National Institutes of Health State-of-the-Science Conference Statement: Preventing Alzheimer Disease and Cognitive Decline
Authors: Martha L. Daviglus
Journal: Annals of Internal Medicine (2010)

NIH Conferences3 August 2010National Institutes of Health State-of-the-Science Conference Statement: Preventing Alzheimer Disease and Cognitive DeclineFREEMartha 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†Martha L. Daviglus, MD, PhD, MPHFrom 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., Carl C. Bell, MDFrom 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., Wade Berrettini, MD, PhDFrom 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., Phyllis E. Bowen, PhDFrom 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., E. Sander Connolly Jr., MDFrom 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., Nancy Jean Cox, PhDFrom 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., Jacqueline M. Dunbar-Jacob, PhD, RNFrom 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., Evelyn C. Granieri, MD, MPH, MSEdFrom 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., Gail Hunt, BAFrom 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., Kathleen McGarry, PhDFrom 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., Dinesh Patel, MDFrom 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., Arnold L. Potosky, PhDFrom 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., Elaine Sanders-Bush, PhDFrom 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., Donald Silberberg, MDFrom 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., and Maurizio Trevisan, MD, MS†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.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-3-201008030-00260 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 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 atconsensus.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.Question 1What 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 KnowStrong 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.LimitationsOne 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.Question 2What 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 KnowFor 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 FactorsThe 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 FactorsSeveral 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 HealthDepression and depressive symptoms have been consistently found to be associated with mild cognitive impairment and cognitive decline.MedicationsNo 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 FactorsChildhood 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 EngagementWhereas 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 ActivitiesPreliminary 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 UseEvidence indicates that current smoking is associated with increased risk for cognitive decline; evidence for past smoki