Also Known As
Alzheimer Dementia
Presenile Dementia
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This article waslast modified on December 14, 2017.
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 million Americans.

Although some aspects of AD mimic changes found in the brain as we age, AD is not a normal part of the aging process. Due to the build-up of abnormal protein structures in the brain called senile plaques (SPs) and neurofibrillary tangles (NFTs), nerve cell injury and cellular death occur. 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 genetically linked.

Genetic Relationship
Alzheimer disease appears to be caused by a variety of still not well understood factors. Three genes, whose normal function has yet to be determined, have been associated with rare forms of early onset familial Alzheimer disease (EOFAD, also called Alzheimer disease type 3 or AD3). Certain mutations in each of these genes (known as PSEN1, PSEN2, and APP) produce abnormal proteins that result in AD. There is a 50% chance that the gene mutation will be passed on to each of the affected person's children. So far, mutations in these three genes have only been found in a very small number of families.

At this time, testing for the presenilin 1 gene (PSEN1 on chromosome 14), presenilin II gene (PSEN2 on chromosome 1), and amyloid precursor protein gene (APP on chromosome 21) is available but not frequently ordered.

Other genes have been identified and have been linked to late onset AD yet are not thought to be a direct cause. 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 is some combination of these three. The e3 is the most common allele, found in 60% of the general population. Presence of the APOE e4 allele has been associated with the majority of familial cases and with an increased risk of AD.

The risk of AD may vary by ethnicity, with African Americans' risk as much as four times greater and Hispanics' as much as two times greater, respectively, than that of Caucasians. Other risk factors that have been associated with AD are type 2 diabetes and milder forms of insulin resistance, obesity, high blood pressure, dyslipidemia, and high levels of inflammatory markers such as C-reactive protein (CRP).

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.

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: 

  1. Preclinical Alzheimer disease – Measurable changes in biomarkers but no outward symptoms (intended only to help guide research for now)
  2. Mild cognitive impairment (MCI) due to Alzheimer disease – Mild changes in memory and thinking abilities that do not compromise day to day activities
  3. Dementia due to Alzheimer disease – Memory, thinking and behavioral symptoms that impair a person's ability to function 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.

Accordion Title
About Alzheimer Disease
  • Tests

    There are no laboratory tests available that will positively diagnose Alzheimer disease (AD) during life. Currently, the only definite 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.

    Health 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 health 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.

    The health practitioner may use a range of traditional laboratory tests to rule out deficiencies and other diseases and conditions that could be affecting the person's memory. The health care provider will also look for overmedication and 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.

    If the health practitioner suspects AD, other less common laboratory tests (see Table) may be done to differentiate between AD and other forms of dementia and to check for genetic risk factors.

    Tests to Aid in Categorization of Dementia

    These tests are used to rule out causes of dementia other than Alzheimer disease.
    Test Sample Associated with
    Vitamin B12 Blood B12 deficiency
    T4 Blood Thryroid function
    TSH Blood Thryroid function
    CBC Blood Anemia, infection
    Electrolytes Blood Na+, K+, Cl-, CO2 and pH balance
    CRP, ESR Blood Inflammation
    HIV antibody Blood AIDS
    Syphilis test Blood Syphilis
    Drug screen Urine Illicit drug use


    Other Tests Used to Help Categorize Dementia

    Test Type Test Sample Use Associated With
    Imaging tests CT (computed tomography) Body scan Rule out AD or with late stage AD Stroke and brain atrophy (shrinkage associated with late stage AD)
    MRI (magnetic resonance imaging) Body scan Rule out AD or with late stage AD Stroke and brain atrophy
    Less common lab tests Amyloid Beta 42 peptide and Tau protein correlation (Tau/Aß42) CSF Used in research settings to establish presence of "tangles" or "plaque burden"; may help differentiate AD from other forms of dementia; Aβ42 used in some treatment trials In symptomatic people, decreased Aß42 level along with an elevated Tau protein level indicates an increased likelihood of AD, regardless of the cause.
    APOE genotype Blood Determine APOE genotype to provide risk factor assessment; adjunct test to confirm/rule out probable AD Roughly 65% of AD patients have at least one APOE e4 allele; persons with 2 APOE e4 alleles have a much higher risk for AD, but this genotype is much less prevalent.
    PSEN1 Blood Test for genetic mutation Associated with about half of the cases of early onset familial AD
    PSEN2 Blood Test for genetic mutation; available in only a few labs Early onset familial AD; mutation very rare, identified in only a few family lines
    APP Blood Test for genetic mutation; available in only a few labs Early onset familial AD; mutation very rare, identified in only 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 slow the progression of the disease, 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 normal lives with small amounts of 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, drugs that preserve intellectual ability by preserving the function of the neurotransmitter acetylcholine, such as galantamine, donepezil, and rivastigmine. Whenever possible, the person's other medications are evaluated and he or she is taken off drugs that may worsen confusion, such as central nervous system depressants, antihistamines, sleeping pills, and analgesics.

    Throughout the progression of AD, antidepressants and other drugs may also be used in small quantities, along with environmental modifications intended to make the home environment safer and more familiar, to moderate personality and behavioral issues such as depression, agitation, paranoia, and violence, 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 normal 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:
    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 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.
View Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

(April 1, 2013) Stetka B. Alzheimer Biomarkers in Clinical Practice. Medscape Today. Available online at through Accessed March 2014.

Anderson, H. (Updated 2014 March 3). Alzheimer Disease. Medscape Reference [On-line information]. Available online at through Accessed March 2014.

Small, G. (Updated 2012 February 8). Alzheimer Disease and APOE-4. Medscape Reference [On-line information]. Available online at through Accessed March 2014.

Alvarez, N. (Updated 2012 March 2). Alzheimer Disease in Down Syndrome. Medscape Reference [On-line information]. Available online at through Accessed March 2014.

Anderson, P. (2013 March 21). 1 in 3 Seniors Dies With Alzheimer's or Other Dementia. Medscape Today News [On-line information]. Available online at through Accessed March 2014.

(2013 January 14). 2011-2012 Alzheimer's Disease Progress Report. Alzheimer's Disease Education and Referral Center [On-line information]. Available online at through Accessed March 2014.

(Reviewed 2012 December). Alzheimer's Disease. NIHSeniorHealth [On-line information]. Available online at through Accessed March 2014.

(Updated 2014 February 20). Alzheimer's Disease: Unraveling the Mystery. Alzheimer's Disease Education and Referral Center [On-line information]. Available online at through Accessed March 2014.

Mayo Clinic Staff (2011 March 31) Early-onset Alzheimer's: When symptoms begin before age 65. Mayo Clinic [On-line information]. Available online at through Accessed March 2014.

(© 2014) What We Know Today About Alzheimer's Disease. Alzheimer’s Association [On-line information]. Available online at through Accessed March 2014.

McKhann, G. et. al. (2011 April 22). The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia 7 (2011) 263–269 [On-line information]. Available online at through Accessed March 2014.

Leslie M Shaw, PhD. Director, Toxicology Laboratory, Biomarker Research Laboratory, Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Sloane, P. (1998, November 1). Advances in the Treatment of Alzheimer's Disease. American Family Physician by the American Academy of Family Physicians [On-line journal]. Available online at through

Eastman, P. (2002 March). Keeping Alzheimer's at Bay, Early Diagnosis Keeps Patients Functioning Longer. AARP Bulletin Online [On-line serial]. Available online at through

McConnell, S., et. al. Unraveling the Mysteries of Alzheimer's Disease: Exciting New Developments in Research. From panel sponsored by the Alzheimer's Association [On-line information]. Available online at through

Galasko, D., et. al. (1998). High Cerebrospinal Fluid Tau and Low Amyloid b42 Levels in the Clinical Diagnosis of Alzheimer Disease and Relation to Apolipoprotein E Genotype. Arch Neurol [On-line journal], vol (55) pages (937-945). Available online at through

ARF (1996-2002). Standard Medical Workup for Alzheimer's Disease. Alzheimer Research Forum [On-line information]. Available online at through

Family Caregiver Alliance. Fact Sheet: Alzheimer's Disease [On-line information]. Available online at through

Bird, T. (2001 June 22 last update). Alzheimer Overview. GeneReviews [On-line information]. Available online through

Gottlieb, F. and Lambert, J. G. (2002, January 2, last update). Alzheimer’s Disease. MEDLINEplus [On-line information]. Available online at

Miller, M. (1998 February 18). 26 national Alzheimer's Disease Centers Collaborate on Study of the Utility of Genetic Testing for Alzheimer's. National Institutes of Health News Release [On-line press release]. Available online at through

NIH (2000). Progress report on Alzheimer's disease, taking the next steps. NIH Publication No. 00-4859 [On-line report]. Available online at through

UniSci (2002, April 08). New Approaches Seen For Early Alzheimer’s Diagnosis. Daily University Science News [On-line Article]. Review of two studies found in Neuropsychology, Vol 16 (2). Available online at through

Eldercare (2002 February 28, last update). Is it Alzheimer's ...or Just Forgetfulness? Sponsored by Nebraska's Area Agencies on Aging [On-line information]. Available online at through

Hain, T. (2000 February 13). Alzheimer's Disease. Neurology, Northwestern University Medical School [3rd year neurology medical student curriculum material]. Available online at through

Kleiner-Fisman, G., Updated by (2002 January 2, last update). CSF Collection. MEDLINEplus [On-line information]. Available online at

Boston University Medical Center, Clinical Research & Resource Center: Alzheimer’s Disease, Brain Tissue Donation. Available online at through

Michigan Alzheimer's Disease Research Center. Available online at through

Robert C. Green, M.D., M.P.H. Professor of Neurology, Genetics and Epidemiology. Director, Alzheimer's Disease Clinical and Research Program. Boston University Schools of Medicine and Public Health, Boston, MA.

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

Anderson, H. and Kuljis, R. (2008 November 24). Alzheimer Disease. EMedicine [On-line information]. Available online at through Accessed April 2009.

Alvarez, N. (Updated 2008 January 10). Alzheimer Disease in Individuals With Down Syndrome. EMedicine [On-line information]. Available online at through Accessed April 2009.

(Updated 2009 February 24) Alzheimer's Disease Fact Sheet. National Institute on Aging, Alzheime's Disease Education & Referral Center [On-line information]. Available online at through Accessed April 2009.

(2009 March 17). Scientists Report Important Step in Biomarker Testing for Alzheimer's Disease. National Institute on Aging, Alzheimer’s Disease Education & Referral Center [On-line information]. Available online at through Accessed April 2009.

Brown Rodgers, A. (2008 September). Alzheimer's Disease: Unraveling the Mystery. National Institute on Aging, Alzheimer's Disease Education & Referral Center [On-line information]. Available online at through Accessed April 2009.

(2009). 2009 Alzheimer's Disease Facts and Figures. Alzheimer's Association [On-line information]. PDF available for download at through Accessed April 2009.