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Saint Louis UniversitySchool of Nursing Fernandez, Gain Carlo I. BSN3-a2 Submitted to: Mr. Marc Ernest Biala, RN

[COGNITIVE DISORDERS]

COGNITIVE DISORDERS 1. Delirium a. Definition st a.1 According to Ramos, L. Biala M. , et. al.sPsychiatric Nursing (1 edition)  is a set of symptoms that involves a disruption of awareness acoompanied by alteration in cognition.  Common among hospitalized older adults a.2 According to Kozier and Erbs Fundamentals of Nursing (8th ed. Vol. 2)  Is often called Acute Confusion  Has an abrupt onset and a cause which when treated, reverses the confusion a.3 According to Ignatavicius, D. and Bayne , M.s Medical- Surgical Nursing (1st ed.)  Delirium has multiple causes including medication, metabolic disturbances, infections, circulatory and pulmonary disorders and nutritional deficiencies. a.4 According to Wikipedia.org  is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attention deficits and generalized severe disorganization of behavior. It typically involves other cognitive deficits, changes in arousal (hyperactive, hypoactive, or mixed), perceptual deficits, altered sleepwake cycle, and psychotic features such as hallucinations and delusions. b. DSM-IV-TR classification of delirium y y y y y Delirium due to general medical condition Substance intoxication delirium Substance withdrawal delirium Delirium due to multiple etiologies Delirium not otherwise specified

b.1 DSM-IV-TR diagnostic criteria for delirium y y Disturbance of consciousness (ie, reduced clarity of awareness of the environment) occurs, with reduced ability to focus, sustain, or shift attention. Change in cognition (eg, memory deficit, disorientation, language disturbance, perceptual disturbance) occurs that is not better accounted for by a preexisting, established, or evolving dementia. The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day. Evidence from the history, physical examination, or laboratory findings is present that indicates the disturbance is caused by a direct physiologic consequence of a general medical condition, an intoxicating substance, medication use, or more than one cause.

y y

c. Causes c.1 Biophysical y Based on the state of arousal, 3 types of delirium are described. Hyperactive delirium is observed in patients in a state of alcohol withdrawal or intoxication with phencyclidine (PCP), amphetamine, and lysergic acid diethylamide (LSD). Hypoactive delirium is observed in patients in states of hepatic encephalopathy and hypercapnia. In mixed delirium, individuals display daytime sedation with nocturnal agitation and behavioral problems.

The mechanism of delirium still is not fully understood. Delirium results from a wide variety of structural or physiological insults. The neuropathogenesis of delirium has been studied in patients with hepatic encephalopathy and alcohol withdrawal. Research in these areas still is limited. The main hypothesis is reversible impairment of cerebral oxidative metabolism and multiple neurotransmitter abnormalities. The following observations support the hypothesis of multiple neurotransmitter abnormalities. Acetylcholine

Data from animal and clinical studies support the hypothesis that acetylcholine is one of the critical neurotransmitters in the pathogenesis of delirium. Clinically, good reasons support this hypothesis. Anticholinergic medications are a well-known cause of acute confusional states, and patients with impaired cholinergic transmission, such those with Alzheimer disease, are particularly susceptible. In patients with postoperative delirium, serum anticholinergic activity is increased. y Dopamine In the brain, a reciprocal relationship exists between cholinergic and dopaminergic activities. In delirium, an excess of dopaminergic activity occurs. Symptomatic relief occurs with antipsychotic medications such as haloperidol and other neuroleptic dopamine blockers. y Other neurotransmitters Serotonin: Human and animal studies have found that serotonin is increased in patients with hepatic encephalopathy and septic delirium. Hallucinogens such as LSD act as agonists at the site of serotonin receptors. Serotoninergic agents also can cause delirium. Gamma-aminobutyric acid (GABA): In patients with hepatic encephalopathy, increased inhibitory GABA levels also are observed. An increase in ammonia levels occurs in patients with hepatic encephalopathy, which causes an increase in the amino acids glutamate and glutamine, which are precursors to GABA. Decreases in CNS GABA levels are observed in patients with delirium resulting from benzodiazepine and alcohol withdrawal. Cortisol and beta-endorphins: Delirium has been associated with the disruption of cortisol and beta-endorphin circadian rhythms. This mechanism has been suggested as a possible explanation for delirium caused by exogenous glucocorticoids. Disturbed melatonin disturbance has been associated with sleep disturbances in delirium. y Inflammatory mechanism Recent studies have suggested a role for cytokines, such as interleukin-1 and interleukin-6, in the pathogenesis of delirium. Following a wide range of infectious, inflammatory, and toxic insults, endogenous pyrogen, such as interleukin-1, is released from the cells. Head trauma and ischemia, which frequently are associated with delirium, are characterized by brain responses that are mediated by interleukin-1 and interleukin-6. y Structural mechanism The specific neuronal pathways that cause delirium are unknown. Imaging studies of metabolic (eg, hepatic encephalopathy) and structural (eg, traumatic brain injury, stroke) factors support the hypothesis that certain anatomical pathways may play a more important role than others. The reticular formation and its connections are the main sites of arousal and attention. The dorsal tegmental pathway projecting from the

mesencephalic reticular formation to the tectum and the thalamus is involved in delirium. Disrupted blood-brain barrier can allow neurotoxic agents and inflammatory cytokines to enter the brain and may cause delirium. Contrast-enhanced MRI can be used to assess the blood-brain barrier. Visuoperceptual deficits in delirium such as hallucinations and delusions are not due to the underlying cognitive impairment. Visual hallucinations during alcoholwithdrawal delirium are seen in subjects with polymorphisms of genes coding for dopamine transporter and catechol-O-methyltransferase (COMT). c.2 Intrapsychic y Stress reaction mechanism Studies indicate psychosocial stress and sleep deprivation facilitate the onset of delirium. d. Signs and Symptoms y The symptoms of delirium come on quickly, in hours or days, in contrast to those of dementia, which develop much more slowly. Delirium symptoms typically fluctuate through the day, with periods of relative calm and lucidity alternating with periods of florid delirium. The hallmark of delirium is a fluctuating level of consciousness. y A delirious person may have a clouding of awareness and consciousness. This impairment of consciousness typically fluctates, so the person may be aroused and alert for short periods of time before again relapsing into a clouded state. Fluctation may follow a pattern of diurnal variation, where consciousness levels change as the day progresses. Typically, a delirious person may be more consciousness impaired in the evening and at night. y Confusion may occur in delirium, where the sufferer loses the capacity for clear and coherent thought. It may be apparent in disorganized or incoherent speech, the inability to concentrate or a lack of goal directed thinking. Disorientation describes the loss of awareness of the surroundings, environment and context in which the person exists. Disorientation may occur in time (not knowing what time of day, day of week, month, season or year it is), place (not know where you are) or person (not knowing who are). y Hallucinations (perceived sensory experience with the lack of an external source) or distortions of reality may occur in delirium. Commonly these are visual distortions, and can take the form of masses of small crawling creatures (particularly common in delirium tremens, caused by severe alcohol withdrawal) or distortions in size or intensity of the surrounding environment. Strange beliefs may also be held during a delirious state, but these are not considered delusions in the clinical sense as they are considered too short lived. Interestingly, in some cases sufferers may be left with false or delusional memories after delirium, basing their memories on the confused thinking or sensory distortion which occurred. Abnormalities of affect include any distortions to perceived or communicated emotional states. Emotional states may also fluctate, so a person may rapidly change between, for example, terror, sadness and jocularity. y Memory deficits, especially where recent events are concerned (e.g., the reason for hospitalization or for care being given by nursing staff), are also prominent in patients with delirium. Patients may report not being bathed or bedding not being changed when, in fact, these events occurred earlier in the day. Patients with delirium may become agitated as a result of the disorientation and confusion they are experiencing. For example, a patient who is disoriented may think he or she is at home instead of in a hospital, and nursing staff may be mistaken for intruders in the

home. Consequently, this patient may not comply with bed or activity restrictions and may try to climb over the bedrails to get out of bed. Likewise, intravenous (IV) and oxygen tubing may not be recognized as such, and the patient may remove them. Sleep disturbances are common in patients with delirium. They may periodically fall asleep during the day and then be awake for several hours during the night. This pattern, combined with confusion, disorientation, and decreased nighttime environmental cues, can create an especially hazardous situation in patients who are at risk for falling and pulling out an IV, Foley catheter, or nasogastric tubing. Several neurologic signs and symptoms may be present in delirium regardless of cause. They include unsteady gait; tremor; asterixis; myoclonus, paratonia (e.g., gegenhalten) of the limbs and especially of the neck; difficulty reading and writing; and visuoconstruction problems, such as copying designs and finding words.

e. Pharmacotherapy y Neuroleptics,is the medication of choice in the treatment of psychotic symptoms.  Older neuroleptics such as haloperidol, a high-potency antipsychotic, are useful but have many adverse neurological effects.  Newer neuroleptics such as risperidone, olanzapine, and quetiapine relieve symptoms while minimizing adverse effects. Initial doses may need to be higher than maintenance doses. Use lower doses in patients who are elderly. y Discontinue these medications as soon as possible. Attempt a trial of tapering the medication once symptoms are in control. Neuroleptics can be associated with adverse neurological effects such as extrapyramidal symptoms, neuroleptic malignant syndrome, and tardive dyskinesia. Doses should be kept as low as possible to minimize adverse effects. Paradoxical and hypersensitivity reactions may occur. y Short-acting sedatives - reserved for delirium resulting from seizures or withdrawal from alcohol or sedative hypnotics. Co administration with neuroleptics is considered only in patients who tolerate lower doses of either medication or have prominent anxiety or agitation.  Benzodiazepines are preferred over neuroleptics for treatment of delirium resulting from alcohol or sedative hypnotic withdrawal. They also may be used when unknown substances may have been ingested and may be helpful in delirium from hallucinogen, cocaine, stimulant, or PCP toxicity. y Use special precaution when using benzodiazepines because they may cause respiratory depression, especially in patients who are elderly, those with pulmonary problems, or debilitated patients. Vitamins - Patients with alcoholism and patients with malnutrition are prone to thiamine and vitamin B-12 deficiency, which can cause delirium.  Vitamin B-12 deficiency can cause confusion or delirium in patients who are elderly. Deoxyadenosylcobalamin and hydroxocobalamin are active forms of vitamin B-12 in humans. Vitamin B-12 is synthesized by microbes but not by humans or plants. Vitamin B-12 deficiency may result from intrinsic factor deficiency (pernicious anemia), partial or total gastrectomy, or diseases of the distal ileum.  Thiamine is for alcohol withdrawal and in cases of Wernicke encephalopathy

f.

Psychotherapy y Treatment of delirium begins with recognizing and treating the underlying cause. Delirium itself is managed by reducing disturbing stimuli, or providing soothing ones; use of simple, clear language in communication; and reassurance, especially from family members. Physical restraints may be needed if the patient is a danger to himself or others, or if he insists on removing necessary medical equipment such as intravenous lines or monitors. Sedatives or antipsychotic drugs may be used to reduce anxiety, hallucinations, and delusions. y The standard approach to managing delirium is to find and treat the causes. Symptoms may be treated at the same time. Identifying the causes of delirium will include a physical examination to check general signs of health, including checking for signs of disease. A medical history of the patient's past illnesses and treatments will also be taken. In a terminally ill, delirious patient being cared for at home, the doctor may do a limited assessment to

2. Dementia a. Definition a.1 According to Ramos, L. Biala M. , et. al.sPsychiatric Nursing (1st edition)  is a loss of mental ability severe enough to interfere with normal activities of daily living, lasting more than six months.  A syndrome caused by the gradual death of the brain cells. a.2 According to Kozier and Erbs Fundamentals of Nursing (8th ed. Vol. 2)  is often called Chronic Confusion with symptoms that are gradual and irreversible. (e.g. Alzheomers Disease) a.3 According to Ignatavicius, D. and Bayne , M.s Medical- Surgical Nursing (1st ed.)  a disorder that is characterized by a disturbance in cognition occurring in Elders.  It represents global impairment of intellectual function. a.4 According to Wikipedia.org  taken from Latin, originally meaning "madness", from de- "without" + ment, the root of mens "mind" is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging. It may be static, the result of a unique global brain injury, or progressive, resulting in long-term decline due to damage or disease in the body. Although dementia is far more common in the geriatric population, it may occur in any stage of adulthood. b. DSM-IV-TR Definition of dementia  define dementia as an overall decline in intellectual function, including difficulties with language, simple calculations, planning and judgment, and motor (muscular movement) skills as well as loss of memory c. Causes c.1 Biophysical y Dementia can be caused by nearly forty different diseases and conditions, ranging from dietary deficiencies and metabolic disorders to head injuries and inherited diseases. The possible causes of dementia can be categorized as follows: y Primary dementia. These dementias are characterized by damage to or wasting away of the brain tissue itself. They include Alzheimer's disease (AD), frontal lobe dementia (FLD), and Pick's disease. FLD is dementia caused by a disorder (usually genetic) that affects the front portion of the brain, and Pick's disease is a rare type of

primary dementia that is characterized by a progressive loss of social skills, language, and memory, leading to personality changes and sometimes loss of moral judgment. y Multi-infarct dementia (MID). Sometimes called vascular dementia , this type is caused by blood clots in the small blood vessels of the brain. When the clots cut off the blood supply to the brain tissue, the brain cells are damaged and may die. (An infarct is an area of dead tissue caused by obstruction of the circulation.) Lewy body dementia. Lewy bodies are areas of injury found on damaged nerve cells in certain parts of the brain. They are associated with Alzheimer's and Parkinson's disease, but researchers do not yet know whether dementia with Lewy bodies is a distinct type of dementia or a variation of Alzheimer's or Parkinson's disease. Dementia related to alcoholism or exposure to heavy metals (arsenic, antimony, bismuth). Dementia related to infectious diseases. These infections may be caused by viruses (HIV, viral encephalitis); spirochetes (Lyme disease, syphilis); or prions (CreutzfeldtJakob disease). Spirochetes are certain kinds of bacteria, and prions are protein particles that lack nucleic acid. Dementia related to abnormalities in the structure of the brain. These may include a buildup of spinal fluid in the brain (hydrocephalus); tumors; or blood collecting beneath the membrane that covers the brain (subdural hematoma). Low levels of thyroid hormone, or niacin or vitamin B 12 deficiency is also associated with Dementia

y y

c.2 Intrapsychic y Dementia may also be associated with depression d. Signs and Symptoms
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The first signs of dementia are short-term memory loss. Symptoms of dementia are dependent upon the areas of brain that are affected and the key symptoms are include: y Loss of Memory: Forgetting some recent incidents and inability to recall information. y Disorientation: People forget their familiar surroundings, neighborhood, wondering how they got there and do not know how to get back home. y Communicating: People suffering from dementia forget simple words and substitute some irrelevant words in their speech, thus making it difficult to understand for the listener. y Abstract thinking: People suffering from dementia have trouble carrying out simple calculations such as adding numbers, multiplying, dividing, subtracting and sometimes even forget the purpose of numbers and calculation. y Poor or reduced judgment: People suffering with dementia have poor judgment and do not know how to react in emergencies. y Performance of familiar tasks: People face difficulty in performing daily activities such as preparing a meal or coffee, operating an oven, making a telephone call, playing a game, etc. y Mood or behavioral changes: People suffering from dementia exhibit rapid changes in moods such as a happy/joyous mood to tears or anger for no apparent reason. Dementia patients can also experience depression. y Misplacing articles: People with dementia tend to misplace articles in unusual places, such as placing a wristwatch in a sugar bowl or a plastic container on a gas stove. y Loss of initiative: People suffering from Alzheimers disease become passive. For example watching TV for longer duration, sleeping for longer hours and not performing normal activities.

Change in personality: Dramatic changes in personality of people suffering from dementia are also observed.

e. Pharmacotherapy Treatment of dementia begins with treatment of the underlying disease, where possible. The underlying causes of nutritional, hormonal, tumor-caused and drugrelated dementias may be reversible to some extent. Treatment for stroke-related dementia begins by minimizing the risk of further strokes, through smoking cessation, aspirin therapy, and treatment of hypertension, for instance. There are no therapies which can reverse the progression of Alzheimer's disease. Aspirin, estrogen, vitamin E, and selegiline are currently being evaluated for their ability to slow the rate of progression. Drug therapy can be complicated by forgetfulness, especially if the prescribed drug must be taken several times daily Two drugs, tacrine (Cognex) and donepezil (Aricept), are commonly prescribed for Alzheimer's disease. These drugs inhibit the breakdown of acetylcholine in the brain, prolonging its ability to conduct chemical messages between brain cells. They provide temporary improvement in cognitive functions for about 40% of patients with mild-to-moderate AD. Hydergine is sometimes prescribed as well, though it is of questionable -benefit for most patients. Psychotic symptoms, including paranoia, delusions, and hallucinations, may be treated with antipsychotic drugs, such as haloperidol, chlorpromazine, risperidone, and clozapine. Side effects of these drugs can be significant. Antianxiety drugs such as Valium may improve behavioral symptoms, especially agitation and anxiety, although BuSpar has fewer side effects. The anticonvulsant carbamazepine is also sometimes prescribed for agitation. Depression is treated with antidepressants, usually beginning with selective serotonin reuptake inhibitors (SSRIs) such as Prozac or Paxil, followed by monoamine oxidase inhibitors or tricyclic antidepressants. Electroconvulsive therapy may be appropriate for some patients with severe depression who are unresponsive to drug therapy. In general, medications should be administered very cautiously to demented patients, in the lowest possible effective doses, to minimize side effects. Supervision of taking medications is generally required. Several drugs are currently being tested for their ability to slow the progress of Alzheimer's disease. These include acetyl-l-carnitine, which acts on the cellular energy structures known as mitochondria; propentofylline, which may aid circulation; milameline, which acts similarly to tacrine and donezepil; and ginkgo extract. Ginkgo extract, derived from the leaves of the Ginkgo biloba tree, interferes with a circulatory protein called platelet activating factor. It also increases circulation and oxygenation to the brain. Ginkgo extract has been used for many years in China and is widely prescribed in Europe for treatment of circulatory problems. A 1997 study of patients with dementia seemed to show that gingko extract could improve their symptoms, though the study was criticized for certain flaws in its method

f.

Psychotherapy Care for a person with dementia can be difficult and complex. The patient must learn to cope with functional and cognitive limitations, while family members or other caregivers assume increasing responsibility for the person's physical needs. In progressive dementias such as Alzheimer's disease, the person may ultimately become completely dependent. Education of the patient and family early on in the disease progression can help them anticipate and plan for inevitable changes.

Behavioral approaches may be used to reduce the frequency or severity of problem behaviors, such as aggression or socially inappropriate conduct. Problem behavior may be a reaction to frustration or overstimulation; understanding and modifying the situations which trigger it can be effective. Strategies may include breaking down complex tasks, such as dressing or feeding, into simpler steps, or reducing the amount of activity in the environment to avoid confusion and agitation. Pleasurable activities, such as crafts, games, and music, can provide therapeutic stimulation and improve mood.

Modifying the environment can increase safety and comfort while decreasing agitation. Home modifications for safety include removal or lock-up of hazards such as sharp knives, dangerous chemicals, and tools. Child-proof latches or Dutch doors may be used to limit access as well. Lowering the hot water temperature to 120F (48.9C) or less reduces the risk of scalding. Bed rails and bathroom safety rails can be important safety measures, as well. Confusion may be reduced with simpler decorative schemes and presence of familiar objects. Covering or disguising doors (with a mural, for example) may reduce the tendency to wander. Positioning the bed in view of the bathroom can decrease incontinence. Insights: Delirium, dementia, and amnesia are three closely related conditions. The DSV-IV-TR (2000) defines delirium as, a disturbance of consciousness and a change in cognition that develop over a short period of time. Dementia is defined as multiple cognitive deficits that include impairment in memory. Finally, amnesia is defined as, memory impairment in the absence of other significant accompanying cognitive impairments. Symptoms of these disorders are focused around clinically significant drop in cognitive functioning from a previous level. The most prevalent presenting symptoms include: (a) disrupted and wandering attention, (b) inability to think with a purpose, (c) disorganized thinking, (d) incoherence, and (e) confusion about time, place, or both. Emotional and personality change symptoms can include: (a) anxiety, (b) anger, (c) apathy, (d) depression, (e) euphoria, and (f) irritability (Delirium, 2010). Causes of these disorders can range from a general medical condition to a specific substance including drug abuse, medication, or other toxin. Treatments for these disorders are difficult due to the debilitative physical causes that underlie them. The first thing that a psychologist should do is ensuring that the patient has receives an adequate physical examination and refer them to a physicians care if they have not. The medications that can be used to delay or offset the symptoms of these disorders must be prescribed by a physician, not a psychologist. Therefore, it is critical that getting the patient to a physician is the first step to maintaining the patients quality of life. Where the psychologist can add the greatest value to the patients situation is to teach them coping skills and, if necessary, ensure the loved ones of the patient seek care themselves. Psychological interventions can include: (a) reorientation therapy, (b) reminiscence, (c) validation therapy, (d) memory therapy, or (e) resolution therapy (Twinings). In conclusion, these disorders affect a great number of people, and with the baby boomer generation aging, the chances that a psychologist will help others confront these issues is on the rise. A psychologist should know and understand how they can help people with these conditions add value to their lives.

Sources: y y y y y y Ramos, L. Biala M. , et. al.sPsychiatric Nursing (1st edition) th Kozier and Erbs Fundamentals of Nursing (8 ed. Vol. 2) st Ignatavicius, D. and Bayne , M.s Medical- Surgical Nursing (1 ed.) http://www. Wikipedia.org http://neurology.health-cares.net http://www. medscape.com

Updates:

Delirium in Elderly People: An Update

Albert F.G. Leentjens; Rose C. van der Mast Authors and Disclosures Posted: 05/03/2005; Curr Opin Psychiatry. 2005;18(3):325-330. 2005 Lippincott Williams & Wilkins

Abstract and Introduction

Abstract

Purpose of Review: To review recent studies on epidemiology, diagnosis, pathophysiology, treatment and prevention of delirium in elderly people. Recent Findings: There is no evidence that the clinical picture of delirium in elderly people differs from that in younger patients, although it may run a more chronic course. Diagnosing delirium in demented patients, however, may be difficult due to overlap in symptoms of delirium and dementia. Systematic use of screening and diagnostic instruments may help to diminish the common underdiagnosis of delirium. Delirium is best understood as the result of multiple interacting predisposing and precipitating factors. In the elderly, predisposing factors that make patients more susceptible for delirium include cognitive dysfunction and older age, while important precipitating factors that directly cause delirium are any somatic events and the use of anticholinergic drugs. Delirium has a significant negative prognostic impact on functional and cognitive outcome, as well as on morbidity and mortality. Haloperidol remains the standard treatment for delirium, while there is some evidence for the efficacy of risperidone. Other atypical antipsychotics, as well as cholinesterase inhibitors, have not yet been sufficiently studied. Results of studies on the effectiveness of systematic screening of populations at risk and standardized interventions to prevent delirium have been inconclusive. Summary: In recent years, the emphasis in the approach to delirium has shifted from ad hoc treatment to systematic screening and prevention. Interest has been raised in treatment options other than haloperidol, such as atypical antipsychotics and procholinergic drugs.
Introduction

Although it is increasingly recognized that delirium is a serious complication of physical illness, there is still relatively little research in this area. Perhaps this is due to the fact that in clinical practice, delirium is seen primarily by consultationliaison psychiatrists and consultation geriatricians, who may find it difficult to set up a study outside their own ward. Furthermore, research with delirious patients poses special ethical problems, including informed consent.

Epidemiology and Prognosis

The fact that, especially in elderly patients, delirium has a negative impact on prognosis has been confirmed in several recently published prospective studies that were mainly focussed on length of hospital stay, functional ability, cognitive function and mortality. Length of hospital stay is usually, though not invariably, reported as being increased.[1*, 2] Functional outcome has consistently been described as being negatively affected by the occurrence of delirium.[1*, 37] In a prospective follow-up study, Rahkonen et al .[3] found that within the first year after discharge, 20% of 51 elderly patients with in-hospital delirium had been admitted to long-term care. In a

controlled study of 92 patients that underwent hip surgery, 27% of the 26 patients who had suffered from postoperative delirium were admitted to a nursing home within 3 months of discharge from hospital compared to 8% of the 66 non-delirious patients.[4] McCusker et al .[5] found no difference for admission rates to long-term care facilities between patients with delirium and a non-delirious control group (odds ratio 1.15; 95% confidence intervals 0.33-4.05). The odds ratio for admission to long-term care, however, increased to 3.18 (95% CI 1.19-8.49) for demented delirious patients.[5]Also, in a study by Edelstein et al .,[1*] the 5.1% of 921 patients who became delirious after hip-fracture surgery were less likely to recover to their pre-fracture level of ambulation than non-delirious patients. In patients newly admitted to postacute care facilities after discharge from hospital, persistent delirium symptoms were prevalent in 23% of patients, being associated with poor functional recovery.[7] Cognitive decline is not only a predisposing factor for delirium, but it has also been shown that delirium independently worsens cognitive function. In both delirious and non-delirious patients who underwent hip surgery, the score on the Mini-Mental State Examination (MMSE) decreased significantly during hospital stay. In the delirious group, however, the average MMSE score decreased significantly more (from 23.06 to 20.44 points) than in the non-delirious group (from 26.74 to 25.83 points; P < 0.001).[6] Twelve months after discharge, the reduction in MMSE score was significantly greater in pre-morbid demented patients (mean reduction 4.99 points, 95% CI 2.8-7.2) than in non-demented patients who had suffered from delirium (mean reduction 3.36 points, 95% CI 0.58-6.15).[5] In the study of Rahkonen et al .,[3] 14 of the 51 delirious patients (27%) who were not known with pre-morbid dementia were diagnosed as demented immediately after the delirious symptoms had remitted, while another 14 patients received a diagnosis of dementia in the first year after discharge from hospital, bringing the cumulative incidence of dementia in the first year after delirium to 55. Higher mortality rates after discharge have been reported repeatedly for patients who experienced an episode of delirium, up to 10% in the first year after delirium had occurred.[1*, 3] Thus, in both medical and surgical elderly patients, most studies show an increased hospital stay, a decline of functional and cognitive outcome, and increased mortality following delirium.

Diagnosis
There is no evidence that the clinical picture of delirium in the elderly differs from that in younger patients, although symptoms of delirium may be more persistent and follow a more chronic course.[7, 8] In 193 medical inpatients aged 65 and over with delirium diagnosed at admission or during the first week in hospital, symptoms of delirium persisted up to 12 months after diagnosis, in patients both with and without dementia.[8] Diagnosing delirium in demented patients may be hard due to the overlap in symptoms of delirium and dementia. In an original study, Cole et al .[9] try to identify specific symptoms of delirium in demented patients that would help in making the diagnosis of delirium. Demented patients suffering from delirium showed more psychomotor agitation, disorientation and disorganized thinking.
Psychometric Scales

It is a fact that delirium is often under-diagnosed. In elderly people, up to 70% of all deliria are missed by clinicians.[10] In spite of the guidelines of the Society of Critical Care Medicine, in a sample of intensive care unit (ICU) personnel, including physicians and nurses, only 40% reported routinely screening for delirium, while only 16% used a specific tool for delirium assessment.[11*] Although research has shown a high specificity for the diagnosis delirium (99%) in 'care as usual' clinical assessment of elderly patients visiting the emergency department, the sensitivity of this approach is very low (35%).[12] A study by Zou et

al .[13] showed that, compared with the Confusion Assessment Method (CAM) and multiple observation points, clinical diagnosis by a psychiatrist had a lower sensitivity (89 versus 73%) and specificity (100 versus 93%). Therefore, systematic assessment of delirium using validated rating scales has been regularly advised. Over 13 delirium instruments exist for diagnosis, screening or assessing symptom severity. After their initial development and validation, however, most scales have not been further studied or improved.[14] The only systematic review, by Schuurmans et al .,[14] showed that all known delirium instruments have good reliability and fair to good validity, depending on the goal for which the instrument was designed. The authors advise use of the NEECHAM Confusion Scale[15] or the Delirium Observation Screening Scale (DOSS)[16] for screening high-risk elderly hospitalized patients. The CAM is the best diagnostic tool,[17] and the Delirium Rating Scale (DRS) is the best instrument to rate symptom severity.[18] In research, the CAM is probably the most widely used and best-studied instrument. Laurila et al .[19] showed that the CAM is acceptable for screening purposes as well, but the diagnosis should still be confirmed according to the formal criteria of the DSM IV. The validity of the CAM in detecting delirium depended on the professional and training background of the user, showing a significantly higher sensitivity when administered by physicians than by nurses (1.00 vs 0.13).

Aetiology and Risk Factors

In the aetiology of delirium, a distinction is made between 'predisposing' and 'precipitating' factors. Predisposing factors make the individual more susceptible for delirium, while precipitating factors constitute the direct somatic cause of delirium. Recently, several prospective studies have assessed potential predisposing factors for delirium in elderly people. Most were well-designed studies, using a multivariate approach that enabled them to identify independent risk factors. Next to increasing age,[2125] pre-existing cognitive decline is probably the most confirmed risk factor.[1*, 2124, 26, 27] Moreover, delirium may be the first indicator of dementia in elderly people.[28] Other factors that were found to lower the threshold for delirium in old age are high blood pressure,[26, 29] the use of multiple medications, especially those with anticholinergic properties,[27, 30] general anaesthesia,[1*] male gender[1*] and the use of alcohol[21, 22] or benzodiazepines.[23]Furthermore, Zakriya et al .[31] reported elevated serum sodium concentration, reduced general physical health status and reduced potential for stress response as independent risk factors for delirium in 48 patients after hipfracture surgery. Santos et al .[29] found that a combination of nine factors, including, among others, age, blood urea level, hypertension and smoking habits, predicted delirium in 220 patients undergoing coronary artery bypass graft (CABG) surgery, although none proved to be an independent predictor. In a study by Inouye,[32] vision impairment, severe illness, cognitive impairment and a BUN/creatinine ratio of more than 17 were shown to increase the likelihood of delirium in hospitalized older patients. Precipitating factors that are often summarized by the 'I WATCH DEATH' acronym, as mentioned in many textbooks,[33] have received far less research attention. Rahkonen et al .[3] found that the most important precipitating factors in 51 community-dwelling people over 65 years of age, who were admitted to the hospital because of delirium, were infections (43%) and cerebrovascular attacks (25%). Inouye et al .[32] reported the combination of five precipitating factors consisting of the use of physical restraints, malnutrition, the addition of four or more medications on the previous day, the use of a bladder catheter and any iatrogenic event or complication as a valid model to predict delirium in older patients during the course of hospitalization.[32] Although almost all medications may give rise to delirium, the use of medication with anticholinergic properties is another established precipitating factor in elderly patients.[30]

The aforementioned study and review of Inouye et al .[32] is especially interesting because it provides a clear conceptualization of the aetiology of delirium. The risk of delirium is probably best represented by a multi-factorial model of interacting predisposing and precipitating factors. Patients with many or severe predisposing factors may develop delirium in the presence of relatively benign precipitating factors, while patients with a low vulnerability will require multiple noxious insults to develop delirium.

Pathophysiology
Pathophysiology of delirium has not been studied much and is not well understood. The most comprehensive update on all literature and research on the pathophysiology of delirium was written by Trepacz and Van der Mast.[34] They pose that certain neuroanatomical and neurotransmitter systems may represent a 'final common neural pathway' for the diverse aetiologies of delirium. Particular brain regions, especially right-sided, are implicated in delirium. Reduced cholinergic function, excess release of dopamine and both decreased and increased serotonergic activity may underlie the different symptoms of delirium. Disease and trauma that are main risk factors for delirium lead to a physical stress response and may alter cerebral neurotransmission. Age-related changes in central neurotransmission, stress management and hormonal regulation, and immune response may underlie the vulnerability of elderly people to delirium.

Treatment
Given the negative influence of delirium on outcome, delirium should be considered an important complication of the underlying disease or its treatment, and treated accordingly. Although in need of an update, the 'Practice guidelines for the treatment of patients with delirium' of the American Psychiatric Association (APA) is the most comprehensive guideline on the treatment of this disorder. According to this guideline, haloperidol is the standard drug treatment of delirium.[35] Ample experience with haloperidol in elderly and in medically ill patients exists. The possibility of intravenous administration, although not approved by the Food and Drug Administration (FDA), may also be an advantage. Although, because of their more favourable motor side-effect profile, atypical antipsychotics may be preferred in elderly people, there is, as yet, no convincing evidence of their efficacy, with the exception of some lower-level evidence of risperidone. Several trials have recently demonstrated the positive effects of risperidone in older patients with delirium. One small double-blind randomized trial has directly compared risperidone and haloperidol in 28 patients with delirium. Both groups showed considerable improvement on the Memorial Delirium Assessment Scale, without any in-between group differences.[36*] In an open study in 10 patients, a dosage of risperidone 0.5 mg twice daily was effective in reducing the delirious symptoms, as measured by the Cognitive Test for Delirium (CTD) and the DRS.[37] One patient had to discontinue risperidone treatment because of sedation and hypotension. No patient developed extrapyramidal side effects. Parella et al.[38] reported effectiveness of an average dosage of 2.6 mg risperidone daily in 91% of 64 patients who were hospitalized for delirium. One patient experienced drowsiness and one suffered from nausea, but, again, no patient developed extrapyramidal symptoms. Other atypical antipsychotics have not been studied for the treatment of delirium in elderly people. There have been no studies of delirium treatment in patients with Parkinson's disease, who have a strong contraindication for haloperidol because of potential exacerbation of extrapyramidal symptoms. There have been, however, quite a number of studies on treatment of medication-induced psychosis that may be potentially helpful in our choice of treatment for delirium in these patients. Evidence at the highest level exists for clozapine. This agent has been shown to be effective in reducing medication-induced hallucinations and psychosis in patients with Parkinson's disease in two double-blind, randomized,

placebo-controlled trials, without negatively affecting motor symptoms.[39, 40] Risperidone worsened extrapyramidal symptoms to some degree, while olanzapine was not more effective than placebo.[41, 42] In one study that compared quetiapine and clozapine in a randomized open-label trial with blinded raters, 60 patients showed substantial improvement in delirious symptoms, without negative effects on motor function for both drugs.[43] There is no evidence that delirium in demented patients has to be treated differently from delirium in nondemented patients, although, in Lewy body dementia, haloperidol is contraindicated and pro-cholinergic agents may be considered. In a large, randomized, double-blind, placebo-controlled trial among patients with Lewy body dementia, rivastigmine was significantly more effective than placebo in the treatment of apathy and psychotic symptoms, without negative effects on motor function.

Prevention
Given the negative prognostic implications of delirium, the attention is shifting from treatment to prevention. Primary prevention aims at preventing the occurrence of delirium, while secondary prevention aims at reducing duration and severity of delirium and optimizing functional outcome, mostly by way of proactive psychiatric or geriatric consultation or by standardized interventions.
Primary Intervention

Several strategies for primary prevention of delirium have been investigated. Most patients are screened for risk factors of delirium by way of proactive psychiatric or geriatric consultations being incorporated in the routine care of an inpatient ward. In cases of 'treatable risk factors', patients undergo clinical or psychosocial interventions or pharmacological prophylaxis. Studies into the effectiveness of proactive screening and intervention, including 'internistic or geriatric consultation' and treatment considered necessary by the consultant, have yielded inconsistent and inconclusive results. Some studies confirm the effectiveness of such strategies in reducing incidence, duration or severity of delirium, while others found no evidence for any beneficial effects. These studies may have yielded inconclusive results because the interventions were, contrary to the screening methods, mostly ill-defined. Inouye et al .[45] were the first to use a standardized intervention strategy, randomizing 852 patients of at least 70 years of age in an intervention or a 'care as usual' group. The intervention consisted of standardized management of six risk factors for delirium, including cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment and dehydration. The incidence of delirium in the intervention group was significantly lower than in the 'care as usual' group (odds ratio 0.60; 95% CI 0.39-0.92), as was the number of days with delirium and the total number of delirious episodes. Moreover, intervention was associated with significant improvement in cognitive functioning in patients with cognitive impairment, and with a reduction of sleep medication use in all patients. Unfortunately, due to the methodology and the statistical analysis used in the study, the individual contribution of the different components of the intervention remains unclear.[45] Once delirium had occurred, however, the intervention strategy had no effect on severity of delirium and likelihood of recurrence. Therefore, Inouye et al . concluded that primary intervention is to be preferred over secondary prevention.[45] A study by Marcantonio et al .[46] reported a reduction in the incidence of delirium by one-third in 126 elderly hipfracture patients by way of proactive geriatric consultation, with a 'number needed to treat of 5.6. Lundstrm et al .[47]found that reorganization of nursing and medical care on an orthogeriatric rehabilitation unit, comprising staff-education, active nutrition, improvement of ward environment, continuity of care and planning of rehabilitation, greatly reduced the incidence of delirium and functional outcome in 42 elderly patients with hip fractures when compared to a historic control group of the same

and other hospitals. Unfortunately, the use of a historical control group introduced many possible confounding factors, weakening the conclusions of the study.[47] In a randomized study of 120 elderly hipfracture patients, a standardized intervention, consisting of education of nursing staff, systematic cognitive screening, specialized consultation and a scheduled pain protocol, was not effective in decreasing the incidence of delirium, although severity and duration of delirium were reduced.[48]
Pharmacological Primary Intervention

The effectiveness of pharmacological prophylaxis was assessed in several studies. In 400 elderly hipfracture patients, the incidence of delirium was not reduced by prophylactic administration of 1 mg haloperidol in comparison to placebo, although duration and severity of delirium were decreased.[49] A dose of 1 mg haloperidol, however, may have been too low to bring about a prophylactic effect. Although one retrospective study reported a reduced incidence of delirium in patients using rivastigmine, a randomized, placebo-controlled trial with citicoline (CDP-choline) in 81 hip-surgery patients could not confirm this finding.[50, 51] In a randomized study, 42 patients who underwent resection of gastric or colon cancer received either 'care as usual' or a so-called 'delirium-free protocol' consisting of continuous intravenous infusion of diazepam and pethidine over 8 hours for the first three nights, postoperatively, to regulate the sleep-wake cycle and control pain. This very novel and unusual approach resulted in a significantly decreased incidence of delirium (5%) compared to 35% in the non-intervention group.[52]
Secondary Intervention

Cole et al .[53] showed only marginal benefits of systematic detection and intervention by geriatric consultation in a group of 88 delirious patients. According to a Cochrane review of systematic multidisciplinary interventions for delirium in elderly patients with chronic cognitive impairment, only one study met the methodological standard.[54*] In this study, by Cole et al.,[55] 227 delirious patients, of whom 131 were suspected of having prior cognitive impairment, were randomized between systematic detection and multidisciplinary intervention or 'care as usual'. No difference between the groups regarding improvement of delirium, length of hospital stay, discharge to a care facility or mortality occurred. The conclusion of the Cochrane review was that there are insufficient data to provide a guideline in the multidisciplinary diagnosis and treatment of delirium in cognitively impaired elderly patients.

Conclusions
In the last few years, only a limited number of original research articles on delirium have been published. Many studies confirmed that delirium in old age has a significant negative impact on prognosis in terms of functional as well as cognitive outcome, morbidity and mortality. Also, delirium in the elderly may run a more chronic course, being difficult to discern from dementia. Under-detection of delirium may be improved by the use of psychometric scales for screening and diagnosis. Multiple predisposing and precipitating factors for delirium have been reported. Even though the effectiveness of systematic screening of populations at risk, as well as the effectiveness of standardized interventions aimed at primary prevention, have not been confirmed, this will be the direction in which to move if we want to improve our clinical practice. Also, in the elderly, haloperidol remains the standard treatment for delirium, although, recently, other drug-treatment options have raised interest, such as the use of risperidone and cholinesterase inhibitors.

Vitamin E and Dementia: An Update

Laurie Barclay, MD Authors and Disclosures Posted: 07/28/2010

Dietary Antioxidants and Long-term Risk of Dementia

Devore EE, Grodstein F, van Rooij FJ, et al Arch Neurol. 2010;67:819-825
Summary

Higher dietary consumption of vitamins E and C was previously associated with lower risk for dementia and Alzheimer disease (AD), according to 6-year findings from the Rotterdam Study. The goal of the present population-based, prospective study was to further examine the relationship between intake of major dietary antioxidants and long-term risk of dementia in the same Dutch cohort. The study sample consisted of 5395 participants at least 55 years old who had no dementia and who provided dietary information at study baseline. Mean duration of follow-up was 9.6 years. Of 465 participants in whom dementia developed during follow-up, 365 were diagnosed with AD. Higher baseline intake of vitamin E was associated with lower long-term risk of dementia (P=.02 for trend), after adjustment for age, education, apolipoprotein E4 genotype, total energy intake, alcohol intake, smoking, body mass index, and use of supplements. Dementia was 25% less likely to develop in participants in the lowest tertile vs the highest tertile of vitamin E intake (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.59-0.95). After multivariate adjustment, dietary intake of vitamin C, beta carotene, and flavonoids were not linked to dementia risk. Findings were similar for AD risk.
Viewpoint

Compared with previous research, important contributions of this study are population-based estimates of incident dementia risk over a decade, evaluation of food-based antioxidants typically found in a Westerntype diet, and assessment of various antioxidants and total vitamin E, including all 8 forms. Despite study limitations of observational design with possible residual confounding, the findings suggest a modest reduction in long-term risk for dementia and AD associated with increased consumption of vitamin E-rich foods. Although an earlier study suggested a possible inverse association between vitamin C intake and dementia risk, this was not observed in this study. A possible explanation is that intake of different antioxidants may affect risk at different time points in the course of dementia, supporting the need for additional research to address this question.