Alzheimer Disease

BASICS

DESCRIPTION

A degenerative organic mental disease characterized by progressive intellectual deterioration and dementia; usually occurring after age 65. The diagnosis is made on clinical grounds after ruling out treatable disorders with similar characteristics. Long-term care cost to the nation is approximately $100 billion/year.
Usual course - progressive; chronic.

System(s) affected: Nervous
Genetics: Positive family history in 50% of cases. Markers on chromosomes: 1 and 14 (early onset disease); 12,19 (late onset); 21 (onset age 50-65).
Incidence/Prevalence in USA: 4 million cases/350 million people. 40% of those over age 85 are affected.
Predominant age: > 60
Predominant sex: Female > Male (slightly)

SIGNS AND SYMPTOMS

Acalculia
Agnosia
Anhedonia
Anxiety
Apathy
Aphasia
Apraxia
Confabulation
Delusions
Dementia
Depression
Impaired abstraction
Intellectual decline
Loss of interest
Occupational dysfunction
Personality change
Progressive cognitive impairment
Recent memory loss (key finding)
Restlessness
Sleep disturbances
Social withdrawal
Visuospatial distortion
Weight loss
Late signs - seizures, myoclonus, extrapyramidal dysfunction, incontinence

CAUSES

Unknown, but toxic beta-amyloid deposits in neuritic plaques and arteriolar walls appear critical to pathogenesis. Beta-amyloid precursor gene localized to chromosome 21.
Unsubstantiated possibilities - slow virus, bacterial infection (Chlamydia pneumoniae), metals (aluminum), accelerated aging, autoimmune attack

RISK FACTORS

Aging
Head trauma
Low education level
Down syndrome
Positive family history
Inheritance of the E4 allele of apolipoprotein E gene on chromosome 19 (E4 is much less of a risk factor for African Americans and Hispanics)
Smoking (2-4fold increases)

DIAGNOSIS

LABORATORY

To help rule out other causes of dementia:
- CBC
- Chemistry panel
- Thyroid function studies
- Folate and B-12 levels
- VDRL
- Sedimentation rate
- HIV antibody (selected cases)

Drugs that may alter lab results: N/A
Disorders that may alter lab results: N/A

PATHOLOGICAL FINDINGS

Gross - diffuse cerebral atrophy in association areas, hippocampus, amygdala and some subcortical nuclei
Micro - pyramidal cell loss
Micro - decreased cholinergic innervation (other neurotransmitters variably decreased)
Micro - neuritic senile plaques
Micro - degeneration of locus ceruleus and basal forebrain nuclei of Meynert
Neurofibrillary tangles
Amyloid angiopathy common
Inflammatory cells present

SPECIAL TESTS

Cerebrospinal fluid (depending on circumstances and clinical information)
Extensive neuropsychological battery - only needed if clinical picture is confusing
Controversy exists about need for routine cerebral imaging. MRI or CT clearly needed if cognitive decline is recent, there is history of stroke, or focal neurologic signs are present.

IMAGING

Head CT/MRI - moderate cortical atrophy, ventricular enlargement - to rule out infarcts, subdural hematomas, normal pressure hydrocephalus, neoplasm
MRI-based hippocampal volumetry, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have not yet reached clinical reality as tools to distinguish early Alzheimer's disease from other dementias

DIAGNOSTIC PROCEDURES

This is a clinical diagnosis - history, physical examination, tests (neurological and memory)
More specific tests (CSF beta-amyloid, tau, AD7C levels; urinary AD7C; serum beta-amyloid precursor protein; excessive pupillary dilatation to mydriatics), 3-item smell test still investigational
Testing for E4 allele of apolipoprotein E gene is available (but is not officially recommended) for assessing prognosis of early memory loss or predicting risk of dementia in patient's relatives

TREATMENT

APPROPRIATE HEALTH CARE

Outpatient, day care, assisted living center, nursing home (when necessary)

GENERAL MEASURES

Supportive
Optimize treatment of associated co-morbidities
Exercises to reduce restlessness
Occupational therapy
Music therapy
Continued cognitive challenge - shown to slow deterioration rate
Analyze environment for safety and security
Consider day care centers
Assess needs of spouse/care giver
Consider nursing home
Referrals to:
- Visiting nurse
- Social worker
- Physical therapist
- Occupational therapist
- Lawyer
- Support groups for patient and family
- Assess driving safety

SURGICAL MEASURES

N/A

ACTIVITY

To whatever extent possible

DIET

No special diet

PATIENT EDUCATION

Printed patient and family information available from: Alzheimer's Association, 919 N. Michigan Ave., Suite 1000, Chicago, IL, (312)335-8700, (800)272-3900
Help family understand the progressive nature of the disease
Arrange durable power of attorney
Advance directives planning as early as possible

FOLLOW UP

PREVENTION/AVOIDANCE

None known for patient
Family members may seek genetic screening for presence of E4 allele of apolipoprotein E gene (kits already marketed), but such screening is not recommended

POSSIBLE COMPLICATIONS

Behavioral - hostility, agitation, wandering, uncooperativeness
Metabolic - infection, dehydration, drug toxicity, malnutrition
Others - falls, "sundowning"
Family or caregiver burnout
Depression occurs in third of patients
Suicide - in early stages, especially if depression present

EXPECTED COURSE AND PROGNOSIS

Poor; 8-10 year average survival

MISCELLANEOUS

ASSOCIATED CONDITIONS

Down syndrome
Depression
Insomnia

AGE-RELATED FACTORS

Pediatric: N/A
Geriatric: A frequent and serious problem in this age group
Others: N/A

PREGNANCY

N/A

OTHER NOTES

N/A

ABBREVIATIONS

DAT = dementia of Alzheimer's type

Clinical Investigations

ROLE OF HOMOEOPATHY

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