AD is a kind of dementia, with the essential feature the development of multiple cognitive deficits, including memory impairment, and at least one other deficit, such as impaired language functioning (aphasia). The definition of dementia also requires that the condition be severe enough to cause a significant impairment in social or occupational functioning that represents a decline from a previous level of functioning. Common clinical signs of dementia include emotional and behavioral disturbances. AD is a dementia of gradual onset and progressive decline. It may be difficult to distinguish clinically between mild—that is, early—AD and normal aging, but severe AD is characterized by a need for much help with personal care as the result of incontinence and almost total lack of comprehension of the environment. AD is said to be differentiated from other dementias on the basis of its cause, but that cause is not, in fact, well understood. That AD is accepted as a distinct disease entity is because AD patients manifest specific kinds of abnormalities in the brain—observable only in those who are autopsied or undergo a brain biopsy, a rare procedure—differing from the abnormalities found in other dementias with better understood causes. The prevalence of AD is defined as the number of people in a specific population who suffer from the disease at some specified time. It is often expressed as a rate, the number of cases of that disease existing at a given point in time divided by the total population at that same time. When the number of cases in the target population is too costly to count, prevalence may be estimated by testing, in a prevalence survey, a representative sample of the population. An alternative is to develop a register of people seeking services, but this does not work well for AD because many cases are not treated. The restriction of AD prevalence surveys to the elderly population, 65 years of age or older, makes sense because the majority of cases of AD are elderly. In addition, because AD prevalence tends to increase sharply with age, doubling about every 5 years, at least over the age range of 65 to 85 years, it is common to estimate age-specific prevalence rates of AD. Thus, the population studied is divided into age groups—for example, 65 to 69 years, 70 to 74 years, 75 to 79 years—and a prevalence rate is estimated for each group. This is especially important when comparing AD rates across groups so that differences in prevalence stemming from differences in age distribution can be separated from those stemming from real health differences. Although the dependence of AD rates on gender is not as well established in the scientific literature as dependence on age, there is some tendency for prevalence to be greater for women than for men; therefore, rates that are specific to both age and gender are of interest. The reasons for this tendency are not known. It may be that (1) women are more likely than men to contract the disease or (2) women live longer once they get AD and are therefore more likely to be counted when a prevalence survey is conducted or (3) both of these factors operate. When severity is measured, people with AD are categorized into degrees or levels of illness; thus, for every specific prevalence rate, several categories are used to describe the different levels of severity. For the dementias (including AD), descriptive categories like mild, moderate, and severe are commonly used to indicate how severe a person’s AD is. Sometimes a borderline category, “questionable,” is used for those whose impairment is not great enough to qualify as even mild AD. Today, there are standardized systems for rating severity, often using such descriptive categories. According to one system, the Clinical Dementia Rating (CDR), a person with mild AD needs only prompting in personal care activities, a person with moderate AD needs some assistance, and a person with severe AD needs much assistance and is frequently incontinent. The results of our meta-analysis, based on the pooling of the data of individuals from each of the studies, were used to project the numbers of Americans, in 1995, with (1) AD of any level of severity (mild, moderate, or severe) and (2) moderate or severe AD (see table 1). The AD prevalence estimates are generated by multiplying prevalence rates (discussed in the section below called “Estimated Prevalence Rates”) by the corresponding age- and gender-specific 1995 estimates from the Bureau of the Census.When these results are summed over the several age intervals and both genders, the overall estimate for Americans 65 years of age or older with any AD is 1.9 million. Of these 1.9 million cases, an estimated 1.1 million have moderate or severe AD. To see how this overall prevalence estimate compares with the projections that would be derived from individual studies, we calculated comparable estimates when it was possible to do so. Most of the people with AD—58 percent, or 1.1 million—fall between the ages of 75 and 89. Within this age group, it was possible to project from 9 of the 15 studies dealing with any AD and provide age- and gender-specific estimates for the population based on each study. Two of the studies yield estimates below 1 million. Six fall between 1.1 million and 1.4 million; one (the East Boston study) provides the basis for an estimate of 3.2 million. (For further detail, see app. VIII.) These numbers correspond to overall percentages for Americans 65 years of age or older of 5.7 and 3.3 with any AD and with moderate or severe AD, respectively. When adjusted for the cases of mixed dementia and missed cases not included in some of the studies, these percentages become 6.3 and 4.1, respectively. As noted, individual studies of the AD prevalence rate have produced varied estimates of the percentage of elderly with any AD, ranging from less than 2 percent to 12 percent. We also developed projections into the next century of the number of AD cases and the number of AD cases requiring assistance. We derived these results from the prevalence rates, which we used in conjunction with age- and gender-specific population projections from the Bureau of the Census. These projections, which take the aging of the U.S. population into account, are presented in 5-year intervals until 2015. As shown in table 2, based on the Bureau’s middle series of population projections, the numbers of cases of AD are expected to increase approximately 12 percent every 5 years. When adjusted to include all mixed cases and missed cases, the numbers in this table increase by 10 percent and 24 percent for any AD and moderate or severe AD, respectively. These adjustments yield, for example, in 2015, 3.2 million cases for any AD and 2.1 million cases for moderate or severe AD. Because prevalence is partially determined by the length of time people with AD survive, improvements in AD care will tend to increase future prevalence, just as any general improvements in human longevity will.Thus, significant unanticipated improvements in the longevity of either the elderly in general or people with AD in particular may lead to even greater numbers of people with AD in the future. We developed age- and gender-specific prevalence rates based on our meta-analysis, stopping at the age of 95, when the data become sparse for both any AD and moderate or severe AD (see tables 3 and 4). Our first step in generating these estimates was to take severity of disease into account by excluding any data presented in the 18 published studies that included persons with questionable AD. Even with this exclusion, the estimates of AD prevalence for a given combination of age and gender that we obtained from the 18 studies varied greatly. (See app. II for a list of the studies.) For example, the estimated prevalence for men in the age interval from 85 to 95 ranged from 12 percent to 54 percent (see app. IV). Before attempting to integrate these data, we took severity of disease further into account by dealing separately with the three studies—numbers 1, 5, and 18 (see table IV.1)—that excluded mild cases. In our first integration of these data, the results of our meta-analysis show prevalence rates for any AD in the 15 studies that do not exclude mild cases. (See table 3.) These results tend to differ only slightly from estimates presented in previous articles reviewing AD prevalence. These rates are each increased by 10 percent when all mixed cases and missed cases are included. These results demonstrate that the AD prevalence rate increases sharply with age, doubling about every 5 years at least until about the age of 85, as expected from previous reports of this relationship. In addition, the rate is greater for women than for men. In our second integration of these data, we included only studies that provided number of cases with moderate or severe AD. These studies either excluded mild cases (the three studies mentioned earlier) or enabled us to exclude mild cases by presenting the data for these cases separately (numbers 6 and 13). When only cases with moderate or severe AD are counted, the rates are lower. But the increase in prevalence with age and the higher rates for women are observed at the moderate and severe levels too. These rates are each increased by 24 percent when all cases of mixed dementia and missed cases are included. Two of the studies allow for the counting of only the cases with severe AD. When this is done, the resulting rates are still lower, as logic would dictate, but the margins of error are so large that we do not present these results for severe AD. NIA is currently supporting a number of studies of AD prevalence in the United States. Many of these studies include minority groups in addition to whites. For example, one such study looks at prevalence among African-Americans, Hispanics, and whites in a neighborhood of New York City. The results of these studies are expected to be published within the next several years. When they are, our knowledge about the extent of AD in the United States will be enhanced. Not only will our ability to estimate AD prevalence for the whole country improve but so will our ability to make such estimates for specific racial and ethnic populations.