Alzheimer’s disease

Alzheimer’s disease

•Dementia is a syndrome characterized by progressive loss of previously acquired cognitive skills including memory, language, insight, and judgment.

•Alzheimer's disease accounts for the majority (50% to 75%) of all cases of dementia.

•Approximately 10% of all persons over the age of 70 have significant memory loss, and in more than half the cause is AD

EPIDEMIOLOGY & DEMOGRAPHICS

•INCIDENCE: Risk doubles every 5 yr after the age of 65; above the age of 85th incidence is about 8%.

•PREVALENCE: Currently an estimated 4 million Americans have AD; 7% between the ages of 65 and 74, 53% between the ages of 75 and 84, and 40% over the age of 85.

•PREDOMINANT SEX: Female

The Brain and Alzheimer’s Disease

Two major structural changes:

1.Neurofibrillary tangles-Bundles of twisted threads that are the product of collapsed neural structures (contain abnormal forms of tau protein

2.Amyloid plaques-Dense deposits of deteriorated amyloid protein, surrounded by clumps of dead nerve and glial cells.

earliest and most severe degeneration is usually found in the medial temporal lobe

: (entorhinal/perirhinal cortex hippocampus),

   lateral temporal cortex, nucleus basalis of Meynert

These images represent a cross-section of the brain as seen from the front. The cross-section on the left represents a normal brain and the one on the right represents a brain with Alzheimer's disease.In Alzheimer's disease, there is an overall shrinkage of brain tissue. The grooves or furrows in the brain, called sulci (plural of sulcus), are noticeably widened and there is shrinkage of the gyri (plural of gyrus), the well-developed folds of the brain's outer layer. In addition, the ventricles, or chambers within the brain that contain cerebrospinal fluid, are noticeably enlarged. In the early stages of Alzheimer's disease, short-term memory begins to fade (see box labeled ‘memory') when the cells in the hippocampus, which is part of the limbic system, degenerate. The ability to perform routine tasks also declines. As Alzheimer's disease spreads through the cerebral cortex (the outer layer of the brain), judgment declines, emotional outbursts may occur and language is impaired. As the disease progresses, more nerve cells die, leading to changes in behavior, such as wandering and agitation. In the final stages of the disease, people may lose the ability to recognize faces and communicate; they normally cannot control bodily functions and require constant care. On average, the disease lasts for 8 to 10 years, but individuals with Alzheimer’s can live for up to 20 years.

Severe Alzheimer’s Disease

Several competing hypotheses:

Cholinergic hypothesis

-Caused by reduced synthesis of acetylcholine

-Destruction of these neurons causes disruptions in distant neuronal networks (perception, memory, judgment)

Amyloid hypothesis

-Abnormal breakdown; buildup of amyloid beta deposits

-Damaged amyloid proteins build to toxic levels, causing call damage and death

Tau hypothesis

-Caused by tau protein abnormalities

-Formation of neurofibrillary tangles

PHYSICAL FINDINGS & CLINICAL PRESENTATION

•Family member, not the patient, often notes insidious memory impairment.    

•Patients have difficulties learning and retaining new information, handling complex tasks (e.g., balancing the checkbook), and have impairments in reasoning, judgment, spatial ability, and orientation (e.g., difficulty driving, getting lost away from home). 

•Behavioral changes, such as mood changes and apathy, may accompany memory impairment.

In later stages patients may develop agitation and psychosis.

DIAGNOSIS

•Diagnosis is dependent on clinical history, a thorough physical and neurologic examination, and use of reliable and valid diagnostic criteria (i.e., DSM-IV or NINDCS-ADRDA) such as the following:

•  Loss of memory and one or more additional cognitive abilities (aphasia, apraxia, agnosia)

• Insidious onset and gradual progression of symptoms

• Impairment in social or occupational functioning

• Cognitive loss documented by neuropsychologic tests  

• No physical signs, neuroimaging, or laboratory evidence of other diseases that can cause dementia (i.e., metabolic abnormalities, medication or toxin effects, infection, stroke, Parkinson's disease, subdural hematoma, or tumors)

•There is no definitive imaging or laboratory test for the diagnosis of dementia.

•NINCDS–ADRDA :National Institute of Neurological Disorders and Stroke—Alzheimer’s Disease and Related Disorders Association

•DSM-IV :Diagnostic and Statistical Manual of Mental Disorders

DIFFERENTIAL DIAGNOSIS

•Cancer (brain tumor, meningeal neoplasia)

•Infection (AIDS, neurosyphilis, progressive multifocal leucoencephalopathy)

•Metabolic (alcohol, hypothyroidism, B12 deficiency)

•Organ failure (dialysis dementia, Wilson's disease)

•Vascular disorder (chronic subdural hematoma)

•Depression

WORKUP

•HISTORY & GENERAL PHYSICAL EXAMINATION:   

• Medication use should always be reviewed for drugs that may cause mental status changes.  

•Patients should be screened for depression, because it can sometimes mimic dementia but also often occurs as a coexisting condition and should be treated.

•On examination, look for signs of metabolic disturbance, presence of psychiatric features, or focal neurologic deficits.

•MENTAL STATUS TESTING:

•Brief mental status testing.

•Most commonly used is the Folstein Mini-Mental Status Examination (MMSE). A MMSE score <24 (scores range from 0 to 30, with lower scores reflecting poorer performance) suggests dementia;

•MMSE is not sensitive enough to detect– mild dementia,
– dementia in patients with high baseline IQ.– Scores may be spuriously low in patients with limited education, poor motor function, poor language skills, or impaired vision.

•Attention is usually preserved until the late stages of AD, so consider alternate diagnoses in patients who do poorly on tests of attention.

LABORATORY TESTS

•CBC
•Serum electrolytes. BUN/creatinine •Glucose , Liver and thyroid function tests•Serum vitamin B12 and methylmalonic acid•Syphilis serology, if high clinical suspicion•Lumbar puncture if history or signs of cancer, infectious process, or when the clinical presentation is unusual (i.e., rapid progression of symptoms)
•EEG if there is history of seizures, episodic confusion, rapid clinical decline, or suspicion of Creutzfeldt-Jakob disease
•Measurement of apolipoprotein E genotyping, CSF tau and amyloid,

•Functional imaging including positron emission tomography (PET) or scanning proton emission computed tomography (SPECT) are not routinely indicated

•IMAGING STUDIES

•CT scan or MRI to rule out hydrocephalus and mass lesions, including subdural hematoma.

TREATMENT

•NONPHARMACOLOGIC THERAPY

•Patient safety, including risks associated with impaired driving, wandering behavior, leaving stoves unattended, and accidents, must be addressed with the patient and family early and appropriate measures implemented.

•Wandering, hoarding or hiding objects, repetitive questioning, withdrawal, and social inappropriateness often respond to behavioral therapies.

•ACUTE GENERAL Rx
–None

•CHRONIC Rx

1.    Symptomatic treatment of memory disturbance:a.    Cholinesterase inhibitors (ChEI): for mild to moderate AD (MMSE 10-26). Common side effects include nausea, diarrhea, and anorexia.b.    NMDA (N-methyl-D-aspartate )receptor antagonist: Memantine). for moderate to severe AD. Common side effects include constipation, dizziness, or headache. Memantine is contraindicated in patients with renal insufficiency or history of seizures.

2.    Symptomatic treatment of neuropsychiatric and behavioral disturbances: Depression, agitation, delusions, or hallucinations.