A Wimo

BM Egan

EB Larson

EM Schrijvers

EW Gregg

FE Matthews

GS Becker

Kenneth M Langa

KM Langa

KY Chan

M Hurd

M Kivipelto

M Pahor

M Prince

MJ Valenzuela

P Muntner

S Norton

YT Wu

Crossref

Langa Alzheimer's Research & Therapy  (2015) 7:34 DOI 10.1186/s13195-015-0118-1DEBATE Open AccessIs the risk of Alzheimer’s disease and dementiadeclining?Kenneth M Langa1,2,3,4,5AbstractBackground: The number of older adults with dementia will increase around the world in the decades aheadas populations age. Current estimates suggest that about 4.2 million adults in the US have dementia and thatthe attributable economic cost of their care is about $200 billion per year. The worldwide dementia prevalenceis estimated at 44.3 million people and the total cost at $604 billion per year. It is expected that the worldwideprevalence will triple to 135.5 million by 2050. However, a number of recent population-based studies from countriesaround the world suggest that the age-specific risk of dementia may be declining, which could help moderate theexpected increase in dementia cases that will accompany the growing number of older adults.Discussion: At least nine recent population-based studies of dementia incidence or prevalence have shown adeclining age-specific risk in the US, England, The Netherlands, Sweden, and Denmark. A number of factors,especially rising levels of education and more aggressive treatment of key cardiovascular risk factors such ashypertension and hypercholesterolemia, may be leading to improving ‘brain health’ and declining age-specificrisk of Alzheimer’s disease and dementia in countries around the world.Summary: Multiple epidemiological studies from around the world suggest an optimistic trend of decliningpopulation dementia risk in high-income countries over the past 25 years. Rising levels of education and morewidespread and successful treatment of key cardiovascular risk factors may be the driving factors accounting forthis decline in dementia risk. Whether this optimistic trend will continue in the face of rising worldwide levels ofobesity and diabetes and whether this trend is also occurring in low- and middle-income countries are keyunanswered questions which will have enormous implications for the extent of the future worldwide impact ofAlzheimer’s disease and dementia on patients, families, and societies in the decades ahead.Dementia, a decline in memory and other cognitivefunctions severe enough to cause disability in daily activ-ities, has a large and growing impact on older adults,their families, and government programs in the US andaround the world. In 2010, about 4.2 million adults in theUS and more than 135 million around the world had de-mentia [1]. The economic impact of dementia, including alarge burden of unpaid caregiving provided by families, isestimated at $200 billion per year in the US [2] and $600billion worldwide [3], which is greater than the economicimpact of important and common chronic diseases, suchas heart disease and cancer. Because the incidence ofCorrespondence: klanga@umich.edu1Division of General Medicine, University of Michigan Health System, 2800Plymouth Road, Bldg 16, Room 430 W, Ann Arbor, MI 48109-0429, USA2Veterans Affairs Center for Practice Management and Outcomes Research,2215 Fuller Road, Ann Arbor, MI 48105, USAFull list of author information is available at the end of the article© 2015 Langa; licensee BioMed Central. This isAttribution License (http://creativecommons.organy medium, provided the original work is p(http://creativecommons.org/publicdomain/stated.dementia rises sharply over the age of 75, the estimatedgrowth in the worldwide elderly population in the decadesahead (from about 600 million now to 1.5 billion in 2050)is expected to lead to a tripling of dementia cases by 2050unless new interventions prevent or slow the trajectory ofcognitive decline [1].Owing to this large and growing impact of dementia,governments around the world have made a priority ofexpanding the collection of data on individuals andpopulations to better understand, address, and track thecurrent and future impact of the dementia epidemic.For instance, President Obama signed the NationalAlzheimer’s Project Act into law in 2011, directing newUS government efforts for improving treatments andprevention and collecting data to track progress of theseefforts over time. The G8 Dementia Summit was held inLondon in 2013 in recognition of the growing globalan Open Access article distributed under the terms of the Creative Commons/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction inroperly credited. The Creative Commons Public Domain Dedication waiverzero/1.0/) applies to the data made available in this article, unless otherwiseLanga Alzheimer's Research & Therapy  (2015) 7:34 Page 2 of 4impact of Alzheimer’s disease (AD) and dementia and tobegin to coordinate efforts for international collaborationand data sharing. Finally, the World Health Organizationrecently declared dementia to be a ‘public health priority’which should be on the public health agenda of allcountries.Although the large growth in the number of olderadults in the coming decades will lead to an increase indementia cases in countries around the world, a numberof recent studies have suggested that the age-specific riskof dementia has actually decreased in high-income coun-tries over the last 25 years, possibly due to increasinglevels of education and more aggressive treatment of car-diovascular risk factors that increase the risk of cognitivedecline (for example, hypertension, hypercholesterolemia,and diabetes) [4]. However, it is unclear whether this opti-mistic trend in high-income countries will continue in theface of rising levels of obesity and diabetes, and it is alsounclear whether there has been a similar or opposite trendin low- and middle-income countries [5,6].Recent trends important to brain healthOver the last 25 years, many countries have seen in-creases in obesity, diabetes, and hypertension, all ofwhich have been linked to an increase in dementia risk.However, at the same time, there have been importantchanges in treatments for these cardiovascular risk fac-tors, including more widespread and intensive medica-tion treatments. For instance, in the US, achievement ofblood glucose targets for diabetes has increased from51% in 1990 to 58% in 2010, and adequate control ofblood pressure (from 27% of those with diagnosedhypertension in 1990 to 50% in 2008) and high choles-terol (9% in 1999 to 27% in 2008) has also increased sig-nificantly [7-9]. These improvements in cardiovascularrisk factor control have helped cut the key vascular-related complications of diabetes—myocardial infarction,stroke, and amputations—in half over the last 25 years[9] and by extension have likely had important ‘spillover’benefits for brain health and the risk for cognitive de-cline and dementia.A recent study used current estimates of the propor-tion of AD cases that are due to various cardiovascularrisk factors (that is, the population-attributable risk forthese risk factors), including hypertension, diabetes, andphysical inactivity, to identify the proportion of casesthat could theoretically be avoided by better preventionor control of these risk factors [10]. The study estimatedthat about 3% of worldwide cases of AD are due to dia-betes, 5% to hypertension, and 13% to physical inactivity,suggesting that better prevention and control of theserisk factors, while certainly not eliminating the majorityof dementia cases, could help prevent millions of casesworldwide in the decades ahead.A number of ongoing randomized clinical trials aredirectly testing whether lifestyle interventions to im-prove the vascular risk profiles of middle-aged and olderadults will decrease their risk for cognitive decline anddementia. The Lifestyle Interventions and Independencefor Elders (LIFE) Study tested whether a structuredmoderate-intensity physical-activity program would de-crease the risk for mobility limitations and cognitivedecline in adults who are 70 to 89 years old [11]. TheLIFE intervention had a significant effect on decreasingmobility limitations, but the trial results for cognitiveoutcomes have not yet been reported. The FinnishGeriatric Intervention Study to Prevent Cognitive Impair-ment and Disability (FINGER) is randomly assigningadults who are 60 to 77 years old to a multi-pronged inter-vention that included diet advice, physical exercise,cognitive training, social activities, and management ofcardiovascular risk factors, while the control group re-ceived only standard health advice [12]. The preliminaryresults from FINGER were reported at the Alzheimer’sAssociation International Conference in 2014 and showedthat, after 2 years of follow-up, individuals randomlyassigned to the multi-pronged lifestyle intervention hadsignificantly better cognitive outcomes than the controlgroup. The final results from FINGER have yet to bepublished.The other important worldwide trend relevant to brainhealth over the last 25 years has been the large growthin educational attainment in both developed and devel-oping countries. The proportion of 30- to 34-year-oldswith a college education has increased in wealthy coun-tries from 12% in 1970 to 27% in 2010 and from 3% to11% in low- and middle-income countries [13]. A majortenet of the ‘cognitive reserve’ hypothesis is that educa-tion facilitates the development of compensatory neuralcircuits that provide an increased capacity to withstanddamage from vascular and inflammatory brain insults,thereby delaying dementia onset and compressing cogni-tive morbidity closer to the end of life [14]. Therefore,rising levels of education may be contributing to a de-creasing risk for AD and dementia among individualsaround the world by increasing the stock of cognitive re-serve among those who have been able to take advantageof these expanding educational opportunities. Of course,it should be noted that increased levels of educationlikely have an impact on later-life brain health throughmultiple and complex pathways, not just a direct effecton brain biology and cognitive reserve. For instance,more education is associated with higher levels of wealth,occupations that lead to more cognitive stimulationduring one’s working life, and health behaviors (forexample, lower rates of smoking and obesity and higherrates of physical activity) that confer increased protec-tion against cognitive and physical decline [15].Langa Alzheimer's Research & Therapy  (2015) 7:34 Page 3 of 4Recent studies of trends in dementia incidenceand prevalenceA growing number of studies, at least nine over the past10 years, have shown a declining risk for dementia inci-dence or prevalence in high-income countries, includingthe US, England, The Netherlands, Sweden, and Denmark.The Rotterdam Study, an ongoing population-basedprospective cohort study, has provided the most directevidence that improved cardiovascular risk factor con-trol may be leading to healthier brains. Dementia inci-dence decreased in cohorts of older adults in Rotterdambetween 1990 and 2010, and brain magnetic resonanceimaging (MRI) performed in more recent cohorts showssignificantly less brain atrophy and fewer vascular-related brain lesions compared with MRI performed inthe earlier cohorts [16].Recent findings from the UK Cognitive Function andAgeing Study (CFAS) provide additional support for adeclining risk of dementia in older adults over the last20 years [17]. CFAS studied adults 65 or older inCambridgeshire, Newcastle, and Nottingham in theearly 1990s (CFAS I) and again around 2010 (CFAS II).Importantly, the same standardized algorithmic diag-nostic process was used for both time periods in orderto avoid diagnostic drift and to maximize the validity ofthe prevalence comparisons across the two time periods.Between 1991 and 2011, the age- and sex-standardizeddementia prevalence declined from 8.3% to 6.5% inthese regions in England. This decline translated to a24% decrease in the expected number of dementia casesin England in 2011. The CFAS authors hypothesizedthat increased education levels and better primary pre-vention of cardiovascular risk factors have likely con-tributed to the declining risk for dementia in Englandover the past 25 years.An important methodological issue to consider indrawing conclusions from the CFAS findings, as well asfindings from other studies of trends in dementia preva-lence, consists of potential changes in study responserate over time. The response rate for the CFAS I fieldwork was 80%, whereas the response rate for CFAS IIwas 56%. If individuals with dementia were more likelyto be excluded from CFAS II, this could lead to a falselylow dementia prevalence rate. However, the CFAS in-vestigators performed sensitivity analyses to addresswhether the drop in response rates could explain all ofthe decline in dementia prevalence, and still foundevidence for significant decline even assuming a highlikelihood of dementia in those who refused to partici-pate in CFAS II. Nonetheless, with response rates formany population-based surveys declining over the lastdecades, it is important to consider and address this keymethodological issue when drawing conclusions abouttrends in dementia and other chronic diseases.Conclusions and future uncertaintiesWorldwide dementia cases will likely grow significantlyover the next 40 years because of increasing life expect-ancies and the aging of populations worldwide. However,a growing number of studies now suggest a decliningage-specific risk of dementia in high-income countriesover the last 25 years, which, if continued, could helpmoderate the future worldwide growth in dementiacases. Rising levels of education and more widespreadand successful treatment of key cardiovascular riskfactors may be the driving factors accounting for thisdecline in dementia risk. Whether this optimistic trendwill continue in the face of rising worldwide levels ofobesity and diabetes and whether this trend is alsooccurring in low- and middle-income countries are keyunanswered questions which will have enormous impli-cations for the extent of the future worldwide impact ofAD and dementia on patients, families, and societies inthe decades ahead. Future studies that track the preva-lence and costs of dementia in countries around theworld will be extremely important as populations ageworldwide, both to better understand the full societalimpact of dementia and to help identify key medical andsocioeconomic factors that should be targeted by inter-ventions to decrease dementia risk.AbbreviationsAD: Alzheimer’s disease; CFAS: Cognitive function and ageing study;FINGER: Finnish geriatric intervention study to prevent cognitive impairmentand disability; LIFE: Lifestyle interventions and independence for elders;MRI: Magnetic resonance imaging.Competing interestsThe author declares that he has no competing interests.AcknowledgmentsThe information in this article was presented in a plenary lecture at theAlzheimer’s Association International Conference in Copenhagen, Denmark,in July 2014.Author details1Division of General Medicine, University of Michigan Health System, 2800Plymouth Road, Bldg 16, Room 430 W, Ann Arbor, MI 48109-0429, USA.2Veterans Affairs Center for Practice Management and Outcomes Research,2215 Fuller Road, Ann Arbor, MI 48105, USA. 3Institute for Social Research,University of Michigan, 426 Thompson Street, Ann Arbor, MI 48105, USA.4Institute of Gerontology, University of Michigan, 300 N. Ingalls Street, AnnArbor, MI 48109, USA. 5Institute for Healthcare Policy and Innovation,University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.References1. Prince M, Guerchet M. Prina M; Alzheimer’s Disease International. Policy Brieffor Heads of Government: The Global Impact of Dementia 2013–2050.London: Alzheimer’s Disease International; 2013.2. Hurd M, Martorell F, Delevande A, Mullen K, Langa KM. The monetary costsof dementia in the United States. N Engl J Med. 2013;368:1326–34.3. Wimo A, Jönsson L, Bond J, Prince M, Winblad B. Alzheimer DiseaseInternational. The worldwide economic impact of dementia 2010.Alzheimers Dement. 2013;9:1–11.Langa Alzheimer's Research & Therapy  (2015) 7:34 Page 4 of 44. Larson EB, Yaffe K, Langa KM. New insights into the dementia epidemic. NEngl J Med. 2013;369:2275–7.5. Chan KY, Wang W, Wu JJ, Liu L, Theodoratou E, Car J, et al. Epidemiology ofAlzheimer’s disease and other forms of dementia in China, 1990–2010: asystematic review and analysis. Lancet. 2013;381:2016–23.6. Wu YT, Lee HY, Norton S, Chen C, Chen H, He C, et al. Prevalence studies ofdementia in mainland china, Hong Kong and taiwan: a systematic reviewand meta-analysis. PLoS One. 2013;8:e66252.7. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment,and control of hypertension, 1988–2008. JAMA. 2010;303:2043–50.8. Muntner P, Levitan EB, Brown TM, Sharma P, Zhao H, Bittner V, et al. Trendsin the prevalence, awareness, treatment and control of high low densitylipoprotein-cholesterol among United States adults from 1999–2000through 2009–2010. Am J Cardiol. 2013;112:664–70.9. Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, et al. Changes indiabetes-related complications in the United States, 1990–2010. N Engl JMed. 2014;370:1514–23.10. Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primaryprevention of Alzheimer’s disease: an analysis of population-based data.Lancet Neurol. 2014;13:788–94.11. Pahor M, Guralnik JM, Ambrosius WT, Blair S, Bonds DE, Church TS, et al.Effect of structured physical activity on prevention of major mobilitydisability in older adults: the LIFE study randomized clinical trial. JAMA.2014;311:2387–96.12. Kivipelto M, Solomon A, Ahtiluoto S, Ngandu T, Lehtisalo J, Antikainen R,et al. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairmentand Disability (FINGER): study design and progress. Alzheimers Dement.2013;9:657–65.13. Becker GS, Hubbard WH, Murphy KM. Explaining the worldwide boom inhigher education of women. J Human Capital. 2010;4:203–41.14. Valenzuela MJ, Sachdev P. Brain reserve and dementia: a systematic review.Psychol Med. 2005;35:1–14.15. Langa KM, Larson E, Karlawish J, Cutler D, Kabeto M, Kim S, et al. Trends inthe prevalence and mortality of cognitive impairment in the United States:is there evidence of a compression of cognitive morbidity? AlzheimersDement. 2008;4:134–44.16. Schrijvers EM, Verhaaren BF, Koudstaal PJ, Hofman A, Ikram MA, BretelerMM. Is dementia incidence declining? Trends in dementia incidence since1990 in the Rotterdam Study. Neurology. 2012;78:1456–63.17. Matthews FE, Arthur A, Barnes LE, Bond J, Jagger C, Robinson L, et al.Medical Research Council Cognitive Function and Ageing Collaboration. Atwo-decade comparison of prevalence of dementia in individuals aged65 years and older from three geographical areas of England: results of theCognitive Function and Ageing Study I and II. Lancet. 2013;382:1405–12.

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Is the risk of Alzheimer’s disease and dementia declining?

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Is the risk of Alzheimer’s disease and dementia declining?

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