In this study of more than 12 800 individuals, incidence rates for 10/66 dementia were roughly 1·5–2·5 times higher than those for DSM-IV dementia. Mortality hazards were higher in individuals with dementia at baseline than in dementia-free individuals. Informant reports suggested a high incidence of dementia before death; overall incidence could be between 4% and 19% higher if these data were included. 10/66 dementia incidence was independently associated with increased age, female gender, and low education, but not with occupational attainment.
This is one of the largest studies of dementia incidence. The EURODEM pooled analysis from four prospective studies (in Denmark, France, the Netherlands, and the UK) consisted of 528 incident dementia cases and 28 768 person-years of follow-up.20
Other than a large national cohort study from Mexico (333 incident cases with 12 980 person-years),23
incidence studies in countries with low or middle incomes have been modest in scale—eg, Ballabgarh, India (nine incident cases with 1160 person-years);2
Cantanduva, Brazil (50 incident cases with 3623 person-years);3
Ibadan, Nigeria (70 incident cases with 2459 at risk);1
and Beijing, China (13 incident cases with 825 at risk).4
We are therefore able to compare the incidence of dementia across rural and urban sites in Latin America, the Caribbean, and China, and estimate prospective associations with indicators of cognitive reserve with reasonable precision. Loss to follow-up is the main challenge to validity, but was modest in most sites, and generally non-differential with respect to the risk exposures studied; however, a relatively high loss to follow-up in urban Peru and Venezuela, which was more substantial in those with higher levels of education, might have led to overestimation of dementia incidence in these sites.
The incidence of 10/66 dementia, when age standardised to the age distribution of the EURODEM cohort, was consistently higher than that for DSM-III-R dementia in Europe. Incidence might have been between 4% and 19% higher still, had probable incident cases in individuals who died before reinterview been included. Post-mortem interviews with collateral informants is a valid approach for detection of cases.24
This source of underestimation is rarely alluded to in published work,3
and we are not aware that it has been addressed in other studies. In a large multisite population-based cohort study in the UK,25
the prevalence of dementia in the year before death was 30% for those interviewed within this interval, with International Classification of Disease 10 dementia coded on death certificates also taken as evidence.
DSM-IV dementia incidence was around half that of 10/66 dementia, although the discrepancy was larger in Venezuela and smaller in urban Peru and urban China than in other sites. The DSM-IV dementia criterion identifies a severe form of dementia with high diagnostic reliability, but findings from our previous work7,13,15
suggests systematic underestimation, particularly in low-income and middle-income countries where awareness of dementia is lower than in high-income countries, and where older people are routinely supported in many core and instrumental activities of daily living. The validity of the 10/66 dementia diagnosis is supported through its cross-cultural development, calibration, and validation in a 25 centre pilot study in Latin America, Africa, India, China, and southeast Asia,6
and, in the context of our population-based studies, by showing concurrent validity against local clinician judgment in Cuba,15
and of its predictive validity in Chennai, India.13
In our study, individuals with 10/66 dementia but not meeting criteria for DSM-IV dementia at baseline had a very high incidence of DSM-IV dementia during the follow-up period, further supporting the validity of 10/66 dementia and clarifying the relation between the two diagnoses.
Mortality in those with 10/66 dementia at baseline was increased in all sites (pooled HR 2·77, 95% CI 2·47–3·10), with moderate heterogeneity. Effect sizes from studies in countries with low or middle incomes have tended to be higher than those indicated by a meta-analysis of studies mainly from countries with high incomes (relative risk 2·63, 95% CI 2·17–3·21);26
with an HR of 2·83 (95% CI 1·10–7·27) in Nigeria,27
and 5·16 (95% CI 3·74–7·12) in Brazil.28
Therefore a relatively high incidence of dementia in less developed countries might be balanced (with respect to effect on prevalence), by a high case mortality. In the three studies so far that have compared dementia with other health and sociodemographic factors affecting mortality in countries with low or middle incomes, dementia was the leading contributor.14,27,28
Previous evidence for cognitive reserve in less developed countries was limited and inconclusive (panel
). In a national cohort study in Mexico,23
education was inversely associated with dementia incidence, particularly among younger age groups. Investigators of two small cohort studies, in urban settings in China and Brazil, reported non-significant trends towards a protective effect of literacy3,4
Our findings regarding indicators of cognitive reserve and the incidence of dementia suggest that the protective effect of education extends to middle-income country settings. We identified an additional independent effect of literacy, perhaps because literacy is an important indicator of the quality of education,29
which, in many settings, does not correlate well with years of education. The absence of association with occupational attainment contrasts with studies in countries with high incomes, where nine of 12 studies showed a statistically significant protective effect (pooled odds ratio 0·56, 95% CI 0·49–0·65).11
The reason for this discrepancy is not immediately clear. Only one of the positive studies in the systematic review11
controlled for education; however, inspection of our models showed that controlling for education did not account for the null effect.
Panel. Research in context
We searched Ovid and Medline databases for studies of the incidence of dementia since 1980, with the search terms [“Dementia”[Mesh] AND (“incidence”[Mesh] OR “epidemiology”[Mesh])]. We identified 1718 abstracts but only five previous studies from countries with low or middle incomes. We also searched for evidence of population-based cohort studies assessing evidence of education as a potential protective factor for the incidence of dementia or Alzheimer's disease, with the search terms [(“dementia”[Mesh] OR “Alzheimer disease”[Mesh]) AND “educational Status”[Mesh] AND (“risk factors”[Mesh] OR “etiology”[Subheading])], (354 abstracts), and for occupational attainment by substituting the Mesh term “occupations”, which indentified (52 abstracts). In the course of these searches we identified a systematic review of brain reserve (the effects of education, occupation, premorbid IQ, and mental activities) and the incidence of dementia or Alzheimer's disease covering work published up to 2004; all the studies were done in high-income countries.10
Our own searches identified only three relevant studies done in countries with low or middle incomes, from Brazil examining the effects of literacy and education,3
from China examining the effects of literacy,4
and from Mexico investigating years of education.11
Our study suggests that the incidence of dementia in six urban and three rural catchment area sites in Latin America and China might be much the same as that typically recorded in countries with high incomes, when using our cross-culturally calibrated and validated 10/66 dementia diagnosis. DSM-IV dementia incidence is lower than that with 10/66 criteria, probably because mild to moderate cases are missed. Our findings confirm that incidence increases exponentially with age, and is higher in women than in men. The protective effects of education seem to extend to settings where many older people have had little or no formal education, and literacy confers an additional independent benefit. These findings, together with evidence of protective effects of better baseline executive function, support the notion that cognitive reserve might counter the effects of neurodegeneration in later life.
Both the animal naming verbal fluency task and the Luria FEP motor sequencing task were independently associated with dementia incidence, after adjustment for age, sex, education, and occupational attainment. Other population-based studies have shown predictive associations with category fluency for long periods before dementia onset.30–32
Semantic processing could be an important underlying mechanism,30,33
which is also relevant to effective performance of the Luria FEP task, according to findings from functional neuroimaging studies.34–36
Such processes are susceptible to neurodegeneration, but are hard-wired through educational and other lifetime experiences, as shown by research that fails to discriminate clearly between measures of executive function and either crystallised intelligence9
or latent traits of cognitive reserve.10
Ultimately, to distinguish between cognitive reserve and the long clinical prodrome for dementia as alternative explanations for prospective associations with dementia onset is difficult. The activation of disparate cortical areas when doing seemingly simple motor tasks such as the Luria FEP task34–36
attests to important functional connections between language, verbal and non-verbal semantic knowledge, and praxis. The development of neural networks fit for this purpose might be an important component of cognitive reserve, stimulated through education and the acquisition of literacy.37
In conclusion, the incidence of dementia in middle-income countries might be as high, if not higher than that recorded in countries with high incomes, offset, with respect to prevalence, by a high case mortality. Our studies provide supportive evidence for the cognitive reserve hypothesis, showing that, in settings with diverse cultures and lifestyles, and much greater variance in levels of education and literacy than occurs nowadays in countries with high incomes, these variables, together with better performance on verbal fluency and motor sequencing tasks, confer substantial protection against the onset of dementia. To answer the question “Why is there not an epidemic of dementia in countries with very low levels of education?” will probably need a much better understanding of what constitutes cognitive reserve, and how its indicators might vary across cultures.