Although cognitive decline in advanced age has been recognized throughout history, the understanding that it represents the result of specific disease states is more recent. Longer life spans and increasing knowledge of the causes of cognitive decline, particularly Alzheimer's disease, has led to the prediction of dementia as an epidemic extending into the 21st century. The cost of caring for patients with dementia is already immense, approximately $100 billion annually in the US. The number of AD cases is expected to triple to nearly 15 million over the next 50 years.

Clinical Manifestations

The primary cognitive feature of AD is usually progressive memory impairment. The memory dysfunction involves impairment of learning new information which is often characterized as short-term memory loss. In the early (mild) and moderate stages of the illness, recall of remote well-learned material may appear to be preserved, but new information cannot be adequately incorporated into memory. Disorientation to time is closely related to memory disturbance.

Language impairments are also a prominent part of AD. These are often manifest first as word finding difficulty in spontaneous speech. The language of the AD patient is often vague, lacking in specifics and may have increased automatic phrases and cliches. Difficulty in naming everyday objects is often prominent. Complex deficits in visual function are present in many AD patients, as are other focal cognitive deficits such as apraxia, acalculia and left-right disorientation. Impairments of judgement and problems solving are frequently seen.

Non-cognitive or behavioral symptoms are common in AD and may account for an event larger proportion of caregiver burden or stress than the cognitive dysfunction. Personality changes are commonly reported and range from progressive passivity to marked agitation. Patients may exhibit changes such as decreased expressions of affection. In some cases, personality changes may predate cognitive abnormality. Depressive symptoms are present in up to 40%. A similar rate for anxiety has also been recognized. Psychosis occurs in 25%.

Differential Diagnosis

In order to bring uniformity to the diagnosis of such diverse symptoms, a joint National Institute of Health (NIH)/Alzheimer's Association working group (NINCDS-ADRDA) developed criteria for the clinical diagnosis of probable and possible AD. Of the patients diagnosed with probable AD using these criteria, the diagnosis is confirmed at autopsy 85-90%. In brief, the criteria require a one-year course of decline in two or more areas of cognition such as memory, language, visuospatial function, orientation, judgement and problem solving. Neurologic exam should be otherwise normal.

Pick's disease(now know as Frontal Type Dementia) is characterized by prominent behavioral disturbances, with relatively preserved cognition. Evidence of significant vascular disease can be found in as many as one-third of cases of dementia. A history of hypertension, stroke or clear-cut transient ischemic attacks and the presence of localizing signs on neurologic exam makes a vascular contribution to the dementia very likely. Other common dementias have prominent motor signs at presentation and have been called "subcortical dementias." These include a wide variety of Parkinson-like motor presentations accompanied by fluctuating cognitive abilities and, frequently, hallucinations. Normal pressure hydrocephalus is often raised as a possibility on radiologic studies. It should only be seriously considered when the dementia is mild and follows a more severe gait disturbance. Incontinence is variable.

Diagnostic Workup

The clinical approach to the patient presenting with memory problems is based on the identification of the specific cognitive changes noted in the NINCDS-ADRDA criteria. This involves physical and neurological examination accompanied by cognitive testing to identify the characteristic memory, language and other cognitive and non-cognitive symptoms. Mental status testing should include remembering three unrelated words, naming parts of common objects(lab coat: lapel, pocket, sleeve, cuff) and the clock-drawing test. The neurologic exam should focus on identifying localizing signs and Parkinsonism.

The screening for illness states which may mimic AD involves laboratory testing with particular emphasis on thyroid function, vitamin B12 levels and inflammatory or infectious states such as neurosyphilis or HIV. Head CT or MRI are useful to exclude structural lesions which may contribute to the dementia such as cerebral infarctions, neoplasm, extracerebral fluid collections and hydrocephalus. No currently available ante-mortem tests can provide definitive diagnosis despite the commercial availability of genetic and spinal fluid markers and neuroimaging.

Prognosis/Complications

The average survival for patients diagnosed with probable Alzheimer's disease is about eight years, though the range is quite wide and may extend in excess of 15 years. Younger onset patients may have somewhat more aggressive courses, with prominent language and visuospatial problems. Those individuals with onset in their eighties often have primarily memory loss and a more gradual decline. Delirium or acute confusion is a common complication of dementia even with fairly mild metabolic derangements.

Management

The management of dementia is complex; ideally, it involves an interdisciplinary approach to assessment, treatment and education. The roles of nursing, social work, psychology and case management can be vital to the effective longitudinal care of the patient with AD. The impact of a multidisciplinary treatment approach can be much greater than any medical or pharmacologic intervention in isolation. An important resource to draw upon is the Alzheimer's Association, a support and advocacy group which has many local chapters and provides a telephone help line (1-800-272-3900).

Non-pharmacologic management of patients is desirable whenever possible. Increased socialization, such as through day-care programs and improved sleep hygiene may minimize the need for pharmacologic intervention for many difficult behaviors. Acute changes in behavior suggest a complicating factor such as infection or metabolic disturbance. A major goal of the overall treatment plan should be the prevention of excess disability. This can be achieved by minimizing adverse drug effects and by maximizing caregiver skills and knowledge.

Pharmacologic approached include cognitive enhancers, such as tacrine (Cognex) and donepezil (Aricept). These cholinesterase inhibitors have been shown to improve cognition and delay functional decline in AD. Their use has been associated with reduced cost of illness and delayed nursing home placement. SSRI antidepressants are useful in managing depression and anxiety. Low doses of antipsychotic drugs (e.g. haloperidol 0.5 mg qd-bid) are useful in mild delusional states as well as more nonspecific agitation. Acute acting anxiolytics such as lorazepam are best reserved for patients with clear episodic anxiety, since they can increase confusion. Recently, clinical trials have suggested that antioxidants such as Vitamin E may slow the progression of AD. Other disease modifying agents such as estrogen and anti-inflammatory drugs are also in trials.

Participation in research programs is also of great value to caregivers, as it can convey a sense of hope for positive outcomes from an otherwise devastating illness. Research programs in northeastern Ohio may be accessed by calling the University Memory and Aging Center at (216) 844-6326.