Dement Geriatr Cogn Disord 2015;39:294–302DOI: 10.1159/000375366Accepted: January 17, 2015Published online: March 14, 2015 2015 S. Karger AG, Basel1420–8008/15/0396–0294 39.50/ Research ArticlePrevalence of Dementia and MainSubtypes in Rural Northern ChinaYong Ji a, b Zhihong Shi a, b Ying Zhang a, b Shuling Liu a, b Shuai Liu a, bWei Yue a, b Mengyuan Liu b Ya Ruth Huo c Jinhuan Wang bThomas Wisniewski da Departmentof Neurology, and b Tianjin Key Laboratory of Cerebrovascular andNeurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China; c School ofMedicine, University of New South Wales, Kengsington, N.S.W., Australia;dDepartments of Neurology (Aging and Dementia Division), Pathology and Psychiatry,NYU Neurology Associates, NYU Pearl Barlow Center for Memory Evaluation andTreatment, New York, N.Y., USAKey WordsAlzheimer’s disease · Dementia · Prevalence · Rural China · Risk factorsYong Ji, MD, PhDTianjin Huanhu HospitalQixiangtai Road 122, Tianjin, Hexi 300060 (China)E-Mail jiyongusa @ 126.comDownloaded by:NYU Medical Center Library216.165.126.139 - 3/21/2015 5:14:00 PMAbstractBackground/Aims: The aim of this article was to estimate the prevalence of and to determinethe sociodemographic risk factors for dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) among individuals residing in rural northern China. Methods: Between 2011 and2012, residents aged 60 years and residing in rural areas of northern China were clinicallyassessed for symptoms of dementia, AD and VaD. Diagnoses were made using establishedcriteria and standard procedures. Results: Among 5,578 enrolled study participants aged 60years, the prevalence rates of dementia, AD and VaD were 7.7, 5.4 and 1.7%, respectively. Older age (OR 1.17; 95% CI: 1.14–1.19) and female gender (OR 2.13; 95% CI: 1.51–3.00) wereidentified as independent risk factors for AD. In turn, a higher educational level (OR 0.36;95% CI: 0.21–0.60) and engagement in social activities (OR 0.219; 95% CI: 0.163–0.295) wereprotective factors. Risk factors associated with VaD were older age (OR 1.11; 95% CI: 1.1–1.12) and hypertension (OR 1.83; 95% CI: 1.18–2.86), while a higher educational level (OR 0.53, 95% CI: 0.44–0.65) and engagement in social activities (OR 0.34; 95% CI: 0.29–0.41)were protective factors. Conclusion: High rates of dementia (7.7%) and AD (5.4%) were foundin the rural areas of northern China. Older age and female gender were identified as risk factors for AD, while older age and hypertension were risk factors for VaD. A higher educationallevel and engagement in social activities were identified as protective factors against both AD 2015 S. Karger AG, Baseland VaD.

295Dement Geriatr Cogn Disord 2015;39:294–302DOI: 10.1159/000375366 2015 S. Karger AG, et al.: Prevalence of Dementia and Main Subtypes in Rural Northern ChinaIntroductionAs the country with the world’s largest population, China will face substantial challengesin adjusting to its ageing population, of which increasing numbers will have some degree ofdementia. Thus, investigating the nationwide epidemiology of dementia in rural and urbanareas will be of great importance for providing information used in developing appropriatepolicies and patient care strategies. However, it is especially essential to understand the prevalence of dementia in rural China, because 70% of China’s 1.29 billion people live in ruralareas, and the majority are primarily engaged in agriculture [1]. A recent meta-analysis estimated that 4.98–5.9% of individuals in China aged 60–65 years have some type of dementia[2, 3] but did not calculate its specific prevalence in rural and urban areas or in regions stratified as northern or southern China. A second recent meta-analysis regarding the prevalenceof dementia in different regions of China found geographic differences in the prevalence ofdementia across China, with higher rates of Alzheimer’s disease (AD) in rural areas comparedto urban areas. Moreover, higher prevalence rates of both vascular dementia (VaD) and ADwere found in northern as compared to southern China [4].Few epidemiological data are available on dementia in rural northern China, and thenumbers of affected individuals in these areas have been estimated using prevalence dataobtained from other regions of China or from cross-sectional studies in which there werelarge numbers of nonresponders [4, 5]. The higher prevalence of dementia in rural comparedto urban areas may result from differences in demographic factors, including education andlifestyle. Moreover, these same factors may account for the large differences in the prevalenceand patterns of dementia across northern and southern China. Our current study wasconducted to estimate the prevalence of dementia and its main subtypes (AD and VaD) inChinese individuals residing in rural northern China. We also analyzed the sociodemographicrisk factors and comorbidities associated with dementia and its subtypes.MethodsPhase I: Screening InterviewPotential subjects were contacted directly by a house visit, at which time they were informed concerningthe objective of the interview and welcomed to participate. After providing signed written informed consent,the home interview was conducted by at least 2 members of a team consisting of 10 medical practitioners. Themedical practitioners had been trained to collect information in a uniform manner by 2 neurologists specializing in dementia and AD from the Dementia Center of Tianjin Huanhu Hospital. During the interview, thepractitioners collected information on each participant’s sociodemographic characteristics, medical history,scores on the Chinese Mini-Mental State Examination (C-MMSE) and also recorded findings from physical andneurological examinations [6]. Reliable informants (the subject’s spouse, children, other relatives or closefriends, in descending order) provided information if the subject was unable to do so alone. Subjects with aC-MMSE score less than certain cutoff points (18 for illiterate persons, 24 for persons with 1–11 years ofeducation and 27 for persons with 12 years of education or a Clinical Dementia Rating 0.5) were deemedeligible for participation in phase II of the study [5–7]. The average duration of this first interview was 60 min.Downloaded by:NYU Medical Center Library216.165.126.139 - 3/21/2015 5:14:00 PMStudy PopulationThis cross-sectional population-based study was conducted in 56 villages selected from 949 villages in therural Ji County in northern China. The local medical practitioner in each village (who had worked there for anaverage of 5.76 3.23 years) was involved in identifying all individuals aged 60 years based on the date of birthprovided on the residence certificate. Inclusion criteria of the study stated that an individual must have legallyresided in the county for 5 years prior to study enrollment. The total number of participants aged 60 years inthese villages was 5,744; however, due to hearing loss (n 112), refusal (n 39), death or migration (n 8) orother issues (n 7), 5,578 completed both phases of the door-to-door interview. The study protocol was approvedby the Committee for Medical Research Ethics at Tianjin Huanhu Hospital and the Tianjin Health Bureau.

296Dement Geriatr Cogn Disord 2015;39:294–302DOI: 10.1159/000375366 2015 S. Karger AG, et al.: Prevalence of Dementia and Main Subtypes in Rural Northern ChinaThe comorbidities of the subjects such as a history of diabetes, hypertension, heart disease or strokewere obtained from a local medical practitioner who had cared for the participant for at least the preceding5 years. A previous history of stroke as defined by the WHO was based on information obtained from thedoctor, patient and a reliable informant. The qualifying symptoms of stroke included sudden or rapidly developing signs of focal or global neurological dysfunction which lasted for 24 h and had no apparent nonvascular cause (e.g., cranial trauma, coma attributable to a metabolic disorder, neoplasia, vasculitis, centralnervous system infection or peripheral neuropathy) [8]. A smoker was defined as an individual with a historyof smoking 5 cigarettes per day for 2 years. An alcohol drinker was defined as an individual with a historyof drinking an alcoholic beverage 1 time per week for 2 years. Engagement in social activities was definedas attending any social activity 1 time per week.Phase II: Neurological ConsultationSubjects who were eligible for phase I were further examined to confirm or exclude the presence ofdementia. If dementia was present, its subtype was determined. This assessment was performed during asecond home interview; however, this time, the interview was conducted by 2 of 6 board-certificatedneurologists from the Dementia Center of Tianjin Huanhu Hospital. The 6 neurologists had been trainedtogether to ensure uniform neurological consultation across all participants. A detailed medical historywas obtained from all patients in phase II, and each patient received a physical and neurological examination.Statistical AnalysisThe overall prevalence of dementia was calculated taking into account the total number of dementiacases with respect to the total study sample. The overall prevalence of dementia and its specific prevalenceper 5-year age group, sex and educational level were calculated. Additionally, the age- and sex-specific prevalence rates of dementia and its various subtypes were also determined. A subject’s marital status was classified as either married or widowed/separated (single or divorced). Educational attainment was categorizedas having 5 or 5 years of formal education.In each analysis, the dependent variable was dementia and its subtypes were AD and VaD. Frequencydistributions were used for the analysis of qualitative variables and the numbers of individuals (%). Ageadjusted and sex-adjusted ORs were calculated to identify sociodemographic and clinical factors associatedwith dementia. Variables with an OR p value 0.05 were included in a multivariate analysis to identifysociodemographic and clinical factors independently associated with dementia, AD and VaD. p values 0.05were considered statistically significant. All data were analyzed using IBM SPSS Statistics for Windows(Version 20.0; IBM Corp., Armonk, N.Y. USA).Downloaded by:NYU Medical Center Library216.165.126.139 - 3/21/2015 5:14:00 PMCriteria for Dementia and Its SubtypesIndividuals were classified as having dementia if they fulfilled the criteria listed in the Diagnostic andStatistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and had experienced dementia symptomsfor 3 months [9, 10]. Assessments were based on data obtained from the interviews, health examinations,previous health and social work records and tests for cognitive function and functional capacity. The NationalInstitute of Neurological and Communicative Disorders-AD and Related Disorders Association criteria wereused for the clinical diagnosis of AD [11], and criteria of the National Institute of Neurological Disorders andStroke – Association Internationale pour la Recherche et I’Enseinement en Neurosciences were used for theclinical diagnosis of VaD [12]. The clinical criteria used for diagnosing AD included an insidious onset andprogressive impairment of memory and other cognitive functions. Since there are no specific motor, sensoryor coordination deficits associated with early-stage AD, other possible causes of dementia were excludedbefore diagnosing AD. The clinical criteria used for diagnosing VaD included a history of ischemic or hemorrhagic strokes, cerebral hypoxic-ischemic events or senile leukoencephalopathic lesions. However, becausethe clinical course of VaD can be static, remitting or progressive, there is a temporal relationship betweenstroke and dementia onset, and brain imaging findings are required for a definitive diagnosis. Other dementias(ODs) defined by globally accepted criteria include mixed dementia, frontotemporal dementia, dementiawith Lewy bodies, Parkinson’s disease with dementia, alcoholic dementia, hydrocephalus dementia and posttraumatic dementia. Cognitive impairment no dementia was diagnosed as either (1) mild cognitive or functional impairment that did not meet the criteria for dementia or (2) performance on neuropsychological orfunctional tests that was below expectations and 0.5 standard deviations below the published norms onany test [9].

297Dement Geriatr Cogn Disord 2015;39:294–302 2015 S. Karger AG, 10.1159/000375366Ji et al.: Prevalence of Dementia and Main Subtypes in Rural Northern ChinaTable 1. Prevalence rates of dementia, AD and VaD according to sex, age and educational levelIndividuals, Dementiancases,n (%)TotalGenderMaleFemaleAge60 – 64 years65 – 69 years70 – 74 years75 – 79 years80 – 84 years85 yearsEducationIlliterate 5 years 5 yearsAD95% CIcases,n (%)VaD95% CIcases,n (%)95% CI5,578429 (7.7)6.99 – 8.39299 (5.4)4.77 – 5.9596 (1.7)1.38 – 2.062,4823,096148 (6.0)281 (9.1)5.03 – 6.898.06 – 10.1093 (3.7)206 (6.7)3.00 – 4.505.78 – 7.5342 (1.7)54 (1.7)1.18 – 2.201.28 – 2.211,6831,39498371945218958 (3.4)39 (2.8)55 (5.6)77 (10.7)112 (24.8)63 (33.3)2.57 – 4.321.93 – 3.664.16 – 7.038.45 – 12.9720.80 – 28.7626.61 – 40.051.40 – 2.761.04 – 2.412.83 – 5.306.57 – 10.6713.57 – 20.5016.77 – 28.7319 (1.1)15 (1.1)12 (1.2)13 (1.8)23 (5.1)10 (5.3)0.62 – 1.630.53 – 1.620.53 – 1.910.83 – 2.783.06 – 7.112.10 – 8.482,2402,0221,316286 (12.8)119 (5.9)24 (1.8)11.39 – 14.154.86 – 6.911.10 – 2.557.71 – 10.063.20 – 4.920.74 – 1.2058 (2.6)34 (1.7)4 (0.3)1.93 – 3.251.21 – 2.240.01 – 0.6035 (2.1)24 (1.7)40 (4.1)62 (8.6)77 (17.0)43 (22.8)199 (8.9)82 (4.1)18 (1.4)% values represent % prevalence rates of dementia.Of the 5,578 study participants aged 60 years, 429 (7.7%) were diagnosed with someform of dementia. Among these individuals, 34.5% were men and 65.5% were women. Thedementia diagnoses included 299 (5.4%) cases of AD, 96 (1.7%) cases of VaD and 34 (0.6%)cases of OD. The mean ages of individuals with normal cognition, VaD and AD were 67.9 6.0,74.1 8.3 and 76.7 8.2 years, respectively. The study group also included 1,307 (23.4%)individuals with cognitive impairment no dementia and 3,842 individuals with normalcognition.Table 1 shows the prevalence rates of dementia, AD and VaD according to gender, 5-yearage groups and educational level. The overall rate of dementia was higher in females (9.1%)than in males (6.0%). AD was more common in females than in males (6.7 vs. 3.7%, respectively), while VaD was equally common in both genders (1.7 vs. 1.7%). Dementia becameprogressively more common as individuals aged beyond 70 years and was also more commonamong participants with fewer years of education. Among the 429 individuals with dementia, AD was the main diagnosis (299 cases; 70%) followed by VaD (96 cases; 22%) and OD(34 cases; 8%).The age-adjusted ORs for AD and VaD are shown in table 2. Our analysis showed significant positive associations between AD and other factors including female gender, having 5years of formal education, being without a partner and having no engagement in social activities. A subsequent multivariate analysis found that independent risk factors for AD wereolder age (OR 1.17; 95% CI: 1.14–1.19) and female gender (OR 2.13; 95% CI: 1.51–3.00).Independent protective factors against AD were having 5 years of formal education (OR 0.36; 95% CI: 0.21–0.60) and engagement in social activities (OR 0.219; 95% CI: 0.163–0.295) (table 3).VaD was associated with having 5 years of formal education, no engagement in socialactivities and the presence of hypertension. No gender differences were identified for VaD inDownloaded by:NYU Medical Center Library216.165.126.139 - 3/21/2015 5:14:00 PMResults

298Dement Geriatr Cogn Disord 2015;39:294–302 2015 S. Karger AG, 10.1159/000375366Ji et al.: Prevalence of Dementia and Main Subtypes in Rural Northern ChinaTable 2. Univariate analysis of variables significantly associated with AD and VaDGenderMaleFemaleEducation 5 years0 – 5 yearsSmokingAlcohol consumptionWidowed/separatedNo social activitiesComorbiditiesHypertensionDiabetes mellitusHeart diseaseNormalcognition(ref.), n (%)AD, n (%)1,838 (47.8)2,004 (52.2)Age-adjustedOR (95% CI)pvalueVaD, n (%) Age-adjustedOR (95% CI)pvalue93 (31.1)206 (68.9)2.75 (2.09 – 3.63) 0.00142 (43.8)54 (56.3)1.46 (0.96 – 2.22)1,130 (29.4)2,712 (70.6)1,006 (26.2)734 (19.1)492 (12.8)410 (10.7)18 (6.0)281 (94.0)58 (19.4)28 (9.4)111 (37.1)119 (39.8)3.79 (2.31 – 6.22)0.62 (0.46 – 0.86)0.44 (0.29 – 0.67)1.65 (1.21 – 2.23)4.20 (3.16 – 5.58) 0.0010.003 0.0010.001 0.0014 (4.2)92 (95.8)18 (18.8)11 (11.5)25 (26.0)22 (22.9)6.82 (2.48 – 18.72) 0.0010.60 (0.36 – 1.01)0.0550.53 (0.28 – 1.01)0.0521.12 (0.67 – 1.88)0.6752.42 (1.44 – 4.07)0.0011,449 (37.7)280 (7.3)289 (7.5)119 (39.8)22 (7.4)25 (8.4)1.14 (0.88 – 1.48)1.47 (0.90 – 2.39)0.78 (0.50 – 1.27)0.3390.120.3452 (54.2)8 (8.3%)9 (9.4)1.93 (1.28 – 2.92)1.48 (0.70 – 3.14)0.99 (0.49 – 2.02)0.0740.0020.300.98Table 3. Multivariate analysis of variables significantly associated with AD or VaDBOR (95% CI)p valueAge (years)Female genderEducation ( 5 years)Current smokerAlcohol consumptionWidowed/separatedEngages in social activitiesVaDAgeEducation ( 5 years)Engages in social 540.310–1.521.17 (1.14 – 1.19)2.13 (1.51 – 3.00)0.36 (0.21 – 0.60)1.11 (0.73 – 1.68)0.635 (0.37 – 1.089)1.364 (0.988 – 1.88)0.219 (0.163 – 0.295) 0.001 0.001 0.0010.6370.0990.059 0.0010.103–0.632–1.070.6081.11 (1.1 – 1.12)0.53 (0.44 – 0.65)0.34 (0.29 – 0.41)1.83 (1.18 – 2.86) 0.001 0.001 0.0010.007the univariate analysis. The subsequent multivariate analysis identified older age (OR 1.11;95% CI: 1.1–1.12) and hypertension (OR 1.83; 95% CI: 1.18–2.86) as independent riskfactors for VaD. Independent protective factors against AD included having 5 years of formaleducation (OR 0.53; 95% CI: 0.44–0.65) and engagement in social activities (OR 0.34; 95%CI: 0.29–0.41) (table 3).Results of a further evaluation of the association between hypertension and VaD areshown in table 4. Hypertension was twice as prevalent among individuals with VaD ascompared to those with normal cognition. Additionally, hypertension accompanied bydiabetes mellitus was 3-fold more prevalent among individuals with VaD; however, no significant association was identified between having VaD combined hypertension and heartdisease.Downloaded by:NYU Medical Center Library216.165.126.139 - 3/21/2015 5:14:00 PMAD

299Dement Geriatr Cogn Disord 2015;39:294–302DOI: 10.1159/000375366 2015 S. Karger AG, et al.: Prevalence of Dementia and Main Subtypes in Rural Northern ChinaTable 4. Age-adjusted ORs for the association of hypertension alone and hypertension accompanied bycardiovascular risk factors with VaDNo hypertensionHypertensionHypertension onlyHypertension and diabetesHypertension and heart diseaseNormalcognitionVaDAge-adjustedOR (95% CI)pvalue2,3931,4491,159165159445239861.0 (ref.)1.93 (1.28-2.92)1.83 (1.18-2.86)3.35 (1.51-7.43)1.62 (0.67-3.94)0.0020.0070.0030.288This large population-based cross-sectional study is one of only a few which have investigated the prevalence rates of AD and VaD in the rural areas of northern China. Moreover,this study explored and identified numerous risk factors for dementia; many of which had notbeen previously examined for their relation to dementia subtypes AD and VaD in the Chinesepopulation. Our data showed that the prevalence rates of dementia, AD and VaD amongChinese individuals aged 60 years were 7.7, 5.4 and 1.7%, respectively. These prevalencerates were slightly higher than those found in a previous study of individuals aged 65 yearsand residing in rural areas of northeast and southwest China. In