makes mistakes when paying his bills, and finds
medical treatment (see Causes of Dementia on
that he’s often confused or anxious about the normal
page 50 for more information). For the small
hustle and bustle of life around him. One evening, he percentage of dementias that are treatable or suddenly finds himself walking in a neighborhood he even reversible, early diagnosis increases the doesn’t recognize. He has no idea how he got there or
chances of successful treatment. Increasing early
how to get home.
diagnosis and improving treatment are among
N
NIA’s most important goals.
ot so long ago, this man’s condition
Even when the cause of a loved one’s dementia
would have been swept into a broad
turns out to be AD, it is best to find out sooner
catch-all category called “senile
rather than later. One benefit of knowing is medi-
dementia” or “senility.” Although we
cal. The drugs now available to treat AD can help
now know that AD and other causes of dementia are some people maintain their mental abilities for distinct diseases, in the early stages it is difficult to months to years, although they do not change the differentiate between the onset of AD and other types underlying course of the disease (see Helping of age-related cognitive decline. We have improved People with AD Maintain their Mental Function-our ability to diagnose AD correctly, and doctors
ing on page 55 for more about these drugs).
experienced in AD can diagnose the disease with up
Other benefits are practical. The sooner the per-
to 90 percent accuracy. A definitive diagnosis of AD, son with AD and the family have a firm diagnosis, however, is still only possible after death, during an the more time they have to make future living autopsy, and we are still far from the ultimate goal— arrangements, handle financial matters, establish a reliable, valid, inexpensive, and early diagnostic
a durable power of attorney and advance direc-
marker that can be used in any doctor’s office.
tives, deal with other legal issues, create a support
Early diagnosis has several advantages. For
example, many conditions cause symptoms that
48 ALZHEIMER’S DISEASE Unraveling the Mystery
Current Tools for Diagnosing AD
With the tools now available, how behavior and personality They may do a computed experienced physicians
have changed; many times,
tomography (CT) scan or a
can be reasonably confident about
family and friends know some-
magnetic resonance imaging
making an accurate diagnosis of
thing is wrong even before
(MRI) test:
AD in a living person. Here is
changes are evident on tests.
■ CT and MRI scans can detect
how they do it.
strokes or tumors or can reveal
They conduct physical and
changes in the brain’s structure
They take a detailed
neurological examinations
that indicate early AD.
patient history, including:
and laboratory tests:
■ A description of how and when ■ Blood and other medical tests Exams and tests may be repeated
symptoms developed.
help determine neurological
every so often to give physicians
■ A description of the person’s
functioning and identify possible information about how the person’s and his or her family’s overall
non-AD causes of dementia.
memory and other symptoms are
medical condition and history.
changing over time.
■ An assessment of the person’s
They conduct neuro-
Based on findings from these
emotional state and living
psychological testing:
exams and tests, experienced
environment.
■ Question-and-answer tests
physicians can diagnose or rule
or other tasks that measure
out other causes of dementia, or
They get information
memory, language skills, ability determine whether the person has from family members or
to do arithmetic, and other
MCI, “possible AD” (the symptoms
close friends:
abilities related to brain func-
may be due to another cause), or
■ People close to the person can
tioning help show what kind of
“probable AD” (no other cause for
provide valuable insights into
cognitive changes are occurring. the symptoms can be found).
network, and even consider joining a clinical trial
with them for as long as possible. Finally, early
or other research study. Being able to participate
diagnosis gives family caregivers the opportunity to
for as long as possible in making personal decisions learn how to recognize and cope with changes over is important to many people with AD.
time in their loved one as well as to develop strate-
Early diagnosis also gives families time to rec-
gies that support their own physical, emotional,
ognize that life does not stop with a diagnosis of
and financial health.
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
ALZHEIMER’S DISEASE Unraveling the Mystery 49
P A R T 3
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
Other Causes of Dementia
■ Alzheimer’s disease
■ Medication side effects
■ Vascular dementia
■ Depression
■ Parkinson’s disease with dementia
■ Vitamin B deficiency
12
■ Frontotemporal lobar degeneration, including:
■ Chronic alcoholism
■ frontotemporal dementia
■ Certain tumors or infections of
■ frontotemporal dementia with parkinsonism
the brain
linked to chromosome 17 (FTDP-17)
■ Blood clots pressing on the brain
■ Pick’s disease
■ Metabolic imbalances, including
■ supranuclear palsy
thyroid, kidney, or liver disorders
■ corticobasal degeneration
Scientists also see advantages to early diagnosis. measured through memory and recall tests. Tests Developing tests that can reveal what is happen-that measure a person’s abilities in areas such as
ing in the brain in the early stages of AD will help abstract thinking, planning, and language can them understand more about the cause and devel-help pinpoint changes in these areas of cognitive
opment of the disease. It also will help scientists
function. Researchers are working to improve
learn when and how to prescribe the use of drugs
standardized tests that might be used to point
and other treatments so they can be most effective. to early AD or predict which individuals are at higher risk of developing AD in the future.
EXCITING NEW DEVELOPMENTS
Other studies are examining the relation-
IN AD DIAGNOSIS
ship between early damage to brain tissue and
Scientists are now exploring ways to help physicians outward clinical signs. Still others are looking diagnose AD earlier and more accurately. For
for changes in biomarkers in the blood or cere-
example, some studies are focusing on changes
bro-spinal fluid that may indicate the progression
in mental functioning. These changes can be
of AD (see Very Early Signs and Symptoms on
page 28 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
50 ALZHEIMER’S DISEASE Unraveling the Mystery
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 fol-
lowing 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
Biological samples also are available for approved
and MCI, and with the progression of AD. By
biomarker projects. NIA hopes that this initiative
using MRI and PET scans at regularly scheduled will help create rigorous imaging and biomarker intervals, study investigators hope to learn when
standards that will provide measures for the
and where in the brain degeneration occurs as
success of potential treatments. This would
memory problems develop.
substantially increase the pace and decrease the
Another innovative aspect of ADNI is that
cost of developing new treatments. The ADNI
scientists are correlating the participants’ imaging study is being replicated in similar studies by information with information from clinical,
researchers in Europe, Japan, and Australia.
memory, and other cognitive function tests, and
These types of neuroimaging scans are still
with information from blood, cerebrospinal fluid, primarily research tools, but one day they may be and urine samples. Results from these samples
used more commonly to help physicians diagnose
may provide valuable biomarkers of disease
AD at very early stages. It is conceivable that
progress, such as changing levels of beta-amyloid these tools also may someday be used to monitor and tau, indicators of inflammation, measures of the progress of the disease and to assess responses oxidative stress, and changing cognitive abilities.
to drug treatment.
An important ADNI achievement is the
creation of a publicly accessible database of
images, biomarker data, and clinical information
available to qualified researchers worldwide.
ALZHEIMER’S DISEASE Unraveling the Mystery 51
P A R T 3 AD Research: Better Questions, New Answers New Technologies Help People Participate in AD Research at Home Traditionally, AD scientists have collected data by Science University is exploring the use of unobtrusive, asking people to come to a clinic once or twice a simple technology and intelligent systems to detect year over a period of years. They give the participants and monitor subtle changes in movement that may a physical exam and ask them to take a series of
indicate age-related cognitive changes. This project is
memory, language, and other cognitive function tests.
building on research that has suggested that motor-
These studies collect much useful information, but
function changes may arise before memory changes
they have their limitations. For one thing, participants become apparent (see Very Early Signs and are seen only once or twice during the year, so the
Symptoms on page 28 for more on this research).
data collected represent only a “snapshot” in time.
All of the 300 study participants are 80 years or
The studies cannot effectively capture day-to-day
older or have a spouse of a similar age, and live
fluctuations in behaviors and cognitive abilities.
independently in Portland-area retirement commu-
Another limitation is that participants are seen in
nities. Wireless, infrared motion sensors, like those
a research setting, not in their natural community
used to automatically open grocery store doors, have
environment. For many, coming to the clinic can be
been placed strategically throughout the participants’
inconvenient, difficult, or both.
homes to gather data about changes in their walking
Advances in technology, as shown in the two
or dressing speed over time. Special software also
research projects described here, offer some hope
has been installed on each participant’s home
for dealing with these challenges by bringing
computer to measure motor skills and speed in typing
research to people right in their own homes.
or using a mouse. The sensors and computer software
collect data about motion, not what the volunteer
MOTION DETECTORS TELL
is actually doing. Privacy is largely not a concern
AN INTERESTING STORY
therefore, because the volunteers are not directly
Scientists who are trying to develop methods for
observed and no video or photographs are taken.
diagnosing AD as early as possible continually
The 3-year study began in early 2007, so results
grapple with two challenges in conducting their
are not yet available. However, a small pilot study
research. First, they need to find easy and accurate
using the same type of sensors showed a clear
ways to collect data from older people, who often
difference in the walking speeds of people age 65
have physical, emotional, or cognitive problems.
and older who had MCI, compared with cognitively
Second, they need to find ways to assess accurately
healthy people of the same age, over time periods
the very early changes in physical or cognitive
of nearly a year. These data suggest that a remote
abilities that could indicate that AD is progressing.
sensing system like this is a feasible technology and is
Under an NIA grant, the Oregon Center for Aging potentially sensitive enough to distinguish accurately and Technology (ORCATECH) at Oregon Health &
between affected and unaffected people.
52 ALZHEIMER’S DISEASE Unraveling the Mystery
This photo shows ORCATECH
study participants at home. The
small device between the photo-
graphs on the wall is an infrared
motion sensor.
USING TECHNOLOGY
mood. This study is looking at questions such as
TO COLLECT DATA AT HOME
how likely people are to complete the questions
Researchers at nearly 30 sites nationwide are
using each method, which method is the most
comparing various ways of collecting data, including efficient, and how sensitive each method is.
the use of an in-home “kiosk” that combines a
Having a data collection system that is easy to
touch-screen computer monitor with a telephone
use and that collects data accurately and completely
handset, an interactive voice-response system, and
may encourage wider participation in AD clinical
traditional mail and telephone. All three methods
trials. It also may reduce the expense and burden of
gather the same data about several areas known to
conducting AD research. Early results from this study
be important in early detection of cognitive decline:
show that the older participants were skeptical at first
memory; language skills; attention and concentration; about using the kiosk, but once they learned how to activities of daily living; quality of life; health care
use it, they became enthusiastic and excited about
and resource use; and changes in “global” well-being participating.
as measured by self-rating of health, cognition, and
ALZHEIMER’S DISEASE Unraveling the Mystery 53
P A R T 3 AD Research: Better Questions, New Answers Search
The
for New Treatments
More and more, scientists are able most immediate need is for treatments to control to think about ways to treat, slow,
cognitive loss as well as problem behaviors, such as
or perhaps even prevent AD at a
aggression, agitation, wandering, depression, sleep
number of possible points during
disturbances, hallucinations, and delusions. Safe
the years-long continuum of disease progression.
medications that remain effective over time are
This continuum begins with the very earliest
needed to ease a broad range of symptoms and to
disease stage, even before symptoms are evident,
improve a person’s cognitive function and ability
moves to the first signs of memory and cognitive
to carry out activities of daily living. Scientists also
problems, then continues through the mild and
are investigating treatments that combine medica-
moderate stages, and ends with the very late stages tions with lifestyle strategies to lessen the risk of and the person’s death.
developing cognitive decline or AD. Eventually,
As a result, researchers who focus on developing scientists hope to develop treatments that attack AD treatments think a lot about the importance
the earliest manifestations and underlying causes
of timing: When would it be best to intervene
of AD, thereby slowing, delaying, or preventing
and what interventions are most appropriate at
the disease from progressing and damaging cog-
which time? These questions are similar to those
nitive function and quality of life. Scientists use
asked with other conditions, such as heart disease. clinical trials to pursue all these goals.
For example, a physician would prescribe different
Today, NIA, other NIH institutes, and private
treatments for a patient who is seemingly healthy
industry are conducting many clinical trials of
but who is at risk of having future heart disease
AD interventions (see page 59 for more about
than for a patient who is actually having a heart
clinical trials). These studies focus on several
attack or whose heart disease is well established. The key areas: same decision process now can be applied to AD.
It has become clear that there probably is no
■ Helping people with AD maintain their mental
single “magic bullet” that will, by itself, prevent or
functioning
cure AD. Therefore, investigators are working to
■ Managing symptoms
develop an array of options from which physicians ■ Slowing, delaying, or preventing AD
can choose. For people who already have AD, the
54 ALZHEIMER’S DISEASE Unraveling the Mystery
HELPING PEOPLE WITH
AD MAINTAIN THEIR MENTAL
FUNCTIONING
In the mid-1970s, scientists discovered that
levels of a neurotransmitter (a chemical that carries
messages between neurons) called acetylcholine
fell sharply in people with AD. This discovery was
one of the first that linked AD with biochemical
changes in the brain. Scientists found that
acetylcholine is a critical player in the process of
forming memories. It is used by neurons in the
hippocampus and cerebral cortex, which are areas
of the brain important to memory function. This
discovery was an important initial breakthrough in
the search for drugs to treat AD.
Four medications, tested in clinical trials, have
been approved by the FDA for use in treating AD
symptoms. Donepezil (Aricept®), rivastigmine
(Exelon®), and galantamine (Razadyne®) are pre-
scribed to treat mild to moderate AD symptoms.
Donepezil was recently approved to treat severe
AD as well. These drugs, known as cholinesterase
inhibitors, act by stopping or slowing the action of
acetylcholinesterase, an enzyme that breaks down
acetylcholine. They help to maintain higher levels
of acetylcholine in the brain. In some people, the
drugs maintain abilities to carry out activities of
daily living. They also may maintain some think-
ing, memory, or speaking skills, and can help with
certain behavioral symptoms. However, they will
not stop or reverse the underlying progression of
AD and appear to help people only for months to
a few years. The newest approved AD medication
is memantine (Namenda®), which is prescribed to
treat moderate to severe AD symptoms. This drug
appears to work by regulating levels of glutamate,
another neurotransmitter involved in memory
function. Like the cholinesterase inhibitors,
memantine will not stop or reverse AD.
ALZHEIMER’S DISEASE Unraveling the Mystery 55
P A R T 3 AD Research: Better Questions, New Answers MANAGING SYMPTOMS
The damage of AD affects many different parts
“My father is often agitated. He paces up and down,
of the brain. This presents a problem because even
wringing his hands and crying. I know he’s sad or
small tasks require the brain to process signals that
anxious about something but he can’t tell me what’s
often involve more than one region of the brain. If
bothering him. Asking him about it just makes him
this processing is disrupted because of AD, the
more upset.”
person may not be able to do the task or may act
in a strange or inappropriate way.
“Last week, I visited Mom in the nursing home. We
In light of our growing understanding about the
had a great time. Then yesterday, I went to see her
effects of AD on the brain, behaviors like the ones
again. When I walked into her room, she didn’t know highlighted above suddenly make sense or even me. She thought I was her sister.”
provide a loving opportunity for caregivers:
“My husband used to be such an easy going, calm
For a man who can no longer distinguish between past
person. Now, he suddenly lashes out at me and uses
and present, the anguish caused by the death of a par-
awful language. Last week, he got angry when our
ent may be as real today as it was many years before.