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Alzheimer's

Behavioral problems

Patient management

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 		Managing Cognitive Dysfunction

John E. Morley, M.D.

Cognitive dysfunction includes conditions ranging in seriousness from the relatively benign mild cognitive impairment (MCI) to dementia, which can be extremely debilitating. Once grouped under the catch-all term senility, these conditions have different causes, different symptoms and different treatments.

Taken together, the various forms of cognitive dysfunction represent one of the greatest health problems affecting the elderly in the United States today. Approximately 8% of Americans over 65 years of age have dementia. If you add those suffering from milder cognitive dysfunctions, the numbers rise to nearly 16%. All types of cognitive dysfunction become more common and more serious with age. Studies indicate that as many as 47% of Americans 85 years old or older have dementia; and the disease has been estimated to cost the United States nearly $100 billion annually.1

Mild Cognitive Impairment (MCI)
A number of older persons have cognitive impairment that is worse than expected for their age and educational level but they are not "demented." Persons with mild cognitive impairment have, primarily, a decline in memory function, while early Alzheimer's Disease sufferers, for example, usually have impairments in several cognitive areas (e.g., memory and speech; speech and control of bodily movements).2

MCI sufferers bounce back more slowly than the average person of their age from physical problems such as a hip fracture. They have a lower life expectancy and are more likely to develop dementia.3 Therefore, it is important to treat early mild cognitive impairment. Recent studies show that hormone replacement therapy is a promising new treatment for MCI in both men (testosterone) and women (estrogen).8

Table 1. How Doctors Diagnose Mild Cognitive Impairment

  1. Complaints and objective evidence of memory problems
  2. Daily living skills are normal
  3. Thinking ability, other than memory, is normal
  4. Score on MMSE (more than 23 if high school education or more than 17 if less than high school education
  5. Not depressed

Alzheimer's and the Different Dementias
Alzheimer's is the major cause of dementia. If a doctor determines that the patient has deficits in at least two of the following (memory, language, control of bodily movement, perception, loss of ability to make decisions), as well as worsening of cognitive function, no alteration in consciousness, onset between 50 and 90 years and absence of other possible causes, then the patient most likely has Alzheimer's.5

Dementia is subtle. Family members fail to recognize it almost one-quarter of patients.6,7 A number of studies have shown that doctors are not much better.

The clinical features of the common dementias are outlined in the table below.

Table 2. The Different Types of Dementia

Type Onset Progression Clinical Features
Alzheimer's Insidious Slow progressive with fluctuation Deficits in at least two areas of cognition. No disturbance of consciousness. Altered behavior

Illusions,delusions and hallucinations

Increased muscle tone

Seizures (late)

Gait disturbances (late)
Vascular Abrupt Stepwise Emotional incontinence

Focal neurological disease

Evidence of vascular disease

Patchy cognitive defects
Depression Insidious Progressive with remissions Subjective complaints exceed objective findings

Sad

Poor motivation
Lewy-Body Dementia Insidious Progressive and more rapid Interferes early with social functions

Memory impairment may be late

Prominent attention and visuospatial defects

Fluctuating levels of alertness

Recurrent visual hallucinations

Parkinsonism

Repeated falls

Systemized delusions
Fronto-Temporal (Pick's) Early age Progressive Apathy

Disinhibition

Antisocial behavior

Poor insight

Language deficits

Memory deficits late


Drug Treatments for Alzheimer's and the Role of Homocysteine
There is a wide variety of drugs used to treat the cognitive problems caused by Alzheimer's Disease. These include: tacrine, donapezil, rivastigmene, metrifonate, muscarine--xanomelline, deprenyl (Selegeline®), vitamin E, the hormones estrogen and testosterone,8 corticosteroids such as prednisone, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors herbs such as gingko biloba, ergot alkaloid and propenofylline.

In addition, researchers are now investigating many experimental drugs:
  • Tau protein phosphorylation blockers
  • b-amyloid blockers
  • APOE e4 metabolizers
  • Brain membrane modifiers, e.g., ganglioside GMI and phosphatidylserine
  • Nerve growth factor
  • Presenilin and/or g secretase inhibitors
Recent studies have shown a relationship between elevated blood levels of homocysteine, a protein breakdown product, and memory dysfunction.9,10,11,12,13 Independently, low vitamin B12 and folate levels (folate is a vitamin found in liver, green vegetables and yeast) are associated with cognitive dysfunction. Folate deficiency, by itself, can make homocysteine levels rise and too much homocysteine can provoke atherosclerosis. It is, therefore, possible that hardening of the arteries may act as a trigger for Alzheimer's disease. Future studies may confirm the role of elevated homocysteine in Alzheimer's disease; in the meantime it would make good sense to give multivitamins to people with dementia.

Behavioral Problems: What Can You Do?
Patients with dementia often suffer from depression and a variety of behavior problems.14 Depression is particularly common in patients with vascular dementia but can also occur in those with Alzheimer's disease. Doctors use the Cornell Scale for Depression in Dementia to help identify depression in dementia sufferers. Thoughts of death or suicidal thinking occur in as many as one-third of dementia patients early in the course of the disease; and hallucinations, delusions and paranoid thoughts occur in approximately a quarter of patients. Anxiety is also common. Other behavior problems include agitation, irritability, wandering, restlessness, sleep disturbances, aggressiveness, screaming and inappropriate sexual behavior.

It should also be remembered that some of these behavioral problems, especially agitation, may be caused by delirium. Delirium is an extremely dangerous altered state of consciousness whose symptoms include confusion, distractability, disorientation, disordered thinking and memory, illusions and hallucinations, hyperactivity and overactivity. Demented patients are particularly vulnerable to developing delirium. When this occurs, the patient should be taken to an Emergency Room and treated as soon as possible (usually with the drug haloperidol).

Few studies have focused on anxiety and its treatment in Alzheimer's sufferers. Anxiety may result from a fear of becoming a burden to friends or family members, or from a fear of being left alone. It is often associated with suspiciousness. The best way to treat this problem is by providing the patient with reassurance and a consistent environment. If drug treatment is needed, short-acting benzodiazepines and buspiridone may be useful. Trazodone can help the anxious patient go to sleep.

Many of the behavioral symptoms seen in demented patients are related to disturbances of the internal biological clock ("phase shifting"). Patients with Alzheimer's are particularly vulnerable to phase shifting. For instance, their activity level may peak late in the day, typically around dinnertime. Use of high lux (2000 lux) lighting for two hours in the morning may reverse this problem. There have also been case reports that melatonin can help.

In the case of agitation, the best interventions are behavioral ones.15 These include:
  1. Career support and education. The ability to deal with agitation is often more important than treating the agitation itself.
  2. Psychotherapy. A variety of psychotherapeutic approaches have been utilized. These include Reality Orientation, Validation Therapy (accept the person's reality - better in late disease), Reminiscence and Music and other Creative Arts Therapies. Strong evidence for the use of many of these therapies is lacking.
  3. Environmental Modification. These should include a safe and easy-to-manage environment in which no restraints are necessary.
  4. Special Care Units. Though heralded by their adherents, controlled studies have not demonstrated any benefit.
  5. A hearing amplifier. Some demented patients scream all the time. Giving them a hearing amplifier can often solve this problem.
When agitation first occurs, it is important to rule out an underlying medical cause. Delirium occurs, commonly, in persons with dementia. Pain is often a precipitant of disruptive behaviors and it needs to be carefully assessed in agitated patients.

Drug Therapy
A number of drugs can be utilized to regulate severe agitation. These include:
  • Typical Antipsychotics16
  • Atypical Antipsychotics: Resperidone and olanzapine are less likely to produce pseudoparkinsonism. A small number of studies suggest that they are as effective as the typical antipsychotics.17
  • Serotonin Selective Reuptake Inhibitors (SSRIs): Citalopram was better than placebo in decreasing irritability, fear and restlessness in Alzheimer's patients.18 Similar results were found with fluvoxamine.19
  • Cholinergic Drugs: There is evidence that these drugs may cause a modest improvement in disruptive behaviors.17
  • Trazodone: This can be used to calm agitated behavior but no large-scale study has been done.
  • b-blockers: These have been used in agitated patients with reported positive effects.
  • Divalproex sodium: Often used in the United States. In uncontrolled trials, improvement was reported in 68% of patients.
  • Carbamazepine: Positive in one double blind trial.
  • Estrogens: These can be helpful in some males with aggressive sexual behavior. They should not be used until behavior modification, staff education and SSRIs have been used.
Summary
The following is a simple graphic approach to the management of disruptive behaviors in demented patients:

Is the problem the caregiver? YES support education

NO
  
Are adequate behavior modification techniques in place? YES exclude environmental
triggers. No physical
restraints

NO
  
Is the patient delirious? YES treat cause

NO
  
Is the patient in pain? YES treat

NO
  
Is the patient sad? YES treat depression

NO
  
Is the patient hallucinating and/or paranoic? YES antipsychotics

NO
  
Does the patient sundown? YES high lux lighting

NO
  
Is the patient sexually aggressive? YES staff education, behavior
modification, SSRIs, estrogen

NO
  
Does the patient scream consistently? YES hearing amplification bio-
feedback, trazodone or SSRI,
electroconvulsive therapy+

NO
  
Is the patient physically and/or verbally
aggressive and non-responsive to the above?		 YES antipsychotics, trazodone,
Na Valproate
+Use of ECT is controversial in Europe but good results have been seen in the U.S.A.

March 2000 Email this article to a friend

References
1. Schumock GT. Economic considerations in the treatment and management of Alzheimer's disease. Am J Health-Syst Pharm 55(Suppl 2):S17-21, 1998. return

2. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment - Clinical characterization and outcome. Arch Neurol 56(3):303-8, 1999. return

3. Kelman HR, Thomas C, Kennedy GJ, Cheng J. Cognitive impairment and mortality in older community residents. Am J Pub Health 84(8):1255-60, 1994. return

4. Miller DK, Lewis LM, Nork MJ, Morley JE. Controlled trial of a geriatric case-finding and liaison service in an emergency department. J Am Geriatr Soc 44(5):601-2, 1996.

5. Miller DK, Morley JE, Rubenstein LZ, Pietruszka FM, Strome LS. Formal geriatric assessment instruments and the care of older general medical outpatients. J Am Geriatr Soc 38(6):645-51, 1990. return

6. Richards SS, Hendrie HC. Diagnosis, management, and treatment of Alzheimer disease. Arch Intern Med 159:789-98, 1999. return

7. Doraiswamy PM, Steffens DC, Pitchumoni S, Tabrizi S. Early recognition of Alzheimer's disease: What is consensual? What is controversial? What is practical? J Clin Psychiatry 59(Suppl 13):6-18, 1998. return

8. Janowsky JS, Oviatt SK, Orwoll ES. Testosterone influences spatial cognition in older men. Behav Neurosci 108(2):325-32, 1994. return

9. Uno H, Eisele S, Sakai A, Shelton S, Baker E, DeJesus O, Holden J: Neurotoxicity of glucocorticoids in the primate brain. Horm Behav 1994 Dec;28(4):336-48. return

10. Bell IR, Eilman JS, Selhub J, et al. Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people. Acta Psychiatr Scand 86:385-90, 1992. return

11. Riggs KM, Spiro A, Tucker K, Rush D. Relations of vitamin B12, vitamin B6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 63:306-14, 1996. return

12. McCadden A, Davies G, Hudson P, et al. Total serum homocysteine in senile dementia of the Alzheimer's type. Int J Geriatr Psychiatr 13:235-239, 1998. return

13. Clarke R, Smith AD, Jobst KA. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer's disease. Arch Neurol 55:1449-45, 1998. return

14. Bolger JP, Carpenter BD, Strauss ME. Behavior and affect in Alzheimer's disease. Clin Geriatr Med 10(2):315, 1994. return

15. Mintzer JE, Hoernig KS, Mirski DF. Treatment of agitation in patients with dementia. Clin Geriatr Med 14(1):147, 1998. return

16. Schneider LS, Pollock VE, Lyness SA. A metaanalysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc 38(5):553-63, 1990. return

17. Raskind MA. Psychopharmacology of noncognitive abnormal behaviors in Alzheimer's disease. J Clin Psychiatry 59(Suppl 9):28-32, 1998. return

18. Nyth AL, Gottfries CU. The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders: A Nordic multicenter study. Br J Psychiat 157:844-901, 1990. return

19. Olafsson K, Jorgensen S, Jensen HV, et al. Fluvoxamine in the treatment of demented elderly patients: A double blind, placebo-controlled study. Acta Psychiatr Scand 85:453-6, 1992. return



  

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