Alzheimer's Disease: Unraveling the Mystery

New Techniques Help in Diagnosing AD

A man in his mid-60s begins to notice that his memory isn’t as good as it used to be. More and more often, a word will be on the tip of his tongue but he just can’t remember it. He forgets appointments, makes mistakes when paying his bills, and finds that he’s often confused or anxious about the normal hustle and bustle of life around him. One evening, he suddenly finds himself walking in a neighborhood he doesn’t recognize. He has no idea how he got there or how to get home.

Not so long ago, this man’s condition would have been swept into a broad catch-all category called “senile dementia” or “senility.” Although we now know that AD and other causes of dementia are distinct diseases, in the early stages it is difficult to differentiate between the onset of AD and other types of age-related cognitive decline. We have improved our ability to diagnose AD correctly, and doctors experienced in AD can diagnose the disease with up to 90 percent accuracy. A definitive diagnosis of AD, however, is still only possible after death, during an autopsy, and we are still far from the ultimate goal—a reliable, valid, inexpensive, and early diagnostic marker that can be used in any doctor’s office.

Early diagnosis has several advantages. For example, many conditions cause symptoms that mimic those of AD. Finding out early that the observed changes in cognitive abilities are not AD but something else is almost always a relief and may be just the prod needed to seek appropriate medical treatment (see "Causes of Dementia" on page 50 for more information). For the small percentage of dementias that are treatable or even reversible, early diagnosis increases the chances of successful treatment. Increasing early diagnosis and improving treatment are among NIA’s most important goals.

Even when the cause of a loved one’s dementia turns out to be AD, it is best to find out sooner rather than later. One benefit of knowing is medical. The drugs now available to treat AD can help some people maintain their mental abilities for months to years, although they do not change the underlying course of the disease (see "Helping People with AD Maintain their Mental Functioning" for more about these drugs).

Other benefits are practical. The sooner the person with AD and the family have a firm diagnosis, the more time they have to make future living arrangements, handle financial matters, establish a durable power of attorney and advance directives, deal with other legal issues, create a support network, and even consider joining a clinical trial or other research study. Being able to participate for as long as possible in making personal decisions is important to many people with AD.

Early diagnosis also gives families time to recognize that life does not stop with a diagnosis of AD. The person is still able to participate in many of the daily activities he or she has always enjoyed, and families can encourage the person to continue with them for as long as possible. Finally, early diagnosis gives family caregivers the opportunity to learn how to recognize and cope with changes over time in their loved one as well as to develop strategies that support their own physical, emotional, and financial health.

Scientists also see advantages to early diagnosis. Developing tests that can reveal what is happening in the brain in the early stages of AD will help them understand more about the cause and development of the disease. It also will help scientists learn when and how to prescribe the use of drugs and other treatments so they can be most effective.

Current Tools for Diagnosing AD

With the tools now available, experienced physicians can be reasonably confident about making an accurate diagnosis of AD in a living person. Here is how they do it.

They take a detailed patient history, including:

  • A description of how and when symptoms developed.
  • A description of the person’s and his or her family’s overall medical condition and history.
  • An assessment of the person’s emotional state and living environment.

They get information from family members or close friends:

  • People close to the person can provide valuable insights into how behavior and personality have changed; many times, family and friends know something is wrong even before changes are evident on tests.

They conduct physical and neurological examinations and laboratory tests:

  • Blood and other medical tests help determine neurological functioning and identify possible non-AD causes of dementia.

They conduct neuropsychological testing:

  • Question-and-answer tests or other tasks that measure memory, language skills, ability to do arithmetic, and other abilities related to brain functioning help show what kind of cognitive changes are occurring.

They may do a computed tomography (CT) scan or a magnetic resonance imaging (MRI) test:

  • CT and MRI scans can detect strokes or tumors or can reveal changes in the brain’s structure that indicate early AD.

Exams and tests may be repeated every so often to give physicians information about how the person’s memory and other symptoms are changing over time.

Based on findings from these exams and tests, experienced physicians can diagnose or rule out other causes of dementia, or determine whether the person has MCI, “possible AD” (the symptoms may be due to another cause), or “probable AD” (no other cause for the symptoms can be found).

Causes of Dementia

Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—to such an extent that it interferes with a person’s daily life and activities. It is not a disease itself, but a group of symptoms that often accompanies a disease or condition. Some dementias are caused by neurodegenerative diseases. Dementia also has other causes, some of which are treatable.

Neurodegenerative Diseases That Cause Dementia

  • Alzheimer’s disease
  • Vascular dementia
  • Parkinson’s disease with dementia
  • Frontotemporal lobar degeneration, including:
    • frontotemporal dementia
    • frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17)
    • Pick’s disease
    • supranuclear palsy
    • corticobasal degeneration

Other Causes of Dementia

  • Medication side effects
  • Depression
  • Vitamin B12 deficiency
  • Chronic alcoholism
  • Certain tumors or infections of the brain
  • Blood clots pressing on the brain
  • Metabolic imbalances, including thyroid, kidney, or liver disorders


MRI scan in progressScientists are now exploring ways to help physicians diagnose AD earlier and more accurately. For example, some studies are focusing on changes in mental functioning. These changes can be measured through memory and recall tests. Tests that measure a person’s abilities in areas such as abstract thinking, planning, and language can help pinpoint changes in these areas of cognitive function. Researchers are working to improve standardized tests that might be used to point to early AD or predict which individuals are at higher risk of developing AD in the future.

Other studies are examining the relationship between early damage to brain tissue and outward clinical signs. Still others are looking for changes in biomarkers in the blood or cerebrospinal fluid that may indicate the progression of AD (see "Very Early Signs and Symptoms" for more on this work).

One of the most exciting areas of ongoing research in this area is neuroimaging. Over the past decade, scientists have developed several highly sophisticated imaging systems that have been used in many areas of medicine, including AD. PET scans, single photon emission computed tomography (SPECT), and MRI are all examples. These “windows” on the living brain may help scientists measure the earliest changes in brain function or structure in order to identify people who are at the very first stages of the disease—well before they develop clinically apparent signs and symptoms.

To help advance this area of research, NIA launched the multi-year AD Neuroimaging Initiative (ADNI) in 2004. This project is following about 200 cognitively healthy individuals and 400 people with MCI for 3 years and 200 people with early AD for 2 years. Over the course of this study, participants undergo multiple MRI and PET scans so that study staff can assess how the brain changes in the course of normal aging and MCI, and with the progression of AD. By using MRI and PET scans at regularly scheduled intervals, study investigators hope to learn when and where in the brain degeneration occurs as memory problems develop.

Another innovative aspect of ADNI is that scientists are correlating the participants’ imaging information with information from clinical, memory, and other cognitive function tests, and with information from blood, cerebrospinal fluid, and urine samples. Results from these samples may provide valuable biomarkers of disease progress, such as changing levels of beta-amyloid and tau, indicators of inflammation, measures of oxidative stress, and changing cognitive abilities.

An important ADNI achievement is the creation of a publicly accessible database of images, biomarker data, and clinical information available to qualified researchers worldwide. Biological samples also are available for approved biomarker projects. NIA hopes that this initiative will help create rigorous imaging and biomarker standards that will provide measures for the success of potential treatments. This would substantially increase the pace and decrease the cost of developing new treatments. The ADNI study is being replicated in similar studies by researchers in Europe, Japan, and Australia.

These types of neuroimaging scans are still primarily research tools, but one day they may be used more commonly to help physicians diagnose AD at very early stages. It is conceivable that these tools also may someday be used to monitor the progress of the disease and to assess responses to drug treatment.

New Technologies Help People Participate in AD Research at Home

older couple by computerThis photo shows ORCATECH study participants at home. The small device between the photographs on the wall is an infrared motion sensor.

Traditionally, AD scientists have collected data by asking people to come to a clinic once or twice a year over a period of years. They give the participants a physical exam and ask them to take a series of memory, language, and other cognitive function tests.

These studies collect much useful information, but they have their limitations. For one thing, participants are seen only once or twice during the year, so the data collected represent only a “snapshot” in time. The studies cannot effectively capture day-to-day fluctuations in behaviors and cognitive abilities. Another limitation is that participants are seen in a research setting, not in their natural community environment. For many, coming to the clinic can be inconvenient, difficult, or both.

Advances in technology, as shown in the two research projects described here, offer some hope for dealing with these challenges by bringing research to people right in their own homes.


Scientists who are trying to develop methods for diagnosing AD as early as possible continually grapple with two challenges in conducting their research. First, they need to find easy and accurate ways to collect data from older people, who often have physical, emotional, or cognitive problems. Second, they need to find ways to assess accurately the very early changes in physical or cognitive abilities that could indicate that AD is progressing.

Under an NIA grant, the Oregon Center for Aging and Technology (ORCATECH) at Oregon Health & Science University is exploring the use of unobtrusive, simple technology and intelligent systems to detect and monitor subtle changes in movement that may indicate age-related cognitive changes. This project is building on research that has suggested that motor-function changes may arise before memory changes become apparent (see "Very Early Signs and Symptoms" for more on this research).

All of the 300 study participants are 80 years or older or have a spouse of a similar age, and live independently in Portland-area retirement communities. Wireless, infrared motion sensors, like those used to automatically open grocery store doors, have been placed strategically throughout the participants’ homes to gather data about changes in their walking or dressing speed over time. Special software also has been installed on each participant’s home computer to measure motor skills and speed in typing or using a mouse. The sensors and computer software collect data about motion, not what the volunteer is actually doing. Privacy is largely not a concern therefore, because the volunteers are not directly observed and no video or photographs are taken.

The 3-year study began in early 2007, so results are not yet available. However, a small pilot study using the same type of sensors showed a clear difference in the walking speeds of people age 65 and older who had MCI, compared with cognitively healthy people of the same age, over time periods of nearly a year. These data suggest that a remote sensing system like this is a feasible technology and is potentially sensitive enough to distinguish accurately between affected and unaffected people.


Researchers at nearly 30 sites nationwide are comparing various ways of collecting data, including the use of an in-home “kiosk” that combines a touch-screen computer monitor with a telephone handset, an interactive voice-response system, and traditional mail and telephone. All three methods gather the same data about several areas known to be important in early detection of cognitive decline: memory; language skills; attention and concentration; activities of daily living; quality of life; health care and resource use; and changes in “global” well-being as measured by self-rating of health, cognition, and mood. This study is looking at questions such as how likely people are to complete the questions using each method, which method is the most efficient, and how sensitive each method is.

Having a data collection system that is easy to use and that collects data accurately and completely may encourage wider participation in AD clinical trials. It also may reduce the expense and burden of conducting AD research. Early results from this study show that the older participants were skeptical at first about using the kiosk, but once they learned how to use it, they became enthusiastic and excited about participating.


Publication Date: September 2008
Page Last Updated: January 22, 2015

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