Heart rate variability and delirium in acute non-cardioembolic stroke: a prospective, cross-sectional, cohort study.

OBJECTIVES: Delirium is an acute fluctuating disorder of attention and awareness. It is associated with autonomic dysfunction and increased mortality. The primary endpoint of our study was to measure autonomic activity in acute stroke patients, by means of heart rate variability analysis, in order to identify autonomic modifications that can predispose to delirium. METHODS: Patients were consecutively enrolled from the stroke unit. Inclusion criteria were age ≥ 18 years and diagnosis of stroke with onset within the previous 72 h confirmed by neuroimaging. Exclusion criteria were atrial fibrillation, congestive heart failure, and conditions requiring intensive care unit. Patients were evaluated by means of Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) at baseline, after 72 h, or when symptoms suggesting delirium occurred. For each patient, ECG was recorded at baseline assessment and HRV analysis was conducted on five consecutive minutes of artifact-free ECG traces. RESULTS: Fifty-six ECGs were available for analysis. During the study period, 11 patients developed delirium. Patients with and without delirium did not differ for sex, age, severity of stroke, and comorbidities. The delirium group had greater standard deviation of the heart rate (DLR - :9.16 ± 8.28; DLR + : 14.36 ± 5.55; p = 0.026) and lower power spectral density of the HF component (DLR - : 38.23 ± 19.23 n.u.; DLR + : 25.75 ± 8.77 n.u.; p = 0.031). CONCLUSIONS: Acute non-cardioembolic stroke patients with increased variability of heart rate and decreased vagal control are at risk for delirium.

Delirium in acute stroke: A prospective, cross-sectional, cohort study.

BACKGROUND AND PURPOSE: Delirium is a neuropsychiatric disorder of attention and awareness that develops over a short time and fluctuates in severity. Although delirium has been extensively studied in intensive care units, the incidence of delirium in stroke units and its predictors in stroke patients need further investigation. The endpoints of our study were incidence of delirium in acute stroke and the risk factors that predispose to this condition. METHODS: Patients were consecutively enrolled in a stroke unit from April to October 2020. Inclusion criteria were: age ≥18 years, acute stroke and National Institute of Health Stroke Scale (NIHSS) score ≥1 at the time of clinical assessment of delirium. Exclusion criteria were: transient ischemic attack; absence of neuroimaging evidence of brain lesion; cerebral venous thrombosis; subarachnoid hemorrhage; and clinical conditions requiring intensive care unit treatment. All patients were evaluated by means of Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) scores at baseline, evaluations which were repeated within 72 h or when patients developed symptoms suggesting delirium. RESULTS: The overall incidence of delirium was 36/120 (30%). Delirium was associated with aphasia (odds ratio [OR] 9.77; confidence interval [CI] 1.2-79.6), chronic obstructive pulmonary disease (COPD; OR 16.67; CI 1.1-263.0), deep Fazekas score (OR 5.05; CI 1.7-14.8), and physical restraint (OR 45.02; CI 1.4-1411.5). Diabetes was associated with a lower incidence of delirium (OR 0.04; CI 0.026-0.7). CONCLUSIONS: Nearly one-third of patients (30%) had delirium in the acute phase of stroke. This finding supports the notion that delirium is a common complication of stroke. Delirium was associated with speech disorder, leukoencephalopathy, COPD and early use of physical restraint.

Impact of delirium on the outcome of stroke: a prospective, observational, cohort study.

INTRODUCTION: Delirium is an acute fluctuating disorder of attention and awareness, which often complicates the clinical course of several conditions, including acute stroke. The aim of the present study was to determine whether delirium occurrence impacts the outcome of patients with acute stroke. METHODS: The study design is single center, prospective, observational. We consecutively enrolled patients admitted to the stroke unit from April to October 2020. Inclusion criteria were age ≥ 18 years and diagnosis of acute stroke. Exclusion criteria were stroke mimics, coma, and terminal conditions. All patients were screened for delirium upon admission, within 72 h, and whenever symptoms suggesting delirium occurred by means of the Confusion Assessment Method for Intensive Care Unit and the Richmond Agitation Sedation Scale. Outcomes were evaluated with the 90-days modified Rankin Scale (mRS) by telephone interview. RESULTS: The final study cohort consisted of 103 patients (62 men; median age 75 years, interquartile range 63-81). Thirty-one patients (30%) developed delirium. In the multivariate ordinal logistic regression, patients with delirium had higher mRS scores at 3 months (DLR + : mRS = 4 (3-6); DLR-: mRS = 1 (1-3); adjusted odds ratio = 4.83; CI = 1.88-12.35; p = 0.006). Delirium was a risk factor for death (mRS = 6) in the univariate logistic regression (OR 4.5, CI = 1.44-14.07; p = 0.010), but not in the adjusted analysis (OR 3.45; CI = 0.66-17.95; p = 0.142). Survival time during 90-days follow-up was shorter in the delirium group (Log Rank χ2 3.89; p = 0.048). CONCLUSION: Delirium negatively impacts the prognosis of patients with acute stroke. Patients with post-stroke delirium have a worse functional outcome and a shorter survival.

Delirium in hospitalized patients with COVID-19 pneumonia: a prospective, cross-sectional, cohort study.

Delirium is an acute confusional state characterized by altered level of consciousness and attention. Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), can manifest itself with this neuropsychiatric disorder. The endpoints of our study were: the frequency of delirium in subjects with COVID-19 pneumonia; the risk factors that predispose to this condition; and the impact of delirium on mortality. Subjects were consecutively enrolled in a Geriatric Unit from January 5th to March 5th, 2021. Inclusion criteria were: diagnosis of SARS-CoV-2 infection, a radiologically documented pneumonia, and the ability of providing informed consent. Exclusion criteria were: absence of radiological evidence of pneumonia, sepsis, and the need of intensive care unit treatment. All subjects were evaluated by means of Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) at least twice per day. In the study cohort (n = 71), twenty patients (28.2%) had delirium. Delirium was present on admission in 11.3%, and occurred during hospitalization in 19.0%. Compared to patients without delirium, patients who developed this neuropsychiatric disorder had a higher mortality rate (35% vs 5.9%) and an increased average hospital length of stay (21 days vs 17 days). In the multivariate analysis delirium was associated with frailty (OR = 2.81; CI = 1.4-5.8) and helmet ventilation (OR = 141.05; CI = 4.3-4663.9). Delirium was an independent predictor of mortality. Nearly a third of subjects (28.2%) had delirium during hospitalization for COVID-19. This finding supports the notion that delirium is a common complication of SARS-CoV2 infection. Since delirium is associated with longer hospital stay, and it is an independent marker of increased mortality, clinicians should assess and prevent it.

Semantic Memory as an Early Cognitive Marker of Alzheimer's Disease: Role of Category and Phonological Verbal Fluency Tasks.

BACKGROUND: The assessment of semantic memory may be a useful marker to identify individuals with mild cognitive impairment (MCI) who will progress to Alzheimer's disease (AD) in the early stages of the disease. OBJECTIVE: The aim of this five-year follow-up longitudinal study is to assess whether semantic assessment could predict progression in MCI. METHODS: A population of MCI (N = 251); mild (N = 178) and moderate AD (N = 114); and a sample of healthy participants (HP; N = 262) was investigated. The five-year follow-up of the MCI group was completed by 178 patients. Semantic and episodic memory measures were used, including a measure of the discrepancy between categorical and phonological verbal fluency, the semantic-phonological delta (SPD). The main outcome was the progression of MCI due to AD to dementia. RESULTS: A general linear model showed a significant effect of diagnosis on SPD (Wilks' Lambda = 0.591; p < 0.001). The estimated marginal means were -0.91 (SE = 0.185) in HP, -1.83 (SE = 0.187) in MCI, -1.16 (SE = 0.218) in mild AD, and -1.02 (SE = 0.275) in moderate AD. Post-hoc comparisons showed a significant difference between MCI and HP (p < 0.001). The follow-up was completed by 178 MCI individuals. SPD in MCI patients who progress to dementia was significantly lower than in MCI that will not progress (p = 0.003). Together with the Mini-Mental State Examination, the SPD was the only measure with a significant predicting effect at the five-years follow-up (p = 0.016). CONCLUSION: The SPD indicates the impairment of semantic memory in individuals with underlying AD at the MCI early stage, reflecting the early involvement of perirhinal and entorhinal cortices in the earliest stages of AD neuropathological process.

Intronic rs2147363 variant in ATP7B transcription factor-binding site associated with Alzheimer's disease.

Copper homeostasis abnormalities have been shown to be associated with Alzheimer's disease (AD), possibly by accelerating amyloid-ß toxicity and plaque formation. The ATP7B gene plays a key role in controlling body copper balance. Our previous studies showed an association between ATP7B variants and AD risk. Among these variants, an intronic single nucleotide polymorphism, rs2147363, was associated with AD risk. In order to understand this intronic association, we screened a population of 286 AD patients and 283 healthy controls, and verified the presence of other functional coding variants in linkage disequilibrium (LD). Then we searched for a regulatory function region close to rs2147363. An LD analysis revealed the presence of an LD between rs2147363 and a Wilson's disease-causing variant, rs7334118. However, this mutation did not explain the observed genetic association. Conversely, in silico analyses of rs2147363 functionality highlighted that this variant is located in a binding site of a transcription factor, and is, consequently, associated with regulatory function. These data suggest that the genetic variation in cis-regulatory elements located in non-coding regions can have a role in determining ATP7B functionality and account for some of the AD missing hereditability.