Trends in Prevalence of Dementia

Abstract

Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation of how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be based on population-based studies that use similar diagnostic and research methods consistently over time. This review synthesizes the findings from 14 studies investigating trends in dementia prevalence (N=9) and incidence (N=5) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout the lifecourse, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the underlying neuropathology in relation to occurrence of dementia in the general population.

Dementia has become an important public health, economic, social and political issue, and attracts increasing investment on research. According to estimates in the World Alzheimer Report 2015, 46.8 million people worldwide have dementia, and this number is expected to increase to 74.7 million by 2030 and 131.5 million by 2050. In light of the predicted dementia epidemic and consequent economic burden, the G8 dementia summit in 2013 and the WHO Ministerial Conference in 2015 resulted in calls for global action against dementia.  The summit set up a goal to identify a cure or disease-modifying therapy by 2025. To date, most dementia research has focused on the neurological features, pathophysiological mechanisms and drug discovery. This basic science approach has provided knowledge about dementia at the individual or biological level, but a predominantly reductionist approach that focuses on single mechanisms does not suffice to provide an understanding of the full spectrum of dementia in the general population and to identify risk factors across different populations and life courses. These aspects can only be investigated fully with population-based epidemiological research.

Investigating changes in the incidence and prevalence of dementia over time is challenging, as changes in diagnostic standards and other methodological variation can affect the prevalence and incidence estimates. Primary evidence must, therefore, be based on population-based studies with consistent study designs and measurement methods over time. In the past five years, several population-based studies of dementia have been published in which consistent research methods were used, providing new insight into the descriptive epidemiology of dementia and challenging the accepted forecasts of increasing prevalence and incidence.

Findings from five population-based studies in Western Europe have previously been reviewed, but in this Review, we synthesize worldwide evidence on trends in dementia prevalence and incidence from up to date research. We first discuss the historical context of previous studies of dementia prevalence and incidence and consider in detail the challenges involved in obtaining accurate estimates of changes across time. We then bring together the findings of worldwide population-based studies, discussing variations in the study designs and methodologies, and classifying primary and secondary evidence based on their research methods. Finally, we consider possible reasons for the observed changes in dementia prevalence and incidence and how basic neuroscience and population-based studies must be combined to gain a more complete understanding of dementia and its evolution. 

Investigating dementia trends

Previous studies

Population-based studies of dementia epidemiology were initiated in the 1980s in order to inform policy development on population ageing and dementia. These investigations started by examining prevalence, the proportion of people with dementia in a defined population, before moving on, with longitudinal results, to incidence, the occurrence of new cases over a specific period. Results from studies carried out in western Europe contributed to the European Studies of Dementia (EURODEM) reports, which synthesized epidemiological measures across European countries and had a substantial impact on policy and research. This pan-European collaboration has been reconvened to combine research resourcesand insight from old and new population-based cohorts to update the descriptive epidemiology of dementia in contemporary older European populations. In the USA, several nationwide and regional studies of ageing cohorts conducted since the 1960s have included measures of cognitive function, but the diagnosis of dementia is less often included in these studies. Nationwide estimates of dementia prevalence in the USA have been based on extrapolation of results from various localities to the total population in the USA. In the late 1980s and early 1990s, a small number of epidemiological investigations were also conducted beyond western Europe and the USA such as Australia, Canada, Japan, China and Taiwan. Before the turn of the century, data on low and middle income countries were lacking, but many active studies are now being conducted in these societies¹.All of these studies worldwide  have provided population metrics of dementia that are widely used for policy making and lobbying for awareness and resources.

Challenges

Descriptive population-based studies of dementia have been conducted for over 30 years, but studies that investigate changes in its prevalence or incidence over time have emerged only recently. Estimates of changes in incidence and prevalence have been made with statistical modelling and systematic reviews, but the extent of comparable data on these changes has been limited by inconsistent methodologies across studies. Diagnostic criteria have changed substantially during these decades different criteria are known to identify different groups of patients with dementia¹³, and any differences in the approach to diagnosis will affect estimates of prevalence and incidence. Given that many studies of dementia prevalence and incidence have used diverse diagnostic methods (as well as different contexts and time points), comparability even between geographical locations has been poor, and has been more so across time. These changes in diagnostic boundaries combined with parallel increases in awareness of dementia among the public and medical professionals has led to earlier diagnosis on average. Furthermore, a consensus diagnosis, even when made with use of standardized data collection methods and standardized diagnostic criteria, can be affected by changes in clinicians’ perceptions of diagnostic thresholds and criteria over time.

Ultimately, diagnosis of dementia remains heavily influenced by clinical judgement, medical records and characteristics of study population, particularly in population-based studies. For this reason, dementia remains a clinical syndrome, with an emphasis on cognitive and functional states, and identifying subtypes is particularly challenging. For example, Alzheimer-type dementia can be diagnosed with varying levels of investigation, but regardless of the investigations used, diagnosis is based on the assumption that the underlying pathology is Alzheimer-type pathology. Subtype analysis is, therefore, more difficult to keep consistent over time than is syndromic diagnosis, limiting the possibility of making valid comparisons of prevalence or incidence between subtypes.

Primary evidence

We identified 14 population-based studies in which the study methods used at all time points were sufficiently similar and in which the geographical areas were sufficiently well-defined to enable a meaningful comparison. Of these 14 studies, nine investigated prevalence and five investigated incidence. The populations included were from the USA, Western Europe, Japan and Nigeria.

Five other studies have also investigated trends in dementia prevalence or incidence but were not included because of methodological aspects that mean they cannot be meaningfully compared with the other 14 studies (Box 1). Studies that focused on only Alzheimer disease or cognitive impairment were also excluded, due to considerably heterogeneous definitions and diagnostic methods across time and studies.Those using medical records, healthcare administrative databases, systematic reviews and meta-analyses will be described briefly in the latter part of this review.

Trends in prevalence

Study details

Nine studies have investigated trends in dementia prevalence in France (the Bordeaux farmer study), Sweden (the Gothenburg, Nordanstig and Stockholm studies), Spain (the Zaragoza study), the UK (the Cognitive Function and Ageing Study (CFAS)), the USA (the Health and Retirement Study (HRS) and the Indianapolis–Ibadan Dementia Project (IIDP), and Japan (the Hisayama study) (Table 1). The earliest of these is the Gothenburg study (1976–1977) and the most recent is the HRS (investigated in 2012). The Zaragoza study, the CFASand the IIDP had similar designs: two independent cohorts were recruited across two time points in defined geographical areas. In the Gothenburg study, age-specific prevalence at ages 70 years and 75 years were compared over three decades in random samples of local populations. In the Nordanstig and Stockholm studies, the prevalence of dementia from the earlier investigations (the Nordanstig Project and the Kungsholmen Project) was used to compare the regional prevalence from a recent nationwide cohort (Sweden National Study on Aging and Care (SNAC)). The Bordeaux farmer study included only farmers living in the Bordeaux area. The HRS is a dynamic study in which new cohorts are enrolled every 6 years to ensure a representative sample of older adults in the USA. The only study from East Asia, the Hisayama study conducted in Japan, included all residents of the study area who were aged ≥65 years at four time points. In the Zaragoza study, the CFAS, the IIDP and the Bordeaux farmer studies, considerable drops in response rate were seen across two cohorts. A wide range of sensitivity analyses were conducted in the CFAS and the Bordeaux farmer studies to address potential selection bias owing to this differential response rate, and revealed limited impacts on the results. In the Zaragoza study, a sampling strategy was used to account for the population that did not respond, so the estimates are considered to be representative of the entire older population in the study area.

The nine studies had either one-stage or two-stage designs: a one-stage design which included only a diagnosis phase that involved detailed examination and application of clinical criteria, and a two-stage design included a screening phase to identify potential participants with dementia as well as a diagnostic phase. Clinical diagnoses were mainly based on the Diagnostic and Statistical Manual of Mental Disorders, third edition revised (DSM‑III‑R) criteria. Algorithmic diagnosis was used in the CFAS, and algorithmic historical criteria were used in the Gothenburg study, but these approaches were similar to the DSM‑III‑R criteria. In the French study, an algorithm approach based on Mini-Mental State Examination (MMSE) and Instrument Activity of Daily Living (IADL) scores was used in addition to clinical diagnosis to identify potential participants with dementia. Diagnosis in the HRS was based on a 27-point cognitive test, or a proxy assessment if the participant was unable to complete the interview³³. The assessment was conducted as a phone or face-to-face interview, and was validated in a sub-sample of the HRS cohort (the Aging, Demographics, and Memory Study (ADAMS)); this approach had a 78% concordance with clinical diagnosis made by medical professionals.

The intention in each of these studies was to implement the same diagnostic methods over time, but changes in subjective clinical opinion cannot be ruled out as a major factor that might have influenced case identification and prevalence estimates. Measures were taken in several of the studies to address this issue. In the Nordanstig and Stockholm studies, the same physicians made the diagnoses in the two cohorts within each study. In the IIDP, a clinical consensus process was used, in which the same group of clinicians made diagnoses in the two cohorts. In the CFAS and the Gothenburg study, algorithmic diagnosis with a structured psychiatric interview was used to avoid variation in subjective opinions. Small changes in study designs and methodologies were made in the Hisayama study, Stockholm study and the CFAS; to ensure that these changes had minimal impacts on prevalence estimates, the new measurements used in these studies were tested and validated before their application to later cohorts.

Findings

In contrast to the increase in prevalence of dementia that is predicted on the basis of projection methods, most of the nine population-based studies reported stable or declining prevalence over time (Fig 1). The three Swedish studies indicate generally stable prevalence within the total population, albeit with wide confidence intervals in all but the Stockholm study. The CFAS demonstrates a 23% reduction in prevalence over two decades in the total study population in England, and the HRS suggests a 26% decrease in prevalence over 12 years in the older US population. The Bordeaux farmer study found conflicting results when the two diagnostic approaches were used: with the algorithmic diagnosis, a 40% decline in prevalence was seen, but when clinical diagnosis was used, an increase in prevalence by more than twofold was seen. The Nordanstig and Zaragoza studies did not indicate significant reductions in prevalence in the total population, but demonstrated decreases of >50% among men. Taken together, and given the fact that the longevity of people with dementia is increasing, these results may suggest an actual decline in the age-specific risk of dementia.

Trends in incidence

Study details

Five studies have investigated trends in the incidence of dementia in the Netherlands (the Rotterdam study), France (the Bordeaux study), the UK (the CFAS), the USA (the IIDP and the Framingham Heart Study (FHS)), and Nigeria (the IIDP) (Table 2). The IIDP examined trends in African Americans in Indianapolis, USA, and in a Yoruba population in Ibadan, Nigeria⁴¹. The Bordeaux incidence study focused on urban residents rather than farmers, but used the same reference cohort as the prevalence study. The CFAS and IIDP reported both prevalence and incidence trends within the same study cohorts.

In the Bordeaux study, the CFAS and the IIDP, incidence was measured in two independent cohorts, whereas the Rotterdam study involved analysis of non-overlapping sub-cohorts, and the FHS involved analysis of participants from two generations. In the Rotterdam study, the 1990 cohort included all residents of the study area aged 60–90 years, and the 2000 cohort included a non-overlapping sample of residents who had since entered that age range or were of the correct age and had moved into the study area. The FHS combined data from an original cohort and a cohort of their offspring, and divided them into four epochs to compare incidence across these periods. The follow-up periods and intervals varied between studies.To address differential response rate and potential impact of missing data, several sensitivity models were tested in the Bordeaux study and CFAS.

Different sets of diagnostic criteria were used in the Rotterdam study (DSM-III-R), IIDP (DSM-III-R, ICD-10) and FHS (DSM-IV) In the Bordeaux study and the CFAS, algorithmic diagnosis was used. In the Bordeaux study, MMSE and IADL scores were used to define dementia, and in the CFAS, a differential diagnosis procedure derived from a structured psychiatric interview was used. The Bordeaux study also included clinical diagnosis, but different clinical criteria were applied to the two cohorts, so these data were not used to assess temporal trends.

Findings

Despite different study designs and methods, all five studies suggest a decrease in the incidence of dementia in the total population across cohorts and time periods, although notable differences were seen in subpopulations, particularly between the sexes. In the Bordeaux study, the decrease was mainly driven by an effect in women, whereas in the CFAS, the reduction was confined to men. In the FHS, the reduction occurred earlier and was sustained across the three epochs in women, but occurred only in the last epoch in men. The results of the IIDP suggest that the incidence was reduced in African Americans over a 10‑year period, and indicate a 20% reduction in incidence in Nigerian cohorts, but this effect was not statistically significant. In the Bordeaux study, the results obtained with clinical diagnosis differed from those obtained with algorithm diagnosis; only the latter resulted in a decrease in incidence³⁹.

Secondary evidence

Secondary evidence for trends in dementia prevalence and incidence is provided by studies that are based on medical records, healthcare and insurance administrative databases, systematic reviews and meta-analyses, as these types of research do not provide the option of controlling for changes in diagnostic methods, subjective clinical opinions and public awareness. Several studies conducted in Western Europe and North America have reported trends in the prevalence or incidence of dementia on the basis of analysis of medical records or healthcare administrative databases. These studies tend to include large populations and are often based on patients’ contact with medical services over time. These analyses have mainly focused on short-term trends, and advanced analytical strategies have been required to estimate prevalence or incidence over continuous time periods and overlapping study populations. Bias in ascertainment and differences in diagnostic practice between clinical settings cannot be fully addressed in these analyses, making interpretation of the findings challenging. Some such studies have suggested stability or reductions in the annual prevalence or incidence of dementia, whereas others have reported increases in prevalence or incidence.

Owing to a lack of comparable data, trends in the prevalence of dementia outside western countries have been estimated mainly based on systematic reviews and meta-analyses, which aggregate estimates from individual studies conducted around the same time period. Systematic reviews of numerous prevalence studies conducted in East Asian countries have suggested that the prevalence of dementia is increasing in Japan, South Korea, Hong Kong, Taiwan and China, although the increase in China is no longer significant when methodological factors, including changes in diagnostic criteria, are controlled for. Furthermore, preliminary results from the Chinese Longitudinal Healthy Longevity Surveys, a dynamic cohort across 22 provinces in China, indicate a stable prevalence of cognitive impairment (measured by the MMSE) between 1998 and 2011⁶³. Whether any changes reported in East Asia are attributable to heterogeneity of study designs and implementation or differences between high-income and low-income countries, or eastern and western society remains unclear, but the different results obtained from primary investigation and systematic reviews might underline the substantial impact that changes in diagnostic methods and social contexts over time can have on estimates of prevalence.

Current evidence on dementia trends

Diagnosis of dementia, as of any disorder, is contextual and changes across time and geographies. The secondary evidence discussed above was based on the analysis of healthcare administrative databases, medical records, systematic reviews and meta-analyses, and the mixed findings emphasize the fact that comparisons should not rely on an overview of reported numbers but must include careful appraisal of methodologies and study contexts. Changes in diagnostic methods, knowledge and public awareness all influence identification of who meets and does not meet study diagnostic criteria for dementia. The different results obtained with use of clinical and algorithmic diagnoses in the two Bordeaux studies^16,39 discussed above further emphasize the effects of changes in diagnostic boundaries and the substantial impact they can have estimates of prevalence and incidence over time.

Identification of true prevalence and incidence trends, therefore, requires population-based studies that use similar research methods across different time periods and the 14 primary studies discussed above are all such studies. In many of these studies, decreases in response rates and changes in diagnostic boundaries used to make consensus diagnoses were reported, factors that are likely to affect the results. Nevertheless, despite different study designs, methodologies and settings between the individual studies, these population-based studies generally report stabilization of or a reduction in the prevalence and incidence of dementia. Given declining mortality in the general population, stabilization of dementia prevalence may also suggest a decrease of varying sizes in the incidence. The primary evidence indicates a reduction in dementia occurrence in more recent generations, particularly in western countries.

Possible explanations

Western countries

In this Review, the primary evidence from western countries have suggested a reduction in the risk of developing dementia and improved health in old age across generations. Indeed, in the Rotterdam study, improvement of brain health — larger brain volume, less brain atrophy and less cerebral small vessel disease — was reported in the most recent cohort. Several possible explanations for these findings have been suggested, but only four of the studies identified the key factors associated with the trend of decreasing dementia incidence (Box 2), and these factors vary between American, French and Dutch cohorts.

Educational level explained some of the decline in incidence: up to 6% in the FHS and nearly 10% in the Bordeaux incidence study. In the HRS, education along with other socioeconomic factors explained 10% of the decrease in prevalence. However, in the Rotterdam study, the percentage of preventable dementia cases related to low education remained similar over two decades, suggesting that education still contributed to  a substantial part of dementia occurrence in the more recent cohort.

The change in the proportion of cases that were preventable by cessation of smoking partly explained the changes in incidence in the Rotterdam study, but smoking did not explain the decline in incidence in the FHS and Bordeaux study.

In these four studies, the changing prevalence of several chronic diseases that are associated with dementia, such as stroke, heart diseases, hypertension and diabetes, was reported but differed across studies. These changes explain only a limited proportion (<10%)of the reduction in incidence and prevalence of dementia, although any positive effects would be subject to time lags, the lengths of which are unknown. Most medications for cardiovascular disease and other chronic diseases (for anti-hypertensives, anti-depressants and statins) have only been widely available since the 1960s and may have had limited impact on the observed changes in dementia prevalence and incidence; further improvements in these treatments for chronic conditions might change the risk of developing dementia in later life and might, therefore, have further effects on dementia incidence and prevalence in the future. Other lifestyle factors, such as changes in diet and physical activity, have been suggested as reasons for a declining incidence of dementia, but primary evidence to confirm such hypotheses is currently lacking, and these patterns are changing with each generation.

Some of the prevalence and incidence studies revealed sex differences in the changes (Table 3), and these differences could provide further insight into possible reasons.Life expectancy at the age of 60 years is a good marker of the overall health status of older people, and despite the fact that women in western countries have consistently had a longer life expectancy at the age of 60 years, the life expectancy of men has increased to a greater degree over the past two decades.Reductions in smoking and improvements in the prevention and treatment of cardiovascular disease might have had a larger impact on the health and life expectancy of men than that of women, and such major changes in risk factors might be important in the observed sex difference in dementia occurrence.

Although the reasons for stable or decreasing prevalence and incidence of dementia remain unclear, a single risk factor is unlikely to be responsible. Changes in Western societies and improvements in living conditions since the two World Wars have led to improvements in overall health and in cognitive development and reserve throughout the lifecourse⁶⁹. Population-level investments in infrastructure, education, health services and social welfare have contributed to substantial improvements in multiple dimensions of physical, mental and cognitive health from early life and may consequently reduce  the risk of dementia in later life. For example, education level has been related to an increase in cognitive reserve. A higher level of education has been associated with better cognitive performance, but not with lower rates of cognitive decline. The latest generations to reach old age have had more years of statutory education than previous generations, which might be associated with greater cognitive reserve, which, in turn, might partly explain a delayed onset of dementia. Such effects on incidence can only be observed over decades. Nevertheless, the observations we have indicate that factors that are related to social disadvantage and health inequality might have an important role in cognitive health over the lifecourse.

Beyond Western countries

Primary evidence that provides information about the prevalence and incidence of dementia outside Western Europe and the USA is lacking. Systematic reviews and meta-analyses can be used to synthesize evidence on dementia prevalence and incidence in low and middle income countries, but such analyses of trends are unlikely to be robust if variations in methodologies and population characteristics are not taken into account¹². Of the primary, population-based studies discussed above, two were conducted outside Western Europe and the USA, one in Japan and one in Nigeria, and these reported different trends.

The Hisayama study reported an increasing prevalence of dementia between 1985 and 2005, and a subsample of autopsy specimens suggested an even higher prevalence in 2012. However, the analysis of the autopsy subsample did not take into account age and potential selection bias. Another study conducted in Diasen-Cho area, Japan, which was excluded from the above discussion because the screening approaches used did not ensure representation of the whole populations, also identified an increase in prevalence across three time points (1980, 1990 and 2000). By contrast, the incidence of dementia in the Nigerian cohort of the IIDP was stable

A unifying explanation for these different results is difficult to formulate because these countries have different economic, political, social and cultural backgrounds and rates of change over the past few decades. Some insight might be gained by considering the changes in life expectancy at birth over the past century (Figure 3). Changes in life expectancy are associated with the effects of societal factors and might therefore also indicate different determinants of cognitive health across generations. Different life events, health statuses and disease profiles experienced by different generations, and trends in the prevalence and incidence of dementia might reflect complex interactions between these factors. The life expectancy profiles of Japan and Nigeria over the past century differ dramatically from those of the western countries. In Japan, the life expectancy was lower than that in western countries in the first half of the 20th century and increased dramatically in the 1960s. Life expectancy in Nigeria has increased by 30 years over the past century, but is still 20 years lower than the other countries. These dramatic changes are generally related to war and historical events, with a consequence of extremely deprived living conditions, interruption of education and lack of health and social care in the early life of the study cohorts. The prolonged impact of these societal factors can lead to variation in population health, cognitive reserve and dementia occurrence across generations in countries. Future trends in dementia occurrence outside western countries are currently less predictable because the interplay between health during the lifecourse, protective factors and risk factors varies hugely between social contexts.

The Hisayama study includes longitudinal data on cardiovascular disease in middle-aged cohorts, which might also provide some insight into potential reasons for the observed trend in dementia prevalence in Japan. Since the mid-1980s, the prevalence of hypertension, stroke and smoking has declined in this population, and the prevalence of diabetes mellitus, hypercholesterolaemia and obesity has increased. The increasing prevalence of dementia might, therefore, be related to changes in lifestyle, such as an increasingly western diet, physical inactivity and increasing obesity, metabolic syndromes and diabetes. An analysis published in 1995 showed that these factors were not associated with an increased risk of all-type dementia after a 7-year follow-up, and a subtype analysis found only one significant association, between diabetes and vascular dementia, the prevalence of which appeared to be stable. However, a more recent analysis after a 15-year follow-up showed that diabetes was related to an increased risk of all-type dementia and Alzheimer disease, but not with vascular dementia. Although these findings may indicate the long-term impact of diabetes on dementia in old age and a possible time-tagged effect on the increasing prevalence, increasing recognition of mixed dementia will make interpretation of any these changes in the occurrence of dementia subtypes over time even more challenging. Until deeper phenotyping, both during life and after death, is conducted and consistent across time,the detail of neurobiological changes that underlie the risks and clinical manifestations of dementia will be unknown.

Population ageing and an increasing burden of noncommunicable diseases are important challenges worldwide, but the impact of chronic diseases on dementia trends might vary between contexts, with time-lags of uncertain length. Forecasts of dementia burden must take into account these different contexts of health profiles, deprivation and social environments rather than focusing on the potential impact of individual risk factors.

Neuroscience and epidemiology

Basic neuroscience research into the pathology and treatment of dementia has largely remained separate from epidemiological research into dementia. However, both areas of research have limitations, and taking an approach that combines them is likely to improve our overall understanding of dementia.

Current basic research into dementia largely focuses on mechanistic aspects to inform the development of treatment, potential biomarkers for the diagnosis of dementia subtypes before clinical signs develop, and treatment efficacy in highly selected clinical samples. However, population-based studies have repeatedly shown serious inconsistencies in the association between the degree of neuropathology and cognitive performance, as well as considerable overlap of pathology seen in people with and without dementia, demonstrating that our understanding of the pathology that underlies dementia remains incomplete. New techniques for defining brain pathology and so-called normal function might therefore be needed,and these techniques must be grounded on research within contemporary populations so as to provide insight into the neurobiology that underlies the population changes in dementia incidence and prevalence that population-based studies have demonstrated. Observational risk factor analysis can only go so far towards identifying determinants and factors related to dementia symptoms and needs to be accompanied by deep phenotyping that can be mapped back to populations in order to provide a further understanding of underlying neurobiological mechanisms. For example, the population-based studies seem to have identified sex-related differences in the changes in dementia occurrence, but basic research will be needed to understand the neuroscience that underlies these differences.It is also clear that there is a lack of data on different populations such as migrants, aborigines and disadvantaged sectors of society in the existing population-based studies and new cohorts will be needed to provide a comprehensive picture of brain health in the whole population as well as address health inequality.

The concept of population-based studies, recruiting participants from community-based contexts to ensure representations of the whole population, should be incorporated into future neuropathological research in dementia. Results from small, clinically based samples which only include patients from memory clinics or other medical services inherently have limited generalizability and considerable potential for bias owing to highly selective recruitment. In particular, people who are socially disadvantaged are less likely to take part in such research. Given ongoing changes of brain health in the general population, the integration of neuroscience with population-based studies and analytical epidemiological approaches (neuroscientific epidemiological approaches) is vitally important and provides an opportunity to gain an understanding of brain health, neurobiology and neuropathology within the general population that can support better prevention, care and cure of dementia.

Conclusions

Recent descriptive epidemiological studies in which the impacts of changing diagnostic criteria and study methods were minimized, have strengthened the evidence that dementia — age for age — is declining in some countries and that the number of people with dementia can remain stable despite population ageing. Substantial reductions in the risk of dementia in whole populations can balance out growing numbers of older people. Given that the global population is ageing, identifying the factors that are contributing to reductions in the prevalence and incidence of dementia in particular countries and regions should become a major priority, as the findings will have important implications on health and social policies in relation to dementia prevention and risk reduction.

No single factor has been identified that fully explains the observed changes in dementia prevalence and incidence, but reductions in absolute inequalities — including improvements in living conditions, better access to education and improved healthcare systems — are likely to have influenced multiple risk and protective factors throughout the lifecourse that are related to physical, mental and cognitive health and thereby reduced the risk of dementia in later life. This conclusion sends an important message to all in society about the need for long-term action to address factors that determine both healthy and unhealthy ageing, and to make further efforts to reduce inequalities within and between nations, with the expectation of health with age, including a lower risk of dementia. Only an integrated approach that incorporates lifecourse health and brings together many disciplines underpinned by neuroscience and population-based epidemiological studies can provide the robust evidence required to understand the observed changes.

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Box 1 | Excluded studies of dementia prevalence and incidence

Five studies have investigated trends in dementia prevalence and incidence but used methods that prevent them from being meaningfully compared with others and were therefore not included in our Review. Two Swedish studies were excluded. In one, prevalence and incidence trends during 1947–1957 and 1957–1972 were investigated, and findings from these periods are likely to have limited relevance to contemporary older populations. The other focused on short-term prevalence trends in populations aged ≥85 years, but had two methodological flaws: the study cohorts were not sampled independently but the analysis did not account for the overlapping of the study population, and medical records were used to support dementia diagnosis, which might have led to bias owing to differences in the diagnostic boundaries applied for different patients.

One Japanese study that investigated prevalence trends between 1980 and 2000 was excluded because the screening for dementia was based on self-reported cognitive problems rather than objective cognitive testing, and clinical diagnosis was only applied to those who reported cognitive problems. This approach might have led to biased prevalence estimates because a marked change in awareness of dementia within the population is likely to have affected patient self-reporting. Another report, from the Hisayama study, in Japan was excluded because it focused on an autopsy subsample that was not representative of the older population in the study area. One study has compared prevalence and incidence trends in dementia in China, but used different diagnostic criteria at the two time points studies, so was also excluded.

Box 2 | Investigation of factors related to decreasing prevalence or and incidence of dementia

The four studies below investigated analysed the effect on dementia prevalence or incidence trends when common risk factors and protective factors were controlled for. The common factors included in the analysis for all four studies were education, smoking, hypertension, cardiovascular disease, diabetes mellitus, BMI and cholesterol levels.

Bordeaux study, France²⁹

• Adjusted for factors to test whether the observed decreases in dementia prevalence and incidence were attenuated.
• Education and vascular factors had a small effect, but the trends of decreasing prevalence and incidence remained significant.

Framingham Heart Study, USA⁴²

• Adjusted for factors to test whether the observed decrease in dementia incidence was attenuated.
• No significant effect of any investigated factor — changes were <10%

Health and Retirement Study, USA³³

• Adjusted for factors to test whether the observed decrease in dementia prevalence was attenuated.
• Education, cardiovascular factors and BMI attenuated the change by up to 12%, but the decrease in prevalence remained significant.

Rotterdam Study, Netherlands⁶⁶

• Calculated population attributable risk (PAR; the proportion of dementia cases that could be prevented if the risk factor was removed) for each risk factor in the two cohorts studied.
• The PAR was reduced by smoking and cholesterol levels.
• The PAR was unaffected by education and cardiovascular disease.
• The PAR was increased by diabetes mellitus and hypertension.