Alzheimer Disease - Risks, Symptoms and Related Tests

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Alzheimer Disease
Also Known As: AD, Alzheimer Dementia, Presenile Dementia
This article was last modified on June 14, 2021
What is Alzheimer disease?

Alzheimer disease (AD) is an irreversible form of dementia characterized by memory loss, a
progressive decline in intellectual ability, deteriorating language and speech skills, and
personality and behavioral changes that eventually interfere with daily living. Currently,
Alzheimer disease has been estimated to affect more than 5.5 million Americans over the age
of 65 and about 200,000 under the age of 65.
Although some aspects of AD mimic changes found in the brain as we age, AD is not a normal
part of the aging process. Nerve cell injury and death occur due to the build-up of abnormal
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Alzheimer Disease - Risks, Symptoms and Related Tests 21.09.21, 19:48
protein structures in the brain called amyloid plaques, also known as senile plaques, and
neurofibrillary tangles. The destruction of nerve cells also results in decreased levels of
substances called neurotransmitters (the most important being acetylcholine) that help transmit
brain signals. Over time, AD results in decreased interaction between different areas of the
brain.
Relationship with Aging

The risk of having AD and other forms of dementia increases greatly with age. About 10% to
12% of the population will have dementia by the time they are 65 years old, with the risk
increasing to 50% for those who reach the age of 100. According to the Alzheimer’s
Association, with the U.S. population aging and living longer, it is estimated that the number of
those living with AD may be up to 16 million by 2050.
In general, “late onset” AD begins after the age of 65 and is not thought to be inherited. “Early
onset” AD, starting before the age of 65, accounts for about 5% to 10% of all AD cases and is
more likely to be caused by inherited mutations (disease-causing variants) in one of several
genes.
Genetic Relationship
While the more common, late onset Alzheimer disease appears to be caused by a variety of
factors that are still not well understood, three genes have been identified in association with a
certain form of early-onset familial Alzheimer (also known as Alzheimer disease type 3)
disease: PSEN1, PSEN2, and APP. A mutation in any one of these genes can lead to
abnormal protein production, which contributes to the senile plaques that cause progressive
dementia. Only one copy of one of these genes needs to be altered for it to cause AD, which
means that there is a 50% chance of inheriting this mutation from an affected parent. Genetic
testing of these genes may be recommended when a person has several generations of
individuals who are all diagnosed with AD prior to age 65.
No causative genes have been identified for late onset AD. However, a few genes have been
found to be associated with the disorder, meaning that people who have variants in these
genes aren’t guaranteed to develop late onset AD, but their risk is increased compared to
others in the general population who do not have these variants. These “susceptibility” genes
may explain why there is an increased risk of developing late onset AD in individuals who have
other affected family members.
The APOE gene is the most clearly established susceptibility gene for late onset AD. This gene
directs the production of apolipoprotein E, a protein that helps transport lipids (fats and
cholesterol) in the blood. The APOE gene exists in three different forms (alleles): e2, e3, and
e4. Everyone inherits a pair of APOE genes that contains some combination of these three
alleles. The e3 allele is the most common. It is present in approximately 60% of the general
population. The e4 allele has been established as a risk factor (particularly in familial versus
sporadic) for AD.
Most individuals with Down syndrome (DS), caused by the abnormal trisomy of chromosome
21, will eventually show some of the mental changes associated with AD, usually by the time
they are in their 40’s or 50’s. The pathology found in the brains of these adults with DS is very
similar to that found in AD. The extra copy of chromosome 21 causes an increased production
of the protein that accumulates and forms senile plaques similar to that seen in AD. Relatives
of individuals with DS do not have an increased risk of AD since they do not have the extra
copy of chromosome 21.
Other Risk Factors

The risk of AD appears to vary by ethnicity. Compared to Caucasians, individuals of African
American ancestry have a risk for AD that is approximately four times greater and individuals of
Hispanic ancestry have a risk approximately two times greater. In addition to ethnic
background, other risk factors that are associated with AD include: type 2 diabetes and milder
forms of insulin resistance, obesity, high blood pressure, unhealthy lipid levels, and high levels
of inflammatory markers such as C-reactive protein (CRP).
In 2011, new criteria and guidelines for the diagnosis of Alzheimer disease were released by
three expert workgroups spearheaded by the Alzheimer’s Association and the National Institute
on Aging (NIA) of the National Institutes of Health (NIH).
Their articles expand the definition of Alzheimer disease to include three stages:
1. Preclinical Alzheimer disease – measurable changes in biomarkers, including brain

imaging and certain proteins in the cerebrospinal fluid, but no outward symptoms; the
purpose of defining a preclinical stage is to help guide research.
2. Mild cognitive impairment (MCI) – mild changes in memory and thinking abilities that do
not compromise day to day activities; people with MCI may or may not progress to AD-
related dementia.
3. Dementia due to Alzheimer disease – memory, thinking and behavioral symptoms that
impair a person’s ability to function independently in daily life
These guidelines are intended to provide more information about the current understanding of
Alzheimer disease, provide a framework for future research, and to propose a stronger role for
biomarker use in the future.
About Alzheimer Disease
Signs and Symptoms #

According to the Alzheimer Association, there are 10 early signs and symptoms of
Alzheimer disease. While some memory problems are a normal part of aging, those
associated with Alzheimer disease usually are more serious and become more frequent.
They include:
Loss of memory that affects daily life—forgetting information that was recently learned.
This can occur with normal aging, but the information is usually remembered later.
This includes forgetting important dates or events, having to rely on memory aids, and
asking for the same information again and again.
Difficulty planning or problem solving, such as keeping track of bills and payments
Problems completing usual tasks, such as forgetting how to get to a familiar location
Confusion about place or time—losing track of time, forgetting where you are or how
you got there
Increasing difficulty reading or judging distances
Problems speaking or writing—forgetting words, repeating the same thing, struggling
with vocabulary
Losing things more frequently and not being able to logically retrace steps to find them
Impaired judgment, such as giving away unusually large amounts of money
Increasing withdrawal from activities, including social, work or family events
Changes in mood and personality, such as increasing anxiety, fear, suspicion and
depression
Tests #
There are no laboratory tests available that can determine whether or not a person has
Alzheimer disease (AD) during life. Currently, the only definitive way to establish a
diagnosis of AD is to microscopically examine a section of the person’s brain tissue after
death. Pathologists look for senile plaques and neurofibrillary tangles characteristic of AD.
Since plaque and tangle formation is also seen in normal aging, the sample must be
compared to a control sample of normal, non-AD brain tissue from a person of the same
age.
Healthcare practitioners can make a reasonably accurate clinical diagnosis of AD by using

a variety of tests and procedures to rule out other causes of dementia. When someone
presents with symptoms of dementia, the healthcare practitioner will evaluate the
individual’s personal and family history (preferably of several generations); perform a
physical exam; determine the age of onset, and give the person neuropsychological tests
to measure memory, language skills, and other cognitive functions.
Healthcare practitioners may use a range of general laboratory tests to rule out nutritional
deficiencies and other diseases and conditions that could be affecting the person’s
memory. They will also look for overmedication as a cause of symptoms. In addition,
they may use imaging tools, such as computed tomography (CT) and magnetic resonance
imaging (MRI) scans, to look for evidence of trauma, tumors, and stroke that could be
causing dementia and to look for brain atrophy, shrinkage that may be present later in the
Alzheimer disease progression.
These tests may be used to rule out causes of potentially reversible

dementia other than Alzheimer disease.
TEST SAMPLE ASSOCIATED WITH
Vitamin B12 Blood B12 deficiency
T4 Blood Thyroid disorder
TSH Blood Thyroid disorder
CBC Blood Anemia, infection
Electrolytes Blood Na+, K+, Cl-, CO2 and pH imbalance
CRP, ESR Blood Inflammation
HIV antibody Blood HIV/AIDS
Syphilis test Blood Syphilis
Drug screen Urine Illicit drug use
If a healthcare practitioner suspects AD, other less common laboratory tests (see Table
below) may be recommended to help differentiate between AD and other forms of
dementia, and to check for genetic risk factors.
Other Tests Used to Help Categorize Dementia
TEST
NAME TEST USE ASSOCIATED WITH
TYPE
Rule out AD Stroke and brain atrophy

CT (computed Body
or with late (shrinkage associated with
tomography) scan
stage AD late stage AD)
Imaging
tests MRI
Rule out AD
(magnetic Body
or with late Stroke and brain atrophy
resonance scan
stage AD
imaging)
TEST
NAME TEST USE ASSOCIATED WITH
TYPE
Used in research In symptomatic

Amyloid settings to establish people, decreased
Beta 42 presence of “tangles” Aß42 level along with
peptide or “plaque burden”; an elevated Tau
and Tau may help differentiate protein level
CSF
protein AD from other forms indicates an

correlation of dementia; Aβ42 increased likelihood
(Tau/Aß42) used in some of AD, regardless of
treatment trials the cause.
Roughly 65% of AD
patients have at least
Determine APOE
one APOE e4 allele;
genotype to provide
persons with 2 APOE
APOE risk factor
Blood e4 alleles have a
genotype assessment; adjunct
Less much higher risk for
test to confirm/rule
common AD, but this
out probable AD
lab tests genotype is much
less prevalent.
Associated with
Test for genetic about half of the
PSEN1 Blood
mutation cases of early onset
familial AD
Early onset familial

Test for genetic
AD; mutation very
PSEN2 Blood mutation; available in
rare, identified in only
only a few labs
a few family lines
Early onset familial

Test for genetic
AD; mutation very
APP Blood mutation; available in
rare, identified in only
only a few labs
a few family lines
Research is ongoing and new biomarkers, in addition to those listed in the table above,
are being studied.
Treatment #
There is currently no prevention or cure for Alzheimer disease (AD). People may live with
AD for up to 25 years, but the average is 8 to 10 years. Treatment consists of attempting

to maintain function, easing symptoms, managing behavioral issues, and providing the
affected person and caregivers with support and education. Early in the disease, those
with AD may be able to live fairly independent lives with some assistance, such as
memory aids and a structured environment. This is the time when the person can make
plans and participate in decisions about future care.
Early diagnosis of AD may allow some people to receive moderate benefit from
cholinesterase inhibitors. These medications may help to maintain intellectual ability by
preserving the function of the neurotransmitter acetylcholine.
Memantine may be prescribed to improve memory and attention, and antidepressants and
other drugs may also be used in small quantities throughout the progression of AD to
moderate personality and behavioral issues such as depression, agitation, paranoia, and
violence.
Whenever possible, the affected person’s other medications are evaluated and the
individual is taken off drugs that may worsen confusion. These may include central
nervous system depressants, antihistamines, sleeping pills, and analgesics.
Environmental modifications may be made to make the person’s home safer and more
familiar, and to make the person more comfortable.
While current research into the protective and therapeutic influences of certain substances
is promising, specific agents cannot yet be recommended. They each carry their own
associated risks and side effects. Further studies are needed to determine their actual
effectiveness and long-term safety.
Common Questions #
1. Besides Alzheimer disease, what are some other causes of confusion, memory
lapses, and cognitive decline?
Occasional forgetfulness is a normal part of aging and should not be a cause for
concern unless it increases in frequency or interferes with daily living. However, some
of the causes of cognitive decline, besides AD, include:
Medication interactions or side effects and over-medication; make sure you tell
your healthcare provider about all the medications you are taking.
Nutritional deficiencies, such as vitamin B12 deficiency
Having a history of another condition that may contribute to mental changes,

including diabetes, hypertension, or kidney, liver, or thyroid disorders
Structural disorders like brain tumors, head injuries, and normal pressure
hydrocephalus
Degenerative diseases, including age-related cognitive decline,
Huntington disease, Parkinson disease, and Pick disease
Infectious diseases like HIV/AIDS, Creutzfeldt-Jakob disease, meningitis,
encephalitis, or syphilis
Anxiety, depression
Heavy metal poisoning (for example, lead poisoning)
Seizures
2. Is there a way to get involved in research efforts related to Alzheimer disease?
Yes. Both affected and unaffected individuals can participate in clinical trials. In
addition, people can donate the brain tissue of a family member after their death. For
scientists to continue to study the causes of AD and to potentially find a cure, samples
are needed of brain tissue from people who had AD as well as from elderly people
who did not. You can find more information on clinical trials involving AD at the
ClinicalTrials.gov website.
3. Is there a link between mad cow disease and Alzheimer disease?
There is no evidence at this time of any connection between bovine spongiform
encephalopathy, commonly called mad cow disease, and Alzheimer disease even
though some of the symptoms may appear similar.
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Disease Facts and Figures
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Leslie M Shaw, PhD. Director, Toxicology Laboratory, Biomarker Research Laboratory,

Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of
Pennsylvania.
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Alzheimer Disease - Risks, Symptoms and Related Tests 21.09.

For COVID-19 information, see Coronavirus (COVID-19) Resources.

To order a COVID-19 test, see available tests here.

This article was last modified on June 14, 2021

What is Alzheimer disease?

Relationship with Aging

Other Risk Factors

1. Preclinical Alzheimer disease – measurable changes in biomarkers, including brain

biomarker use in the future.

About Alzheimer Disease

Signs and Symptoms #

Healthcare practitioners can make a reasonably accurate clinical diagnosis of AD by using

These tests may be used to rule out causes of potentially reversible

TEST SAMPLE ASSOCIATED WITH

Vitamin B12 Blood B12 deficiency

T4 Blood Thyroid disorder

TSH Blood Thyroid disorder

CBC Blood Anemia, infection

Electrolytes Blood Na+, K+, Cl-, CO2 and pH imbalance

CRP, ESR Blood Inflammation

HIV antibody Blood HIV/AIDS

Syphilis test Blood Syphilis

Drug screen Urine Illicit drug use

Other Tests Used to Help Categorize Dementia

Rule out AD Stroke and brain atrophy

Used in research In symptomatic

protein AD from other forms indicates an

Early onset familial

Early onset familial

AD for up to 25 years, but the average is 8 to 10 years. Treatment consists of attempting

Having a history of another condition that may contribute to mental changes,

Related Video and Images

On This Site Elsewhere on the Web

(© 2018). Treatment Horizon. Alzheimer’s association. Available online at

Sources Used in Previous Reviews

Functioning Longer. AARP Bulletin Online [On-line serial]. Available online at

Gottlieb, F. and Lambert, J. G. (2002, January 2, last update). Alzheimer’s Disease.

Michigan Alzheimer’s Disease Research Center. Available online at

Ian R.A. Mackenzie, MD FRCPC. Department of Pathology, Vancouver General Hospital,

s. Accessed April 2009.

(Reviewed 2012 December). Alzheimer’s Disease. NIHSeniorHealth [On-line information].

Leslie M Shaw, PhD. Director, Toxicology Laboratory, Biomarker Research Laboratory,

© 2021 Lab Tests Online. All rights reserved.

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