0
Conferences |

National Institutes of Health State-of-the-Science Conference Statement: Preventing Alzheimer Disease(1) and Cognitive Decline FREE

Martha L. Daviglus, MD, PhD, MPH; Carl C. Bell, MD; Wade Berrettini, MD, PhD; Phyllis E. Bowen, PhD; E. Sander Connolly Jr., MD; Nancy Jean Cox, PhD; Jacqueline M. Dunbar-Jacob, PhD, RN; Evelyn C. Granieri, MD, MPH, MSEd; Gail Hunt, BA; Kathleen McGarry, PhD; Dinesh Patel, MD; Arnold L. Potosky, PhD; Elaine Sanders-Bush, PhD; Donald Silberberg, MD; and Maurizio Trevisan, MD, MS
[+] Article and Author Information

* The term Alzheimer's disease was used in the name of the conference but has been changed here to Alzheimer disease for this article to conform to current standards of usage of the American Medical Association Manual of Style.

Panel statement from an NIH State-of-the-Science Conference held on 26–28 April 2010 at the National Institutes of Health, Bethesda, Maryland. For a list of the members of the NIH State-of-the-Science Conference Panel and other participants, see the Appendix.


From Feinberg School of Medicine at Northwestern University, Institute for Juvenile Research, University of Illinois at Chicago, Community Mental Health Council, and University of Chicago, Chicago, Illinois; Center for Neurobiology and Behavior, University of Pennsylvania, and University of Pennsylvania Medical Center, Philadelphia, Pennsylvania; Columbia University Medical Center, New York-Presbyterian Hospital, and Columbia University, New York, New York; School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania; National Alliance for Caregiving, Bethesda, Maryland; University of California, Los Angeles, Los Angeles, California; George Washington University School of Medicine, Rockville, Maryland; Georgetown University Medical Center and Lombardi Comprehensive Cancer Center, Washington, DC; Vanderbilt University Medical Center, Nashville, Tennessee; and Nevada System of Higher Education and University of Nevada School of Medicine, Las Vegas, Nevada.


Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-1019.

Requests for Single Reprints: Reprints are available from the NIH Consensus Development Program Web site (www.consensus.nih.gov) and in print through the NIH Consensus Development Program Information Center (888-644-2667).

Current Author Addresses: Dr. Daviglus: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 North Lake Shore Drive, Suite 1400, Chicago, IL 60611.

Dr. Bell: Department of Psychiatry and School of Public Health, University of Illinois at Chicago, 1747 West Roosevelt Road, Room 155, Chicago, IL 60608-1264.

Dr. Berrettini: Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, 125 South 31st Street, Philadelphia, PA 19104.

Dr. Bowen: Department of Kinesiology and Nutrition, University of Illinois at Chicago, College of Applied Health Sciences, 1919 West Taylor Street, MC 528, Chicago, IL 60612

Dr. Connolly: Columbia University Medical Center, 710 West 168th Street, Room 435, New York, NY 10032.

Dr. Cox: Department of Human Genetics, University of Chicago, AMB A612, MC6091, 5841 South Maryland Avenue, Chicago, IL 60637.

Dr. Dunbar-Jacob: School of Nursing, University of Pittsburgh, 3500 Victoria Street, #350, Pittsburgh, PA 15261.

Dr. Granieri: Division of Geriatric Medicine and Aging, College of Physicians and Surgeons, Columbia University, The Allen Pavilion 3-105, 5141 Broadway, New York, NY 10034.

Ms. Hunt: National Alliance for Caregiving, 4720 Montgomery Lane, 2nd Floor, Bethesda, MD 20814.

Dr. McGarry: Department of Economics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095.

Dr. Patel: Charles E. Smith Life Community Hebrew Home of Greater Washington, 6121 Montrose Road, Rockville, MD 20852.

Dr. Potosky: Cancer Control Program, Lombardi Comprehensive Cancer Center, 3300 Whitehaven Street NW, Suite 4100, Washington, DC 20007.

Dr. Sanders-Bush: Department of Pharmacology, Vanderbilt University Medical Center, 7160A Medical Research Building 3, Nashville, TN 37232.

Dr. Silberberg: Department of Neurology, Hospital of the University of Pennsylvania, Gates 3, 3400 Spruce Street, Philadelphia, PA 19104.

Dr. Trevisan: Health Sciences System, 5550 West Flamingo Road, Suite C-1, Las Vegas, NV 89103.

Author Contributions: Conception and design: C.C. Bell, E.S. Connolly, J.M. Dunbar-Jacob, A.L. Potosky.

Analysis and interpretation of the data: M.L. Daviglus, W. Berrettini, P.E. Bowen, E.S. Connolly, J.M. Dunbar-Jacob, E.C. Granieri, K. McGarry, D. Patel, E. Sanders-Bush, D. Silberberg, M. Trevisan.

Drafting of the article: M.L. Daviglus, C.C. Bell, P.E. Bowen, E.S. Connolly, N.J. Cox, E.C. Granieri, G. Hunt, K. McGarry, D. Patel, A.L. Potosky, D. Silberberg, M. Trevisan.

Critical revision of the article for important intellectual content: M.L. Daviglus, C.C. Bell, W. Berrettini, P.E. Bowen, E.S. Connolly, E.C. Granieri, G. Hunt, D. Patel, A.L. Potosky, E. Sanders-Bush, D. Silberberg, M. Trevisan.

Final approval of the article: M.L. Daviglus, C.C. Bell, W. Berrettini, P.E. Bowen, E.S. Connolly, N.J. Cox, E.C. Granieri, G. Hunt, A.L. Potosky, E. Sanders-Bush, D. Silberberg, M. Trevisan.

Statistical expertise: G. Hunt.

Collection and assembly of data: M.L. Daviglus, E.S. Connolly, J.M. Dunbar-Jacob.


Ann Intern Med. 2010;153(3):176-181. doi:10.7326/0003-4819-153-3-201008030-00260
Text Size: A A A

National Institutes of Health (NIH) consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality, 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, 3) questions and statements from conference attendees during open discussion periods that are part of the public session, and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of NIH or the U.S. government. The following statement is an abridged version of the panel's report, which is available in full athttp://consensus.nih.gov/2010/alzstatement.htm.

Alzheimer disease is the most common cause of dementia. It was first described in 1906 by German psychiatrist and neuropathologist Alois Alzheimer, who observed the pathologic hallmarks of the disease—abnormal clumps of protein (β-amyloid plaques) and tangled bundles of protein fibers (neurofibrillary tangles)—in the brain of a woman who had experienced memory loss, language problems, and unpredictable behavior. An important breakthrough was the invention of the photomicrograph in the early 1900s by the psychiatrist Solomon Carter Fuller; this key innovation provided a method for taking photographs through the lens of a microscope, allowing visualization of amyloid plaques and neurofibrillary tangles.

Since its first description, Alzheimer disease has gone from a rarely reported disorder to one of the most common disabling diseases among older adults. The increasing proportion of older adults in the U.S. population reinforces the urgent need for prevention and treatment of all chronic diseases, including Alzheimer disease. In most people, cognitive health and performance remain stable over the lifetime, with only a gradual decline in short-term memory and processing speed. For others, however, the decline in cognitive function progresses to a more serious state of cognitive impairment or into various forms of dementia. Mild cognitive impairment is characterized by problems with memory, language, or other essential cognitive functions that are severe enough to be noticed by others and are reflected on cognitive tests but are not severe enough to interfere with daily life. Dementia is characterized by progressive global deterioration of cognitive abilities in multiple domains, including memory, and at least 1 additional area—learning, orientation, language, comprehension, and judgment—severe enough to interfere with daily life.

The diagnosis of Alzheimer disease is difficult and often imprecise, but its importance is without question. Depending on the diagnostic and pathologic criteria used, Alzheimer disease accounts for 60% to 80% of all dementia cases, and as many as 5.1 million Americans may currently have the disease; the prevalence of mild cognitive impairment is even higher. Furthermore, the number of persons affected by Alzheimer disease or mild cognitive impairment is expected to increase considerably with the aging of the baby-boom generation. Alzheimer disease and other forms of dementia cost more than $148 billion in the United States annually, and these conditions also exact a substantial toll on patients and caregivers in terms of financial costs, stress, and anguish.

To date, numerous studies have attempted to describe the causes and factors associated with the risk for development and progression of mild cognitive impairment and Alzheimer disease, generating an abundance of theories on potential risk factors and therapies. Age is the strongest known risk factor for Alzheimer disease; most people with the late-onset form receive the diagnosis after age 60 years. An early-onset familial form also occurs, but it is rare. Genetic, cardiovascular, and lifestyle factors also have been implicated.

The National Institute on Aging and the Office of Medical Applications of Research of the NIH convened a State-of-the-Science Conference on 26–28 April 2010 to assess the available scientific evidence. During the first 2 days of the conference, experts presented information on each of 6 key questions. After weighing the scientific evidence—including the data presented by the speakers and a formal evidence report from the Evidence-based Practice Center at Duke University's Clinical Research Institute that was commissioned by the Agency for Healthcare Research and Quality (available at www.ahrq.gov/clinic/tp/alzcogtp.htm)—an independent panel prepared and presented the state-of-the-science statement addressing the conference questions.

The panel review included relevant studies on the relationship of multiple factors, including nutritional, medical, social, economic, behavioral, environmental, and genetic, with mild cognitive impairment or Alzheimer disease. The scope of the review was restricted to human studies conducted in developed countries, with sample sizes of at least 50 participants for randomized, controlled trials (RCTs) and 300 participants for observational studies and a minimum duration between exposure to preventive interventions and outcomes (see full report for details). Only studies published in English that included participants 50 years or older, of both sexes, and of diverse racial and ethnic populations were considered. The Evidence-based Practice Center rated study quality by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. The panel's charge was confined to answer questions related to prevention of established Alzheimer disease and cognitive decline.

What factors are associated with the reduction of risk of Alzheimer disease?

Currently, no evidence of even moderate scientific quality exists to support the association of any modifiable factor (such as nutritional supplements, herbal preparations, dietary factors, prescription or nonprescription drugs, social or economic factors, medical conditions, toxins, or environmental exposures) with reduced risk for Alzheimer disease.

What We Know

Strong evidence indicates that genetic factors, particularly the apolipoprotein E (ApoE) gene variation, are associated with risk for Alzheimer disease. Although better understanding of genetic risk factors for Alzheimer disease may ultimately lead to effective therapies, the observed genetic associations are currently relevant largely as stratification factors in studies designed to identify additional risk factors and in clinical trials designed to test effectiveness of therapies.

Numerous modifiable factors have been reported to show association with risk for Alzheimer disease across multiple studies, but the overall scientific quality of the evidence is low. Thus additional studies on these factors may change, perhaps substantially, the magnitude or direction of the observed associations. Chronic diseases and conditions, such as diabetes, elevated blood cholesterol level in midlife, and depression, have been associated with increased risk for Alzheimer disease. Several dietary and lifestyle factors and medications have also been linked to a decreased risk for Alzheimer disease; these include adequate folic acid intake, low saturated fat consumption, high fruit and vegetable consumption, use of statins, light to moderate alcohol consumption, educational attainment, cognitive engagement, and participation in physical activities. Current smoking, never having been married, and having low social support are all reported to be associated with increased risk for Alzheimer disease. However, the quality of evidence for the association of these factors with Alzheimer disease is low. No consistent associations were found for other vitamins; fatty acids; the metabolic syndrome; blood pressure; plasma homocysteine level; obesity and body mass index; antihypertensive medications; nonsteroidal anti-inflammatory drugs; gonadal steroids; or exposures to solvents, electromagnetic fields, lead, or aluminum.

Limitations

One of the challenges of interpreting findings of existing studies on risk factors for Alzheimer disease is the lack of a consistent and uniformly applied definition of Alzheimer disease. Another key challenge is distinguishing factors associated with Alzheimer disease from factors associated with other late-onset disorders that are prevalent in older adults. For example, vascular disease can lead to dementia, and because vascular disease is common in elderly persons, it may often be present in individuals with Alzheimer disease. Thus, it can be difficult to differentiate between factors associated with Alzheimer disease because of their contribution to vascular disease and related dementias and factors that are truly associated with Alzheimer disease. Similarly, it is unclear whether some of the observed associations, such as depression, might reflect early features of Alzheimer disease.

The primary limitation of most of these studies is the distinction between association and causality. Diseases are complex; they are determined and shaped by many variables, and associations often involve correlated factors. For example, individuals with higher levels of education are also more likely to have greater cognitive engagement, making it difficult to determine whether either factor (or both factors) has a causal role.

What factors are associated with the reduction of risk of cognitive decline in older adults?

Cognition is a combination of skills that include attention, learning, memory, language, and visuospatial skills and executive function, such as decision making, goal setting, planning, and judgment. Decline in cognition ranges from severe dementia, such as Alzheimer disease, to mild cognitive impairment and age-related cognitive decline. Cognitive decline is multicausal, and mild cognitive impairment does not always progress to dementia. Moreover, functional cognitive decline is only moderately associated with pathologic changes typical of Alzheimer disease. The idea of cognitive reserve (the mind's resilience to neuropathologic damage of the brain) explains variances in ability to cope physiologically and mentally with existing pathology. Despite the hopeful insights provided by this concept, these issues complicate attempts to design robust studies to determine factors that might prevent cognitive decline.

What We Know

For most factors, existing studies either show no association with cognitive decline or provide inconclusive evidence. Where an association was seen, the overall quality of the evidence is low.

Nutritional and Dietary Factors

The available evidence does not support a clear role for most of the nutritional and dietary factors that have been examined. The most consistent evidence is available for longer-chain ω-3 fatty acids (often measured as fish consumption), with several longitudinal studies showing an association with reduced risk for cognitive decline. For the other factors, the evidence varies from no consistent association (vitamin B, vitamin E, vitamin C, folate, and β-carotene) to very limited evidence suggesting a possible protective effect (low saturated fat and high vegetable intake).

Medical Factors

Several cardiovascular risk factors have been consistently associated with increased risk for cognitive decline. High blood pressure has been most consistently associated with cognitive decline, and particularly with severe cognitive decline. Diabetes also has been associated with an increased risk for cognitive decline, but this association is modest and less consistent. The metabolic syndrome, a cluster of metabolic abnormalities, has been consistently associated with a modest risk for cognitive decline. For other medical factors, good-quality studies are lacking (for example, sleep apnea and traumatic brain injury) or findings have been inconclusive (for example, obesity).

Psychological and Emotional Health

Depression and depressive symptoms have been consistently found to be associated with mild cognitive impairment and cognitive decline.

Medications

No consistent epidemiologic evidence exists for an association with statins, antihypertensive medications, or anti-inflammatory drugs. Data are insufficient to comment on cholinesterase inhibitors. Existing reports are difficult to interpret because of variation in formulations, dosage, duration, route of administration (as for postmenopausal estrogens), and drug treatment effect (for example, antihypertensive medications).

Socioeconomic Factors

Childhood socioeconomic status or cognitive milieu does not seem to strongly influence cognitive decline later in life. Evidence on the putative association between years of education and cognitive decline is inconsistent.

Social and Cognitive Engagement

Whereas findings on the association of cognitive decline with living alone or being without a partner are inconsistent, a robust association exists between the loss of a spouse and cognitive decline. Limited but inconsistent evidence suggests that increased involvement in cognitive activities in later life may be associated with slower cognitive decline and lower risk for mild cognitive impairment.

Physical Activity and Other Leisure Activities

Preliminary evidence suggests beneficial associations of physical activity and other leisure activities (such as club membership, religious services, painting, or gardening) with preservation of cognitive function.

Tobacco and Alcohol Use

Evidence indicates that current smoking is associated with increased risk for cognitive decline; evidence for past smoking is less consistent. Findings on the association between cognitive decline and alcohol use are inconsistent.

Genetic Factors

Most studies suggest that the ApoE gene variation is associated with an increased rate of cognitive decline in elderly persons, especially on some memory tasks and tasks of perceptual speed. The ApoE gene variation does not seem to affect all cognitive domains, and there is variability among studies.

Limitations

Much of the available evidence derives from studies that were originally designed and conducted to investigate other conditions, such as cardiovascular disease and cancer. Thus, evidence from studies conducted to date is limited by methodological issues in the assessment of the outcome (cognitive decline) or exposures (risk factors). Limitations in the evaluation of outcome include the lack of a clear definition of and standardization of criteria for cognitive decline (cognitive decline is not a single entity and may have different causes). Instruments used by different studies varied in their scope, making it difficult or impossible to compare results across studies and to identify the reasons for inconsistency in findings. The ascertainment of cognitive decline was often limited to a single measurement at follow-up. This approach severely limits the ability to determine validly whether cognitive decline really exists, especially because cognitive decline is not linear, many factors affect cognitive performance, and these factors may change in the same individual. Many studies were limited by the relatively short duration of follow-up. The studies also differ widely in the quality of the measurements of important exposures (for example, dietary factors, lifestyle habits, medications, health history, social factors, and engagement). Many of the available studies characterized their participants only at a single time point.

What are the therapeutic and adverse effects of interventions to delay the onset of Alzheimer disease? Are there differences in outcomes among identifiable subgroups?

Although numerous interventions have been suggested to delay Alzheimer disease, the evidence is inadequate to conclude that any are effective. Our conclusions are based on a review of published literature of adequately powered RCTs, the most rigorous, highest-quality evidence.

Assessment of Detailed Interventions
Vitamins, Nutrients, and Dietary Supplements

A recent RCT of vitamin E found no evidence that this factor changed the onset of Alzheimer disease. Other nutritional factors (such as other vitamins or the Mediterranean diet) may be beneficial, but evidence to support this conclusion is insufficient. It has been suggested that patients with vitamin deficiency may demonstrate a greater response, but no trials have examined this issue. Ginkgo biloba was reported to have some benefit in small, short-term clinical trials. However, a recent large, long-term RCT comparing G. biloba with placebo showed no reduction in the incidence of Alzheimer disease, leading to the conclusion that evidence is insufficient to support the efficacy of G. biloba.

Medications

Cholinesterase inhibitors are the most common treatment for mild to moderate Alzheimer disease and have been the focus of several RCTs evaluating prevention of Alzheimer disease. Although there is some inconsistency in the literature, the body of evidence led us to conclude that this class of drugs does not effectively prevent Alzheimer disease. Evidence from RCTs of antihypertensive medications and hormone replacement (conjugated equine estrogen) is also insufficient to indicate that these agents protect against Alzheimer disease. Some available evidence shows that certain medications may increase the incidence of Alzheimer disease. Two RCTs of specific nonsteroidal anti-inflammatory drugs—rofecoxib, naproxen, and celecoxib—suggested an increased incidence of Alzheimer disease with treatment. However, these studies were limited by high dropout rates and early termination because of concerns about toxicity. Two RCTs of conjugated equine estrogen, one combined with methylprogesterone, suggested an increased incidence of dementia (including Alzheimer disease) with treatment. These trials suggest that no known medication can be said to reliably delay the onset of Alzheimer disease.

Other Factors

No RCTs were identified that evaluated the effects of cognitive engagement, physical activities, or other leisure activities on delaying the onset of Alzheimer disease.

What are the therapeutic and adverse effects of interventions to improve or maintain cognitive ability or function? Are there different outcomes in identifiable subgroups?

Several interventions have been evaluated with respect to improving cognitive function or preventing cognitive decline. Despite some encouraging associations found in observational studies, RCTs of specific interventions have not definitively established positive therapeutic effects on maintaining or improving cognitive function or preventing cognitive decline. However, there is also little evidence to suggest that interventions designed to improve cognitive function either worsen it or produce unwanted side effects. In addition, no data are available from which to draw firm conclusions about differences in outcomes among identifiable subgroups.

Assessment of Detailed Interventions
Vitamins, Nutrients, and Dietary Supplements

Several RCTs did not find a role of vitamin supplementation in preventing cognitive decline. However, these trials used varying doses of the nutrients, did not uniformly measure and monitor patients' cognitive function and baseline nutritional status, had short and variable follow-up, and mostly measured cognitive decline as a secondary or tertiary outcome. Thus, these trials may have been underpowered.

In a randomized trial complicated by poor adherence to therapy, G. biloba coadministered with vitamin E did not improve or maintain cognitive function in elderly persons. A randomized trial of ω-3 fatty acids with only 26 weeks of follow-up found no effect on cognitive functioning. Another 4 trials in progress may revise this evidence, but currently no interventional trials convincingly demonstrate that dietary supplements improve or maintain cognitive functioning.

Medications

With the exception of 1 trial of antihypertensive medication in patients with hypertension, known vascular disease, and history of stroke, all existing evidence suggests that antihypertensive treatment results in no cognitive benefit. Similarly, treatment with statins, low-dose aspirin, or celecoxib did not result in cognitive benefit, and naproxen was found to possibly increase cognitive decline. Randomized trials of estrogen have not shown any preventive effects on cognitive decline, and conjugated equine estrogen plus methylprogesterone may worsen cognitive outcome. However, trials examining the effect of gonadal steroids to date have had several shortcomings, including inconsistencies in types of steroid used, duration and timing of use, type of menopause (surgical or natural), and mode of delivery. Finally, multiple trials of cholinesterase inhibitors have shown no consistently positive effects on cognitive decline. Together, these data suggest that no currently available medications can prevent the onset of cognitive decline.

Cognitive Engagement

A large randomized trial of cognitive training (consisting of memory, reasoning, and speed) over 5 to 6 weeks with a subsequent booster period showed modest benefits on cognitive functioning and a small, statistically significant effect on reducing the extent of age-related cognitive decline at 5-year follow-up. This trial also showed a very small significant benefit on instrumental activities of daily living—for example, managing finances, managing medications, and keeping house—and, in a subgroup analysis, benefit on driving performance in elderly persons. However, these findings need to be replicated to confirm the benefits of cognitive engagement on preventing cognitive decline over a longer period and in persons with varying levels of baseline cognitive abilities before firm recommendations can be made. The sustainability of these behaviors must also be assessed in large, community-based samples, in which other, less rigorous interventions showed no benefit.

Physical Activity

Some evidence from small interventional studies and selected observational studies suggests that increased physical activity, including walking, may help maintain or improve cognitive function in normal adults. A meta-analysis of several RCTs, many with methodological limitations, concluded that data were insufficient to state that aerobic activity improves or maintains cognitive function. A small, higher-quality randomized trial of physical activity in persons with confirmed memory problems showed modest benefit in reducing cognitive decline; however, these data should be viewed as preliminary. Work is ongoing to further investigate the benefits of physical activity.

What are the relationships between the factors that affect Alzheimer disease and the factors that affect cognitive decline?

Inconsistent and varied assessments of “age-associated cognitive decline,” “mild cognitive impairment,” and “Alzheimer disease” in the literature prevent clear and concise answers to this question.

What We Know

Diabetes mellitus, ApoE gene variation, current smoking, and depression are associated with increased risk for Alzheimer disease and cognitive decline. Limited evidence indicates that estrogens and nonsteroidal anti-inflammatory drugs increase the risk for Alzheimer disease; no evidence exists that these medications increase risk for age-associated cognitive decline.

There are no consistent findings of increased risk for Alzheimer disease and cognitive decline associated with obesity, hypertension, and blood homocysteine levels. Likewise, no decreased risk with cholinesterase inhibitors has been found.

Cognitive engagement (indicated by literacy and social enrichment), physical activities in later life, and a diet low in saturated fat and high in vegetable intake were associated with decreased risk for Alzheimer disease and cognitive decline. Light to moderate alcohol intake is associated with reduced risk for Alzheimer disease, but findings for cognitive decline are inconsistent.

No consistent association has been found between Alzheimer disease or cognitive decline and intake of G. biloba, β-carotene; flavonoids; multivitamins; and vitamins B12, C, and E.

Limitations

Most studies conducted to date had limited data, and the quality of evidence was generally low. In addition, the risk modification effect of reported associations was generally small to moderate for Alzheimer disease and small for cognitive decline.

If recommendations for interventions cannot be made currently, what studies need to be done to provide the quality and strength of evidence necessary to make such recommendations to individuals?

Specific recommendations for research are summarized in the Appendix Table.

Table Jump PlaceholderAppendix Table.  Recommendations for Further Research in Alzheimer Disease

Cognitive decline and Alzheimer disease are major causes of morbidity and mortality worldwide and are substantially burdensome to the affected persons, their caregivers, and society in general. Currently, firm conclusions cannot be drawn about the association of any modifiable risk factor with cognitive decline or Alzheimer disease. Highly reliable consensus-based diagnostic criteria for cognitive decline, mild cognitive impairment, and Alzheimer disease are lacking, and available criteria have not been uniformly applied. Evidence is insufficient to support the use of pharmaceutical agents or dietary supplements to prevent cognitive decline or Alzheimer disease. We recognize that a large amount of promising research is under way; these efforts need to be increased and added to by new understandings and innovations (Appendix Table).

For example, ongoing studies on antihypertensive medications, ω-3 fatty acids, physical activity, and cognitive engagement may provide new insights into the prevention or delay of cognitive decline or Alzheimer disease. This important research needs to be supplemented by further studies. Large-scale population-based studies and RCTs are critically needed to investigate strategies to maintain cognitive function in individuals at risk for decline, identify factors that may delay the onset of Alzheimer disease among persons at risk, and identify factors that may slow the progression of Alzheimer disease among persons in whom the condition is already diagnosed.

Appendix
State-of-the-Science Panel

Martha L. Daviglus, MD, PhD, MPH (Panel and Conference Chairperson), Professor of Preventive Medicine and Medicine, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Carl C. Bell, MD, Director, Institute for Juvenile Research; Professor, Department of Psychiatry and School of Public Health, University of Illinois at Chicago; and President and Chief Executive Officer, Community Mental Health Council, Chicago, Illinois; Wade Berrettini, MD, PhD, Karl E. Rickels Professor of Psychiatry, Department of Psychiatry and Director, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, Pennsylvania; Phyllis E. Bowen, PhD, Professor Emerita of Human Nutrition, Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois; E. Sander Connolly Jr., MD, Bennett M. Stein Professor of Neurological Surgery and Vice Chairperson of Neurosurgery, Columbia University Medical Center, New York-Presbyterian Hospital, New York, New York; Nancy Jean Cox, PhD, Professor, Genetic Medicine, University of Chicago, Chicago, Illinois; Jacqueline M. Dunbar-Jacob, PhD, RN, Dean and Professor, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania; Evelyn C. Granieri, MD, MPH, MSEd, Chief, Division of Geriatric Medicine and Aging, College of Physicians and Surgeons, Columbia University, New York-Presbyterian Hospital, New York, New York; Gail Hunt, BA, President and Chief Executive Officer, National Alliance for Caregiving, Bethesda, Maryland; Kathleen McGarry, PhD, Professor of Economics, Department of Economics, University of California, Los Angeles, Los Angeles, California; Dinesh Patel, MD, Senior Geriatrician, Charles E. Smith Life Communities and Assistant Clinical Professor of Medicine, George Washington University School of Medicine, Rockville, Maryland; Arnold L. Potosky, PhD, Professor of Oncology and Director of Health Services Research, Georgetown University Medical Center, Cancer Control Program, Lombardi Comprehensive Cancer Center, Washington, DC; Elaine Sanders-Bush, PhD, Professor of Pharmacology and Psychiatry, Vanderbilt University Medical Center, Nashville, Tennessee; Donald Silberberg, MD, Professor, Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania; Maurizio Trevisan, MD, MS, Executive Vice Chancellor and Chief Executive Officer, Health Sciences System; Nevada System of Higher Education; and Professor of Medicine, University of Nevada School of Medicine, Las Vegas, Nevada.

Speakers

Paul Aisen, MD, Professor, Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, California; Marilyn Albert, PhD, Professor of Neurology, Division of Cognitive Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland; David A. Bennett, MD, Robert C. Borwell Professor of Neurological Sciences and Director, Department of Neurological Sciences, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois; James Burke, MD, PhD, Associate Professor of Medicine-Neurology; Associate Director, Bryan Alzheimer's Disease Research Center; and Director, Duke Memory Disorders Clinic, Duke University, Durham, North Carolina; Carl Cotman, PhD, Professor, Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California; Charles DeCarli, MD, Professor of Neurology, Department of Neurology, Center for Neuroscience and Director, Alzheimer's Disease Center, Imaging of Dementia and Aging (IDeA) Laboratory, University of California at Davis, Sacramento, California; Laura Fratiglioni, MD, PhD, Professor of Geriatric Epidemiology and Director, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden; Mary Ganguli, MD, MPH, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Hugh Hendrie, DSc, MB, ChB, Professor, Department of Psychiatry, Indiana University School of Medicine; Scientist, Indiana University Center for Aging Research; and Research Scientist, Regenstrief Institute, Indianapolis, Indiana; Tracey Holsinger, MD, Assistant Professor, Department of Geriatric Psychiatry, Duke University, Durham, North Carolina; Arthur Kramer, PhD, Professor of Psychology and Neuroscience, Beckman Institute, University of Illinois, Urbana, Illinois; Constantine Lyketsos, MD, MHS, The Elizabeth Plank Althouse Professor, Johns Hopkins University and Chairperson of Psychiatry, Johns Hopkins Bayview Medical Center, Baltimore, Maryland; Jennifer Manly, PhD, Associate Professor, Department of Neurology, Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, New York; Martha Clare Morris, ScD, Director, Sections of Nutrition and Nutritional Epidemiology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois; Dan Mungas, PhD, Adjunct Professor, Department of Neurology, University of California at Davis School of Medicine, Sacramento, California; Ronald C. Petersen, PhD, MD, Cora Kanow Professor of Alzheimer's Disease Research and Director, Alzheimer's Disease Research Center, Mayo Clinic College of Medicine, Rochester, Minnesota; Joseph Quinn, MD, Associate Professor, Department of Neurology, Oregon Health & Science University and Portland Veterans Affairs Medical Center, Portland, Oregon; Yaakov Stern, PhD, Professor, Departments of Neurology, Psychiatry and Psychology, Sergievsky Center and Taub Institute, Columbia University College of Physicians and Surgeons, New York, New York; Frederick W. Unverzagt, PhD, Professor of Psychiatry, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana; John W. Williams Jr., MD, Professor, Department of General Internal Medicine, Duke University, Durham, North Carolina.

Planning Committee

Neil Buckholtz, PhD (Chairperson), Chief, Dementias of Aging Branch, Neuroscience and Neuropsychology of Aging Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland; Lisa Ahramjian, MS, Communications Specialist, Office of Medical Applications of Research, Office of the Director, National Institutes of Health, Bethesda, Maryland; Shilpa Amin, MD, MBSc, Medical Officer, Evidence-based Practice Centers Program, Center for Outcomes and Evidence, Agency for Healthcare Research and Quality, Rockville, Maryland; Lynda A. Anderson, PhD, Director, Healthy Aging Program, Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia; Nancy C. Andreasen, MD, PhD (Conference and Panel Chairperson‡), Director, Mental Health Clinical Research Center; Director, Psychiatric Iowa Neuroimaging Consortium; and Andrew H. Woods Chair and Professor of Psychiatry, University of Iowa, Iowa City, Iowa; Sanjay Asthana, MD, Duncan G. and Lottie H. Ballantine Chair in Geriatrics and Professor and Head, Section of Geriatrics and Gerontotogy, University of Wisconsin-Madison Medical School; Director, Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veterans Hospital; and Associate Director, Wisconsin Alzheimer's Institute, Madison, Wisconsin; Stephanie Chang, MD, MPH, Medical Officer, Evidence-based Practice Centers Program, Center for Outcomes and Evidence, Agency for Healthcare Research and Quality, Rockville, Maryland; Charles DeCarli, MD, Professor, Department of Neurology, University of California, Davis, Sacramento, California; Emmeline M. Edwards, PhD, Deputy Director, Division of Extramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; Jovier D. Evans, PhD, Chief, Geriatric Translational Neuroscience and Geriatric Pharmacologic, Intervention Research Programs, Geriatrics Research Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; Steven Fox, MD, MPH, SM, Center for Outcomes and Evidence, Agency for Healthcare Research and Quality, Rockville, Maryland; Hugh C. Hendrie, MB, ChB, DSc, Professor, Department of Psychiatry, Indiana University School of Medicine Center; Scientist, Indiana University Center for Aging Research; and Research Scientist, Regenstrief Institute, Indianapolis, Indiana; Jonathan W. King, PhD, Division of Behavioral and Social Research, National Institute on Aging, National Institutes of Health, Bethesda, Maryland; Kathy Mann Koepke, PhD, Program Director, Neuroscience, National Institute of Nursing Research Centers and Program Projects Coordinator, Division of Extramural Activities, National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland; Barnett S. Kramer, MD, MPH, Associate Director for Disease Prevention and Director, Office of Medical Applications of Research, Office of the Director, National Institutes of Health, Bethesda, Maryland; Kelli K. Marciel, MA, Communications Director, Office of Medical Applications of Research, Office of the Director, National Institutes of Health, Bethesda, Maryland; Arthur A. Meltzer, PhD, Office of Clinical Standards and Quality, Centers for Medicare & Medicaid Services, Baltimore, Maryland; Martha Clare Morris, ScD, Associate Professor, Internal Medicine; Director, Section of Nutrition and Nutritional Epidemiology; Assistant Provost for Community Research, Rush University Medical Center, Chicago, Illinois; Marcelle Morrison-Bogorad, PhD, Director, Neuroscience and Neuropsychology of Aging Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland; Richard Nahin, PhD, MPH, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland; Lata S. Nerurkar, PhD, Senior Advisor for the Consensus Development Program, Office of Medical Applications of Research, Office of the Director, National Institutes of Health, Bethesda, Maryland; Susan C. Rossi, PhD, MPH, Deputy Director, Office of Medical Applications of Research, Office of the Director, National Institutes of Health, Bethesda, Maryland; Yaakov Stern, PhD, Professor, Columbia University, New York, New York; Christine A. Swanson, PhD, Office of Dietary Supplements, Office of the Director, National Institutes of Health, Bethesda, Maryland; Frederick W. Unverzagt, PhD, Professor of Psychiatry and Director, Neuropsychology Clinic in Psychiatry; Training Director, Clinical Neuropsychology Residency, Indiana University School of Medicine, Indianapolis, Indiana; Molly V. Wagster, PhD, Chief, Behavioral and Systems Neuroscience Branch, Division of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.

‡ Dr. Nancy Andreasen stepped down as panel chair on 20 January 2010, because of a relationship that was unforeseen to be a possible conflict of interest; we thank her for her invaluable service in the process.

Conference Sponsors

National Institute on Aging (Richard Hodes, MD, Director), Office of Medical Applications of Research (Jennifer M. Croswell, MD, MPH, Acting Director).

Conference Cosponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (Alan Guttmacher, MD, Acting Director), National Center for Complementary and Alternative Medicine (Josephine P. Briggs, PhD, Director), National Institute of Mental Health (Thomas Insel, MD, Director), National Institute of Neurological Disorders and Stroke (Story C. Landis, PhD, Director), National Institute of Nursing Research (Patricia Grady, PhD, RN, Director), Office of Dietary Supplements (Paul Coates, PhD, Director).

Conference Partners

Centers for Disease Control and Prevention (Janet Collins, PhD, Director), Centers for Medicare & Medicaid Services (Barry M. Straube, MD, Chief Medical Officer, Director), Office of Clinical Standards and Quality.

Figures

Tables

Table Jump PlaceholderAppendix Table.  Recommendations for Further Research in Alzheimer Disease

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Want to Subscribe?

Learn more about subscription options

Advertisement

Want to Subscribe?

Learn more about subscription options

Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)