Confusion, Delirium and Dementia Samira Khazravan, M.D. Geriatric Fellow Department of Geriatrics Mary Immaculate Hospital DELIRIUM “Acute Confusional State” DELIRIUM Word delirium is derived from Latin term meaning "off the track“. Not a disease but a syndrome with multiple causes that result in a similar constellation of symptoms. The clinical hallmarks are ed attention span & a waxing & waning type of confusion. A transient, usually reversible, impairment of consciousness with a ed ability to focus, sustain or shift attention. Should be treated as a medical emergency (early diagnosis & resolution of symptoms are correlated with the most favorable outcomes). CRITERIA FOR DIAGNOSING DELIRIUM A ∆ in cognition or development of a perceptual disturbance that is not better accounted for by a preexisting, established or evolving Dementia. Develops over a short period of time & tends to fluctuate during the course of the day. There is evidence that the disturbance is caused by a medical condition, intoxication or med use. There is no clear evidence of any underlying pathologic process. EPIDEMIOLOGY 14-56% of hospitalized elderly patients. Delirium is present in 10-22% of elderly patients at the time of admission, with an additional 10-30% of cases developing after admission. found in 40% of patients admitted to ICU. Extremely common among nursing home residents. Can occur at any age. MC in pts who are elderly & have compromised mental status. ed risk in pts w/dementia (2/3 of cases of delirium occur in pts w/dementia). Delirium due to physical illness is MC among very young & those older than 60 years. Delirium due to drug & alcohol intoxication or withdrawal is most frequent in persons aged mid teens to the late 30s. RISK FACTORS Advanced age Dementia Functional impairment in ADLs Medical co morbidity History of alcohol abuse ♀ > or < ♂ MC whites than in other races Sensory impairment – decreased vision & hearing Acute cardiac/pulmonary events HIV/AIDS MORBIDITY/MORTALITY 10-fold risk of death. 3-5-fold increase risk of nosocomial complications. Poor functional recovery & ed risk of death up to 2 years Some causes of delirium (Delirium Tremens, Severe Hypoglycemia, CNS infx, Heat stroke, Thyroid storm) may be fatal or result in severe morbidity if unrecognized & untreated. With some exceptions, such as OD of TCAs, drug intoxications generally resolve fully with supportive care. PATHOPHYSIOLOGY Exact pathophysiological mechanisms unclear. The main hypothesis is reversible impairment of cerebral oxidative metabolism & multiple NT abnormalities (Acetylcholine, Dopamine, Serotonin, GABA) Postulated mechanisms: – Interruption of BBB – Inflammatory mechanism [cytokines (interleukin-1 & 6) are ed following infx, inflammation, toxic insults, head trauma & ischemia] – Stress rxn mechanism [psychosocial stress and sleep deprivation facilitate the onset of delirium]. ETIOLOGY Intracranial causes Neurodegenerative – Dementia w/Lewy bodies [only dementia that features transient episodes of impaired consciousness as a typical feature]. -No other dementias feature impairment of consciousness unless complicated by a delirium (i.e. 2° to infx, anoxia, etc). ETIOLOGY Intracranial causes Space-occupying lesions – Tumor – Cyst – Abscess – Hematoma Head injury (esp. Concussion) ETIOLOGY INTOXICATION – Alcohol (Delirium tremens, Wernicke-Korsakoff encephalopathy). – Sedative-Hypnotic use/abuse. Poisons Heavy metals (Lead, Mercury, Manganese) Carbon monoxide ETIOLOGY Drugs (ingestion or withdrawal) – Amphotericin B – Anticholinergics – Anticonvulsants – Antidepressants – Antihistamines – Antihypertensive drugs [– – – – blockers] Antiparkinsonian drugs Antipsychotics Cannabis H2 Blocker (Cimetidine) – – – – – – – – – – Dopaminergic agents Disulfiram Digoxin Insulin Lithium Opiates Phenytoin Salicylates Steroids Sedatives (barbiturates & benzodiazepines) – TCAs ETIOLOGY Intracranial causes Infx – Meningitis & Encephalitis (Bacterial, Viral, Fungal, Parasitic or Tuberculosis organisms) – Neurosyphilis – Sepsis Epilepsy Cerebrovascular disorders – TIA – Cerebral thrombosis or Embolism – Intracranial or SAH – HTNive Encephalopathy Vasculitis (e.g. From SLE) ETIOLOGY Metabolic & endocrine – Electrolyte – – – – – – disturbances (Na+, Mg2+, Ca2+) Acid-Base D/o Renal Failure & Uremia Hepatic encephalopathy Hypoglycemia (DM) DKA Insulinoma – Thyrotoxicosis – & thyroidism – & – – – – parathyroidism & adrenocorticism (Cushing’s syndrome, Addison’s disease) Pheochromocytoma Hypopituitarism Wilson’s disease ETIOLOGY Nutritional Deficiencies – Thiamine (Wernicke’s encephalopathy) – Vitamin B12 (Pernicious Anemia) – Vitamin B1 (Beriberi) – Folic acid – Niacin Anoxia – Respiratory failure (Hypoxia/Hypercarbia) – Heart failure MI, A. Fib ETIOLOGY Neoplasms (1 or metastatic lesions of CNS; CA induced HyperCa2+) Degenerative disease – Alzheimer’s, Pick’s Dz, Multiple Sclerosis, Parkinsonism, Huntington’s chorea, Normal Pressure Hydrocephalus) ETIOLOGY Major causes of delirium – HIDE – Hypoxia – Infections – Drugs – Electrolyte disturbances SIGNS & SYMPTOMS Usually acute onset Fluctuating levels of consciousness (impairment usually least in AM) Perceptual disturbances (hallucinations or illusions) Impaired consciousness: – Reduced awareness of environment clouding of consciousness coma – Reduced ability to sustain attention (easily distracted) SIGNS & SYMPTOMS Impaired cognitive function – Impaired STM (1° memory) & recent memory. – Disoriented to time & often place [orientation to self seldom lost]. – Language abnormalities [rambling, incoherent speech & impaired ability to understand] common. SIGNS & SYMPTOMS Perceptual & thought disturbance – Ranging from misinterpretations (e.g. A door slamming is mistaken for an explosion) illusions (e.g. A crack in the wall is perceived as a snake) hallucinations (especially visual) Psychomotor abnormalities – Patients may be hyper or hypoactive or fluctuate from one to the other – May also have an enhanced startle reaction SIGNS & SYMPTOMS Sleep-wake cycle disturbance – Daytime drowsiness night-time hyperactivity complete reversal of normal cycle – Nightmares of delirious patients may continue as hallucinations after awakening Mood disturbance (Emotional Liability) – Depression, euphoria, anxiety, anger, fear & apathy – Lack of initiative, impaired impulse control, inability to reason thru problems, confabulation A physical illness should always be ruled out whenever a patient presents with prominent visual hallucinations because patients with schizophrenia & other functional psychotic disorders usually experience auditory hallucinations. DIFFERENTIAL DIAGNOSIS Dementia Primary psychiatric illnesses – Depression, Mania, Schizophrenia. Sundowning (mild to mod delirium @ night—MC in pts w/preexisting dementia & may be precipitated by hospitalization, drugs & sensory deprivation)disturbance in circadian rhythm. Focal syndromes – Wernicke’s aphasia, Anton’s syndrome & Bi-frontal lesions. Non-convulsive status. DIFFERENTIAL DIAGNOSIS Delirium often is unrecognized or misdiagnosed & commonly is mistaken for dementia, depression, mania, an acute schizophrenic reaction or part of old age (patients who are elderly are expected to become confused in the hospital). FEATURE DELIRIUM ONSET Acute DURATION Hours – weeks Fluctuating COURSE CONSCIOUSNESS PERCEPTUAL DISTURBANCE SLEEP-WAKE CYCLE Impaired Common Disrupted PROGNOSIS Potentially reversible PRIMARILY AFFECTS Attention MEDICAL EMERGENCY? Yes DEMENTIA Gradual Months – years Progressive deterioration Normal Occurs in late stages Usually normal Not reversible Memory No DIAGNOSIS Under-recognition is a major problem – nurses recognize & document <50%; DSM-IV criteria is precise but difficult to apply. History & Physical – focus on time course of cognitive changes, especially their association w/other symptoms or events; Note recently started meds, overdose, alcohol use, previous history, concurrent medical problems, signs of organ failure & infx (occult UTI is common in elderly), general medical evaluation, neurologic & mental status examination. Remember: Delirium is not a final diagnosis: this syndrome indicates the presence of a very serious medical condition that should be managed on medical not psychiatric, ward. DIAGNOSIS Any pt who presents w/AMS needs a complete PE, w/particular attn to: – General appearance (unkempt, tattooed &/or malnourished) may suggest the possibility of drug or alcohol abuse) – Vital signs – Hydration status – Evidence of physical trauma – Evidence of neurological signs The delirious or obtunded patient should be evaluated for Pupillary, Fundoscopic & extraocular abnormalities; nuchal rigidity; thyroid enlargement & heart murmurs or rhythm disturbances. DIAGNOSIS Other clues to etiology on PE: – A pulmonary exam wheezing, rales or absent breath sounds – An abdominal exam Hepato/Splenomegaly – A cutaneous exam rashes, icterus, petechiae, ecchymosis, track marks or Cellulitis (often hidden under clothing, particularly pants & socks; checking these areas in pts with diabetes is critical; any serious infx can lead to mental status ∆s) CLUES TO DIAGNOSIS Smell for alcohol Musty odor of Fetor Hepaticus Fruity smell of DKA Icterus &/or asterixis liver failure w/ serum ammonia Agitation & tremulousness sedative or A/C withdrawal Fever infx, heat illness, thyroid storm, ASA toxicity or extreme adrenergic overflow of certain drug overdoses & withdrawal syndromes (Esp. delirium tremens) Extreme hyperthermia (w/pinpoint pupils) pontine strokes BP = common in delirium b/c of resulting adrenergic overload Hemotympanum, battle sign, raccoon eyes or otorhinorrhea basilar skull fracture (2° to occult head trauma) DIAGNOSIS A rapid RR DKA (Kussmaul respiration), sepsis, stimulant drug intoxication & ASA OD A slow RR narcotic OD, CNS insult or various sedative intoxications A rapid PR fever, sepsis, dehydration, thyroid storm & cardiac dysrhythmias & stimulants, anticholinergics, quinidine, theophylline, TCAs or ASA OD A slow PR ICP, asphyxia, complete heart block, CCBs, Digoxin & beta-blockers Pupillary dilation intoxication w/ hallucinogen, amphetamine, cocaine or anticholinergic med Pupillary constriction narcotic intoxication Pupillary inequality late sign of uncal herniation A funduscopic examination: – Loss of venous pulsations early ICP elevation – Papilledema severe ICP DIAGNOSIS -- Special cases: In pts w/delirium & severely BP, check ocular fundi for arteriolar spasm, disc pallor, papilledema, flame hemorrhages & exudates ( Malignant HTN). In pregnant pts w/diastolic pressure >75 mm hg in 2nd trimester or >85 mm hg in 3rd trimester Pre-eclampsia (Hyperreflexia, Edema, Proteinuria). In pts w/HTN & Bradycardia ICP With Delirium & Hypotension dehydration, diabetic coma, hemorrhage due to trauma, aneurysmal rupture, GI bleeding, adrenergic depletion (2° to cocaine, amphetamine or TCA OD) & Addisonian crisis (particularly in steroid dependent pts). DIAGNOSIS A brief bedside neurologic exam, to include mental status testing, is essential for workup of delirium when a rapidly treatable cause (hypoglycemia or narcotic OD) is not immediately apparent The mini-mental status examination (MMSE) (a formalized way of documenting severity & nature of mental status ∆s) In addition, or as an alternative to the MMSE, correctly drawing the face of a clock (to include the circle, numbers & hands) is a sensitive test of cognitive function Other simple screening tests include "serial 7's," LABORATORY/RADIOLOGICAL CBC, electrolytes, BG levels, BUN/Cr Also helpful – UA, LFTS (serum ammonia & PT), toxicology screen, ABG, CXR, O2 Sat & cultures Consider: Vitamin B-12 & Folate levels, VDRL test (r/o Neurosyphilis) & thyroid function studies Head CT scan [done b/f LP to r/o CNS infx, trauma, CVA, SAH, hematomas, toxoplasmosis or abscess (especially in pts w/HIV who present w/H/A)] LP (CSF studies including India ink prep & VDRL) Plain abdominal x-ray swallowed bags of drugs ("body packing") or radiodense substances (iron tablets) EKG (MI or a. fib; low voltages Hypothyroidism & pericardial effusion; Tachycardia, widened QRS or prolonged QT interval TCA overdose) MANAGEMENT ABC’s + Normalize fluid & electrolyte status Provide Thiamine when administering glucose [or else may lead to acute Wernicke syndrome (ataxia, confusion, oculomotor palsies in the setting of malnutrition)] Physical or pharmacologic restraints (may be necessary to prevent pts from harming self or others) Low dose Haloperidol (Typical Antipsychotic doc for severe agitation, acute psychosis & severe delirium when no CIs exist) [sedative qualities + effect on DA-Ach balance; Assess for akathisia & EPS; Avoid in elderly w/parkinsonism; in ICU, monitor for QT prolongation, torsades, neuroleptic malignant syndrome & withdrawal dyskinesias; antidote: Dantrolene] Avoid sedative meds if possible [use Benzodiazepines Lorazepam (Ativan) -- doc in ED (if unable to control a dangerous patient; may obscure the MMSE)] Treat underlying cause Multi-factorial approach is most successful MANAGEMENT Highly distressing for pts & anxiety provoking for medical ward staff. Hospitalization is essential. To limit confusion, foster trust & provide reassurance, try to ensure that pt is nursed by same staff consistently. Maximize visual acuity (e.g. Glasses, appropriately lit environment) & hearing ability (e.g. Hearing aid, quiet environment) to avoid misinterpretation of stimuli. Involve friend or family member to remain w/pt to help comfort & orientate them. Avoid complications of delirium – remove indwelling devices ASAP, prevent or treat constipation, urinary retention & encourage proper sleep hygiene. COURSE & PROGNOSIS Average duration of delirium is 7 days Inpatients who develop delirium have an ed mortality, with elderly pts having up to a 75% chance of dying during that admission Delirium is fully reversible in most cases with proper recognition & treatment of the etiology Failure to dx & manage delirium is costly, lifethreatening & can lead to loss of function DEMENTIA WHAT IS DEMENTIA? An acquired syndrome of decline in memory and other cognitive functions sufficient to affect daily life in an alert patient Progressive and disabling NOT an inherent aspect of aging Different from normal cognitive lapses Dementia DSM IV criteria: Development of cognitive deficits manifested by both -impaired memory -aphasia, apraxia, agnosia and disturbed executive function Significantly impaired social and occupational function Gradual onset and continuing decline Not due to CNS and other physical or psychiatric conditions Prevalence 10% percent of persons over age 70 20 to 40% of individuals over age 85 Affects more than 4 million Americans Costs more than $50 billion annually Causes of Dementia & the differential diagnosis: Alzheimer’s disease Vascular (multi-infarct) dementia Dementia associated with Lewy bodies Delirium Depression OTHER: ETOH, exposure to heavy metals (arsenic, antimony, bismuth) Parkinson’s disease, Pick’s disease, frontal lobe dementia Infectious diseases: These infections may be caused by viruses (HIV, viral encephalitis); spirochetes (Lyme disease, neurosyphilis); or prions (Creutzfeldt-Jacob disease) Abnormal brain structure: Hydrocephalus, subdural hematoma Most common REVERSIBLE causes Hypothyroidism Vitamin B-12 Folate deficiency Dementia of depression Drugs Alcoholism Assessment History Onset and Duration of the memory loss A) Elderly person with slowly progressive memory loss over several years AD B) Change in personality with disinhibition and intact memory may suggest FTD C) History of sudden stroke with an irregular stepwise progression suggests Multi-infarct dementia D) Rapid progression with rigidity and myoclonus suggests CJD Assessment (cont.) E) Gait disturbances+memory problems+resting tremors may suggest PD F) Multiple sex partners or intravenous drug use may indicate CNS infection G) Hx of Recurrent head trauma suggests Subdural Hematoma H) Alcoholism Thiamine deficiency I) Gait disturbances,urinary incontinence and memory problems suggest NPH Assessment (cont.) Physical Examination • Cogwheel rigidity, bradykinesiaPD • Inability to initiate and coordinate stepsNPH • Myoclonic jerks are present in CJD • Hemiparesis or other focal neurologic deficits MID • Dry cool skin,hair loss,bradycardia Hypothyroidism Cognitive assessment MMSE – most widely used screening exam – used in assessment and follow up – score interpretation depends on patients age and education level Clock drawing – test of visuospatial skills – draw numbers within a pre-drawn circle 3 inches in diameter to make that circle look like the face of a clock – Normal score 0-3 – Dementia 4-7 MMSE Orientation Name: hospital/floor/town/state/country 5 (1 for each name) Registration Identify three objects by name and ask patient to repeat3 (1 for each object) Attention and calculation Serial 7s; subtract from 100 (e.g., 93-86-79-72-65) 5 (1 for each subtraction) Recall Recall the three objects presented earlier 3 (1 for each object) Language Name pencil and watch 2 (1 for each object) Repeat "No ifs, ands, or buts“ 1 Follow a 3-step command (e.g., "Take this paper,, fold it in half and place it on the table") 3 (1 for each command) Write "close your eyes" and ask patient to obey written command 1 Ask patient to write a sentence 1 Ask patient to copy a design (e.g., intersecting pentagons) 1 TOTAL 30 Clock drawing Cortical dementias Alzheimer’s Vascular Diffuse Lewy body Pick’s disease Creutzfeldt-Jacob disease Alzheimer’s Slowly progressive dementing illness associated with diffuse cortical atrophy, amyloid plaques and neurofibrillary tangles CLINICAL MANIFESTATIONS • Progressive memory impairment (predominantly short term) • Language impairment • Complex deficits in visual and spatial abilities • Acalculia • Personality changes - progressive passivity to marked hostility • Increased stubbornness & suspiciousness • Delusions • Hallucinations • Symptoms of depression and anxiety Alzheimer’s (cont.) PLAQUES Brain slice: left from Alzheimer's Disease, right from normal brain TANGLES CT SCAN Alzheimer’s (cont.) A. MRI BRAIN NORMAL 86-year-old male. B. MRI BRAIN 77-year-old male with Alzheimer's disease. c. Fluorodeoxyglucose PET scans of a normal control. D. A patient with Alzheimer's disease. Note that the patient has decreased activity in the parietal lobes bilaterally (arrows) Alzheimer’s (cont.) Management – KISS (keep it simple and short) – Maintain autonomy and independence – Establish routines – Safety issues: cooking, driving, community services referral, discuss legal issues, caregiver education – Medications: donepezil, tacrine Donepezil (ARICEPT) Reversible cholinesterase (ChE) inhibitor In Alzheimer's disease behavioral consequences (e.g., decline in memory and learning) that are partially related to cholinergic deficits Used for the symptomatic management of mild to moderate forms of Alzheimer's disease DOSAGE 5 to 10mg qd CONTRAINDICATIONS Liver disease, alcoholism, peptic ulcer disease, chronic obstructive pulmonary disease; and bradycardia ADVERSE EFFECTS N/V Diarrhea, Bradycardia Dizziness Memantine (Namenda) Non-competitive antagonist at N-methylD- aspartate receptors (NMDA) Indicated for moderate to severe Alzheimer’s disease. Dose: 5 or 10 mg PO QD Seizure disorder and renal disease are contraindications. HTN and Urinary Incontinence are the adverse effects Multi-infarct dementia Results from an accumulation of discrete cerebral strokes that produce disabling deficits of memory, behavior, and other cognitive abilities CLINICAL MANIFESTATIONS Stepwise deterioration Focal neurologic deficits Brain imaging shows multiple areas of stroke Lewy Body Dementia -Lewy bodies are intraneuronal inclusions that stain with periodic acid-Schiff stain. -In addition to chronic progressive dementia, these patients often also have parkinsonian features. -Frequent fluctuations of behavior, cognitive ability,and level of alertness may occur. -No specific treatment -No response to L- DOPA Lewy Body (cont.) Frontotemporal Dementia Presents as disinhibition, apathy, or agitation. Focal lobar atrophy of the frontal and/or temporal lobes seen on MRI. Pick's disease Subcategory of FTD. Microscopic findings include gliosis, neuronal loss, and swollen or ballooned neurons, with Pick bodies. Slowly progressive dementia ,bulimia, language disturbance, emotional disinhibition, irritability, and persistent aimless wandering,language disturbance. Huntington’s disease -Autosomal dominant degenerative brain disorder. -Chorea and behavioral disturbance. -Attention, judgment, awareness, may be seriously deficient at an early stage. -No specific treatment. -Adventitious movements and behavioral changes may partially respond to phenothiazines. Huntington’s (cont.) Creutzfeldt-Jacob disease Atypical infectious agents called “prions” cause the disease. It’s a transmissible neurodegenerative disorder. Manifests in the sixth and seventh decade of life as rapidly progressive dementia with myoclonus. Minimal help with neuroimaging, EEG and CSF analysis. CSF protein 14-3-3, may be diagnostic but the gold standard is………? CJD cont…. Brain biopsy for premortem diagnosis. Universal precautions are recommended for routine patient care as the “prions” are very resistant for routine disinfection methods. The only known disease that can transmit through corneal transplant and growth hormone administration. The disease in animals is called “bovine spongiform encephalopathy”. No effective treatment. HIV dementia Dementia in HIV occurs when the pt develops AIDS(AIDS dementia complex). -This is a diagnosis of exclusion based on neuroimaging and spinal fluid analysis. -Neuropsychiatric testing is helpful in distinguishing from depression. Clinical features… Pts have difficulty with cognitive tasks and have diminished motor speed. Dementia manifestations may wax and wane with periods of lucidity and confusion over the course of a day. First clinical symptom may be deterioration in hand writing. Many pts will improve with effective antiretroviral therapy. Other types of dementia Korsakoff’s syndrome Wernicke’s encephalopathy Parkinson’s disease Chronic metal intoxications Korsakoff’s syndrome Caused by prolonged untreated thiamine deficiency • Memory for new events is seriously impaired, whereas memory of knowledge prior to the illness is relatively intact • Confabulation -MRI Mammillary body atrophy -No specific treatment Wernicke’s encephalopathy -Thiamine (vitamin B1)deficiency damages the thalamus, mammillary bodies. SYMPTOMS Confusion Ataxia Diplopia -Administration of parenteral thiamine may reverse the disease. Parkinson’s disease Develops due to loss of dopaminergic neurons in substantia nigra. Approximately 20% of patients develop dementia. CLINICAL MANIFESTATIONS • Resting tremors • Rigidity • Bradykinesia • Gait disturbances Treatment with L-dopa neither accelerates nor prevents this process. Chronic metal intoxications Lead poisoning Mercury poisoning Arsenic intoxication Dialysis dementia syndrome Dementia is part of normal processing of age… True? False? Dementia impairs physical functioning of the individual… True? False? Delirious patient may have auditory hallucinations… True? False? A person with dementia may develop delirium… True? False? A person with delirium will develop dementia… True? False? A 70 YO man comes and tells you that he has been forgetting certain things and has difficulty of recollecting some names. He is having dementia….? True ? False ? THANK YOU