menu-iconMore mobile-close-icon
Skip Navigation
Skip Navigation
PrintDownload PDFGet Adobe ReaderDownload to WordDownload as HTMLDownload as XMLCitation Manager
Save to Favorites
Guideline Summary
Guideline Title
NIH Consensus Development Conference statement on preventing Alzheimer's disease and cognitive decline.
Bibliographic Source(s)
Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. NIH state-of-the-science conference statement: preventing Alzheimer's disease and cognitive decline. NIH Consens State Sci Statements. 2010 Apr 28;27(4):1-30. PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)
  • Alzheimer's disease
  • Cognitive decline
Guideline Category
Prevention
Risk Assessment
Clinical Specialty
Family Practice
Geriatrics
Internal Medicine
Neurology
Preventive Medicine
Psychiatry
Intended Users
Advanced Practice Nurses
Allied Health Personnel
Health Care Providers
Health Plans
Nurses
Physician Assistants
Physicians
Guideline Objective(s)

To provide healthcare providers, patients, and the general public with a responsible assessment of currently available data on the prevention of Alzheimer's disease and cognitive decline

Target Population

United States population age 50 and older

Interventions and Practices Considered

Identification of modifiable risk factors and interventions for prevention of Alzheimer's disease and cognitive decline, including:

  • Nutritional factors
  • Medical conditions
  • Prescription and non-prescription medications
  • Social/economic/behavioral factors
  • Toxic environmental factors
  • Genetic factors

Note: No specific interventions were recommended.

Major Outcomes Considered
  • Development of Alzheimer's disease or cognitive decline
  • Cognitive function

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

Note from the National Guideline Clearinghouse (NGC): A systematic review of the literature was prepared by the Duke Evidence-based Practice Center (EPC) for the Agency for Healthcare Research and Quality (AHRQ) for use by the National Institutes of Health (see the "Availability of Companion Documents" field).

Inclusion/Exclusion Criteria

After discussion with the technical expert panel (TEP), the ECP staff generated a list of article inclusion and exclusion criteria (see Table 2 in the Evidence Report; see also the "Availability of Companion Documents" field) for the Key Questions. Because of the large number of factors and interventions to review, the ECP staff searched initially for good quality systematic reviews. They included primary literature to update eligible reviews or when good quality reviews were unavailable. They limited the primary literature to comparative studies published in English that enrolled adults age 50 years or older at the time of final cognitive assessment, drawn from general populations in economically developed countries. General populations were defined as those drawn primarily from noninstitutionalized community settings or general medical populations. With three exceptions, observational studies were limited to longitudinal designs where the risk factor or intervention was measured prior to the outcome. Exceptions were made for traumatic brain injury and toxic/environmental exposures because of the difficulties studying these factors longitudinally, and for sleep apnea, because of the absence of cohort studies. Because Alzheimer's disease (AD) is a relatively uncommon event, a sample size greater than 300 was required to focus on studies with higher statistical power. For similar reasons, at least 1 year was required between exposure and outcomes assessment for studies of cognitive decline, and at least 2 years for studies of AD.

Literature Search Strategies

Based on the above-described inclusion/exclusion criteria, a list of Medical Subject Heading (MeSH) search terms was generated, supplemented by keyword searches, to search MEDLINE®. Search terms and strategies were developed in consultation with a medical librarian. The exact search strategies used are given in Appendix A at http://www.ahrq.gov/downloads/pub/evidence/pdf/alzheimers/alzcog.pdf External Web Site Policy. In addition to MEDLINE®, the EPC staff searched the Cochrane Database of Systematic Reviews to identify relevant systematic reviews. For topics with a recent good quality systematic review, the search was updated by identifying relevant primary literature published from 1 year prior to the search date through October 27, 2009. The 1-year overlap is necessary because of delays between publication in journals and availability for searching in MEDLINE®. Relevant older literature missed or excluded in prior reviews that was relevant and met eligibility criteria was included.

When the EPC staff did not identify a relevant good quality review, they searched the primary literature to include studies from 1984 through October 27, 2009. Electronic searching was supplemented by examining the bibliographies of reviews and primary studies. Because of the large volume of literature and availability of specialized registries for genetic studies, they developed a separate search strategy for this literature. The HUGE and ALZGene databases were examined to identify relevant systematic reviews for genes identified as being of special interest in consultation with the TEP.

Using the pre-specified inclusion/exclusion criteria, titles/abstracts were examined independently by two reviewers for potential relevance to the key questions. Articles included by either reviewer underwent full-text screening. At the full-text screening stage, two independent reviewers read each article to determine if it met eligibility criteria. Disagreements were resolved by consensus. At the full-text review stage, simple agreement was 84 percent, and median chance corrected agreement was kappa = 0.63 (range 0.40 to 1.0). Articles meeting the eligibility criteria were included for data abstraction.

Number of Source Documents
  • Twenty-five systematic reviews
  • 250 original research studies
Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Not Given)
Rating Scheme for the Strength of the Evidence

Not stated

Methods Used to Analyze the Evidence
Meta-Analysis
Review of Published Meta-Analyses
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

Note from the National Guideline Clearinghouse (NGC): A systematic review of the literature was prepared by the Duke Evidence-based Practice Center (EPC) for the Agency for Healthcare Research and Quality (AHRQ) for use by the National Institutes of Health (see the "Availability of Companion Documents" field).

Data Abstraction and Data Management

Data from published reports were abstracted into evidence tables by one reviewer and overread by a second reviewer. Data elements abstracted included descriptors to assess applicability, quality elements, intervention/exposure details, and outcomes. Disagreements were resolved by consensus or by obtaining a third reviewer's opinion when consensus could not be reached. The final evidence tables are intended to provide sufficient information so that readers can understand the study and determine its quality. Evidence tables for all included studies are presented in Appendix B of the Evidence Report (see the "Availability of Companion Documents" field). Because some studies address more than one exposure or question, the evidence tables are organized alphabetically by author.

Assessment of Methodological Quality

Separate criteria were developed for assessing the methodological quality of included systematic reviews, randomized controlled trials (RCTs), and observational studies. These criteria are given in Appendices C, D, and E of the Evidence Report, respectively (see the "Availability of Companion Documents" field).

Principles from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group (www.gradeworkinggroup.org External Web Site Policy) were used to summarize the level of evidence for each factor as low, moderate, or high. The GRADE approach was developed to evaluate the overall level of evidence for interventions, but it has been extended to factors (e.g., medical illness) that would not be considered as interventions. The approach considers the body of evidence for each outcome, assigning an initial rating of low quality to observational studies and high quality to RCTs. These initial ratings may be modified by the following factors: detailed study design, consistency, strength of association, dose-response effect, directness, precision, and if all plausible confounding would reduce a demonstrated effect. The resulting judgments about the level of evidence are presented separately in summary tables for Alzheimer's disease (AD) and cognitive decline in Chapter 5 of the Evidence Report (see the "Availability of Companion Documents" field). Judgments about the strength of evidence were made by at least two investigators; final ratings were reached by consensus.

Data Synthesis

When good quality systematic reviews were identified, the EPC staff summarized the findings in narrative form in Chapter 3 of the Evidence Report (see the "Availability of Companion Documents" field). Any new studies identified since the systematic review was published are summarized descriptively in a table that includes the study sample, exposure classification, duration of follow-up, adjustment for confounding, and primary outcomes. The EPC staff evaluated whether the new evidence was likely to change estimates from the prior review by considering the precision and stability of estimates from the original review, the number and size of the new studies relative to studies in the original review, the quality of the new studies, and the consistency in estimates and conclusions between the new evidence and the original review. After considering these issues, prior meta-analyses were updated when substantial new evidence was available and a new summary estimate was likely to lead to different conclusions. Primary meta-analysis was performed when studies were conceptually homogeneous and the needed data were available for the summary estimate. Since meta-analysis of observational studies may give spurious precision, meta-analysis was applied to observational data only when studies were high quality and conceptually homogeneous (similar subjects, exposure, outcomes).

Refer to Chapter 2 of the Evidence Report (see the "Availability of Companion Documents" field) for more information.

Methods Used to Formulate the Recommendations
Expert Consensus (Consensus Development Conference)
Description of Methods Used to Formulate the Recommendations

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 (AHRQ); 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.

The National Institute on Aging and the Office of Medical Applications of Research of the National Institutes of Health convened a State-of-the-Science Conference on April 26–28, 2010, to assess the available scientific evidence related to the following questions:

  1. What factors are associated with the reduction of risk of Alzheimer's disease?
  2. What factors are associated with the reduction of risk of cognitive decline in older adults?
  3. What are the therapeutic and adverse effects of interventions to delay the onset of Alzheimer's disease? Are there differences in outcomes among identifiable subgroups?
  4. What are the therapeutic and adverse effects of interventions to improve or maintain cognitive ability or function? Are there differences in outcomes among identifiable subgroups?
  5. What are the relationships between the factors that affect Alzheimer's disease and the factors that affect cognitive decline?
  6. 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?

A non-Department of Health and Human Services, non-advocate 15-member panel included the fields of preventive medicine, geriatrics, internal medicine, neurology, neurological surgery, psychiatry, mental health, human nutrition, pharmacology, genetic medicine, nursing, health economics, health services research, family caregiving, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience.

The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov External Web Site Policy.

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

Guideline developers reviewed published cost analyses.

Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

Among the more important activities involved in producing a credible evidence report is conducting an unbiased and broadly based peer review of the draft report. External reviewers for the evidence report included clinicians and representatives of professional societies, as well as members of the technical expert panel (TEP). The list of nominees was forwarded to Agency for Healthcare Research and Quality (AHRQ) for vetting and approval. A list of peer reviewers submitting comments on the draft is included in Appendix F of the Evidence Report (see the "Availability of Companion Documents" field).

Recommendations

Major Recommendations

Cognitive decline and Alzheimer's disease are major causes of morbidity and mortality worldwide and are substantially burdensome to the affected persons, their caregivers, and society in general. Extensive research over the past 20 years has provided important insights on the nature of Alzheimer's disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. Currently, firm conclusions cannot be drawn about the association of any modifiable risk factor with cognitive decline or Alzheimer's disease. Highly reliable consensus-based diagnostic criteria for cognitive decline, mild cognitive impairment, and Alzheimer's 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's disease. The guideline developers 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 (as noted in the recommendations for future research).

For example, ongoing studies including (but not limited to) studies on antihypertensive medications, omega-3 fatty acids, physical activity, and cognitive engagement may provide new insights into the prevention or delay of cognitive decline or Alzheimer's disease. This important research needs to be supplemented by further studies. Large-scale population-based studies and randomized controlled trials (RCTs) are critically needed to investigate strategies to maintain cognitive function in individuals at risk for decline, to identify factors that may delay the onset of Alzheimer's disease among persons at risk, and to identify factors that may slow the progression of Alzheimer's disease among persons in whom the condition is already diagnosed.

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is not specifically stated for each recommendation.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Better understanding of currently available data on the prevention of Alzheimer's disease and cognitive decline

Potential Harms

Not stated

Qualifying Statements

Qualifying Statements
  • The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research, and that the information provided is not a substitute for professional medical care or advice.
  • This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health (NIH) or the Federal Government.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Resources
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Staying Healthy
IOM Domain
Effectiveness

Identifying Information and Availability

Bibliographic Source(s)
Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. NIH state-of-the-science conference statement: preventing Alzheimer's disease and cognitive decline. NIH Consens State Sci Statements. 2010 Apr 28;27(4):1-30. PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2010 Apr
Guideline Developer(s)
National Institutes of Health Consensus Development Conference - Independent Expert Panel
Source(s) of Funding

United States Government

Guideline Committee

National Institutes of Health (NIH) State-of-the-Science Panel

Composition of Group That Authored the Guideline

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

Financial Disclosures/Conflicts of Interest

All of the panelists who participated in this conference and contributed to the writing of this statement were identified as having no financial or scientific conflict of interest, and all signed forms attesting to this fact. Unlike the expert speakers who present scientific data at the conference, the individuals invited to participate on National Institutes of Health (NIH) Consensus and State-of-the-Science Panels are reviewed prior to selection to ensure that they are not proponents of an advocacy position with regard to the topic and are not identified with research that could be used to answer the conference questions.

For more information about conference procedures, please see http://consensus.nih.gov/aboutcdp.htm External Web Site Policy.

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the National Institutes of Health (NIH) Consensus Development Conference Program Web site External Web Site Policy.

Print copies: NIH Consensus Statements, State-of-the-Science Statements, and related materials are available by visiting http://consensus.nih.gov External Web Site Policy; by calling toll free 888-644-2667; or by emailing consensus@mail.nih.gov. Written requests can be mailed to the NIH Consensus Development Program Information Center, P.O. Box 2577, Kensington, MD 20891. When ordering copies of this statement, please reference item number 2010-00034-STMT.

Availability of Companion Documents

The following are available:

  • Preventing Alzheimer's disease and cognitive decline. Evidence report/technology assessment. AHRQ Publication No. 10-E005. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ). 2010 Apr. 727 p. Electronic copies: Available in Portable Document Format (PDF) from the AHRQ Web site External Web Site Policy.
  • The National Institutes of Health (NIH) State-of-the-Science Conference: preventing Alzheimer's disease and cognitive decline. Webcast. Apr 26–28, 2010. Bethesda, MD. Available from the NIH Web site External Web Site Policy.
Patient Resources

None available

NGC Status

This summary was completed by ECRI Institute on September 14, 2011.

Copyright Statement

No copyright restrictions apply.

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

Read full disclaimer...