholders were collaboration for the research team; communication, trust, and human resources for managers; heterogeneity for patients and residents. A heatmap framework synthesizing vital stakeholders and themes per research stage was generated. CONCLUSIONS: We identified and quantified the interactions between stakeholders, stages, and themes to characterize heterogeneity in LTC and GAC research. Our framework may serve as a blueprint to co-construct and improve each stage of the research process.

Sleep apnea and the risk of dementia: A systematic review and meta-analysis.

Sleep apnea (SA) is potentially a modifiable risk factor for dementia. However, its associations to specific aetiologies of dementia remain uncertain. A systematic review and meta-analysis of cohort studies investigating the association between sleep apnea and specific aetiologies of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), vascular dementia (VaD), and frontotemporal dementia (FTD) was performed. The use of biomarkers to support clinical diagnoses in eligible studies was collected. Eleven studies were included, comprising 1,333,424 patients. Patients with sleep apnea had an increased risk of developing any type of neurocognitive disorder (HR: 1.43 [95% CI 1.26-1.62]), Alzheimer's disease (HR: 1.28 [95% CI 1.16-1.41]), and Parkinson's disease (HR: 1.54 [95% CI 1.30-1.84]). No statistically significant association was found for vascular dementia. One study reported a two-fold increased risk for Lewy body dementia (HR: 2.06 [95% CI 1.45-2.91]). No studies investigated the risk for frontotemporal dementia and none of the studies reported results pertaining to biomarkers. Sleep apnea is associated with a significantly increased risk of dementia, particularly for Alzheimer's disease and Parkinson's disease, but not for vascular dementia. Future studies should look at the impact of sleep apnea on specific dementia biomarkers.

Appraising clinical applicability of studies: mapping and synthesis of current frameworks, and proposal of the FrACAS framework and VICORT checklist.

BACKGROUND: Not all research findings are translated to clinical practice. Reasons for lack of applicability are varied, and multiple frameworks and criteria exist to appraise the general applicability of epidemiological and clinical research. In this two-part study, we identify, map, and synthesize frameworks and criteria; we develop a framework to assist clinicians to appraise applicability specifically from a clinical perspective. METHODS: We conducted a literature search in PubMed and Embase to identify frameworks appraising applicability of study results. Conceptual thematic analysis was used to synthesize frameworks and criteria. We carried out a framework development process integrating contemporary debates in epidemiology, findings from the literature search and synthesis, iterative pilot-testing, and brainstorming and consensus discussions to propose a concise framework to appraise clinical applicability. RESULTS: Of the 4622 references retrieved, we identified 26 unique frameworks featuring 21 criteria. Frameworks and criteria varied by scope and level of aggregation of the evidence appraised, target user, and specific area of applicability (internal validity, clinical applicability, external validity, and system applicability). Our proposed Framework Appraising the Clinical Applicability of Studies (FrACAS) classifies studies in three domains (research, practice informing, and practice changing) by examining six criteria sequentially: Validity, Indication-informativeness, Clinical relevance, Originality, Risk-benefit comprehensiveness, and Transposability (VICORT checklist). CONCLUSIONS: Existing frameworks to applicability vary by scope, target user, and area of applicability. We introduce FrACAS to specifically assess applicability from a clinical perspective. Our framework can be used as a tool for the design, appraisal, and interpretation of epidemiological and clinical studies.

The Interplay Between Post-traumatic Stress Disorder and Dementia: A Systematic Review.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been reported to increase the risk for dementia in veterans and civilians. Conversely, case reports have described the delayed onset of PTSD in individuals developing dementia, suggesting a complex relationship between these two conditions. OBJECTIVES: To critically review studies investigating the association between PTSD and dementia and to assess the evidence for a bidirectional relationship between the two conditions. METHODS: A systematic review of Web of Science Core databases was carried out from inception of databases up to November 2018 to identify observational studies pertaining to both PTSD and dementia. Populations enrolled, stressors and neuropathologies, and main outcomes of studies were extracted, in addition to age at trauma and at onset of PTSD and dementia. The different temporal relationships between trauma and onset of the conditions were characterized. RESULTS: Twenty-five articles were included in the review; 14 articles assessed the association of PTSD with subsequent dementia and 11 articles reported the delayed onset of PTSD with the onset of dementia. Most reported traumas occurred in early-life (<40 years) and were related to war combat experiences. PTSD in mid-life (between 40 and 60 years of age) was associated with an increased risk of late-onset dementia. Numerous case series reported the delayed onset of PTSD in Alzheimer's disease and vascular dementia. CONCLUSION: Current evidence suggests that PTSD and dementia have a bidirectional relationship: PTSD increases the risk for late-onset dementia and dementia increases the risk for delayed-onset PTSD in those who experienced a significant trauma earlier in life.

Post-traumatic stress disorder mistaken for behavioural and psychological symptoms of dementia: case series and recommendations of care.

In late life, traumas may act cumulatively to exacerbate vulnerability to post-traumatic stress disorder (PTSD). PTSD is also a risk factor for cognitive decline. Major neurocognitive disorder (MND) can be associated with worsening of already controlled PTSD symptoms, late-life resurgence or de novo emergence. Misidentifying PTSD symptoms in MND can have negative consequences for the patient and families. We review the literature pertaining to PTSD and dementia and describe five cases referred for consultation in geriatric psychiatry initially for behavioural and psychological symptoms of dementia (BPSD), which were eventually diagnosed and treated as PTSD in MND subjects. We propose that certain PTSD symptoms in patients with MND are misinterpreted as BPSD and therefore, not properly addressed. For example, flashbacks could be interpreted as hallucinations, hypervigilance as paranoia, nightmares as sleep disturbances, and hyperreactivity as agitation/aggression. We suggest that better identification of PTSD symptoms in MND is needed. We propose specific recommendations for care, namely: clarifying diagnosis by distinguishing PTSD symptoms coexisting with different types of dementia from a specific dementia symptom (BPSD), gathering a detailed history of the trauma in order to personalise non-pharmacological interventions, adapting psychotherapeutic strategies to patients with dementia, using selective serotonin reuptake inhibitors as first-line treatment and avoiding antipsychotics and benzodiazepines. Proper identification of PTSD symptoms in patients with MND is essential and allows a more tailored and efficient treatment, with decrease in inappropriate use of physical and chemical restraints.

Therapeutic trial design for frontotemporal dementia and related disorders.

The frontotemporal dementia (FTD) spectrum is a heterogeneous group of neurodegenerative syndromes with overlapping clinical, molecular and pathological features, all of which challenge the design of clinical trials in these conditions. To date, no pharmacological interventions have been proven effective in significantly modifying the course of these disorders. This study critically reviews the construct and methodology of previously published randomised controlled trials (RCTs) in FTD spectrum disorders in order to identify limitations and potential reasons for negative results. Moreover, recommendations based on the identified gaps are elaborated in order to guide future clinical trial design. A systematic literature review was carried out and presented in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. A total of 23 RCTs in cohorts with diagnoses of behavioural and language variants of FTD, corticobasal syndrome and progressive supranuclear palsy syndrome were identified out of the 943 citations retrieved and were included in the qualitative review. Most studies identified were early-phase clinical trials that were small in size, short in duration and frequently underpowered. Diagnoses of populations enrolled in clinical trials were based on clinical presentation and rarely included precision-medicine tools, such as genetic and molecular testing. Uniformity and standardisation of research outcomes in the FTD spectrum are essential. Several elements should be carefully considered and planned in future clinical trials. We anticipate that precision-medicine approaches will be crucial to adequately address heterogeneity in the FTD spectrum research.

Social inappropriateness in neurodegenerative disorders.

BACKGROUND: New onset of mood and behavioral changes in middle-aged patients are frequently the first manifestations of an unrecognized neurocognitive disorder. Impairment of social cognition, the cognitive ability to process social information coming from others, such as emotions, to attribute mental states to others, and to respond appropriately to them, is often at the origin of behavioral manifestations in neurodegenerative disorders. METHODS: This paper reviews the current literature on social cognition impairment in neurocognitive disorders, particularly in prodromal stages of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), idiopathic Parkinson's disease (IPD), and Lewy body dementia (LBD). The concepts of social cognition will be reviewed, including its impairment and neural basis, its clinical assessment, and the different therapeutic interventions available clinically. RESULTS: Socially inappropriate behaviors, such as loss of empathy, inappropriateness of affect, and disinhibition are frequently reported in prodromal bvFTD and in prodromal AD. Lack of self-control, reduced perception of social cues, such as recognition of facial emotions and sarcastic speech, and impaired Theory of Mind all contribute to the neuropsychiatric symptoms and are secondary to neurodegeneration in specific brain regions. In contrasts to bvFTD and AD, deficits in social cognition in IPD occur later in the course of the disease and are often multifactorial in origin. CONCLUSIONS: Through various manifestations, social inappropriateness is frequently the first clinical sign of a neurodegenerative process, especially in AD and bvFTD, years before noticeable impairment on classical neuropsychological assessment and brain atrophy on imaging.

Quetiapine for Psychosis in Parkinson Disease and Neurodegenerative Parkinsonian Disorders: A Systematic Review.

We performed a systematic review of randomized controlled trials to assess the high-level evidence regarding the role of quetiapine in the treatment of psychosis in patients with neurodegenerative parkinsonian disorders. Studies were included in the qualitative review if they (1) enrolled participants with diagnosis of Parkinson disease, Lewy body dementia, or any other neurodegenerative parkinsonian disorders; (2) assessed the efficacy of quetiapine; and (3) evaluated psychotic and motor outcomes using validated tools. Of the 341 manuscripts identified, 7 studies fulfilled our inclusion criteria. The studies' risk of bias was considered low. A total of 241 participants enrolled in these trials. Heterogeneity was high due to inclusion criteria, user definitions, assessment tools, and study design. Although not causing any motor deterioration, quetiapine failed to significantly reduce psychotic symptoms compared to placebo when objectively assessed on the Brief Psychotic Rating Scale, the most frequently reported scale in these studies. High loss to follow-up and dropout rates as well as significant improvement in psychotic symptoms in the placebo groups may have affected measurements of possible positive medication effects.

Perspectives of Health Care Providers on Peer Support for Adolescents with Cancer in Pediatrics.

Health care providers (HCPs) play a key role in psychosocial care of adolescents with cancer (AWC) and present a unique perspective. This prospective study included a brief survey followed by an interview, seeking to understand HCPs' viewpoints on peer support needs of AWC. Participants were 10 multidisciplinary HCPs with 5-30 years of experience. Three key themes found were: observations made and relationships with AWC; challenges to providing support; and potential peer support interventions. HCPs want to provide peer support resources but lack adequate information. Next steps: interventions should include information dissemination to all HCPs caring for AWC.

Peer Support Perspectives of Parents of Adolescents with Cancer in Pediatrics.

Parents of adolescents with cancer (AWC) provide critical support throughout the cancer journey and could offer key insights into support needs. This prospective study aimed to obtain parent perspectives on peer support needs of AWC. Ten individual parents (9 mothers and 1 father) completed a survey and a semistructured interview. Four themes were identified: cancer journey challenges; emotions, reactions, and coping; personal support preferences; and AWC's support needs. Parents recognized that AWC require various support, but lacked insight into their specific peer support desires. Next step interventions should focus on peer support for AWC, while also incorporating peer support for parents.

Screening for cognitive impairment in adults with sickle cell disease: A systematic review and meta-analysis.

Neurovascular disease such as symptomatic stroke, silent brain infarcts and vascular cognitive impairment are common complications of sickle cell disease (SCD) that can have devastating consequences on quality of life, employment, and social functioning.  Early recognition of neurovascular disease is a prerequisite for the timely optimization of medical care and to connect patients to adaptive resources. While cognitive impairment has been well described in children, currently available data are limited in adults. As a result, guidance on the optimal cognitive screening strategies in adults is scarce. We conducted a systematic review to identify the different screening tools that have been evaluated in SCD. A meta-analysis was performed to estimate the prevalence of suspected cognitive impairment in this population. In this qualitative synthesis, we present 8 studies that evaluated 6 different screening tools. Patient characteristics that impacted on cognitive screening performance included age, education level, and a prior history of stroke. We report a pooled prevalence of 38% [14-62%] of suspected cognitive impairment. We discuss the relative benefits and limitations of the different screening tools to help clinicians select an adapted approach tailored to their specific patients' needs. Further studies are needed to establish and validate cognitive screening strategies in patients with diverse cultural and educational backgrounds.

Peer Support Needs of Adolescents with Cancer in Pediatrics: A Canadian Mixed Methods Study.

Adolescents with cancer (AWC) in pediatrics may not have adequate opportunities for peer support. This mixed methods study aimed to characterize peer support needs of AWC during or shortly after treatment. Ten AWC with median age 16.5 (range 14-18) years completed a survey and semistructured interview. Three themes were apparent: cancer journey difficulties, current support system, and peer support perspectives. Participants felt incompletely understood by existing supports, lacked connection with other AWC, and craved experiential information. Peer support interventions should be flexible, facilitate various interactions, and include social media. The next step is to implement and evaluate an intervention.

CCCDTD5 recommendations on the deprescribing of cognitive enhancers in dementia.

INTRODUCTION: Cognitive enhancers (ie, cholinesterase inhibitors and memantine) can provide symptomatic benefit for some individuals with dementia; however, there are circumstances in which the risks of continuing treatment may potentially outweigh benefits. The decision to deprescribe cognitive enhancers must consider each patient's preferences, treatment indications, current clinical status and symptoms, prognosis, and dementia type. METHODS: The 5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5) established a subcommittee of experts to review current evidence on the deprescribing of cognitive enhancers. The questions answered by this group included: When should cognitive enhancers be deprescribed in persons with dementia and mild cognitive impairment? How should cognitive enhancers be deprescribed? And, what clinical factors should be considered when deprescribing cognitive enhancers? RESULTS: Patient and care-partner preferences should be incorporated into all decisions to deprescribe cognitive enhancers. Cognitive enhancers should be discontinued in individuals without ongoing evidence of benefit or when the indication for cognitive enhancer use was inappropriate (eg, mild cognitive impairment). Deprescribing should occur gradually and cognitive enhancers should be reinitiated if patients' cognition or function deteriorates. Cognitive enhancers should be continued in individuals whose neuropsychiatric symptoms improve in response to treatment. Clinicians should not deprescribe cognitive enhancers in individuals with significant neuropsychiatric symptoms until symptoms have stabilized. CONCLUSION: CCCDTD5 deprescribing recommendations provide evidence-informed recommendations related to cognitive enhancer deprescribing that will facilitate shared decision making among patients, care partners, and clinicians.

The APOE ε4 variant and hippocampal atrophy in Alzheimer's disease and Lewy body dementia: a systematic review of magnetic resonance imaging studies and therapeutic relevance.

Introduction: The apolipoprotein E ɛ4-allele (APOE-ɛ4) increases the risk not only for Alzheimer's disease (AD) but also for Parkinson's disease dementia and dementia with Lewy bodies (collectively, Lewy body dementia [LBD]). Hippocampal volume is an important neuroimaging biomarker for AD and LBD, although its association with APOE-ɛ4 is inconsistently reported. We investigated the association of APOE-ε4 with hippocampal atrophy quantified using magnetic resonance imaging in AD and LBD.Areas covered: Databases were searched for volumetric and voxel-based morphometric studies published up until December 31st, 2020. Thirty-nine studies (25 cross-sectional, 14 longitudinal) were included. We observed that (1) APOE-ε4 was associated with greater rate of hippocampal atrophy in longitudinal studies in AD and in those who progressed from mild cognitive impairment to AD, (2) association of APOE-ε4 with hippocampal atrophy in cross-sectional studies was inconsistent, (3) APOE-ɛ4 may influence hippocampal atrophy in dementia with Lewy bodies, although longitudinal investigations are needed. We comprehensively discussed methodological aspects, APOE-based therapeutic approaches, and the association of APOE-ε4 with hippocampal sub-regions and cognitive performance.Expert opinion: The role of APOE-ɛ4 in modulating hippocampal phenotypes may be further clarified through more homogenous, well-powered, and pathology-proven, longitudinal investigations. Understanding the underlying mechanisms will facilitate the development of prevention strategies targeting APOE-ɛ4.

The state of frailty in research: A mapping review of its clinical applicability to practice.

Research on frailty has expanded in the last decade, but direct evidence supporting its implementation in clinical practice may be limited. This mapping review synthesizes the contexts-of-use and overall clinical applicability of recent pre-COVID frailty research. We sampled 476 articles from articles published on frailty in PubMed and EMBASE in 2017-2018, of which 150 articles were fully appraised for the contexts-of-use, definitions, and interventions. A clinical applicability framework was used to classify articles as practice-changing, practice-informing, or not practice-informing. Of the 476 sampled articles, 31% (n = 150) used frailty in functions that could inform a clinical indication: predictor or mediator (26%, n = 125), selection criterion (3%, n = 15), and effect modifier (2%, n = 10). Articles spanned all health disciplines, and cohort studies comprised 91% (n = 137) of studies and trials 9% (n = 13). Thirty-eight frailty definitions using varied cut-offs and a wide range of interventions were identified. Among all articles, 13% (n = 63) of articles were practice-informing, 2% (n = 11) potentially practice-changing, and 0.2% (n = 1) clearly practice-changing. Lack of well-defined intervention and identifiable effect (96%) or originality (83%) were predominant reasons reducing applicability. Only a minority of recent frailty research provides direct evidence of applicability to practice. Future research on frailty should focus on translating frailty, as a risk factor, into a clinical indication and address definition ambiguity.

Health Heterogeneity in Older Adults: Exploration in the Canadian Longitudinal Study on Aging.

BACKGROUND: A widely held dictum in aging research is that heterogeneity in health increases with age, but the basis for this claim has not been fully investigated. We examined heterogeneity at different ages across health characteristics to describe variation and trends; we investigated the comparative importance of between-age versus within-age heterogeneity. DESIGN: This was a cohort study. SETTING: Community-dwelling older adults. PARTICIPANTS: A total of 30,097 adults aged 45 to 86 years, from the Canadian Longitudinal Study on Aging, were included. MEASUREMENTS: Thirty-four health characteristics in eight domains (physical measures, vital signs, physiological measures, physical performance, function/disability, chronic conditions, frailty, laboratory values) were assessed cross-sectionally. We used regression models to examine heterogeneity in health characteristics (using absolute deviation) and domains (using effective variance) in relation to age. Comparison between between-age and within-age heterogeneity was quantified by estimating the age threshold at which the former exceeds the latter. RESULTS: Of the 34 health characteristics, 17 showed increased heterogeneity, 8 decreased, and 9 no association with age. The associations between heterogeneity and age increased generally but were nonlinear for most domains and nonmonotonic for some. We observed peak heterogeneity at approximately 70 years. Between-age heterogeneity, compared with within-age heterogeneity, was most important for forced expiratory volume in 1 second and grip strength but varied across characteristics. CONCLUSION: Overall health heterogeneity increases with age but does not uniformly increase across all variables and domains. Heterogeneity in aging reinforces the need for geriatric assessment and personalized care, depending on which health characteristics are assessed, their measurement properties, and their referent group. Our findings suggest further research to develop improved single-dimension and multidimensional instruments, as well as specific vital and laboratory reference ranges for older adults.

White matter hyperintensities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer's disease.

BACKGROUND: We aimed to systematically describe the burden and distribution of white matter hyperintensities (WMH) and investigate correlations with neuropsychiatric symptoms in pathologically proven Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). METHODS: Autopsy-confirmed cases were identified from the Sunnybrook Dementia Study, including 15 cases of AD and 58 cases of FTLD (22 FTLD-TDP cases; 10 FTLD-Tau [Pick's] cases; 11 FTLD-Tau Corticobasal Degeneration cases; and 15 FTLD-Tau Progressive Supranuclear Palsy cases). Healthy matched controls (n = 35) were included for comparison purposes. Data analyses included ANCOVA to compare the burden of WMH on antemortem brain MRI between groups, adjusted linear regression models to identify associations between WMH burden and neuropsychiatric symptoms, and image-guided pathology review of selected areas of WMH from each pathologic group. RESULTS: Burden and regional distribution of WMH differed significantly between neuropathological groups (F5,77 = 2.67, P' = 0.029), with the FTLD-TDP group having the highest mean volume globally (8032 ± 8889 mm3) and in frontal regions (4897 ± 6163 mm3). The AD group had the highest mean volume in occipital regions (468 ± 420 mm3). Total score on the Neuropsychiatric Inventory correlated with bilateral frontal WMH volume (ß = 0.330, P = 0.006), depression correlated with bilateral occipital WMH volume (ß = 0.401, P < 0.001), and apathy correlated with bilateral frontal WMH volume (ß = 0.311, P = 0.009), all corrected for the false discovery rate. Image-guided neuropathological assessment of selected cases with the highest burden of WMH in each pathologic group revealed presence of severe gliosis, myelin pallor, and axonal loss, but with no distinguishing features indicative of the underlying proteinopathy. CONCLUSIONS: These findings suggest that WMH are associated with neuropsychiatric manifestations in AD and FTLD and that WMH burden and regional distribution in neurodegenerative disorders differ according to the underlying neuropathological processes.

Delirium and Inflammation in Older Adults Hospitalized for COVID-19: A Cohort Study.

PURPOSE: The occurrence and predictors of delirium in older adults hospitalized for coronavirus disease 2019 (COVID-19) have not been well described. Highlighting the association with inflammatory markers may be useful for identifying delirium. This study aimed to determine the prevalence and incidence of delirium and explore its association with the C-reactive protein (CRP). PATIENTS AND METHODS: This cohort study of adults aged 65 and older with a COVID-19 diagnosis took place at an academic healthcare institution between April and May 2020. COVID-19 was diagnosed by positive nasopharyngeal swab. Serum levels of CRP were collected as a marker of systemic inflammation. The primary outcome was the prevalence and incidence of delirium. Delirium was diagnosed primarily during a patient's stay in hospital based on the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5). To ensure that no delirium diagnosis was missed during hospital stay, clinical records were reviewed by clinicians with geriatric medicine training for retrospective diagnoses. RESULTS: A total of 127 patients aged 65 and older were hospitalized with a diagnosis of COVID-19. The median age was 82 years (IQR: 74-88), with 54 (43%) females. Overall, delirium was present in 62 (49%) patients: manifestations of delirium were present on the first day of hospitalization in 53 of these cases (86%), while 9 cases (14%) developed delirium during hospitalization. After controlling for age and sex, the mean CRP value over the first 3 days since arrival was associated with a higher risk of delirium (OR 1.35; 95% CI: 1.01-1.85) for every 50 mg/L increase. CONCLUSION: In this cohort of older adults hospitalized for COVID-19, delirium was highly prevalent. An early increase in CRP levels should raise suspicion about the occurrence of delirium and could improve its diagnosis.