Delirium: il punto di vista del neurologo Pietro Tiraboschi IRCCS “Carlo Besta”, Milano Venezia, 12 marzo 2016

Objectives Recognize that delirium is a common presentation of disease in the elderly Recognize that delirium is associated with adverse outcomes Know how to distinguish between delirium and other diagnoses (dementia, depression) Identify risk factors for delirium and strategies for risk reduction Adverse outcomes = esiti sfavorevoli

Delirium Sindrome mentale organica acuta transitoria con: Obnubilamento della coscienza ( consapevolezza dell’ambiente circostante), con  capacità di spostare, focalizzare e mantenere l’attenzione agli stimoli ambientali Almeno due dei seguenti elementi: turbe percettive: false interpretazioni, illusioni, allucinazioni linguaggio talora incoerente disturbi del ciclo sonno-veglia con insonnia o sonnolenza diurna attività psicomotoria aumentata o diminuita Disorientamento e deficit di memoria (se valutabili) Sintomi a rapido sviluppo (ore/giorni) e tendenza a fluttuare. Durata di norma breve. Dimostrazione (fondata su anamnesi, obiettività clinica ed esami di laboratorio) di uno specifico fattore organico eziologicamente correlato al disturbo Sinonimi (?): stato confusionale acuto sindrome (reazione) organica cerebrale acuta encefalopatia metabolica psicosi tossica esogena stato crepuscolare

Caratteristiche cliniche (cont’d)

Prevalence of delirium Most prevalence studies have been performed in hospitalised medically ill patients Most at risk are elderly, postoperative, and terminally-ill patients Unknown prevalence rates in primary care and the community but, with shorter length of hospital stay and more surgery on a day case basis, it is likely to be increasingly common in the community and residential care homes Among hospital in patients with delirium, up to 50% have only partially recovered by the time of discharge IN REALTA’ CI SONO ORA DATI DI PREVALENZA ANCHE NELLA COMMUNITY (1-2%) IMPORTANTE RICONOSCERLO E SOPPRATTUTTO PREVENIRLO. LO SI PUO’ FARE NEL 30-40% DEI CASI

Prevalence and Incidence in Hospitalized patients

Prevalence and Incidence in Hospitalized patients Schor 1992 Medical & surgical >65 N=325 11% prevalence, 31% incidence Johnson 1990 Medical >70 N=235 16% prevalence, 5% incidence Francis 1990 Medical >70 N=229 16% prevalence, 8% incidence Gustafson 1988 Femoral Fracture >65 N=111 33% prevalence before surgery, 42% incidence after surgery Schor ‘92: patients from either a geographically defined community or a long-term institution admitted to general medical and surgical wards (11% [34/325] prevalence in community and LT institution, 31% [91/290] incidence of delirium in those not delirious at first exam. Independent risk factors for hospital delirium: prior dementia (OR 8.97), age > 80 (OR 5.22), fractures on admission (OR 6.57), symptomatic infection (OR 2.96), male sex (OR 2.4), neuroleptic use (OR 4.48), narcotic use (OR 2.54). Delirium incidence related to factors (prior dementia, advanced age, fractures) already present on admission and during stay (neuroleptics) I like to highlight how common delirium is after hip fracture and get audience to speculate why. Some possible reasons: Frail elders get hip fractures Dementia and hip fracture Maybe delirium is causative for the fracture Fat emboli Pain meds Other From: Delirium in the Elderly. Bree Johnston MD MPH, UCSF Division of Geriatrics, Primary Care Geriatric Lectures, University of California.

Epidemiology IF 2/3 OF PATIENTS HAD NO SIGNS OF DELIRIUM AFTER SIX MONTHS, 1/3 HAD SIGNS OF DELIRIUM. THIS MEANS THAT DELIRIUM CAN PERSIST FOR MONTHS OR EVEN YESRS BLURRING THE BOUNDARIES BETWEEN DELIRIUM AND DEMENTIA Da: Gail Greendale, MD, Brandon Koretz, MD, Lecture, UCLA.

Delirium: prevalence, incidence, outcomes THE HIGHEST INCIDENCE RATES WERE NOTED IN ICU AND IN POSTOPERATIVE AND PALLIATIVE CARE SETTINGS. WHEN DEMENTIA IS PRESENT AT BASELINE, THE PREVALENCE OF DELIRIUM INCREASES THIS TABLE ALSO LISTS ADVERSE OUTCOMES ASSOCIATEDWITH DELIRIUM DRAWN FROM SELECTED STUDIES THAT INCLUDED ADJUSTMENTS FOR CONFOUNDERS Inouye et al., Lancet 2014

Delirium and its heterogeneous clinical phenotype 5-56% inpatients > 65 years experience delirium (5%: Johnson, 1990; 15%:Rudberg 1977; 25% Francis, 1992; Schor 1992; Inouye 1993; O’Keeffe 1997; Milisen 1999; 51% Williams, 1985) “Hyperactive” form (22%) P. alert, hyperactive, reactive to stimuli “Hypoactive” form (26%) P. drowsy, with decreased psychomotor activity “Mixed” form (42%) Fluctuating course during the day or during the episode “Unclassified” form (10%) With no psychomotor disturbances

Identification of delirium ! 32-67 % of cases go unrecognized ! risk of morbidity and mortality failure to identify the cause(s) failure to counteract the behavioral disorder Immobility pneumonia Wandering falls and fractures

Delirium and underlying illnesses Presentation of Myocardial Infarction in the Elderly AGE # CP SOB Delirium* symptoms >65 387 19% 20% 13% 74 87 59% 22% 16% 76 777 66% 42% 30% >62 110 22% 35% 18% Pathy 1967 Tinker 1981 Bayer 1986 Aronow 1987 Patients could have more than one presentation in these studies Neuro sx including dizziness, focal neuro sx, and mental status changes On this slide I try to make the point that neuro manifestations are typical, not atypical presentations of MI in the elderly From: Delirium in the Elderly. Bree Johnston MD MPH, UCSF Division of Geriatrics, Primary Care Geriatric Lectures, University of California. CP: chest pain SOB: shortness of breath * often, as sole presenting symptom

Atypical disease Presentations “Well Elderly” (n=76) “Frail elderly” (n = 117) % with atypical presentation 25% 59% Type of Presentation Delirium 32% 61% Falls 37% 9% Immobility 5% 6% Functional decline 26% 19% Other 0 5% Jarrett et al. Arch Int Med 1995 This is kind of a confusing study. This was a cohort study that looked at hospitalized “well” or previously “frail” (as defined by Barthel index) elders who were hospitalized for various reasons (pneumonia, MI, CHF, etc.) and categorized as having “typical” or “atypical” presentations. The points are: Atypical presentations are common Delirium is the most common atypical presentation Frail elders are more likely to have atypical presentations than well elders Patients were hospitalized for MI, HF, pneumonia, etc. and classified as being well or frail on the basis of the premorbid Barthel Index (well, score of > or = 95 [n = 76]; frail, score of < 95 [n = 117]) Atypical presentations are common Frail elders are more likely to present atypically than well elders Delirium is the most atypical presentation

Atypical disease Presentations “Well Elderly” “Frail elderly” % with typical presentation 75% 41% % with atypical presentation 25% 59% Poor hospital outcomes 32% 60% Independent predictors of poor hospital outcomes (further functional decline, institutionalization, or death) Premorbid functional dependence OR = 2.5 Atypical disease presentation OR = 2.4 Functional decline at admission OR = 5.6 N.B. Age, sex, and disease severity were unrelated to poor outcomes Jarrett et al. Arch Int Med 1995 This is kind of a confusing study. This was a cohort study that looked at hospitalized “well” or previously “frail” (as defined by Barthel index) elders who were hospitalized for various reasons (pneumonia, MI, CHF, etc.) and categorized as having “typical” or “atypical” presentations. The points are: Atypical presentations are common Delirium is the most common atypical presentation Frail elders are more likely to have atypical presenations than well elders

Delirium Risk. Some Patient’s Risk Factors Age Cognitive impairment 25% delirious are demented 40% demented in hospital became delirious Male gender Severe illness (comorbidities) Hip fracture Fever or hypothermia Hypotension Malnutrition High number of medications Sensory impairment Psychoactive medications Use of lines and restraints Metabolic disorders: Azotemia Hypo- or hyperglycemia Hypo- or hypernatremia Depression Alcoholism Pain Multiple risk factors for delirium have been sited in the literature, and not all of them span out when controlling for other factors. Of note, when a patient is delirius is NOT the time to make a diagnosis of dementia, and one must be very careful in labeling a person as demented during a hospital stay. Most appropriate to question dementia and follow up as outpatient From: Delirium in the Elderly. Bree Johnston MD MPH, UCSF Division of Geriatrics, Primary Care Geriatric Lectures, University of California.

Risk Factors Da: Gail Greendale, MD, Brandon Koretz, MD, Lecture, UCLA.

THE LEADING RISK FACTORS CONSISTENTLY IDENTIFIED AT ADMISSION IN BOTH MEDICAL AND NON-CARDIAC SURGERY POPULATIONS WERE: DEMENTIA OR COGNITIVE IMPAIRMENT FUNCTIONAL IMPAIRMENT VISUAL IMPAIRMENT HISTORY ALCOHOL MISUSE ADVANCED AGE THE LEADING PRECIPITATING FACTORS IN MEDICAL PATIENTS: POLYPHARMACY, PSYCHOACTIVE DRUGS, PHYSICAL RESTRAINTS IN ALL POPULATIONS: ABNORMAL LAB MEASUREMENTS SONO I FATTORI PRECIPITANTI SUI QUALI SI PUO’ INTERVENIRE E PREVENIRE COSI’ IL DELIRIUM Inouye et al., Lancet 2014

primary illness severity major surgery severe dementia ICUs primary illness severity visual/auditory impairment psychoactive drugs Predisposing factors = Baseline vulnerability  Fattori NON correggibili Precipitating factors = Noxious Insults during hospitalization Main outcome measure: new onset delirium by day 9 defined by CAM diagnostic criteria. Five independent precipitating factors for delirium were identified: Use of physical restraints (RR 4.4) Malnutrition (RR 4.0) > 3 meds Use of catheter Any iatrogenic event advanced age sleep deprivation good health no adverse event

Delirium Risk Model Patient Factors + Extrinsic Factors Incidence of delirium per day Baseline characteristics on admission: Vision impairment (< 20/70) Cognitive impairment (MMSE <24) Severe illness (APACHE II>16) BUN/Cr ratio > 18 Precipitating Factors Use of physical restraints RR 4.4 Malnutrition RR 4 3 new meds RR 2.9 Use of bladder catheter RR 2.4. Iatrogenic event 1.9 Graph shows Validation (not derivation) cohort numbers Note that 11.6% incidence of delirium per day corresponds to a rate of 67% for an average hospital stay Baseline Risk Group Precipitating Factor Group Inouye JAMA 1996

Searching for the cause

Pathophysiology Nonspecific manifestation of a widespread reduction in cerebral metabolism & derangement of neurotransmission due to: Cholinergic deficiency GABA Dopamine NE Specific receptors ( e.g., steroid) Alteration of blood flow Inflammatory mediators Derangement of polysynaptic pathways from reticular ascending formation to thalamus, prefrontal cortex, posterior parietal cortex I like to highlight here that there are probably many subtypes of delirium and we tend to treat them all the same. Maybe different sybtypes require different treatments From: Delirium in the Elderly. Bree Johnston MD MPH, UCSF Division of Geriatrics, Primary Care Geriatric Lectures, University of California.

Pathogenesis of delirium Beta-adrenergic and dopaminergic agonists, opiates, barbiturates may interfere with with cholinergic neurotransmission through presynaptic inhibition of acetylcholine release. Serum anticholinergic activity increases with acute illness in febrile elderly patients and decreases with resolution Methyl donors such as serine and methionine are important to the production of acetylcholine . One study of delirium following elective cardiac surgery found an association between delirium and reduced plasma levels of methionine and serine postoperatively. Increased serotonine acitivity (seroronine syndrome) can produce confusion, restlessness, and diaphoresis. Drugs potentially implicated: MAO-I, fluoxetine, tryptophan. Pretreatrment with serotonine antagonists such as methylsergide prevents delirium experimental animals. In humans, CSF 5;hydroxyindoleacetic acid (a metabolite of seroronine), were found to be increased in aptients with delirium tremens and clozapine-induced delirium

Results: ChAT activity, but no other neurochemical markers, was reduced in AD compared with controls. Loss of ChAT activity correlated with cognitive impairment. Lowered ChAT activity also correlated with increasing overactivity in patients with dementia in both frontal and temporal cortex whereas ratios of both ChAT to DA and ChAT to D1 receptors in temporal cortex correlated negatively with aggressive behavior. Conclusions: Disturbance of the cholinergic system may underlie both cognitive and some noncognitive behavioral changes in dementia, providing a basis for rational therapy.

Delirium in the first days of acute stroke Delirium in the first days of acute stroke. Caeiro L, Ferro JM, Albuquerque R, Figueira ML Assessment of delirium prospectively in a sample of 218 consecutive patients (mean age 57 years) with an acute (</= 4 days) stroke (28 subarachnoid haemorrhages, 48 intracerebral haemorrhages, 142 cerebral infarcts) and in a control group of 50 patients with acute coronary syndromes. 29 (13%) of acute stroke patients and only 2 % of acute coronary patient had delirium (chi square p = 0.02). Delirium was secondary to stroke without any additional cause in 1/3, secondary also to medical complications (stroke + infections) in 1/3, and secondary to other multiple potential causes (stroke, infections, diabetes, alcohol abuse, previous cognitive impairment) in 1/3. Delirium was more frequent after haemorrhagic strokes and after hemispherical rather than brainstem/cerebellum strokes (p = 0.02) CONCLUSION: Delirium is more frequent in stroke than in coronary acute patientsit is secondary to hemisphere brain damage and to metabolic disturbances due to medical complications. J Neurol. 2004 Feb 251(2):171- 178.

Abstract—Delusional Ideations were seen in 15 patients in a prospective cohort population (n = 360) with acute stroke admitted within 24 hours of onset. Specific Delusional Ideations may occur during the acute stroke phase, but atypical forms with distinct behavioral findings have also been observed. Delusional Ideations are associated with right posterior temporoparietal lesions. However, distinct lesions were also seen, and duration was relatively short, mostly less than 1 month.

Lesion NMRi T2 topography of patients with delusional ideation. erotomania, grandiose ideation, jealousy, persecutory thought, somatic delusions, atypical delusional form, including Fregoli’s phenomenon (caregiver is taking a variety of faces) and Cotard’s syndrome (patient believes that he or she has lost everything). 15 right handed patients (out of 360) 1-8: g. supramarginalis and angular ± BG 13-14: anterior part of thalamus

RELATION OF DELIRIUM TO DEMENTIA: DELIRIUM MAY BE SUPERIMPOSED TO DEGENERATIVE DEMENTIA AS DEGENERATIVE DEMENTIA IS A RISK FACTOR FOR DELIRIUM DELIRIUM MAY BE A MARKER OF VULNERABILITY TO DEGENERATIVE DEMENTIA, BRINGING PREVIOUSLY UNRECOGNIZED COGNITIVE IMPAIRMENT TO MEDICAL ATTENTION DELIRIUM MAY ITSELF LEAD TO DEMENTIA

Delirium or dementia? Red flags in history and exam Patients may deal with MMSE or clock drawing, although not performing well Patients are often unable to deal with MMSE or clock drawing Hallucinations, fluctuations, and daytime hypersomnolence may occur in Lewy body dementia

                                                                                                                                                                            Fluctuating profiles in choice reaction time (CRT) responses across a single 90-second trial for two individual subjects with different clinical fluctuating cognition (FC) severities. Subject A does not have FC (clinical FC score = 0), demonstrating a relatively fast and consistent CRT attentional performance; Subject B has severe FC (clinical FC score = 12), demonstrating a slower, continuously variable pattern of CRT attentional performance. From:   Walker: Neurology, Volume 54(8).April 25, 2000.1616-1625 Choice Reaction time: each time yes or no was presented in the center of the screen, the participant was required to press the corresponding “yes” or “no” button as quickly as possible

Walker MP et al., Neurology 2000 Mappa delel frequenze EEG A sinistra (AD): ci sono differenze tra area e area ma, in ciascuna area, il pattern di attivazione corticale rimane stabile lungo la durata di 90 secondi A destra (DLB): ci sono differenze tra area e area e, inoltre, in ciascuna area, il pattern di attivazione cortical e’ instabile, continuamente fluttuante

Assessing Cognitive Fluctuation in DLB The Clinician Assessment of Fluctuation (Walker, Br J Psych 2000) Does he/she ever have spontaneous impaired alertness and concentration (ie, appear drowsy but awake, look dazed, unaware of what’s up around)? Have these episodes occurred within the last month? Has the level of confusion experienced by the patient tended to vary a lot recently from day to day or week to week? Has it become worse then improved for a while, ie been up and down? If a positive rating is present (positive answer to ≥ 1 of prior questions), a severity rating based on fluctuation frequency and duration is made Frequency Duration 1 = one per month 0 = seconds 2 = monthly – weekly 1 = ≤ 5 minutes 3 = weekly - daily 2 = 5 minutes – 1 hour 4 = ≥ daily 3 = ≥ 1 hour 4 = ≥ 1 day Drowsy: mezzo addormentato Dazed: stupefatto Cut-off: punteggio uguale o superiore a 5 è apparso quello con migliori capacità discriminative (sens 82%, spec 91%) Tuttavia, 1) poche diagnosi erano confermate post-mortem, 2) non c’erano dati di inter-rater, nè furono prodotti in seguito e, soprattutto, le informazioni derivanti dalla CAF erano incorporate nell’algoritmo diagnostico per separare I gruppi (tautologia)

Assessing Cognitive Fluctuation in DLB Mayo Fluctuations Questionnaire Most carers report fluctuations DLB 87% AD 73% 4 items distinguish DLB and AD Daytime drowsiness and lethargy Daytime sleep >2 hours Staring into space for long periods Episodes of disorganized speech 3 or 4 features in 63% DLB, 12% AD, 0.5% controls Melbourne Fluctuation Scales Most carers report fluctuations DLB 77% AD 67% Yes/no items unhelpful Qualitative differences can distinguish between fluctuations in DLB and AD Examples of “worst and best period of function” discriminated DLB 89% correct AD 94% correct Ferman et al. Neurology. 2004;62:181-187 Bradshaw et al. JNNP. 2004;75:382-387

Frequency of combined clinical symptoms in Lewy Body Disease. VH: visual hallucinations EPS: extrapiramidal signs RBD: REM sleep behavior disorders Controls Alzheimer Disease Lewy Body Disease Mayo brief semistructured interview (administered to informants). Composite Score from 0 to 4

DELIRIUM different from or Superimposed to DEMENTIA

Delirium superimposed on dementia Often unrecognized disruptive behavior in dementia may be due to an underlying delirium medications for treating behavioral disturbances in dementia may worsen or further mask the problem behavioral changes in dementia are often misattributed to diurnal variations of symptoms (sundowning) or to the underlying dementing illness itself rather than to a superimposed delirium delay in diagnosis of delirium and its underlying cause contributes to the poor outcomes associated with delirium superimposed on dementia

Delirium superimposed on dementia: a systematic review Delirium superimposed on dementia: a systematic review. Fick DM, Agostini JV, Inouye SK. Fourteen studies were reviewed, including seven prospective studies, three retrospective studies, two cross-sectional studies, and two clinical trials. The prevalence of delirium superimposed on dementia ranged from 22% to 89% of hospitalized and community populations aged 65 and older with dementia. Studies examining outcomes have found that adverse events are associated with delirium in persons with dementia, including accelerated and long-term cognitive and functional decline, need for institutionalization, rehospitalization, and increased mortality. The importance of early recognition and prevention of delirium in persons with dementia is stressed. J Am Geriatr Soc. 2002 Oct;50(10):1723-32.

Outcomes Inpatients with delirium vs. those without Death: 8% vs. 1%,  inhospital mortality, 90 day mortality 11% vs. 3% Lengthened hospital stay: 12 days vs. 7 days Increased nursing home placement: 16% vs. 3% Functional decline (less transient than commonly believed: 3/4 may still have some symptoms by 6 months after hospital discharge) Francis J et al. JAMA 1990;263:1097. Levkoff SE et al. Arch Intern Med 1992;152:334 Pompei et al. JAGS 1994; 42: 809

Delirium predicts 12-month mortality. METHODS/SUBJECTS: A prospective, observational study of 2 cohorts of medical inpatients (243 with prevalent or incident delirium vs. 118 without) 65 years or older. Apart from delirium, baseline measures included physical function, presence/severity of comorbidity, including dementia RESULTS: The unadjusted hazard ratio of delirium with mortality was 3.44 (95% confidence interval, 2.05-5.75); the adjusted hazard ratio was 2.11 (95% confidence interval, 1.18- 3.77). The effect was stronger among patients without dementia. CONCLUSION: Delirium is an independent marker for increased mortality among older medical inpatients during the 12 months after hospital admission. It is a particularly important prognostic marker among patients without dementia. McCusker et al, Arch Intern Med 2002;162(4):457-63

Delirium in older emergency department patients discharged home: effect on survival Kakuma R, du Fort GG, Arsenault L, Perrault A, Platt RW, Monette J, Moride Y, Wolfson C. RESULTS: The analysis revealed a statistically significant association between delirium and mortality after adjustments for age, sex, functional level, cognitive status, comorbidity, and number of medications for the first 6 months of follow-up CONCLUSION: The results of this study suggests that nondetection of delirium in the ED may be associated with increased mortality within 6 months after discharge. J Am Geriatr Soc. 2003;51(4):443-50.

From: Delirium in Elderly Patients and the Risk of Postdischarge Mortality, Institutionalization, and Dementia:  A Meta-analysis JAMA. 2010;304(4):443-451

Relationship between delirium and dementia But: dementia itself is a major risk of delirium up to half of dementia remains undiagnosed Consequently, in studies where cognitive status at baseline is not carefully assessed, it remains unclear whether: there is merely a greater risk of delirium in patients who are already suffering from dementia (prevalent dementia) OR 2. delirium is a true risk factor for new onset dementia

Delirium increased the risk of: Main questions: does delirium increase the risk of incident dementia? in those with dementia, is delirium related to burden of pathology traditionally associated to dementia? The study population comprised 553 subjects, representing 92% of the 601 adults aged > or = 85 years living in Vantaa 553 subjects aged ≥ 85 years assessed at baseline, 3, 5, 8, and 10 years Delirium increased the risk of: new onset dementia progression of pre-existing dementia functional decline Association of dementia with all pathologies only in demented subjects with no delirium, implying that the relation of delirium to dementia is not mediated by classical pathologies associated with dementia

Flow diagram of follow-up in the Vantaa study. Flow diagram of follow-up in the Vantaa study. Illustration enumerating dementia and mortality events in Vantaa over time. Wave A = 1991; Wave B = 1994; Wave C = 1996 and Wave D = 1999. Davis D H J et al. Brain 2012;135:2809-2816 © The Author 2012. Published by Oxford University Press.

Characteristics of patients at baseline Davis et al, Brain 2012 No history of delirium ≥ 1 episode of delirium P value n at baseline (%) 482 (87) 71 (13) Mean age (SD) 88 (2.9) 90 (3.1) 1.00 Gender (% F) 385 (80) 55 (77) 0.64 Mean comorbidity score at baseline 3 1.0 Functionally independent at baseline 321 (67) 24 (34) <0.01 Prevalent dementia 159 (33) Mean MMSE at baseline 21 15 Mean MMSE at last follow-up 13 Proportion with ≥ 4 years of education 98 (23) 10 (17) 0.31 No group differences in age, gender, or education Subjects with delirium history were more likely to have prevalent dementia and lower MMSE scores, as well as greater functional impairment

Relation of delirium to clinical outcomes Davis et al, Brain 2012 Delirium (n) No delirium (n) Odds ratios P value Incident Dementia 10 311 8.65 (2.1-35.1) <0.01 Dementia worsening 38 226 3.06 (1.4-6.3) Functional worsening 42 230 2.76 (1.4-5.5) Mortality 71 469 1.25 (1.3-2.1) Occurrence of delirium in subjects with no dementia at baseline was related to higher risk of new dementia, worsening of prior dementia, greater functional decline and increased mortality

Relation of delirium to clinical outcomes Davis et al, Brain 2012

Longitudinal trajectory of change in MMSE score over time Longitudinal trajectory of change in MMSE score over time. Predicted trajectory of MMSE change for those with or without a history of delirium at baseline. Co-efficients and P-values are shown. The estimates for the intercept and slope are given when all covariates = 0. The estimate changes with the addition of each covariate, subtracting the appropriate β co-efficient where: delirium = yes; age per year; sex = female; functional status per increase in five-point scale. The full model, along with 95% CIs for each estimate, and related graphs are given in the Supplementary material. Davis D H J et al. Brain 2012;135:2809-2816 © The Author 2012. Published by Oxford University Press.

Relationship between delirium, dementia and neuropathology/genotype Nei soggetti con demenza e senza storia di delirium (n=58), tutte le patologie classiche erano associate alla demenza. Viceversa, nei soggetti con demenza e storia didelirium , non ‘era relazione tra patologie classiche e la demenza Relationship between delirium, dementia and neuropathology/genotype. Display of logistic regression models, with 95% CIs. The y-axis is log-scaled. Models show association between dementia and pathology (or genotype), adjusted by age at death and sex. Markers were treated as dichotomous variables (high/low). For each marker, the relationship is given for the whole population, and then stratified by delirium history (n = 58 with history of delirium; n = 232 no history of delirium). SN = substantia nigra; Syn = synucleinopathy. Davis D H J et al. Brain 2012;135:2809-2816 © The Author 2012. Published by Oxford University Press.

Davis et al, Brain 2012

Inouye et al. Lancet Neurol 2015

Arrivo in Ospedale Stato confusionale Monitora le funzioni corticali superiori Cerca di sapere qual e’ abitualmente lo “status” cognitivo del paziente Indaga se ci siano stati recenti cambiamenti Previeni lo stato confusionale Analizza se ci sono fattori di rischio Previeni la disidratazione Disponi un ambiente confortevole che favorisca il riposo del paziente Evita psicostimolanti Favorisci la mobilizzazione precoce Alterazione delle funzioni cognitive Escludi: Depressione Episodio maniacale Psicosi acuta Demenze rapidamente progressive Acute Croniche Considera le demenze cronico-progressive Stato confusionale

Conferma di Stato Confusionale Identifica fattori di rischio e precipitanti Terapia di supporto e prevenzione di complicanze Protezione vie aeree Supporto nutrizionale Prevenzione trombosi venosa profonda Valutazione iniziale Sostieni parametri vitali Anamnesi dai familiari (abuso di alcool, benzodiazepine, etc.) Esame generale e neurologico Esami di laboratorio Ricerca di infezioni occulte Anamnesi “farmacologica” Farmaci prescritti Farmaci “al bisogno” Farmaci da banco Identifica possibili interazioni Identificazione di potenziali fattori causali o concausali Si No Sospendi/modifica l’uso di farmaci potenzialmente dannosi - ricorri a prodotti piu’ maneggevoli - abbassa le dosi - proponi approcci non farmacologici Trattali e o rimuovili uno per uno Altri esami di laboratorio Funzione tiroidea, B12 Screen tossicologico Emogasanalisi ECG TC encefalo EEG, Puntura Lombare

Trattamento sintomatico dello stato confusionale Tutti i pazienti I pazienti con grave agitazione Strategie non farmacologiche Riorienta il paziente Coinvolgi i familiari Evita mezzi di contenzione Incoraggia uso di occhiali, di protesi acustiche Favorisci mobilizzazione precoce Cerca di ristabilire il corretto ritmo nictemerale (no sonnellini diurni) Durante la notte, fa’ in modo che il paziente riposi in una stanza quieta e non completamente buia Strategie farmacologiche Riserva questo trattamento a pazienti con grave agitazione, o potenzialmente pericolosi per se’ o altri Utilizza le minime dosi efficaci Mantienile per 2 – 3 giorni Neurolettici di prima scelta, tranne che nello stato confusionale da astinenza alcoolica (in questo caso, benzodiazepine)