Dementia

Ann Marie Hake

Martin R. Farlow

Dementia is defined as a decline in memory and at least one other cognitive function that impairs the patient’s ability to function in activities of daily living. Behavioral abnormalities are common and contribute to functional impairment. Neurodegenerative processes, particularly Alzheimer’s disease (AD), account for more than 90% of dementia cases. Therapeutic aims are to identify the few patients with reversible etiologic factors and palliate disabling symptoms for as long as possible, while the condition, inevitably, will eventually worsen.

I. DEMENTIA (REVERSIBLE CAUSES)

The percentage of patients with dementia having reversible underlying etiologic factors is relatively small (2% to 3%). However, as many as 40% of patients with no reversible etiologic factors have treatable conditions, the correction of which can improve temporarily the patient’s ability to function.

A. Structural lesions causing dementia.

Space-occupying masses or abnormalities in brain structure for which the patient can be treated may be identified with brain imaging studies, including CT, MRI, single photon emission computed tomography, and positron emission tomography. Unfortunately, neurosurgical intervention in many of these patients can halt deterioration but not greatly improve clinical symptoms.

1. Normal pressure hydrocephalus.

Patients with gait abnormalities, urinary incontinence, dementia, and ventricular enlargement out of proportion to sulci on CT and MRI images should be referred for neurosurgical evaluation and possible placement of a ventriculoperitoneal shunt. Patients whose symptoms improve after lumbar puncture are particularly likely to improve after shunting. Gait and incontinence are more likely to improve than is memory. Overall, one-third of patients improve, one-third remain unchanged, and one-third have progressive symptoms.

2. Subdural hematoma and hygroma.

Chronic subdural hematoma and hygroma can be asymptomatic or cause cognitive impairment or frank dementia in the elderly. Neurosurgical evaluation is required. Increases in the size of the fluid collection and progressive clinical impairment are indications for surgical intervention. Surgery often does not improve cognition but stops progression of cognitive impairment.

3. Frontal, temporal, and parietal lobe tumors.

Large meningiomas, gliomas, and metastases to the brain that occupy substantial space or cause marked edema in the adjacent frontal, temporal, or parietal lobe can cause dementia. Patients with such tumors should be treated by means of neurosurgical excision or by biopsy and radiation therapy or chemotherapy, as appropriate for the tumor type and location. Among patients older than 65 years, the prognosis for meaningful recovery from cognitive impairment and clinical dysfunction after such treatments is guarded.

4. Closed head injuries,

even mild injuries or injuries involving rapid acceleration or deceleration of the brain without an actual blow to the head can produce a subsequent postconcussive syndrome characterized by impaired memory, concentration, and processing speed; affective symptoms such as irritability, depression, or anxiety; and somatic symptoms including headache, dizziness, nausea, fatigue, disturbed sleep, blurred vision, tinnitus, photophobia, or phonophobia. The severity of the initial head injury does not necessarily correlate with the severity of the postconcussive symptoms. The mechanism of injury is thought to be diffuse axonal injury through axonal shearing, especially in the frontal lobes. Treatment is pharmacological and rehabilitative treatment of the symptoms while avoiding further injury.

B. Metabolic and nutritional abnormalities associated with dementia.

Relatively subtle deviations from the normal ranges for laboratory parameters can cause or significantly exacerbate mental impairment in elderly patients. A history of fluctuating cognitive deficits suggests a metabolic cause of dementia. Changes in mental status often are reversible with correction of the metabolic disturbance or nutritional deficiency.

1. Hyponatremia and hypernatremia.

Hypernatremia is most common in association with dehydration and may be found in physically impaired patients who are dependent on caregivers for their oral intake. For dehydrated patients, both free water and electrolytic deficits should be calculated and corrected, and body weight and electrolytes should be measured frequently and adjusted as necessary. Relatively minor hyponatremia with serum sodium (Na⁺) at 120 to 130 mg per dl can significantly impair cognition in the elderly. Correction of hyponatremia can totally reverse mental impairment. Hyponatremia with Na⁺ <120 mg per dl should be corrected over 3 or more days because overrapid normalization can precipitate CNS demyelination.

2. Hypocalcemia and hypercalcemia.

Abnormalities in serum calcium levels can be associated with hypoparathyroidism or hyperparathyroidism, antihypertensive therapy, cancer, and renal disease. The underlying cause should be determined and managed.

3. Hypoglycemia and hyperglycemia.

Many patients with diabetes mellitus have dementia with varying degrees of reversibility. The long-term effects of diabetes mellitus can contribute to both microvascular disease and accelerate atherosclerosis in the major vessels supplying the brain. Both can cause vascular dementia. Many patients with diabetes have very high-blood glucose levels (>300 to 400 mg per dl) and variable changes in mental status during the day. These changes may be difficult to recognize and treat. Similarly, some patients may have periods of confusion associated with unrecognized hypoglycemia. Management of glucose abnormalities requires careful monitoring of blood glucose levels and correction by adjustments in diet and in dosages of oral hypoglycemic agents, or by means of insulin injections as necessary to achieve normal blood glucose levels.

4. Cobalamin (vitamin B₁₂) deficiency.

Chronic serum levels of cobalamin of 200 pg per ml or lower can be associated with various hematological, gastrointestinal, and neurological abnormalities. Typical reversible neuropsychiatrie deficits that can be seen with B₁₂ deficiency include psychotic symptoms and deficits in concentration and visuospatial and executive function.

C. Endocrine abnormalities that cause dementia.

Chronic endocrine diseases can cause cognitive impairment in elderly persons with few other physical findings associated with hormonal deficiency or excess. Detection and correction of these conditions can lead to complete reversal of dementia, including return to normal activities of daily living.

1. Thyroid disease.

a. Hypothyroidism.

In the elderly, hypothyroidism should be managed initially with levothyroxine (T₄) at a dosage of 0.025 mg per day. The dosage may be increased in 0.025 mg increments at monthly intervals, with routine monitoring of T₄ and thyroid-stimulating hormone levels. The dose should be increased until symptoms improve and until T₄ levels are in the therapeutic range. If the initial T₄ thyroid level is very low in an elderly patient, supplemental steroids, such as prednisone at 5.0 to 7.5 mg per day, may be given for the first 2 weeks after levothyroxine is initiated.

b. Hyperthyroidism.

An endocrinologist should generally be consulted and appropriate therapy begun, including propranolol to decrease pulse rate and anxiety, medical therapy with methimazole or with radioactive iodine, or surgical excision of the thyroid gland. Most mental status changes associated with thyroid disease are reversible.

2. Diabetes mellitus.

See I.B.4.

3. Hypoparathyroidism and hyperparathyroidism.

See I.B.3.

D. Dementia secondary to systemic organ failure.

The CNS depends on normal functioning of all of the major organ systems. Mild abnormalities in systemic organ functions in an elderly patient can cause mental status changes including confusion, disorientation, and memory loss.

1. Pulmonary disease.

Both acute illnesses (such as pneumonia) and chronic obstructive pulmonary disease can cause hypoxemia resulting in dementia. Supplemental oxygen
administered by nasal cannula or face mask can improve cognitive function. Various diseases of the lungs, particularly small-cell cancer, can metastasize or have distant effects on the brain and cause dementia. The underlying tumor should be the focus of treatment.

2. Hepatic disease.

Diseases of the liver, such as hepatitis and cirrhosis, can cause dementia. The dementia is often associated with elevated blood ammonia levels. The underlying liver disease is the focus of treatment. Cognitive improvement results from lowering ammonia levels with lactulose, rifaxamin, or both.

3. Cardiac disease.

Cardiac dysfunction can impair cognitive functioning in different ways. Congestive heart failure can decrease the blood supply to the brain. Enlarged heart chambers and valvular disease can promote formation of thrombi that can embolize to the brain. Arrhythmias may decrease blood flow to the brain. Management of the underlying cardiac disease should be the focus.

4. Renal disease.

Chronic or acute renal failure can cause uremic encephalopathy. Dialysis and transplantation have decreased the frequency of this illness. Patients with renal disease are more prone to fluctuating changes in mental status resulting from a variety of metabolic abnormalities.

E. Autoimmune disorders.

Several autoimmune disorders have been found to cause progressive deterioration of mental function. Paraneoplastic antibodies such as ANNA-1 (Hu), Ma2, CRMP, and voltage-gated potassium channel (VGKC) antibodies may occur in individuals with cancers. These antibodies have been associated most often with cancers of the lung, but have also been described with numerous other neoplasms; in other patients, especially with VGKC antibodies, no tumor is found. Treatment consists of identifying and treating the associated cancer and administering high-dose corticosteroids; additional immunological therapy such as intravenous immune globulin or plasma exchange, or other immunosuppressants may be needed. Other steroid-responsive encephalopathies include Hashimoto’s encephalopathy, which is associated with thyroglobulin or thyroid peroxidase antibodies, and other nonvasculitic autoimmune inflammatory meningoencephalitides in which no specific autoantibody is identified. Impaired mental status can also be seen in individuals with connective tissue disorders such as systemic lupus erythematosus or Sjögren’s syndrome; the underlying condition should be treated.

Only gold members can continue reading. Log In or Register to continue