People age 85 years or older, referred to as the “oldest old,” are the fastest growing segment of the United States population. That segment is expected to increase by 40% in the next decade and quadruple in size over the next four decades [51
]. The expansion of this sub-population will increase the number and proportion of dementia cases among the oldest old [52
]. Consequently, characterization of dementia in the oldest old is of the utmost importance. However, the diagnosis and investigation of cognitive impairment in this population is challenging. This section will review current studies of dementia among the oldest old and describe methodological challenges to diagnosis and study of dementia in this group.
Much of the information regarding cognitive impairment among the oldest old have come from three studies: the 90+ Study, the Leiden 85-Plus Study, and the Vantaa 85+ Study () [53
]. However, many more studies will emerge given the importance of the oldest old. Among the newer studies of the oldest old is the Women Cognitive Impairment Study of Exceptional Aging (WISE), a population-based study of 1,534 oldest old women who have been well-characterized by demographics, co-morbidities, and lifestyle over 20 years.
Characteristics of major studies examining oldest old populations
Each of the major studies of the oldest old included at least 500 participants who were recruited either from an existing longitudinal study (90+ Study, WISE) or from age cohorts (Leiden 85-Plus and Vantaa 85+ Studies). There are advantages and disadvantages to each of these approaches. People who are recruited from a longitudinal study are likely to be well-characterized over years or decades. However, the population prevalence estimates of dementia may be biased due to differential retention over the study period. In contrast, recruitment from an age cohort may be more representative of dementia in the population but the group may be more poorly characterized over time and biased by cohort effects.
Most oldest old studies are not representative of the global oldest old population, and all large population studies originate from Western Europe or from the United States [53
]. In particular, the vast majority of findings involving dementia in ≥ 90 year olds are from the 90+ Study, which is comprised of mostly white elders of high socio-economic status that were part of the Leisure World Cohort Study [59
]. It is important that additional oldest old studies include different race and ethnic groups and geographical areas in order to represent the diverse oldest old population.
Most oldest old studies indicate that the prevalence of dementia is high, approximately 40% among women and 25% among men [53
]. Early studies were inconclusive whether the prevalence increases after age 85 or 90 years [56
]. The rising prevalence among women could be attributable either to higher incidence of dementia or increased survival with dementia relative to men. Evidence from incidence studies is conflicting. The 90+ Study found that the incidence of dementia among people age 90 years or older was similar in men and women [66
], suggesting that differential survival likely caused gender differences in prevalence. However, other studies have suggested that oldest old women have up to a twofold higher incidence of dementia than men [54
]. Because of competing mortality, it is likely that reports underestimate the prevalence of dementia in the oldest old [68
], and more recent studies show an exponential increase in dementia incidence. For example, the 90+ Study reported an incidence of approximately 13% for people 90–94 years old and 22% for people 95 to 99 years old [66
Many characteristics and subtypes of cognitive impairment among the oldest old are understudied. One meta-analysis of European dementia studies that stratified by age indicated that AD and vascular dementia composed most cases of dementia amongst the oldest old [69
]. However, recent reports from the WISE indicated that AD and mixed dementia were the most common types of dementia in an oldest old [58
]. Mixed dementia was not considered by many studies in the meta-analysis, which may account for the difference in findings. The prevalence of MCI and subtypes among the oldest old has also been poorly studied. However, recent findings from the WISE indicated that MCI was common, with an overall prevalence of 23% among oldest old women. Amnestic multiple domain and non-amnestic single domain were the most common MCI types, a pattern similar to younger groups [58
The prevalence and incidence of dementia among the oldest old is, however, influenced by diagnostic challenges (). According to DSM-IV criteria [33
], the diagnosis of dementia requires the presence of multiple cognitive deficits that include memory impairment and impairment in at least one other cognitive domain that is a decline from previous level of functioning and is sufficiently severe to cause impairment in function. However, the criteria by which to define cognitive and functional impairment have not been standardized in this age group. For example, few neuropsychological test norms have been determined for the oldest old and, thus, cut-points for impairment are less clear, particularly for those individuals over 90 years old. This, along with the fact that cognitive deficits are common among the oldest old [53
], means that traditional methods of defining impairment relative to what is expected for age may not be suitable. Furthermore, the vast majority of oldest old people have some level of functional impairment, and it is often difficult to isolate the cause of impairment. For example, cognitive impairment, sensory impairment, arthritis, and other co-morbidities may all contribute to functional impairment. Thus, it is challenging to ascribe causation to one etiology. More research is needed to establish both neuropsychological norms and to better define functional impairment in this age group.
Challenges to diagnosing and studying dementia in the oldest old.
Classic neuropathologic features of AD such as neurofibrillary tangles and neuritic plaques are less predictive of dementia severity in the oldest old [72
]. One study found that cerebral atrophy was the only feature strongly associated with dementia diagnosis in both the young-old and the oldest old [73
]. The oldest old may have a greater number of co-existing neuropathologic features that contribute to cognitive impairment, making any one feature less predictive in isolation. Indeed, a recent study indicated that neuropathologic features consistent with mixed dementia were more common among the oldest old [74
], confirming previous reports that the frequency of AD with vascular pathology is extremely common among very old men [75
If underlying dementia pathology among the oldest old is more heterogeneous, then different diagnostic techniques or even dementia classifications may be needed. Furthermore, pharmaceuticals targeted to one dementia neuropathologic feature—for example, AD—may not be as well-suited to treat dementia in the oldest old.
Preliminary studies have identified risk factors for cognitive impairment among the oldest old, though few results have been replicated and most work stems from only a handful of cohorts. A number of classical risk factors for cognitive impairment in the young-old have also been associated with augmented rates of dementia or cognitive impairment in studies of people 85 years or older—for example, diabetes, dyslipidemia, and physical activity [76
]. In contrast, elevated levels of inflammatory markers were associated with reduced cognitive decline [79
], suggesting that the effect of some risk factors may be in the reverse direction among the very old.
Fewer risk factors for dementia have been identified among populations 90 years or older. In the 90+ Study, anti-oxidant intake, physical activity, and body mass index were not associated with the likelihood of dementia [80
], despite being risk factors for dementia among the young-old [81
]. Results from the 90+ Study also indicate that oxygen saturation was a novel risk factor in dementia [80
]. Why fewer factors are associated with dementia among the ≥ 90 year old population than among the ≥ 85 year old population is unclear but may be due to differential bias or differences in cohort composition.
Studies regarding risk factors for dementia among the oldest old may also be confounded by the competing risks of dementia and death, which may lead to survival bias. Many risk factors for dementia in the young old such as diabetes and physical inactivity also increase risk of death [82
]. As a result, ‘risk factors’ for dementia among the oldest old may be characteristics that protect against dementia or death at an earlier age. The importance of factors that enhance survival and, thus, increase the risk of dementia among the oldest old must be carefully evaluated.
Although a number of publications have examined cognitive impairment in the oldest old, the characterization of dementia and risk factors in the oldest old is incomplete. More studies are needed to address this topic, which will become increasingly important with the expansion of the oldest old population. Most importantly, norms for cognition and function need to be developed for this age group. Future studies should carefully investigate risk factors and dementia etiology among the oldest old and include racially and ethnically diverse populations.