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   Alzheimer's disease and vascular dementia in developingcountries: prevalence, management, and risk factors Raj N Kalaria, FRCPath ,Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK Gladys E Maestre, MD ,Institute for Biological Research, University of Zulia, Maracaibo, Venezuela and G H SergievskyCenter, Columbia University, New York, NY, USA Raul Arizaga, MD ,University of Buenos Aires, and Cognitive Neurology Unit, Neuraxis, Buenos Aires, Argentina Robert P Friedland, MD ,Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH,USA Doug Galasko, MD ,Department of Neurosciences, University of California, San Diego, CA, USA Kathleen Hall, PhD ,Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA José A Luchsinger, MD ,Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University,New York, NY, USA  Adesola Ogunniyi, MBBS ,Departments of Medicine and Psychiatry, University College Hospital, Ibadan, Nigeria Elaine K Perry, FMedSci ,Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK Correspondence to: R N Kalaria, Institute for Ageing and Health, Wolfson Centre, Campus for Ageing and Vitality, NewcastleGeneral Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK r.n.kalaria@ncl.ac.uk. Contributors:  All the authors provided material and ideas on presentation, and contributed to the writing and editing of the Review atvarious stages of preparation. In addition, GEM, RA, RPF, AO, KH, FP, MP, RS, AW, ZXZ, and RNK provided key references and did the analyses presented in the tables. Most of the authors were also lead discussants at the World Federation of NeurologyDementia Research Group meeting in 2007. World Federation of Neurology Dementia Research Group:  Members and guests who contributed to the information compiled inthis Review include Rufus Akinyemi (Nigeria), Belachew D Arasho (Ethiopia), Tarek Bellaj (Tunisia), José Bertelote (WHO), SantyDaya (South Africa), Wiesje M van der Flier (Netherlands), Catherine Dotchin (Tanzania), Angiola Fasanaro (Italy), Valery Feigin(New Zealand), Paul Francis (UK), Samuel Gatere (Kenya), Henry Houlden (UK), Eef Hogervorst (UK), Akira Homma (Japan), PaulInce (UK), Jennifer Jones (USA), Ahmed Mussa Jusabani (Kenya), Zarina Kabir (Sweden-Bangladesh), Touré Kamadore (Senegal),Jean-Marie Kashama (Democratic Republic of Congo), Tharcisse Kayembe (Democratic Republic of Congo), Miia Kivipelto(Sweden), Girish J Kotwal (USA), Ennapadam S Krishnamoorthy (India), Debomoy Lahiri (USA), Donald Lehmann (UK), Mohamed Makrelouf (Algeria), Elizabeta Mukaetova-Ladinska (UK), Ken Nagata (Japan), Noeline K Nakasujja (Uganda), David Ndetei(Kenya), Arthur Oakley (UK), Ante Padjen (Canada), Robert Perry (UK), Stuart Pickering-Brown (UK), Mieczyslaw Pokorski(Poland), Dushyant Purohit (USA), Ingmar Skoog (Sweden), Manjari Tripathi (India), Susan van Rensburg (South Africa), MathewVarghese (India), and Julie Williams (UK). Conflicts of interest:  RPF is a consultant to MIMvista, Inc. AW has been acting as a consultant to drug companies that are purchasingor developing drugs for treatment of Alzheimer's disease or other dementias (Pfizer, Janssen-Cilag, Novartis, Merz, Lundbeck, Forest,GlaxoSmithKline, Wyeth, Sanofi, Elan, Neurochem). All other authors have no conflicts of interest.  NIH Public Access Author Manuscript  Lancet Neurol . Author manuscript; available in PMC 2010 April 28. Published in final edited form as: Lancet Neurol  . 2008 September ; 7(9): 812–826. doi:10.1016/S1474-4422(08)70169-8. NI  H-P A A  u t  h  or M an u s  c r i   p t  NI  H-P A A  u t  h  or M an u s  c r i   p t  NI  H-P A A  u t  h  or M an u s  c r i   p t    Felix Potocnik, MD ,Department of Psychiatry, University of Stellenbosch, Tygerberg, South Africa Martin Prince, MRCPsych ,Health Service and Population Research Department, Section of Epidemiology, King's CollegeLondon, London, UK Robert Stewart, MRCPsych ,Health Service and Population Research Department, Section of Epidemiology, King's CollegeLondon, London, UK  Anders Wimo, MD , Alzheimer's Disease Research Center, Department of Neurobiology, Care Sciences and Society,Karolinska Institute, Stockholm, Sweden Zhen-Xin Zhang, MD , andMemory and Movement Disorder Center, Department of Neurology, and Clinical EpidemiologicalCentre, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing,China Piero Antuono, MD Dementia Research Center, Department of Neurology, Medical College of Wisconsin, Milwaukee,WI, USA for the World Federation of Neurology Dementia Research Group  Abstract Despite mortality due to communicable diseases, poverty, and human conflicts, dementiaincidence is destined to increase in the developing world in tandem with the ageing population.Current data from developing countries suggest that age-adjusted dementia prevalence estimates in65 year olds are high ( ≥ 5%) in certain Asian and Latin American countries, but consistently low(1–3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for ∼ 30% of the prevalence. Early-onset familial forms of dementia withsingle-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The  APOE    ε 4 allele does not influence dementia progression in sub-Saharan Africans.Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment.Dementia costs in developing countries are estimated to be US$73 billion yearly, but caredemands social protection, which seems scarce in these regions. Introduction Older people with dementia exist in nearly every country in the world. Dementia rates are predicted to increase at an alarming rate in the least developed and developing regions of theworld despite mortality resulting from malnutrition, poverty, war, and infectious diseases.WHO projections suggest that by 2025, about three-quarters of the estimated 1.2 billion people aged 60 years and older will reside in developing countries. 1  Thus, by 2040, if growth in the older population continues, and there are no changes in mortality or burdenreduction by preventive measures, 71% of 81.1 million dementia cases will be in thedeveloping world. 2  About 4.6 million new cases of dementia are added every year, with thehighest growth projections in China and its south Asian neighbours. These projections might be confounded by temporal changes due to shorter survival after dementia, 3  lack of education and awareness, inadequate diagnostic assessment, 4  and variability in costs of careof the elderly with dementia, 5  all of which could lead to under-accounting of the dementia Kalaria et al.Page 2  Lancet Neurol . Author manuscript; available in PMC 2010 April 28. NI  H-P A A  u t  h  or M an u s  c r i   p t  NI  H-P A A  u t  h  or M an u s  c r i   p t  NI  H-P A A  u t  h  or M an u s  c r i   p t     burden. 6  In China, for example, 49% of patients with dementia were classified as normallyageing and only 21% had adequate access to diagnostic assessment, 7  compared with 20%and more than 70%, respectively, in Europe. 8 There are no known curative or preventive measures for most types of dementia. Diet and lifestyle could influence risk, and studies suggest that midlife history of disorders that affectthe vascular system, such as hypertension, type 2 diabetes, and obesity, increase the risk for dementia including Alzheimer's disease (AD). 9  –  12  Increased trends in demographictransition and urbanisation within many developing countries are predicted to lead tolifestyle changes. 13  Delaying of onset, by modifying risk or lifestyle, decreases the prevalence and public health burden of dementia; a delay in onset of 1 year would translateto almost a million fewer prevalent cases in the USA. 14  However, this in turn might increasedemands on health services and costs for older populations. 15 We review published prevalence estimates and modifying factors for brain ageing-related dementias in developing regions of the world, as defined by the United Nations. 16  Our report is limited to ageing-related neurodegenerative and vascular dementias and does notaddress dementia secondary to retroviruses (eg, HIV) or other infectious agents, recognisingthat these might assume importance in younger adults or in specific regions. Other reviewshave focussed on these issues, 15 , 17 , 18  but we take particular note of genetic and environmental factors, 18 , 19  in addition to the problems encountered in accounting for differences in dementia occurrence between developed and developing countries. Althoughmore data from developing countries are needed, several comparative dementia prevalenceand risk-factor assessment projects, which use similar designs, survey methods, and investigators, have been invaluable resources to allow examination of phenotypic variationsin dementias in populations living in very different cultures and environments. 18 , 20  –  22 Dementia screening  Neuropsychometric assessment seems to be the best method to screen individuals in mostdeveloping countries. 23  At the outset, the lack of standardisation of screening tools has to berecognised as a major issue in the estimation of the true burden. 20  Standardisation might not be readily achieved because of diversity of language, culture, and levels of literacy. Incertain communities, more than 80% of elderly people do not read or write. 24  The minimental state examination (MMSE) has been translated into many languages, but its usemight be limited even as an initial screening tool. Independent back translations and consistent informant assessments are therefore mandated. Neuropsychological test batterieswith components relatively free of cultural and linguistic factors (eg, verbal tests of delayed recall and of language) have been developed, 25  but experience suggests that assessmentsmust be consistent with the culture and language of the population under study, and localnormative data for test performance need to be compiled. 26 To achieve universal standardisation and to chart the epidemiological transition and itseffect on older people, the 10/66 Dementia Research Group centres have initiated evidence- based procedures for use in different catchment areas worldwide. 27  These include cross-culturally validated assessments for dementia subtype diagnosis, other mental and physicalhealth diagnoses, anthropometry, demographics, non-communicable disease risk factors,disability and functioning, health-service utilisation, care arrangements, and caregiver strain. Nested within the population-based studies is a randomised controlled trial of caregiver intervention for people with dementia and their families. 27  The surveys includeascertainment of other mental disorders, vascular disease, chronic obstructive pulmonarydisease, and arthritis. 27  Documentation of specific functional decline can be a challenge, because in some cultures, elderly individuals might have a restricted range of activities Kalaria et al.Page 3  Lancet Neurol . Author manuscript; available in PMC 2010 April 28. NI  H-P A A  u t  h  or M an u s  c r i   p t  NI  H-P A A  u t  h  or M an u s  c r i   p t  NI  H-P A A  u t  h  or M an u s  c r i   p t    available to them, or family members might take over these activities. However, a history of cognitive decline can generally be combined with psychometric testing to support thediagnosis. Determination of the correct age of individuals who do not possess formaldocumentation of birth is another factor that could hamper comparisons, although methodson how accuracy might be achieved have been recognised. 28 , 29 Dementia prevalence and incidence Since the Delphi study projections, 2  several large-scale dementia prevalence studies have been done. 30  –  39  Dementia prevalence estimates vary widely within developing countries(table 1). This variation might indicate differences in population age structure, genetics, and lifestyle, but could also be due to difficulty in standardising dementia assessment and reduced survival after diagnosis. 15  The mean age-adjusted prevalence estimate for dementiaamong people aged 65 years and older living in developing countries, derived from data published within the past 10 years, was calculated to be 5.3% (95% CI 3.9–6.5; table 1).This estimate was obtained by determining the srcinal sample sizes and numbers of dementia cases reported to be 65 years and older in individual studies per country, and re-calculating mean estimates and variation by use of SPSS 15.0, according to the method byYang. 59 Surprisingly, countries in Latin America, such as Venezuela and Argentina, bear a higher  burden of over 5% prevalence of dementia (figure). By contrast, a systematic analysis of sixIndian studies suggests low prevalence (2–3%) of all dementias, with marginally fewer casesin urban compared with rural areas and in the northern versus southern states. 33  Pooled analysis of 25 Chinese studies by Dong and colleagues, 30  comprising a total population of more than 76 000, suggested that the overall prevalence of dementia was 3.1%, indicating asignificant rise from 1980 to 2004. However, a recent survey of over 34 807 Han Chineseresidents aged at least 55 years in 79 rural and 58 urban communities of four distant areasreported a crude prevalence estimate of 5.0%, and 6.8% after adjustment for negativescreening. 31  Higher prevalence was apparent in northern regions compared with the south, but no difference was evident among urban and rural Chinese residents. 7  In the Upper Assiutregion along the Nile, age-adjusted dementia prevalence in people aged 65 years and older was 5.9%. 51  In the Yoruba (Niger-Kordofanian people) of Nigeria, dementia prevalence waslow (2.3%) compared with an African American population in Indiana, USA (8.2%). 52 Among Arabs living in Wadi Ara, a community south of Haifa in Israel, the crude prevalence estimate for all dementias was 21% in those aged over 60 years. 50 , 74 Consanguinity among families was suggested as a reason for this high prevalence. 74 , 75 Studies from developing countries in Eastern Europe have assessed some risk factors, but prevalence or incidence data in these communities are unknown. 62 The variations in prevalence within developing countries seem close to those found in therecently completed 10/66 survey of 14 960 residents aged over 65 years in 11 sites in sevenlow-income and middle-income countries (China, India, Cuba, Dominican Republic,Venezuela, Mexico, and Peru). 20  Prevalence of dementia according to the Diagnostic and Statistical Manual of Mental Disorders (4th edition) varied widely, from less than 1% in theleast developed countries, such as India and rural Peru, to 6.4% in Cuba. The 10/66 studyalso found that informants in the least developed countries were less likely to reportcognitive decline and social impairment, 20  suggesting possible underestimation of  prevalence estimates in some locations.Few incidence estimates are available to substantiate prevalence figures for those aged 65years and older. Compared with developed countries, relatively lower annual incidenceestimates of 1–2% are reported in certain countries, such as Brazil, Nigeria, India, and  Kalaria et al.Page 4  Lancet Neurol . Author manuscript; available in PMC 2010 April 28. NI  H-P A A  u t  h  or M an u s  c r i   p t  NI  H-P A A  u t  h  or M an u s  c r i   p t  NI  H-P A A  u t  h  or M an u s  c r i   p t  
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