Alzheimer’s Disease

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Chapter 10 Alzheimer’s Disease

INTRODUCTION

Description: Alzheimer’s disease is a degenerative organic mental syndrome characterized by progressive intellectual deterioration and dementia—the most common form of dementia.

Prevalence: Five million cases annually, 40% of patients older than 85, seventh leading cause of death (2004).

Predominant Age: Older than age 65.

Genetics: 2-fold to 3-fold more common in women, increased familial risk (50% of patients). Markers have been found on chromosomes 1 and 14 for early onset and 12 and 19 for late onset.

ETIOLOGY AND PATHOGENESIS

Causes: Unknown. Proposed—slow virus, aluminum exposure, accelerated aging, autoimmune process, genetic alteration in amyloid production or metabolism.

Risk Factors: Aging, head trauma, Down syndrome, and family history.

DIAGNOSTIC APPROACH

Workup and Evaluation

Laboratory: Screening to rule out other causes as indicated.

Imaging: Computed tomography (CT) or magnetic resonance imaging (MRI) may show characteristic changes but are not required to make the diagnosis.

Special Tests: Spinal tap as indicated by the diagnoses being considered. Special paper and pencil tests are available to help with the assessment of cognitive function.

Diagnostic Procedures: History and clinical characteristics.

Pathologic Findings

β-Amyloid deposits in neuritic plaques and on arteriolar walls characterize the disease. Pyramidal cell loss, decreased cholinergic innervation, and neuritic senile plaques are also seen.

MANAGEMENT AND THERAPY

Nonpharmacologic

General Measures: Support, exercise to reduce restlessness and improve sleep, continued cognitive challenge, family support.

Specific Measures: Estrogen replacement is associated with a 50% reduction in risk and a delay in onset of symptoms in some studies, although more recent studies do not confirm these findings. For those with Alzheimer’s changes, estrogen replacement near the time of menopause seems to improve function; late replacement (as in the Women’s Health Initiative study) does not.

Diet: No specific dietary changes indicated.

Activity: No restriction except those imposed by ability.

Patient Education: Reassurance; extensive educational materials are available from support groups, Internet sites, and the Alzheimer’s Association (Chicago).

Drug(s) of Choice

Studies on agents to enhance memory (donepezil [Aricept] 5 to 10 mg daily, galantamine [Razadyne] 4 to 8 mg two times daily, rivastigmine [Exelon] 1.5 to 4.5 mg two times daily) suggest some improvement for 30% to 50% of patients with severe disease. Drugs may be used to improve specific manifestations such as insomnia or depression. Several additional drugs (such as bapineuzumab and lecozotan) are currently in phase 3 trials, but no clearly effective therapy appears imminent.

Contraindications: Avoid anticholinergic drugs, such as tricyclic antidepressants and antihistamines.

Precautions: Tacrine (Cognex) may cause liver toxicity. Benzodiazepines may produce paradoxical excitation. Triazolam (Halcion) can produce memory loss, confusion, or psychotic reactions. Care must be taken in the use of all drugs in these patients; they tend to tolerate them poorly and confusion may lead to dosing errors.

Alternate Therapies: Ginkgo biloba has shown some promise in clinical studies.

FOLLOW-UP

Patient Monitoring: Watch for problems with nutrition, further mental deterioration, and drug use. Provide continuing and aggressive family support. Periodically evaluate the need for nursing home placement or other assistance.

Prevention/Avoidance: None. Some data suggest that remaining intellectually active (games or puzzles), physical activity, and social interaction may reduce the risk or delay the onset.

Possible Complications: Progressive deterioration with metabolic changes, dehydration, drug overdose, falls, depression, and suicide.

Expected Outcome: Poor—progressive deterioration with 8- to 10-year average survival.

MISCELLANEOUS

ICD-9-CM Codes: 331.0, 290.0 (Senile dementia, uncomplicated), 290.10 (Presenile dementia, uncomplicated).

Agency for Health and Research. Recognition and initial assessment of Alzheimer’s disease and related dementias: Clinical Practice Guidelines 19. Rockville, Md: US Dept of Health and Human Services, 1996. AHCPR publication 97–0702.

Birks J, Grimley E, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 4, 2002. CD003120

Geldmacher DS, Whitehouse PJ. Evaluation of dementia. N Engl J Med. 1996;335:330.

Hebert L, Scherr P, Bienias J, et al. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60:1119.

Lott I, Head E. Alzheimer disease and Down syndrome: factors in pathogenesis. Neurobiol Aging. 2005;26:383.

Pendlebury W, Solomon PR. Alzheimer’s disease. Ciba Clin Symp. 1996;48:1.

Progress Report on Alzheimer’s Disease 1996. Washington, DC: National Institute on Aging, US Dept of Health and Human Services, 1996. NIH publication 96–4137.

Wenk GL. Neuropathologic changes in Alzheimer’s disease. J Clin Psychiatr. 2003;64(Suppl 9):7.

Zamrini E. Emerging drug therapies for dementia. Geriatr Aging. 2006;9:107. 110.

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