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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61:951-956 (2006)
© 2006 The Gerontological Society of America

Dementia-Free Survival Among Centenarians: An Evidence-Based Review

James F. Calvert, Jr.1,5,, Joyce Hollander-Rodriguez, Jeffrey Kaye and Marjorie Leahy

Departments of 1 Family Medicine, 2 Neurology, and 3 Biomedical Engineering, Oregon Health & Science University, Portland.
4 Portland Veterans Affairs Medical Center, Oregon.
5 Merle West Center for Medical Research, Klamath Falls, Oregon.

Address correspondence to James Calvert, MD, 1453 Esplanade, Klamath Falls, OR 97601. E-mail: calvertj{at}ohsu.edu


   Abstract
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Methods
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 Discussion
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Background. The 2000 U.S. census identified 50,454 Americans older than 100 years (18 per 100,000). Increased longevity is only of benefit if accompanied by the maintenance of physical, social, and cognitive function into advanced age. The goal of this review was to identify research describing centenarians to find the prevalence of dementia-free survival.

Methods. We reviewed 650 publications to find studies that described the prevalence of dementia in centenarians, were community-based, had data that were specific to persons older than 100 years, and were published in peer-reviewed journals. For each study, we identified the prevalence of dementia, the completeness of the sample, the number of study participants, the method used to diagnose dementia, and the duration of the study.

Results. We identified 20 research groups from 14 countries with publications meeting our search criteria. The studies showed substantial variation in methods of assessing cognitive status, assuring a complete cohort, and sample size. Few studies reported longitudinal data or attempted diagnosis of the cause of dementia. The prevalence of dementia-free survival past 100 years of age varied between 0 and 50 percent.

Conclusions. The methodology used in studies regarding dementia prevalence among centenarians is sufficiently varied that combination of existing studies into a meta-analysis is not possible. Suggestions for assuring quality in future centenarian research are presented.

ALTHOUGH dementia and other disability may come to all of us if we live long enough, even very frail centenarians are often found to be healthy into their 90s (1–4). For this reason, centenarians provide models for healthy aging (4,5), and centenarian studies can guide provision of care for an aging population.

Meta-analyses of current data regarding elderly persons between the ages of 65 and 90 indicate that the rate at which new cases of dementia occur doubles every 5 years after the age of 65. For example, new cases of dementia occur in about 6% of persons in their 85th year and 12% in their 90th, with prevalence rates of 25 and 35 percent (6–9). In this article we critically review studies about the prevalence of dementia in the centenarian age group to see if a meta-analysis could show if dementia incidence and prevalence continue to increase in this age group. We also seek to identify factors that would improve the quality of future studies of centenarians.


   METHODS
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Results
 Discussion
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We searched Medline and other data bases to identify studies describing centenarians. Key words used included "centenarians," "nonagenarians," "prevalence," "dementia," and "epidemiology." We reviewed the citations in articles from the computerized searches to identify older studies, and sought the advice of experts to find more studies. This strategy identified 650 publications. We reviewed these publications to identify studies regarding the prevalence of dementia among centenarians. To be included, studies had to be community-based, contain prevalence data for dementia in persons older than 100 years, and be published in peer-reviewed journals. After a community-based study had been identified, every effort was made to find all articles related to the study. The studies were then rated [on the basis of accepted criteria for studies involving prognosis (10)] by two of the authors (JC and JHR) on six quality indicators as shown in Tables 1 and 2. The studies regarding the prevalence of dementia in centenarians are summarized in Table 3 (11–39).


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  		Table 1. Criteria Used to Evaluate Centenarian Studies.

 

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  		Table 2. Scoring for Studies in Table 3 Based on Criteria From Table 1.

 

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  		Table 3. Studies Assessing the Cognitive Status of the Oldest Old.

 

   RESULTS
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 Methods
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Discussion
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We identified 20 studies from 14 countries that met our search criteria. Other centenarian studies have indicated plans to study dementia prevalence data, but we were unable to find published results (40–42). Additional centenarian studies have not reported prevalence of dementia (43–46) or were not community-based (47), so they are not included in Table 3.

The likelihood of dementia-free survival after the age of 100 varied between 0% in smaller studies to as much as 50% in other studies (see Table 3). All the studies in Table 3 found more female than male centenarians, although in Sardinia (41,48) and among the Uygur people of China (44) the proportion of men is higher. The studies in Table 3 that reported gender data indicate that male centenarians are more likely to be intact cognitively than their female contemporaries, possibly because men tend to die more quickly after they become demented than women do (20,49–51). Unfortunately, because of the variation in methodology used in different centenarian studies, no definitive conclusion regarding the likelihood of dementia-free survival past 100 years of age is possible.


   DISCUSSION
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References
 
The small number of study participants in most of the studies in Table 3 suggests that meta-analysis, which has been used to determine the prevalence and incidence of dementia for younger age groups (5–9) could be used to combine data from the studies in Table 3. However, the inconsistency in methods in the centenarian studies in Table 3 makes meta-analysis inappropriate. The definition of dementia is not consistent from study to study. The method used to assess patients also varies; studies have shown that very elderly persons may appear intact when one method of assessment is used, but impaired when other scales are used (52). Sampling methods vary as well; some studies have convenience samples, whereas others make an effort to get a complete population sample (Table 2). The rest of the discussion follows the six criteria from Table 1.

Validity
As only 1 in 5500 persons in developed countries lives to the age of 100, large populations must be sampled to get an adequate number for research. Formal age verification of centenarians (e.g., birth records) further challenges the ascertainment of centenarians (53). All but one (18) of the studies in Table 3 used census data to identify centenarians. Census data may accurately identify the birth date of citizens but, because of the high mortality rate in this age group, many deceased persons are listed so the total number is often unreliable. Centenarians who live in long-term care facilities are accessible (47); however, they tend to be less functional than are those persons living independently, leading to an overestimation of the prevalence of impairment. In the community, centenarians who are more intact may be more likely to be willing to volunteer to be study participants, leading to underestimation of dementia prevalence. Several "centenarian" studies included persons 95–99 years old; we included those studies in Table 3 (13,16,26), but these studies cloud the picture because they do not provide centenarian-specific data.

Inclusiveness
A number of unique challenges lead to a high refusal rate when centenarians identified by census data are contacted. Elderly survivors tend to be socially isolated because their peer group is deceased. The principal social contact of centenarians is typically a child or other relative who is protective of "their" centenarian. They may view participation as too demanding of a frail elderly persons (54). Elderly persons are generally not attracted by any personal health benefits that might result from participation in medical research, although the idea of "being useful to someone" may motivate them to volunteer to be a research participant (55).

The high mortality rate among very old persons can also affect research results; deaths which occur during the study period can lead to an underestimation of dementia rates because impaired participants may die before they can be assessed. Longitudinal studies indicate that the interval between the onset of dementia and death shortens with increasing age. This means that populations that survive into extreme old age might be expected to have a lower prevalence of dementia, because demented centenarians tend to die after the onset of dementia with less delay than do younger cohorts (2,4,56).

Another limitation of the studies in Table 3 is that most took place in industrialized nations among urban populations. Little research about centenarians in developing countries has been done. Sample sizes for minorities and other special populations are generally small in centenarian studies, so distinctions between these and the majority population are not possible. Rural areas may contain a higher proportion of elderly persons than metropolitan areas (54), but the rural elderly population is underrepresented in research (1), and most published studies include few rural centenarians.

Perhaps because of the reasons cited above, many studies use information obtained from proxies rather than from the centenarians themselves. It is unclear whether information from proxies is more or less accurate than that obtained from the elderly participants themselves. The Heidelberg study group compared proxy and study participant interviews in a group of 85 centenarians and found that centenarians tended to overrate their Activities of Daily Living capability and that their self-ratings were highly mood-dependent (57). This finding occurs in younger elderly persons as well (58).

Sample Size
Sample size in the community-based studies in Table 3 varied from 13 to more than 700. The logistical difficulties outlined above and the time involved in performing a careful assessment of a centenarian are barriers to achieving adequate sample size. Small samples may limit the generalizability of prevalence estimates; however, smaller samples may allow a more thorough and accurate assessment.

Cognitive and Functional Assessment
Detailed cognitive assessment is not always performed in centenarian studies. Some of the studies in Table 3 used screening measures such as the Mini-Mental State Examination rather than more comprehensive tools. The Clinical Dementia Rating scale, which may vary in its administration and is difficult to use in field studies, was the most commonly used test. Although cognitive function is the most important driver of the final score, performing a Clinical Dementia Rating involves an assessment of Activities of Daily Living, physical health, and cognitive function, whereas other scales may provide only an assessment of mental status. However, physical health and cognitive function are closely interrelated in this age group, so it is important to assess both (2,23). Failure to recognize the normal cognitive and physical changes in very old persons leads to an overestimation of the prevalence of dementia or physical impairment among centenarians (2). Similarly, special assessment scales and great patience are required to provide an accurate assessment of a motorically, visually, or hearing-impaired elderly person (33,55).

Need for Multiple Assessments
Increasing age is associated with increased variability on testing, so that studies that involve only one assessment of elderly persons tend to give a less accurate assessment than do those that involve multiple assessments over time. The increased mortality rate of about 50% annually in centenarians makes follow-up more difficult in this age group (37); another factor is the extended interview time needed because centenarians tire so easily. Few of the studies in Table 2 used longitudinal assessments. Some studies indicate that they are following patients longitudinally, but longitudinal data have not been published (27,32,40).

Diagnosis
Few of the studies in Table 3 tried to identify the specific cause of dementia. Existing data indicate that the majority of cases of dementia in younger age groups are due to Alzheimer dementia (8,20); however, the causes of cognitive decline in very old persons are not known. Diagnosis is a particularly challenging problem while study participants are alive, although criteria are available for clinical diagnosis of common causes of dementia (16). Even neuropathologic examination of brains after death, often considered the gold standard of diagnosis, may show evidence of more than one form of dementia or be inconclusive in other ways (59).

Conclusion
Current evidence does not provide robust estimates of the prevalence of dementia among centenarians because of inconsistency of the methods used in various studies. Application of consensus standards regarding the optimal assessment methods for centenarian research would improve our understanding of the dynamic demographics of the oldest old and provide direction for future research on the health of this important population.


   Acknowledgments
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This work was supported by grants from Merle West Center for Medical Research; Northwest Health Foundation; the Alzheimer's Research Alliance of Oregon; the Department of Veterans Affairs; and the National Institute on Aging, National Institutes of Health (AG08017).

A more complete reference list is available on request from the authors.


   Footnotes
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Decision Editor: Darryl Wieland, PhD, MPH

Received October 7, 2005

Accepted April 21, 2006


   References
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