Alzheimer’s Disease

What is Alzheimer’s Disease?

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by memory loss, language deterioration, impaired visuospatial skills, poor judgment, indifferent attitude, but preserved motor function. AD usually begins after age 65, however, its onset may occur as early as age 40, appearing first as memory decline and, over several years, destroying cognition, personality, and ability to function. Confusion and restlessness may also occur. The type, severity, sequence, and progression of mental changes vary widely. The early symptoms of AD, which include forgetfulness and loss of concentration, can be missed easily because they resemble natural signs of aging. Similar symptoms can also result from fatigue, grief, depression, illness, vision or hearing loss, the use of alcohol or certain medications, or simply the burden of too many details to remember at once.

Is there any treatment?

There is no cure for AD and no way to slow the progression of the disease. For some people in the early or middle stages of the disease, medication such as donepezil may alleviate some cognitive symptoms. Also, some medications may help control behavioral symptoms such as sleeplessness, agitation, wandering, anxiety, and depression. These treatments are aimed at making the patient more comfortable.

What is the prognosis?

AD is a progressive disease. The course of the disease varies from person to person. Some people have the disease only for the last 5 years of life, while others may have it for as many as 20 years. The most common cause of death in AD patients is an infection.

What research is being done?

The NINDS conducts and supports research on neurodegenerative and dementing disorders, including AD. The goals of this research are to improve the diagnosis of AD and to find ways to treat and prevent the disorder. The National Institute on Aging and the National Institute of Mental Health also support research related to AD.

FDA Issues Public Health Advisory On Phenylpropan olamine In Drug Products

By Michelle Meadows

On November 6, the Food and Drug Administration issued a public health advisory alerting consumers to stop using over-the-counter (OTC) and prescription drug products containing phenylpropanolamine because this ingredient has been associated with an increased risk of hemorrhagic stroke (bleeding in the brain).

Phenylpropanolamine is commonly used as a decongestant in OTC and prescription cough and cold medications and as an appetite suppressant in OTC weight loss products. FDA recommends that consumers check labels of OTC drugs for phenylpropanolamine and stop using products that contain this ingredient.

Those using a prescription decongestant or cough-cold product should ask their pharmacists and health providers if it contains phenylpropanolamine. A commonly used alternative decongestant is pseudoephedrine, and most manufacturers will reformulate cough and cold products using this ingredient, says Robert Sherman, a biologist with FDA’s Center for Drug Evaluation and Research (CDER). “Although it is in the same drug class as phenylpropanolamine and is effective as a nasal decongestant, we do not have the same concerns with pseudoephedrine,” he says. As for using phenylpropanolamine as an OTC appetite suppressant, there is no alternative OTC drug product.

FDA intends to proceed with the public rulemaking process that will propose the removal of phenylpropanolamine from OTC products. CDER sent letters to drug manufacturers, repackers, and distributors, requesting that they voluntarily discontinue marketing products containing phenylpropanolamine. This interim measure aims to protect the public’s health while FDA moves forward with rulemaking to classify phenylpropanolamine as “not generally recognized as safe and effective.”

About 10,000 hemorrhagic strokes occur each year among people aged 18 to 49 in the United States, and an estimated 200-500 could be associated with phenylpropanolamine, says CDER director Janet Woodcock, MD. “Though the risk of stroke is low,” she says, “FDA is concerned because of the seriousness of the adverse event and advises consumers to stop taking products with phenylpropanolamine.”

In October 2000, FDA’s Nonprescription Drugs Advisory Committee voted that phenylpropanolamine should not be considered safe after it evaluated several reports, including a recent epidemiological study conducted by scientists at Yale University’s School of Medicine.

The study enrolled 702 men and women ages 18 to 49 who were hospitalized because of hemorrhagic stroke and 1,376 control subjects who did not have strokes. Researchers found an association between phenylpropanolamine use and hemorrhagic stroke in women. Because so few men in the study were exposed to the drug, researchers couldn’t determine if their risk is different from women’s. So while the risk of stroke was found mostly in women, men may also be at risk.

FDA requested the Yale study because of previous reports of a potential association between phenylpropanolamine and hemorrhagic stroke. In 1976, an expert panel recommended that the ingredient be generally recognized as safe and effective as a nasal decongestant, and another expert panel made the same recommendation for weight control in 1982. FDA hadn’t finalized phenylpropanolamine’s safe and effective status because of concerns over occasional reports of stroke associated with the drug.

Veggies Reported to Help Women’s Brains

By MALCOLM RITTER
AP Science Writer

Here’s another reason to eat your veggies: A new study suggests certain vegetables like broccoli and spinach may help older women keep their brains sharper.

Researchers found that women in their 60s who ate more cruciferous and green leafy vegetables than other women went on to show less overall decline over time on a bundle of tests measuring memory, verbal ability and attention.

Such foods include broccoli, cauliflower, romaine lettuce and spinach.

The federally funded study didn’t include men, but the effect would probably appear in them too, said Jae Hee Kang, an instructor at Harvard’s Brigham and Women’s Hospital in Boston.

She spoke in a telephone interview before presenting the work Monday in Philadelphia at the International Conference on Alzheimer’s Disease and Related Disorders.

Other studies released Monday showed evidence that obesity, high cholesterol and high blood pressure can raise the risk of developing Alzheimer’s or other dementia later on, and that leisure activities with mental, physical and social aspects may reduce the risk of later dementia.

Kang’s study and the other two “add to the growing understanding that we may be able to reduce our risk of Alzheimer’s by changing our lifestyles _ losing weight, changing our diets and staying mentally and socially active,” said Marilyn Albert, who chairs the Alzheimer Association’s Medical and Scientific Advisory Council.

Kang stressed that her findings need to be confirmed by further studies.

She and colleagues looked at 13,388 nurses participating in a long-running health study. They compared the participants’ questionnaires on long-term eating habits over a span of 10 years, when they were in their 60s, to their performance in two test sessions when they were in their 70s. Researchers noted how much the scores declined in the two years between sessions.

The tests included such tasks as remembering word lists after 15 minutes, naming as many animals as possible in one minute, and reciting a list of numbers backward. A pronounced drop in performance on such tests may foreshadow Alzheimer’s.

While most women in the study showed some decline, those who had habitually eaten the most of the green leafy vegetables showed less decline than those who ate the least, Kang said.

“It was almost like they were younger by one or two years in terms of their cognitive declining,” Kang said.

The contrasts appeared between those who ate about eight servings versus three servings of green leafy vegetables a week, and those who ate about five servings versus two servings of cruciferous vegetables a week.

One of the other new studies found evidence that obesity, high cholesterol and high blood pressure in middle age each added substantially to the risk of developing Alzheimer’s or other dementia later on. Each problem roughly doubled the risk, and study participants with all three traits ran six times the risk of somebody without any of them, said researcher Dr. Miia Kivipelto of the Karolinska Institute in Stockholm.

Her study included 1,449 Finns whose body-mass index, which signals obesity, was calculated when they were around 50 years old. When examined an average of 21 years later, 61 had developed dementia, mostly Alzheimer’s. Results showed the risk of any dementia or Alzheimer’s in particular roughly doubled with a BMI of more than 30 (considered obese), cholesterol of more than 250 or a blood pressure reading in which one of the numbers exceeded 140.

The effect appeared in both sexes, though the obesity factor was slightly stronger in women, Kivipelto said.

Silent Strokes Boost Alzheimer’s Risk

By LINDA A. JOHNSON
Associated Press Writer

Here’s another good reason for healthy living: Symptomless, unnoticed strokes more than double the risk of developing Alzheimer’s disease, according to a large Dutch study.

The researchers and other experts said the finding suggests many people could prevent the mind-robbing disorder by keeping their heart and blood vessels healthy by exercising, eating a balanced diet and quitting smoking.

Elderly people who suffered tiny “silent strokes” _ detected by an MRI _ had their mental function decline more sharply and were about 2.3 times more likely to develop Alzheimer’s or other types of dementia, researchers at Erasmus Medical Center found.

The study, the first major one on silent strokes, was published in Thursday’s New England Journal of Medicine.

The work provides “very powerful confirmation” of evidence linking narrowed blood vessels in the brain, stroke and Alzheimer’s, said Bill Thies, vice president for medical and scientific affairs at the Alzheimer’s Association.

“This is an extraordinarily well-done study in a big group of people,” Thies said. “They have identified an outcome from these small (strokes) that we wouldn’t have suspected.”

In an editorial, Drs. John Blass and Rajiv Ratan of Cornell University’s Weill Medical College said the study and other evidence indicate inadequate blood flow in the brain is an underlying cause of both Alzheimer’s and stroke _ and that silent stroke may be the first sign of Alzheimer’s, not just a risk factor.

Silent strokes are fairly common in the elderly, based on MRI scans of the 1,015 people aged 60 to 90 in the study, said lead investigator Dr. Monique Breteler, head of the Erasmus center’s neuroepidemiology research group.

The scans, performed in 1995 and 1996, found brain cell damage in 217 people that indicated a silent stroke. Over an average of 3.6 years of follow-up, 3 percent, or 30 people, developed dementia; 26 had Alzheimer’s and four had other forms.

A stroke is a “brain attack” in which the flow of blood and oxygen to part of the brain is interrupted. Most often, it is caused by a blood clot or a hardening of arteries in the brain that cuts off blood flow; this type of stroke, called an infarct, was examined in the study.

Damage from a stroke, such as difficulty speaking or weakness in a limb, varies with the stroke’s location and severity. But mental function often declines.

In dementia, mental ability usually declines gradually, impairing memory, learning skills, judgment and attention span. Alzheimer’s disease, which also is linked to excessive buildup of proteins in the brain, accounts for about two-thirds of dementia cases.

Along with following the 1,015 patients to see who developed dementia, the researchers did a second MRI on 619, some of whom had had additional silent strokes. Mental decline was even more severe in those people, as well as those who had lesions deep inside the brain from narrowed blood vessels, Breteler said.

Because many people who did not undergo a second MRI were in poorer shape mentally, Breteler said, the researchers probably underestimated how much silent strokes increase risk of dementia.

Many people with Alzheimer’s have standard risk factors for stroke and heart disease. Those include elevated blood pressure, cholesterol and blood sugar levels; eating a diet high in fat and low in vegetables; smoking; and getting little or no exercise.

Getting the elderly to follow health guidelines to reduce or eliminate those risk factors could prevent dementia or strokes, Breteler said.

Blass and Ratan suggested the same steps for any patients found to have had a silent stroke. They also recommended such patients be monitored by doctors and take baby aspirin every day.

“It’s another reason for keeping your cardiovascular system healthy,” said Dr. Patrick Pullicino, chairman of neurology and neurosciences at University of Medicine and Dentistry of New Jersey in Newark. “This is simple, common sense.”

Pullicino, who is running a 70-center study on preventing stroke and death in heart patients, said there is evidence of mental impairment in elderly people with heart failure, in which the heart can’t pump enough blood and oxygen to the brain and body.

He said when an MRI shows a patient has had a silent stroke, doctors must determine the cause and aggressively treat it to prevent a second stroke.

HHS Awards $10 Million to Expand Alzheimer’s Disease Demonstrations

HHS Secretary Tommy G. Thompson today announced more than $10 million in grants to develop innovative approaches to provide care for people with Alzheimer’s disease and support for their family caregivers.

The awards will support new demonstration programs in eight states — Colorado, Kansas, Michigan, Mississippi, New York, Oklahoma, Pennsylvania and West Virginia — and the continuation of projects in 25 other states — Alabama, Alaska, Arizona, Arkansas, California, Florida, Illinois, Indiana, Iowa, Maine, Maryland, Massachusetts, Minnesota, Missouri, Nebraska, Nevada, New Hampshire, New Mexico, North Carolina, Rhode Island, Tennessee, Texas, Vermont, Virginia and Wisconsin.

“Alzheimer’s disease affects about 4 million Americans and often devastates families who struggle to provide the best possible care to their loved ones,” Secretary Thompson said. “These new grants will expand the community services available to those families and help them overcome the special challenges they face in living with this tragic illness.”

The Alzheimer’s Disease Demonstration Grants to States (ADDGS) program works to improve the responsiveness of home and community-based services to persons with dementia and their caregivers. It supports the goals of President Bush’s New Freedom Initiative, a government-wide framework for helping provide people with disabilities with the tools they need to fully access and participate in their communities.

The demonstration grants focus on expanding the availability of diagnostic and support services to people with Alzheimer’s disease and improving outreach and service delivery to low-income, cultural minority and rural families that are traditionally underserved. HHS’ Administration on Aging oversees the program.

“I’m pleased to celebrate the 10th anniversary of the Alzheimer’s Demonstration Program,” Assistant Secretary for Aging Josefina G. Carbonell said. “Each year, in collaboration with our partners, we provide more than a million hours of home and community-based services to families coping with Alzheimer’s disease, and share information and education about Alzheimer’s disease and dementia with millions of Americans.”

COLORADO STATE BOARD OF AGRICULTURE, Colorado State University, Fort Collins, Colo. — $350,000 — To increase the availability of home health care, companion services, support groups and related services to individuals with dementia and their families in rural Colorado. Models of respite care provided by faith-based groups, civic organizations and volunteers will be examined. The project will also develop and provide family and professional training about Alzheimer’s disease and dementia.

KANSAS DEPARTMENT ON AGING, Topeka, Kan. — $225,000 — To provide care for persons with Alzheimer’s disease by nurturing strengths in an environment that offers art and creativity through the development of an Arts and Inspiration Center. Project also will increase access through respite mini-grants that target rural and Hispanic elders. A statewide education and information campaign includes Breakfast Clubs to support and educate family caregivers.

MICHIGAN DEPARTMENT OF COMMUNITY HEALTH, Lansing, Mich. — $282,373 — To integrate various systems to improve care for persons with dementia. Test models of support services, focus on care coordination between physicians, families, and voluntary health organizations, improve education, training, and access to resources and information and enhance the efficiency of statewide voluntary health organizations for Alzheimer’s, Huntington’s and Parkinson’s diseases.

MISSISSIPPI DEPARTMENT OF MENTAL HEALTH, Jackson, Miss. — $252,000 — To develop volunteer-staffed day respite programs with targeted outreach and service delivery to African- Americans. Project will expand the capacities of existing in-home and group respite, homemakers, and personal care services, and to improve the long-term care workforce by providing educational training programs.

NEW YORK STATE OFFICE FOR THE AGING, Albany, N.Y. — $305,000 — To develop direct services to persons with developmental disabilities (DD) and Alzheimer’s disease (AD) designed to help them remain in family and group homes in their communities. The project will provide information, training and support group services to family caregivers, and develop comprehensive professional training programs to create an AD/DD competent workforce.

OKLAHOMA DEPARTMENT OF HUMAN SERVICES, Oklahoma City, Okla. — $338,363 –To develop an in-home respite and companion visitation and support program using mentors and volunteers, working in teams, to provide direct home and community based services targeted to African- American, Native American and rurally isolated populations. The project will train students to deliver specialized dementia care and support their on-the-job training program through mentors and on-site front line workers at adult day care and respite programs.

PENNSYLVANIA DEPARTMENT OF AGING, Harrisburg, Pa. –$349,012 –To develop the Pennsylvania Memory Loss Screening Program designed to create dementia screening and service delivery focused on serving Latino/Hispanic American, Asian-American, African-American and rural Pennsylvanians. The project will target the integration of medical and social support services. Facility based, in-home and overnight respite and adult day care will be provided.

WEST VIRGINIA BUREAU OF SENIOR SERVICES, Charleston, W.Va. — $250,000 — To identify and address needs of rural, low-income Appalachian and other West Virginia families struggling with Alzheimer’s disease. Start-up grants to senior centers, as well as respite grants to local service organizations and direct respite care grants to families will be provided. A state wide toll-free help line will be created and training materials updated to include dementia training. Scout merit badges in Alzheimer’s disease, dementia and the aging process will also be developed.

Diet Rich in Foods With Vitamin E May Reduce Alzheimer’s Disease Risk

A new population-based study of antioxidants, appearing in the June 26, 2002, “Journal of the American Medical Association” (“JAMA”), suggests that a diet rich in foods containing vitamin E may help protect some people against Alzheimer’s disease (AD). The study is also noteworthy for its finding that vitamin E in the form of supplements was not associated with a reduction in the risk of AD. The latest in a series of reports on vitamin E and dementia, the study findings heighten interest in the outcome of clinical trials now underway to test the effectiveness of vitamin E and other antioxidants in preventing or postponing cognitive decline and AD.

The “JAMA” study was conducted by Martha Clare Morris, Sc.D., of the Rush Institute for Healthy Aging at Rush-Presbyterian-St.Luke’s Medical Center, Chicago, IL, Denis A. Evans, M.D., and colleagues. A related study by Morris and colleagues, “in press” in the July 2002 Archives of Neurology, a “JAMA” publication, also associates vitamin E with protection against more general cognitive decline. (Reporting of additional detail on this study is embargoed for July 14, 2002, 4 p.m. ET.) Both studies were supported by the National Institute on Aging (NIA) at the National Institutes of Health.

The June 26 issue of “JAMA” includes similar findings from scientists in The Netherlands, who also reported a link between high dietary intake of vitamins C and E and protection against AD in certain people. In addition, the journal contains an editorial on the epidemiological study of dietary intake of antioxidants and the risk of AD by Daniel J. Foley, M.S., of the NIA’s Laboratory of Epidemiology, Demography, and Biometry, and Lon White, M.D., Pacific Health Research Institute, Honolulu.

“This and a number of important population studies have pointed to vitamin E as possibly protective against oxidative damage or other mechanisms associated with cognitive decline and dementia,” says Neil Buckholtz, Ph.D., head of the Dementias of Aging Branch at the NIA. “The only way this association can really be tested is through clinical studies and trials now underway. These will help us determine whether vitamin E in food or in supplements — or taken together — can prevent or slow down the development of mild cognitive impairment or AD.”

It is not recommended, based on current evidence, that people take high-dose vitamin E supplements or other antioxidant pills in an effort to prevent mental decline, Buckholtz says. While population-based studies and animal research have suggested that antioxidants may be neuroprotective, clinical trials to test that notion are currently in progress. Little is known about safety, effectiveness, and dosages of various antioxidant supplements that are proposed for neuroprotective purposes, Buckholtz emphasizes. In excessively high doses (above 2,000 International Units daily, or IU/d), for example, vitamin E may be associated with increased risk of bleeding, and patients taking anti-coagulant medications may be especially at risk. Interactions with other medications commonly taken by older people are also of potential concern. People are advised to consult with their physicians before taking high doses of supplemental vitamin E or other antioxidants.

The 815 people participating in the Morris study were part of the Chicago Health and Aging Project (CHAP), a study of a large, diverse community of people age 65 and older. Participants were free of dementia at the start of the study and followed for an average of 3.9 years. At an average of 1.7 years from their baseline assessment, participants completed a questionnaire, asking them in detail about the kinds and quantities of foods consumed in the previous year.

Some 131 participants had been diagnosed with AD by the end of the study period, when researchers examined the relationship between intake of antioxidants, including dietary and supplemental vitamins E and C, beta carotene, and a multivitamin, and development of AD. The most significant protective effect was found among people in the top fifth of dietary vitamin E intake (averaging 11.4 IU/d), whose risk of AD was 67 percent lower when compared to people in the group with the lowest vitamin E consumption from food (averaging 6.2 IU/d). (The recommended dietary allowance of vitamin E is 22 IU/d.) No significant change in risk of AD was found when the scientists looked at vitamin E supplements, the other antioxidants and their supplements, or a general multivitamin. There was some evidence, though not statistically significant, that increased intake of dietary vitamin C and beta carotene was moving in a “protective direction,” the researchers said.

The data were also analyzed to see if age, gender, race, education, or possible genetic risk for AD would influence the findings. Only the presence or lack of apoE-e4, one form of a protein associated with increased risk of late-onset AD, seemed to matter: the protective effect of vitamin E from food was strongest among people who did not have the apoE-e4 risk factor allele. “Dietary vitamin E may protect against Alzheimer’s disease,” says Morris, “but the protection may only occur among people without the apoE-e4 allele.”

Morris suggests that further study in key areas is needed to confirm and explain some of the study’s findings, including the link with apoE status and the study’s striking distinction between dietary intake of vitamin E and use of supplements. For example, the lack of a protective effect for the supplements could be explained by several factors. Some participants in the study started taking supplements only recently and there may not have been sufficient time for the supplement to be found effective. Also, people who believe they have memory problems could be more likely to take the supplements in the first place. Another possible explanation might be variations in the forms of vitamin E, scientists note. Most vitamin E supplements consist of alpha tocopherol while foods are generally more rich in gamma tocopherol. These forms of vitamin E scavenge different types of free radicals, with one possibly more important than another in potentially reducing risk of cognitive decline. To help determine whether vitamin E might play a role in preventing AD, or at least in delaying its onset, a number of clinical trials are now being supported by the NIA. These include:

–MEMORY IMPAIRMENT STUDY — This study targets people with mild cognitive impairment, or MCI, testing the usefulness of vitamin E and donepezil to slow or stop the conversion from MCI to AD. (Study has completed recruitment.) Principal investigator: Dr. Ronald Petersen, Mayo Clinic, Rochester, MN.

–PREVENTION OF AD BY VITAMIN E AND SELENIUM (PREADVISE) — An add-on to the National Cancer Institute’s Selenium and Vitamin E Prostate Cancer Prevention Trial (SELECT), this investigation is testing vitamin E and selenium in healthy men age 60 and older for preventing cognitive decline and AD. (Some study sites have begun recruitment and others will begin enrolling participants over the next few months. See below on obtaining more information from NIA’s ADEAR Center.) Principal investigator: Dr. William Markesberry, University of Kentucky.

–WOMEN’S ANTIOXIDANT CARDIOVASCULAR STUDY (WACS) — Testing vitamin E, vitamin C, beta carotene, and folate for slowing cognitive decline in women age 65 and older at high risk of cardiovascular disease, the WACS is funded by the National Heart, Lung, and Blood Institute (NHLBI). An add-on for cognitive testing is supported by the NIA. (Recruitment and some cognitive testing of participants have been completed.) Principal investigator: Dr. Francine Grodstein, Harvard University.

–WOMEN’S HEALTH STUDY (WHS) — Testing aspirin and vitamin E in healthy women age 65 and older for slowing cognitive decline, the WHS is supported by the NHLBI and the National Cancer Institute. An add-on for the cognitive studies is supported by the NIA. (Recruitment and some cognitive testing of participants have been completed.) Principal investigator: Dr. Francine Grodstein, Harvard University.

–PHYSICIAN’S HEALTH STUDY II (PHS II) — Testing beta carotene, vitamin E, vitamin C and multivitamin with folate in healthy men age 65 and older for slowing cognitive decline. NIA supports the cognitive supplement to this privately funded study. (Recruitment and baseline cognitive testing of participants have been completed.) Principal investigator: Dr. Francine Grodstein, Harvard University.

The ADEAR Center also provides general information on AD research for health professionals, the media, and the general public. ADEAR can be contacted weekdays, toll free, at 1-800-438-4380.

The NIA leads the Federal effort supporting and conducting biomedical, clinical, social, and behavioral research on aging and on Alzheimer’s disease specifically. Press releases, fact sheets, and other materials about aging and aging research can be viewed at the NIA’s general information Web site.

The National Institute on Aging is a component of the National Institutes of Health, U.S. Department of Health and Human Services.

Folic Acid Possibly a Key Factor in Alzheimer’s Disease Prevention

Mouse experiments suggest that folic acid could play an essential role in protecting the brain against the ravages of Alzheimer’s disease and other neurodegenerative disorders, according to scientists at the National Institute on Aging. This animal study* could help researchers unravel the underlying biochemical mechanisms involved in another recent finding that concluded people with high blood levels of homocysteine have nearly twice the risk of developing the disease.**

In the study, published in the March 1, 2002 issue of the “Journal of Neuroscience”, the investigators fed one group of mice with Alzheimer’s-like plaques in their brains a diet that included normal amounts of folate, while a second group was fed a diet deficient in this vitamin. These mice are transgenic, meaning they were bred with mutant genes that cause AD in people. They develop AD-like plaques in their brains that kill neurons.

The NIA team counted neurons in the hippocampus, a brain region critical for learning and memory that is destroyed as plaques accumulate during Alzheimer’s disease. The investigators found a decreased number of neurons in the mice fed the folic acid deficient diet.

The scientists also discovered that mice with low amounts of dietary folic acid had elevated levels of homocysteine, an amino acid, in the blood and brain. They suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the hippocampus. In transgenic mice fed an adequate amount of folate, nerve cells in this brain region were able to repair damage to their DNA. But in the transgenic mice fed a folate-deficient diet, nerve cells were unable to repair this DNA damage.

“These new findings establish a possible cause-effect relationship between elevated homocysteine levels and degeneration of nerve cells involved in learning and memory in a mouse model of Alzheimer’s disease,” said Mark Mattson, Ph.D., chief of the NIA’s Laboratory of Neurosciences and the study’s principal investigator.

People who have Alzheimer’s disease often have low levels of folic acid in their blood, but it is not clear whether this is a result of the disease or if they are simply malnourished due to their illness. But based on emerging research, Dr. Mattson speculates consuming adequate amounts of folic acid — either in the diet or by supplementation — could be beneficial to the aging brain and help protect it against Alzheimer’s and other neurodegenerative diseases.

Green leafy vegetables, citrus fruits and juices, whole wheat bread and dry beans are good sources of the vitamin. Since 1998, the Food and Drug Administration has required the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products. However, because it can take a long time for the symptoms of Alzheimer’s disease to surface, researchers speculate it will be many years before folate supplementation in food could affect the incidence of dementia in the United States. A human clinical trial is being planned.

In AD, plaques develop first in areas of the brain used for memory and other cognitive functions. They consist of largely insoluble deposits of a protein called beta- amyloid. Although researchers still do not know whether amyloid plaques themselves cause AD or whether they are by- products of the AD process, there is evidence that amyloid deposition may be a central process in the disease. But unlike human brain cells, the brain cells in laboratory mice are not killed by the progressive accumulation of beta amyloid. This finding led Dr. Mattson and his research team to suspect folic acid or some other component of the mouse diet might help these nerve cells resist beta amyloid damage. In earlier work, Dr. Mattson found evidence suggesting folic acid deficiency can increase the brain’s susceptibility to Parkinson’s disease.

The NIA leads the Federal effort to support and conduct basic, clinical, and social and behavioral studies on aging and AD. It supports the Alzheimer’s Disease Education and Referral (ADEAR) Center, which provides information on AD research, including clinical trials, to the public, health professionals, and the media. ADEAR can be contacted toll free at 1-800-438-4380 weekdays. Press releases, fact sheets, and other materials about aging and aging research can be viewed at the NIA’s general information website.

*I. Kruman, T.S. Kumaravel, A. Lohani, W. Pedersen, R.G. Cutler, Y. Kruman, N. Haughey, J. Lee, M. Evans, and M.P. Mattson, “Folic Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal Neurons and Sensitize Them To Amyloid Toxicity in Experimental Models of Alzheimer’s Disease,” “Journal of Neuroscience”, 22:5, pp. 1752-1762.

**S. Sesdradri, A. Beiser, J. Selhub, et al., “Plasma Homocysteine As A Risk Factor For Dementia and Alzheimer’s Disease,” “N Eng J Med”, 346:7, pp. 476-483.

Study Suggests Mentally Stimulating Activities May Reduce Alzheimer’s Risk

In recent years, many of us have come to believe that doing crossword puzzles or playing cards might ward off a decline in memory or help us maintain “brainpower” as we age. Now, a new study suggests there might be some truth to the use- it-or-lose-it hypothesis.

The study, by scientists at the Rush Alzheimer’s Disease Center and Rush-Presbyterian-St. Luke’s Medical Center in Chicago, IL, appearing in the February 13, 2002, “Journal of the American Medical Association”, found that more frequent participation in cognitively stimulating activities is associated with a reduced risk of Alzheimer’s disease (AD). The research looked at everyday activities like reading books, newspapers or magazines, engaging in crosswords or card games, and going to museums among participants in the Religious Orders Study, an ongoing examination of aging among older Catholic nuns, priests, and brothers from several groups across the U.S. On a scale measuring cognitive activity — with higher scores indicating more frequent activity — a one-point increase in cognitive activity corresponded with a 33 percent reduction in the risk of AD.

The examination of cognitively stimulating activities and risk of AD was conducted by Robert S. Wilson, Ph.D., and colleagues at the Rush Alzheimer’s Disease Center, including David A. Bennett, M.D., principal investigator for the Religious Orders Study, and Denis A. Evans, M.D., director of the National Institute on Aging (NIA)-supported Rush Alzheimer’s Disease Center. The NIA is part of the National Institutes of Health, Department of Health and Human Services.

The findings are likely to strike a chord among middle-aged and older people interested in preserving cognitive health. “We are asked constantly about this use-it-or-lose-it approach to maintaining memory,” says Elisabeth Koss, Ph.D., Assistant Director of the NIA’s Alzheimer’s Disease Centers Program. “This study provides important new evidence that there may be something to the notion of increased cognitive activity and reduced risk of Alzheimer’s disease. Further research should help better sort out whether cognitive activities can be prescribed to reduce risk of AD and why that may be so.”

The study followed over 700 dementia-free participants age 65 and older for an average of 4.5 years from their initial assessments. At baseline and then yearly, some 21 cognitive tests were administered to assess various aspects of memory, language, attention, and spatial ability. At the initial evaluations, participants also were asked about time typically spent in seven common activities that significantly involve information processing — viewing television; listening to the radio; reading newspapers or magazines; reading books; playing games such as cards, checkers, crosswords, or other puzzles; and going to museums. The frequency of participating in each activity was rated on a five-point scale, with the highest point assigned to participating in an activity every day or about every day and the lowest point to engaging in an activity once a year or less.

During the follow-up period, 111 people in the study developed AD. In comparing the levels of cognitive activity with diagnosis of AD, the researchers found that the frequency of activity was related to the risk of developing AD. For each one point increase in the participants’ scores on the scale of cognitive activities, the risk of developing AD decreased by 33 percent. On average, compared with someone with the lowest activity level, the risk of disease was reduced by 47 percent among those whose frequency of activity was highest.

The researchers also looked at general cognitive decline among the participants. Over the period of the study, the group of older people showed modest age-related declines on several types of memory and information processing tests. There were lower rates of decline, however, in working memory, perceptual speed, and episodic memory among people who did more cognitively stimulating activities.

What accounts for the association between cognitively stimulating activities and reduced risk of cognitive decline and AD is unclear. It may be, some scientists theorize, those cognitive activities are protective in some way. Some speculate that repetition might improve the efficiency of certain cognitive skills and make them less vulnerable to the brain damage in AD. Or, some kind of compensatory mechanisms might be at work, strengthening information processing skills to help compensate for age-related declines in other cognitive areas. The study does not, however, eliminate the possibility that people who develop AD in future years may be less prone, years before, to engage in cognitively stimulating activities. Notes Wilson, “The associations among cognitive activity, Alzheimer’s disease, and cognitive function are extremely complex. Additional study, including testing some of these activities as cognitive interventions, will help to tell us whether such enjoyable and easy-to-do activities could be employed in some way to reduce the risk of memory decline and loss.” Because the participants in the study have agreed to brain donation, the investigators hope to be able to determine the mechanism underlying the association between cognitive activities and cognitive decline.

More than 900 older Catholic clergy from 40 groups across the U.S. are participating in the Religious Orders Study. All participants have agreed to annual memory testing and brain donation at the time of death. “We are grateful for the remarkable dedication and altruism of this unique group of people,” says Bennett. “I expect we will learn a great deal more from them, as we look for insights into how the brain functions with age.”

The NIA leads the Federal effort to support and conduct research on aging and on AD. The Rush Alzheimer’s Disease Center is one of 29 NIA-supported Alzheimer’s Disease Centers across the U.S. which conduct basic, clinical, and social and behavioral research on dementia and AD. NIA also sponsors the Alzheimer’s Disease Education and Referral (ADEAR) Center, which provides information on AD research to the public, health professionals, and the media. ADEAR can be contacted toll-free at 1-800-438-4380 weekdays, during business hours.

The National Institute on Aging is a component of the National Institutes of Health, U.S. Department of Health and Human Services.

Mortality Declines for Several Leading Causes of Death in 1999

Mortality for several leading causes of death declined in 1999, according to preliminary figures from HHS’ Centers for Disease Control and Prevention (CDC), released today by HHS Secretary Tommy G. Thompson.

The report shows age-adjusted death rates continued to fall for heart disease and cancer, the two leading causes of death in the U.S. that account for more than half of all deaths in the country each year. In addition, suicide, homicide and firearm mortality dropped an estimated 6 percent between 1998 and 1999.

At the same time, there were increases for other leading causes of death, including septicemia (6.6 percent); hypertension (5 percent); chronic lower respiratory diseases (4 percent), and diabetes (3.3 percent).

These estimates are featured in a new CDC report, “Deaths: Preliminary Data for 1999,” an analysis of over 99 percent of the death certificates recorded in the United States for 1999.

“The report gives us good news and bad news. We’re encouraged that fewer Americans are dying from some of the leading causes of death and concerned that other causes are taking a larger toll,” said Secretary Thompson. “Many of these deaths are preventable and too many Americans are dying from preventable causes.”

Mortality from HIV infection, which dropped more than 70 percent over the previous three years (1996-1998), continued this trend by decreasing nearly 4 percent in 1999. Though it is no longer ranked among the leading causes of death in the U.S., HIV infection still ranks 5th among 25-44 year-olds, and is the leading cause of death for black men in this age group. Among black women in this age group, HIV ranks 3rd.

“We’re paying very close attention to the trend in HIV mortality,” said CDC Director Jeffrey P. Koplan. “Although HIV as a cause of death has dropped in rank in recent years, we must guard against complacency and continue to emphasize prevention as a key weapon in fighting this disease.”

HIV mortality declined 26 percent in 1996, 48 percent in 1997, and 21 percent in 1998.

This latest report incorporates several significant methodological changes, including a more up-to-date age distribution for the U.S. population for calculating age-adjusted death rates and an updated cause-of-death classification and coding system (the Tenth Revision of the International Classification of Diseases, issued by the World Health Organization (ICD-10)).

While the five leading causes of death in 1999: Heart disease, cancer, stroke, chronic lower respiratory disease (formally classified as “Chronic obstructive pulmonary diseases and allied conditions”) and accidents (unintentional injuries) remained unchanged from the previous year, some significant changes did occur in the ranking of leading causes.

Suicide dropped from 8th to 11th among leading causes of death as the number of suicides in the U.S. fell more than 5 percent from 30,575 in 1998 to 29,041 in 1999.

The new cause-of-death classification system also resulted in a significant shift in ranking for Alzheimer’s disease. In 1998, Alzheimer’s disease ranked 12th among leading causes of death but jumped to 8th in 1999, due mainly to the inclusion of a cause of death formerly classified separately as “presenile dementia,” which accounted for a substantial number of additional Alzheimer’s deaths in 1999. The 44,507 deaths from Alzheimer’s disease in 1999 surpassed the totals for other major causes of death, including motor vehicle accidents and breast cancer.

“The new data on Alzheimer’s mortality adds to our understanding of the magnitude of this serious problem,” said Edward Sondik, director of CDC’s National Center for Health Statistics, which prepared the report. “It is through improvements in our system that we’re able to more accurately measure the impact of this disease and others on our citizens,” he said.

The report also shows that the national infant mortality rate was 7.1 infant deaths per 1,000 live births in 1999, compared with 7.2 in 1998. However, the difference was not statistically significant.

Information on causes of death is recorded on death certificates by physicians, medical examiners, and coroners, and reported to the state vital statistics offices. Demographic information is provided by funeral directors, based on information from informants, who are usually family members.

Fourth Alzheimer’s Drug Approved

By LAURAN NEERGAARD
AP Medical Writer
(AP) WASHINGTON

Alzheimer’s sufferers are about to get a fourth medication option to help slow the worsening of the devastating brain disease.

The Food and Drug Administration approved Reminyl, a drug derived from daffodil bulbs, late Wednesday.

Manufacturer Janssen Pharmaceutica said the twice-a-day pills will be available by prescription in May, but refused to release the price.

Four million Americans suffer from Alzheimer’s, which has no known cure. It afflicts mainly the elderly, robbing them of their memories and ability to care for themselves and eventually killing them.

Reminyl, known chemically as galantamine, works like the nation’s three other Alzheimer’s medications. It modestly slows cognitive decline by inhibiting the breakdown of acetylcholine, a brain chemical vital for nerve cells to communicate. The longer acetylcholine remains in the brain, the longer those cells can call up memories.

Reminyl had sparked intense interest when early animal research suggested it might also activate brain receptors that release chemicals like serotonin, which some scientists suspect could offer additional nerve cell protection.

But Janssen never proved that effect because it only tested Reminyl against dummy pills, not against other Alzheimer’s drugs, the FDA said. “Who knows, maybe if they actually did the work they could show some advantage,” said FDA drug chief Dr. Robert Temple.

Still, having another option is important, said Bill Thies, Alzheimer’s Association vice president.

“We know that probably only half the people that are treated with any one of the existing compounds actually get a good result,” so they need choices, he said.

One study of a small number of early-stage Alzheimer’s patients found Reminyl helped some think and remember as well a year later. “I think that’s pretty substantial,” said Dr. Joseph Coyle of Harvard Medical School, an Alzheimer’s expert who consults for Janssen _ but who wants to see Reminyl directly compared to other medicines.

Like other Alzheimer’s drugs, Reminyl can cause nausea, vomiting and diarrhea _ hitting between 20 percent and 40 percent of patients, depending on the dose _ that can cause worrisome weight loss in certain patients.

Head Injury Linked to Increased Risk of Alzheimer’s Disease

There may be one more reason to wear that bike helmet now, says epidemiologist Richard Havlik, MD, of the National Institute on Aging in Bethesda, Md. Serious head injury in early adulthood may be linked to developing Alzheimer’s disease (AD) and other forms of dementia later in life, according to Havlik and a team of researchers at NIA and Duke University Medical Center in Durham, NC.

The researchers studied the records of more than 7,000 World War II male veterans who were sent to military hospitals with head injuries or unrelated conditions. They then tracked down 1,776 veterans who were eligible for the study–548 of whom had suffered a head injury. The remaining 1,228 without head injuries made up the control group. Telephone interviews with the veterans or a family member were used to determine the current cognitive and functional abilities of the men.

Study results suggested that the more severe the head injury, the greater the risk of developing AD or other forms of dementia. The risk was doubled for individuals with moderate head injury, and men with severe head injuries had a fourfold greater risk. Moderate injury was defined as a skull fracture, or amnesia or loss of consciousness for more than 30 minutes but less than 24 hours. Severe injury was amnesia or loss of consciousness for 24 hours or more. Results for participants who had mild injury–loss of consciousness or amnesia for less than 30 minutes–were inconclusive.

Previous studies have suggested a relationship between head injuries and dementia, but were thought to be influenced by “recall errors” because they relied on patient and family memories of injuries that may have occurred decades earlier. Havlik cautions that the new findings do not show a direct cause-and-effect relationship between head injury and dementia but do show an association that warrants further study. “We now need to hone in on what’s behind these findings, especially what may be happening biologically,” he says.

Each year, an estimated 1.5 to 2 million individuals in the United States suffer a significant head injury, according to the National Institutes of Health. It is estimated that up to 4 million Americans currently have AD. (Neurology, October 24, 2000).

A Ray of Sunshine for Alzheimer’s

Although there’s still no cure for Alzheimer’s disease on the horizon, several recent studies suggest that simple measures can improve the ability of some patients to function.

Professor Dick Swaab, a Dutch Alzheimer’s specialist, says that simply increasing the daily exposure to sunlight can help to reduce the restlessness exhibited by many patients, causing many to wander at night. Increased light may even improve their memory, reports the Sydney Morning Herald. Swaab suspects that the sunlight helps to correct an imbalance in the brain chemical melatonin, although a clinical study under way should confirm whether that’s the actual reason for the improvements seen.

Music can help, too. Researchers in Michigan found that playing recordings of favorite songs during meal times encouraged Alzheimer’s patients to eat about 20 percent more, which may help prevent malnutrition, according to a wire report in The Times of India.

Music also serves as one of the few ways to communicate with patients whose dementia has left them disconnected with the world around them, the BBC News reports. The therapy won’t cure dementia, but it could slow the progression of the disease.

“What could be the case, and this is just an idea,” says neuroscientist Susan Greenfield, “is that by stimulating the brain in this way you’re actually stimulating the connections you’re trying to keep working. And if they are working then perhaps they would be less prone to degenerating.”

Attribution: — Jeff Johnston

Memory Loss With Aging: What’s normal, what’s not

How does the brain store information?

The brain stores information in your memory. The information in your memory includes things that have happened to you in the past what you’ve seen, heard, smelled, tasted, and felt.

Things are stored in different parts of your memory depending on when they happened to you. Information stored in the short-term memory may include the name of a person you met moments ago or a phone number you just looked up.

Information stored in the recent memory may include what you ate for breakfast or what you did yesterday.

Information stored in the remote memory includes things that you stored in your memory years ago, such as memories of childhood, what you wore on your wedding day or the color of the first car you bought.

How does aging change the brain?

Beginning when you’re very young, your brain starts to change. You begin to lose brain cells a few at a time. Your body also starts to make less of the chemicals your brain cells need to work. The older you are, the more these changes can affect your memory.

Aging may affect memory by changing the way you store information. It may also affect memory by making it harder to recall information the brain has already stored.

Your short-term and remote memories aren’t usually affected by aging. But your recent memory may be affected. You may forget names of people you’ve met recently. These are normal changes.

Things to help you remember

• Keep lists.
• Follow a routine.
• Make associations (connect things in your mind), such as using landmarks to help you get around.
• Keep a detailed calendar.
• Put important items, such as your keys, in the same place every time.
• Repeat names when you meet new people.
• Do things that keep your mind and body busy.
• Run through the ABCs in your head to help you think of words you’re having trouble remembering. “Hearing” the first letter of a word may jog your memory.

What about when I know a word but can’t recall it?

This is called a “tip-of-the-tongue” experience. It’s usually just a glitch in your memory. You’ll almost always remember the word with time. This may become more common as you age. It can be very frustrating. But don’t worry. It’s not serious unless it interferes with your daily activities.

What are other causes of memory problems?

Many things other than aging can cause memory problems. These include depression, other illnesses, dementia (severe problems with memory and thinking, such as Alzheimer’s disease), side effects of drugs, strokes, head injury and alcoholism. Hearing and vision problems can add to memory problems by making communication hard.

How can I tell if memory problems are serious?

A memory problem is serious when it affects your daily living. If you sometimes forget names, you’re probably okay. But you may have a more serious problem if you have trouble remembering how to do things you’ve done many times before, getting from one place you’ve been to often to another place, or doing things that use steps, like following a recipe.

The difference between normal memory problems and dementia is that the memory loss that normally occurs with aging doesn’t get much worse over time. Dementia gets much worse over a period of several months to several years.

It may be hard to figure out on your own if you have a serious problem. Talk to your family doctor about any concerns you have. Your doctor may be able to help you if your memory problems are caused by a medicine you’re taking or by depression. Many causes of memory problems can be treated.

How does Alzheimer’s disease change memory?

Alzheimer’s disease starts by changing the recent memory-ability to learn and store new information. At first, a person with Alzheimer’s disease will remember even small details of his or her distant past but not be able to remember recent events or conversations. Over time, the disease affects all parts of the memory. The person with Alzheimer’s disease will no longer be able to care for his or her own needs.

Alzheimer’s disease isn’t a normal part of aging and it’s much less common than most people think. Only 10% of people over age 65 have Alzheimer’s disease. But this number rises to 20% to 30% of people over age 85.

Memory problems that aren’t a part of normal aging

• Forgetting things much more often than you used to.
• Forgetting how to do things you’ve done many times before.
• Trouble learning new things.
• Repeating phrases or stories in the same conversation.
• Trouble making choices or handling money.
• Not being able to keep track of what happens each day.
• Changes in how you act.
• Loss of social graces.
• Losing interest in daily activities and how you look.
• Feeling more depressed, confused, restless and anxious.

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The College of Family Physicians of Canada

This information provides a general overview on this topic and may not apply to everyone. To find out if this information applies to you and to get more information on this subject, talk to your family doctor.

This health education material has been favorably reviewed by the Patient Education Review Committee of the College of Family Physicians of Canada.

The College of Family Physicians of Canada, one of the nation’s largest medical specialty groups, is committed to promoting and maintaining high standards for family doctors the doctors who give ongoing, comprehensive care to people of all ages.

This patient education information was developed by The College of Family Physicians of Canada in cooperation with the American Academy of Family Physicians.

Other Alternative Treatments

Acetyl-L-carnitine

Alzheimer’s disease is associated with decreased levels of the neurotransmitter acetylcholine in the brain. A key ingredient of acetylcholine is the amino acid choline. But for reasons that remain unclear, choline supplementation has little effect on Alzheimer’s progression.

However, another combination of amino acids — a supplemental nutrient called acetyl-L-carnitine, or carnitine for short — has shown some promise. Carnitine is composed of two amino acids, lysine and methionine. Studies have shown that carnitine slows cognitive deterioration in people with Alzheimer’s disease.

In a 1991 Italian study, researchers divided 130 people with Alzheimer’s into two groups. One group took a placebo; the other, a daily dose of 2,000 mg of carnitine. After one year, both groups showed cognitive deterioration, but those taking carnitine showed significantly less decline in memory, logic, verbal skills, and attention to tasks. [1]

In 1992, Mary Sano, Ph.D., of the Neurological Institute in New York City, treated 30 people with mild to moderate Alzheimer’s disease with either a placebo or acetyl-L-carnitine (2.5 g per day for three months, then 3 g/day for three months). At six months, compared with the placebo-takers, the carnitine group showed significantly less cognitive deterioration. [2]

More recently, in a 1995 study, University of Pittsburgh researchers divided 12 people with Alzheimer’s into two groups. Five received a placebo, while seven took 3,000 mg of carnitine daily for one year. Compared with the placebo group, those taking carnitine showed significantly less mental deterioration based on the Mini-Mental Status test and the Alzheimer’s Disease Assessment Scale. [3]

Many Caregivers Try Alternative Therapies on Loved Ones With Alzheimer’s

Fifty-five percent of caregivers give at least one alternative therapy to loved ones with Alzheimer’s disease, according to a survey of 101 caregivers by researchers with the Program on Aging at the University of North Carolina School of Medicine. (Coleman, LM et al. “Use of Unproven Therapies by People with Alzheimer’s Disease,” Journal of the American Geriatric Society (1995) 43:747.)

Among the various alternative approaches:

• 84 percent of caregivers gave vitamins to Alzheimer’s sufferers.
• 22 percent fed them health foods.
• 11 percent tried herbal medicines
• 9 percent tried so-called “smart pills,” over-the-counter products available at health food stores that claim to aid brain function.
• One caregiver in five had tried three or more alternative treatments.

Two-thirds of the caregivers, who were recruited from the North Carolina chapters of the Alzheimer’s Association, reported that the alternative treatments produced no improvement in their loved ones, while one-third said the unconventional approaches had helped “a little.”

However, a one-third response rate is what could be expected from treatment with any placebo. These results suggest that the alternative approaches used in this study have no value in treating Alzheimer’s disease.

But the researchers noted that they were not surprised by the popularity of alternative approaches because conventional medicine currently has so little to offer in the way of Alzheimer’s treatment.

¹Spagnoli, A., et al. “Long-Term Acetyl-L-Choline Treatment in Alzheimer’s Disease,” Neurology (1991) 41:1726

²Sano, M., et al. “A Double-Blind Parallel Design Pilot Study of Acetyl-Levocarnitine in Patients with Alzheimer’s Disease,” Archives of Neurology (1992) 49:1137

^3{FPettegrew, J.W., et al. “Clinical and Neurochemical Effects of Acetyl-L-Carnitine in Alzheimer’s Disease,” Neurobiology of Aging (1995) 16:1

Genetics of Alzheimer’s disease

This page attempts to answer some of the more common questions about Alzheimer’s disease and its genetics. As with all conditions, we urge you to consult your physician about specific issues regarding yourself or your family.

What is Alzheimer’s disease?

Alzheimer’s disease, also known as Alzheimer’s dementia, results in a progressive and irreversible loss of higher brain functions. Thus, persons with Alzheimer’s disease have some or all of these symptoms:

• Problems with intellect — impaired memory, judgment, and abstract thinking.
• Orientation problems — the person may not know what day it is, where they are, or who they are.
• Difficulties with language and communication.
• Changes in personality — for example, anxiety, irritability, and agitation.

It’s important to recognize that all persons with dementia (the symptoms above) do not necessarily have Alzheimer’s disease. It’s important because some cases of dementia (as much as 20% of the total) are reversible, or at least treatable. Alzheimer’s disease accounts for 60% of the irreversible cases of dementia.

Diagnosing dementia is easy, but identifying the specific type is not. Thus, Alzheimer’s dementia is surprisingly difficult to diagnose. Only by looking at brain tissue with a microscope can the diagnosis of Alzheimer’s disease be made with certainty. In practice, this is rarely done. Instead, most physicians make the much more important determination of whether the dementia is irreversible or not and worry less about the specific type.

As we’ll see below, it’s also important to know there are two types of Alzheimer’s disease. Early-onset Alzheimer’s disease begins before age 65. Late-onset: Alzheimer’s disease starts at 65 or older. They are indistinguishable, other than the age of onset.

Can Alzheimer’s disease run in families?

Yes. This has been well established, and applies to both the early-onset and late-onset forms of the disease.

In one study, the close blood relatives of a person with Alzheimer disease had a 25% chance of developing the disease by age 86. This compared to a 10% risk for non-blood relatives. (“Close relative” was defined as a parent, brother, or sister.)

When Alzheimer’s disease runs in families, is the reason genes or environment?

As in most human disease, the answer appears to be “both.” Alzheimer’s disease has strong genetic components. Scientists have had difficulty finding environmental factors, but suspect there may be some.

Studies of twins provide the clearest evidence for genes and environment both having a role. For example, in 1997 researchers looked at 32 pairs of twins in which at least one twin had Alzheimer’s disease.   Type of twin pair Number of twin pairs Twin pairs in which both twins had Alzheimer’s disease (“concordance rate”) Identical twins 9 78% (7 of 9 pairs) Non-identical twins 23 39% (9 of 23 pairs) If Alzheimer’s disease were governed only by genes, then every time one identical twin had Alzheimer’s disease, the other should have it, too. (Because identical twins have the same genes.) In other words, the “concordance rate” should be 100%. The table shows, however, that instead of a 100% concordance, there is a 78% concordance between identical twins. This shows that Alzheimer’s disease has a small environmental component. If Alzheimer’s disease were purely an environmental condition, then genes should make no difference at all. The concordance rate would be the same for identical twins and non-identical twins. The table shows, however, that the concordance rate is twice as high in identical twins (78%) as in non-identical twins (39%). This shows that Alzheimer’s disease has a strong genetic component.

What genes are involved in Alzheimer’s disease?

Researchers have discovered several genes that determine susceptibility to Alzheimer’s disease. The early-onset form of Alzheimer’s disease is influenced by different genes than the late-onset form.

Genes for early-onset Alzheimer’s disease

 

Gene Name	Chromo- some	Comments
presenilin 1	14	Scientists have found more than 50 variations (alleles) of this gene. Overall, variations in this gene account for about half the cases of early-onset Alzheimer’s disease.
presenilin 2	1	Variations in this gene have been found in just a few families with early-onset Alzheimer’s disease.
beta amyloid precursor	21	Long ago (in the mid-1980s), studies of patients with Down syndrome suggested that a gene on chromosome 21 might be involved in Alzheimer’s disease. Persons with Down syndrome have three copies of chromosome 21 instead of two, and they develop Alzheimer’s disease at an early age. Scientists ultimately found that, among persons without Down syndrome, variations in the beta amyloid precursor gene on chromosome 21 lead to about 1% of early-onset cases of Alzheimer’s disease.

 

Genes for late-onset Alzheimer’s disease

 

Gene Name	Chromo- some	Comments
apo lipoprotein E	19	There are three common variants of this gene, named e2, e3, and e4. Persons with one copy of the e4 variant develop Alzheimer’s disease 5 to 10 years earlier than those with e2 or e3 variants. People with two copies of e4 develop Alzheimer’s disease 10 to 20 years earlier. The e4 variant of this gene has also been linked with higher cholesterol levels and with coronary heart disease.
alpha-2 macroglobulin	12	The importance of this gene is still being sorted out. One study found problems with this gene in 30% of persons with Alzheimer’s disease. Later studies did not confirm this finding, however.

To date, none of these discoveries about genes have been turned into routine genetic tests that a physician can order for a patient. Scientists are actively looking for other genes for both types of Alzheimer’s disease.

What environmental factors are involved in Alzheimer’s disease?

Scientists have been seeking environmental contributors to Alzheimer’s disease for some time. However, in the words of one team of experts, “none has yet been convincingly identified”. They continue: “Factors such as low education, head trauma, smoking, [diseases of the arteries,] diabetes, and menopause have modest or inconsequential effects.” There was a scare about aluminum cooking utensils in the 1980s, but that has been discredited.

When Alzheimer’s disease runs in families, why don’t all family members have it?

It helps to frame this question a little differently…. All members of a family do not have the same height, weight, and face. So, it makes sense that they don’t all have the same conditions and diseases — or the same susceptibility to various diseases.

Here again, it’s genetic and environmental differences that explain differences in our appearance and health. Some family members will inherit genes that predispose to Alzheimer’s disease, and others will not. Some family members will be exposed to environmental agents that trigger disease, and others will not.

There is no Alzheimer’s disease in my family. Does this mean I will never get it?

No. Anyone can get Alzheimer’s disease. About 60% of people with Alzheimer’s disease do not have a family history of the disease. But if someone in your family does have Alzheimer’s disease, you are at greater risk.

How will discoveries about DNA help people and families with Alzheimer’s disease?

The most urgent needs for Alzheimer’s disease are effective treatments and effective preventions. Medical scientists have been slow to meet these needs because they do not yet understand the causes of the disease in detail. The modest success in discovering Alzheimer’s-related genes so far (see tables, above) has already increased our understanding of the disease significantly. Further discoveries may provide the knowledge that will allow scientists to design treatments and preventions.

Further discoveries about Alzheimer’s genes could also lead to tests that would predict a healthy person’s risk of developing the disease in the future. Until effective treatments and preventions arrive, however, such a test would be a mixed blessing, since there is nothing to be done if the person’s risk is high. Nothing, that is, except to enjoy life. Which you should be doing anyway.

How can I help other people and families with Alzheimer’s disease?

To help those who are already ill, consider donations of money or time to charitable causes sponsoring research into Alzheimer’s disease. We also hope you will consider participating in The Gene Trust.