In this study, we found that 34.0% of non-demented oldest-old had impaired cognition. The most common type of cognitive impairment was OCI, which was more common than both aMCI and naMCI combined. Participants with OCI were too impaired for MCI criteria (MMSE < 24, functional impairment due to cognition, or both), yet did not meet criteria for dementia. There was no significant relationship between age and cognitive impairment group. Men were more likely to have aMCI than women. We did not find many differences in cardiovascular risk factors between the cognitive groups although history of hypertension occurred more frequently in participants with naMCI and history of stroke was found more frequently in participants with OCI.
A few studies have investigated the prevalence of MCI in the oldest-old and have reported varying results. These studies had different definitions of MCI, as well as variable subject populations and sample sizes. A community-based cohort study in Italy found that 55% of non-demented nonagenarians and centenarians had MCI, but only 20 people were included in the study and the criteria for their MCI definition were not specified in the article27
. Researchers using data from the Mayo Oldest-Old Study, a population-based study, found that 18% of 69 non-demented participants had aMCI28
. Although the researchers used MCI criteria similar to the current study, a neurologist made the determination of memory impairment after a neurological examination. This is in contrast to the current study, which used a 1.5SD cut-off score on a verbal memory test to define memory impairment.
Other studies examined cognitive impairment in “older” elderly, although not specifically those over 90, but generally had relatively few people in the oldest age groups29–31
. Nonetheless, the prevalence of cognitive impairment in these studies was similar to the prevalence of cognitive impairment found in the current study sample. Results from these studies comparing prevalence of aMCI and naMCI have been mixed; some found higher prevalence of naMCI than aMCI12, 32
whereas others found the opposite33, 34
. In the current study, one of the first studies to report the relative prevalence of aMCI and naMCI in the oldest-old, we found aMCI and naMCI to be equally prevalent.
The other cognitive impairment group, OCI, was the largest group and included 17.4% of non-demented participants making it larger than the two MCI groups combined. While we were hesitant to define a new group of cognitively impaired individuals in the cognitive impairment literature, this group is the largest in the current study and we feel it represents a group of participants distinctly different from those with normal cognition or MCI. Other studies have reported data from cognitive groupings similar to OCI. One population study in France used a similar definition of OCI and found a prevalence of 12.5% in a younger sample. They found that OCI was more prevalent than MCI (3.5%) and equally as predictive of future dementia13
. Another study, which modified MCI criteria to include participants with low general cognitive functioning, found higher prevalence rates compared to traditional MCI criteria and higher dementia incidence rates15
. Therefore, OCI is an important cognitive grouping in non-demented elderly in both prevalence and likelihood of developing dementia.
In the current study, we found that aMCI was more prevalent in men than in women. Studies in younger elderly subjects have found similar results. In a cross-sectional analysis of a population-based epidemiological study35
, researchers found that men were nearly twice as likely to have MCI than women. Another study found that men were 1.5 times as likely as women to have MCI, even after controlling for potential confounding variables such as number of comorbidities36
. It has long been known in the neuropsychology literature that men score lower on verbal memory tests than women37, 38
. This difference was accounted for in the current study by using both gender- and age-specific norms to determine the 1.5 SD cut-off scores on the CVLT. Thus, the gender difference in aMCI prevalence does not appear to merely be an artifact of the normative data. One possible explanation for the sex difference is that the duration of aMCI may be longer in men than women. This seems unlikely, however, because the incidence of dementia among non-demented oldest-old participants in our study is equal in men and women2
. Future studies are necessary to determine if duration differences in aMCI in the oldest-old exist between men and women. Another possible explanation for the gender difference is diagnostic bias. The only criterion in the current study that does not rely on objective test scores is the determination of functional status. Although the prevalence rates of OCI in men and women are identical (indicating that women were not placed in the OCI group rather than the aMCI group due to functional impairment), women have been shown to have a higher prevalence of overall functional disability than men in The 90+ Study
and other studies39, 40
. If a gender bias exists in determination of functional status then dementia diagnoses could also be gender biased, as functional impairment is included in the DSM-IV criteria for dementia. Future studies with larger populations of participants with aMCI are needed to more completely examine these gender differences.
Previous studies hypothesized that participants with aMCI are at a higher risk of Alzheimer’s disease and participants with naMCI are at a higher risk of vascular dementia12, 14
. Thus, we predicted that oldest-old participants with naMCI would be more likely than participants with aMCI to have a history of cardiovascular risk factors. History of hypertension was more common in naMCI than aMCI. However, other cardiovascular risk factors did not significantly differ between the groups. Several other studies have found associations between naMCI and hypertension. Data from a sample of seniors (aged 65 and older) in Manhattan found that both a history of hypertension and current hypertensive status were related to incidence of naMCI but not aMCI41
. Researchers from the Canadian Study of Health and Aging found that naMCI participants with current hypertension were more likely to develop dementia in five years than those without hypertension42
. Although we examined prevalence rather than incidence in our participants, our results concerning hypertension and naMCI converge nicely with the results of studies in younger elderly.
Although the current study did not find relationships between naMCI and most cardiovascular risk factors in the oldest-old, studies in younger elderly subjects have noted this relationship. Two studies with large groups of participants with MCI (average age 75 and 80) found that heart disease was more common in naMCI than aMCI34, 43
. A history of stroke has also been linked to naMCI44
in younger age groups. Interestingly, these relationships between naMCI and cardiovascular risk factors were not found in this study of oldest-old. One hypothesis is that the mortality associated with these risk factors is very high and the oldest-old who survive these challenges represent a different population than those who possess the risk factors at younger ages. This hypothesis is supported by the fact that we did find a relationship between naMCI and hypertension, a risk factor with a relatively low mortality rate and a risk factor that exerts its effects over many decades. However, other possibilities exist for the lack of a strong relationship between cardiovascular risk factors and naMCI, including problems associated with the use of self-report variables rather than using a medical record search. Future investigations of cardiovascular risk factors in the oldest-old and their significance to cognitive impairment and other health factors will shed more light on the current findings.
In addition to comparing cardiovascular risk factors between aMCI and naMCI, we examined cardiovascular risk factors in the OCI and normal groups as well. The only significant difference was that OCI participants were more likely to have a history of stroke compared to normal participants. This result is not surprising considering that strokes can cause cognitive impairment, sometimes severe, as well as physical impairment. Participants with low general cognitive function made up the majority of the OCI group.
A risk factor for Alzheimer’s disease, APOE, was also examined in this study. Although the association between APOE e4 and dementia in the oldest-old is not clear in the literature45–48
, we found that the proportion of participants with an APOE e4 allele was greater in aMCI than in the other groups. The difference trended towards significance when comparing the rates in aMCI (30%) to both normal cognition (18%) and OCI (15%). The small sizes of the aMCI and naMCI groups likely kept us from finding a significant difference between these groups, however, 30% of participants with aMCI have an APOE e4 allele compared to 16% of naMCI participants. Controlling for factors related to Alzheimer’s and vascular dementia such as APOE status and education in future analyses examining incident dementia in these cognitive groups will be important.
This study of cognitive impairment and cardiovascular risk factors in the oldest-old has several strengths. Given the extreme age of the participants, the size of the current study is an advantage. Previous studies with oldest-old participants estimated prevalence of cognitive impairment with much smaller populations27–28
. Additionally, we applied well-defined criteria for the different cognitive groupings (aMCI, naMCI, OCI). Frequently these criteria are not specified well, making comparing studies challenging.
There are several limitations of this study. First, this study did not require a subjective memory complaint for inclusion in the aMCI group. Previous studies have shown that subjective memory complaints are useful for predicting cognitive impairment and decline, especially in the oldest-old15, 49
. Unfortunately, a large portion of participants included in the current study did not have data concerning subjective memory complaints so this criterion was not used in the aMCI definition. Second, the participants in this study had very high levels of education. It is very likely that our sample of oldest-old is more highly educated than average for this age group, which may lead us to underestimate the level of cognitive impairment in the overall population of non-demented oldest-old. Third, while we made considerable effort to compensate for any sensory losses in vision and hearing that might compromise performance, it is possible that some participants who were classified as cognitively impaired performed poorly due to sensory loss rather than cognitive decline. Lastly, this study’s requirements included an in-person visit with a complete set of neuropsychological test scores and a full neurological examination. Compared to study participants, the 253 people who were not included because they did not have an in-person visit were older, more likely to be women, and more likely to have a history of cardiac events. Based on the information known about these non-participants, they likely would have had a greater prevalence of cognitive impairment than the participants included in the study. Also, people with an incomplete battery of tests were not included in the study. The reasons varied but frequently listed were fatigue and participant time constraints (such as requesting a short visit or having another appointment). The participants with incomplete testing were older and had lower MMSE scores. Because the people not included in this study likely had worse cognition than people included in the study, it is possible that this study has a non-participation bias causing an underestimation of the prevalence of cognitive impairment in the oldest-old.
For research purposes cognition is generally categorized into discrete states (such as normal, cognitively impaired, and demented), but the process is actually a continuum. Although none of the participants in the current study met DSM-IV criteria for dementia, it is possible that some of the participants with OCI were actually in early stages of dementia. Supporting this notion, 82% of participants in the OCI group were categorized because of low MMSE score and 18% had functional impairment due to cognition. Additionally, of the OCI participants, approximately half had cognitive impairment>1.5SD in any domain. Consequently, although none of the OCI participants met DSM-IV criteria for dementia, they were more impaired than participants with aMCI and naMCI. It is likely that some of the 82% of participants with low MMSE but without function decline would have met criteria for dementia had functional decline been found. This highlights the difficulty of determining functional status in the oldest-old due to the overlap of physical and cognitive disabilities. These challenges make it possible that oldest-old participants with OCI and physical disability but without diagnosed functional decline due to cognition may represent mis-diagnosed dementia. Future studies on incidence of dementia in the oldest-old with cognitive impairment will likely reveal that participants with OCI are indeed closer to a dementia diagnosis than participants with naMCI or aMCI.
In this study, we found a very high prevalence of cognitive impairment in this sample of non-demented oldest-old. Although other studies have found associations between naMCI and cardiovascular risk factors, we found that hypertension was the only risk factor more prevalent in naMCI. We also found that participants with OCI were more likely to have a history of stroke than normal participants. Further studies of cardiovascular risk factors in the oldest-old will help elucidate the potential risks or benefits50
to the very elderly. In order to further examine cognitive impairment in the oldest-old, future research may examine longitudinal change in neuropsychological performance. The oldest-old age group is the fastest growing in the US3
. Given this statistic, the high prevalence of dementia in the oldest-old1
combined with the high prevalence of cognitive impairment in non-demented presented in this study have wide implications for public health. The results of studies such as this one will be useful in making public health decisions regarding cognitively impaired individuals in this age group.