Alzheimer's Disease

The molecular origins of the disease are coming to light, suggesting several novel therapies

Vernon Ingram

The Diagnosis of Alzheimer's Disease

During much of the 20th century a diagnosis of Alzheimer's disease was difficult to confirm until the patient's brain could be examined after death—a thoroughly unsatisfactory situation. During the individual's lifetime the diagnosis was based on exclusion, since some other conditions produce similar cognitive deficits. For example, certain types of memory loss and certain behavioral changes can be caused by depression, malnutrition, medication side effects and vascular accident. The lack of rigor in diagnosis had unfortunate consequences: False positive diagnoses led to needless anxiety, whereas false negatives prevented suitable care and long-term planning.

Current diagnostic criteria rest on a carefully compiled behavioral assessment scale, sometimes combined with one or more forms of noninvasive functional neuroimaging. The diagnostic scale uses as many as a dozen different measurable cognitive parameters, all of which must show considerable changes before a diagnosis is made. This scale is a highly accurate tool in the hands of a skilled physician—even without imaging data, approximately 90 percent of diagnosed Alzheimer's sufferers are confirmed at autopsy.

Two new methods that directly examine brain activity have become invaluable tools in documenting the structural and functional changes associated with Alzheimer's disease. Magnetic resonance imaging (MRI) provides a detailed three-dimensional depiction of brain topography that can reveal the loss of brain tissue accompanying disease progression. The technique has become remarkably sensitive, even detecting the loss of brain volume during early stages of the disease when mild cognitive impairments might not warrant a behavioral diagnosis. Functional MRI (fMRI) and positron-emission tomography (PET) are both widely used to resolve areas of activity in the living brain. During the brain scans the subject performs a memory task. Differences between the images of Alzheimer's subjects and scans of normal brain activity can be dramatic.

Early diagnosis using these tools is important now; it will be crucial once effective therapy is available. Many of the disease symptoms are caused by the death of brain cells, and dead cells cannot be revived. Emerging treatments promise a not-too-distant future in which therapy will need to be applied before the patient becomes seriously demented. Eventually, science may perfect the use of stem cells to replace the dead brain cells, and early diagnostic screening for the disease might include genetic testing.