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cholinergic deficiency in Alzheimer s disease, research has focused on drugs to increase cholinergic activity by inhibiting cholinesterase Tacrine was the first reversible cholinesterase inhibitor approved by the FDA Three better-tolerated FDAapproved cholinesterase inhibitors are donepezil (5 10 mg at night), rivastigmine (3 6 mg twice daily), and galantamine (8 12 mg twice daily) Donepezil and galantamine doses need adjustment for liver disease, and the galantamine dose should be adjusted for renal failure They are thought to be efficacious in the short-term preservation of cognitive function and activities of daily living in mild to moderate dementia and, unlike tacrine, are not thought to be hepatotoxic Gastrointestinal side effects are common but may be least frequent with donepezil Further research continues to clarify the long-term efficacy of these medications on cognition and behavior None of the cholinesterase inhibitors to date are thought to slow disease progression An N-methyl-D-aspartate (NMDA) receptor antagonist, memantine, is the first medication approved by the FDA for the treatment of moderate to severe Alzheimer s disease Memantine may improve performance and cognition in some patients and has been used as an augmenting agent with the cholinesterase inhibitors Aggressiveness and rage states in central nervous system disease can be reduced with lipophilic -blockers (eg, propranolol, metoprolol) in moderate doses Since the serotonergic system has been implicated in arousal conditions, drugs that affect serotonin have been found to be of some benefit in aggression and agitation Included in this group are lithium, trazodone, buspirone, and clonazepam Dopamine blockers (eg, the neuroleptic drugs such as haloperidol) have been used for many years to attenuate aggression Atypical neuroleptics may have a role in selected geriatric patients; however, there are reports of increased mortality in some studies related to the use of atypical neuroleptics in this population There are also recent reports of reduced agitation in Alzheimer s disease from carbamazepine, 100 400 mg/d orally (with slow increase as needed) Emotional lability in some cases responds to small doses of imipramine (25 mg orally one to three times per day) or fluoxetine (5 20 mg/d orally); depression, which often occurs early in the course of Alzheimer s dementia, responds to the usual doses of antidepressant drugs, preferably those with the least anticholinergic side effects (eg, SSRIs and MAO inhibitors) Cerebral vasodilators were originally used on the assumption that cerebral arteriosclerosis and ischemia were the principal causes of the dementias Although there is a slight reduction of blood flow in primary degenerative dementia (probably as a result of the basic disorder), there is no evidence that this is a major factor in this group of disorders or that vasodilators are of value Ergotoxine alkaloids (ergoloid mesylates: Hydergine, others) have been studied with mixed results; improvement in ambulatory self-care and depressed mood has been noted, but there has been no improvement of cognitive functioning on any standardized tests Hyperbaric oxygen treatment has not produced significant improvement Stimulant drugs (eg, methylphenidate) do not change cognitive function but can improve affect and mood, which helps the caretakers cope with the problem Failing sensory functions should be supported as necessary, with hearing aids, cataract surgery, etc.

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Substitute home care, board and care, or convalescent home care may be most useful when the family is unable to care for the patient The setting should include familiar people and objects, lights at night, and a simple schedule Counseling may help the family to cope with problems and may help keep the patient at home as long as possible Information about local groups can be obtained from the Alzheimer s Disease and Related Disorders Association, 70 East Lake Street, Suite 600, Chicago, IL 60601 Volunteer services, including homemakers, visiting nurses, and adult protective services, may be helpful in maintaining the patient at home

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Behavioral techniques include operant responses that can be used to induce positive behaviors, eg, paying attention to the patient who is trying to communicate appropriately, and extinction by ignoring inappropriate responses Alzheimer s patients can learn skills and retain them but do not recall the circumstances in which they were learned

Formal psychological therapies are not usually helpful and may make things worse by taxing the patient s limited cognitive resources

The prognosis is good for recovery of mental functioning in delirium when the underlying condition is reversible For most dementia syndromes, the prognosis is for gradual deterioration, although new drug treatments may prove helpful

McShane R et al Memantine for dementia Cochrane Database Syst Rev 2006 Apr 19;(2):CD003154 [PMID: 16625572] Schneider LS et al Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials JAMA 2005 Oct 19;294(15):1934 43 [PMID: 16234500] Trinh N et al Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease, a meta-analysis JAMA 2003 Jan 8;289(2):210 6 [PMID: 12517232]

1 Delirium with psychotic features secondary to the medical or surgical problem, or compounded by effect of treatment 2 Acute anxiety, often related to ignorance and fear of the immediate problem as well as uncertainty about the future 3 Anxiety as an intrinsic aspect of the medical problem (eg, hyperthyroidism)

macy is often a factor Patients with unsolved diagnostic problems are at higher risk They are desirous of relief, and the quest engenders more diagnostic procedures with a higher incidence of complications The upset patient and family may be very demanding Excessive demands usually result from anxiety Such behavior is best handled with calm and measured responses

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