Download - “ The 10/66 Dementia Research Group Studies”
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“ “ The 10/66 Dementia Research Group Studies”The 10/66 Dementia Research Group Studies”. . Incidence phase.Incidence phase. Juan J. Llibre Rodriguez. For and on behalf of 10/66
2626thth International Conference of Alzheimer’s International Conference of Alzheimer’s Disease International. Disease International.
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INCIDENCE RATES
• Burden of a disease.
• Risk of disease
• I x duration = Prevalence
• I x case fatality = Burden of mortality
• Predict future cases
• Planning health services
• Evaluate the impact of prevention
• Study risk factors.
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Incidence phase (n=13,000)
• Sites– Cuba, DR, Venezuela, Mexico, Peru, China
• Outcomes– Dementia, Stroke, Dependence, Mortality
• Aetiology• Cardiovascular risk (BP/ smoking/ fasting
glucose/ cholesterol)• Diet (anaemia, B12, folate, subclinical
hypothyrodism, albumin, anthropometry)• Developmental factors• APOE and other genetic factors
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Incidence wave, by country
Country Cohort Inter-viewed
Dead Lost to follow-up
Median follow-up (years)
Person years (dementia)
Cuba 2813 2007 608 198 4.5 8701DR 2011 1197 467 347 5.1 5561Peru 1933 1311 152 470 3.3 3914Venezuela 1965 1257 200 508 4.3 5269Mexico 2003 1462 209 332 3.0 4164China 2162 1452 515 195 5.1 7109Total 12887 8137 2151 2050 34718Total (%) 69% 17% 16%
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Mortality in dementia
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Mortality among people with dementia, by site
Site Mortality rate (per 1000 person years)
Age and sex adjusted mortality hazard ratiosNo
dementiaDementia cases
Cuba 44.8 195.4 3.20 (2.61-3.92)Dominican Republic 54.5 148.3 2.22 (1.75-2.81)Peru, urban 18.7 139.3 5.69 (3.33-9.73)Peru, rural 28.9 59.5 1.74 (0.68-4.44)Venezuela 24.3 98.4 2.27 (1.42-3.62)Mexico, urban 31.6 114.4 2.70 (1.56-4.67)Mexico, rural 36.6 89.7 1.56 (0.94-2.59)China, urban 40.7 168.1 3.02 (2.13-4.28)China, rural 57.0 216.1 3.59 (2.47-5.21)India, urban 62.5 171.6 2.33 (1.48-3.67)
Pooled meta-analysed effect
2.77 (2.47-3.10)
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Factors tested as possible predictors of mortality, among people with dementia
Sociodemographic factors
Age Assets
Gender In receipt of pension
Education Health insurance
Dementia related factors
Cognitive function (COGSCORE) Dementia severity (CDR)
Dementia subtype Behavioural symptomsGeneral health factorsPrevious stroke Physical illnessDisability (WHODAS 2.0 score) Undernutrition (arm circumference)DepressionCare-related factorsNumber of co-residents Needs for careCo-resident child Co-resident spouse
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Predictors of mortality (stepwise regression), among people with dementia
Predictor Hazard ratio for mortality (95% CI)
P-value
Sociodemographic factors
Age (per 5 year band) 1.29 (1.16-1.44) <0.001
Male gender 1.92 (1.55-2.39) <0.001
Dementia related factors
Cognitive function (COGSCORE) 0.98 (0.97-0.99) 0.001
Frontotemporal dementia type 0.45 (0.23-0.88) 0.02General health factorsPrevious stroke 0.76 (0.59-0.98) 0.03Disability (WHODAS 2.0 score) 1.01 (1.01-1.02) <0.001Undernutrition (arm circumference) 1.30 (1.02-1.66) 0.03Care-related factorsNumber of co-residents 1.05 (1.00-1.11) 0.06Co-resident child 0.82 (0.72-0.93) 0.02Co-resident spouse 0.74 (0.59-0.92) 0.008
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Carer strain
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Changes in carer strain since baseline
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Factors tested as possible predictors of carer strain at follow-up
Sociodemographic factors
Age Education
Gender Follow-up interval
Dementia related factors
Change in cognitive function Dementia severity (CDR)
Dementia subtype Behavioural symptomsQuality of life at follow-up (DEMQOL)General health factorsPrevious stroke Physical illnessDisability (WHODAS 2.0 score) DepressionCare-related factorsAge Number of co-residentsGender Co-resident childNeeds for care Co-resident spouse
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Predictors of carer strain (stepwise regression), among people with dementia
Predictor Regression coefficient (95% CI)
P-value
Sociodemographic factors
Follow-up period (per year) +1.9 (-0.2 to +4.0) 0.07
Dementia related factors
Change in cognitive function (per one point decline in COGSCORE)
+0.4 (+0.2 to +0.6) <0.001
Behavioural symptoms +0.4 (+0.1 to +0.6) 0.008Frontotemporal dementia type -9.5 (-16.4 to -2.6) 0.007Quality of life at follow-up -0.2 (-0.3 to -0.1) 0.004General health factorsICD-10 depressive episode -4.9 (-9.4 to -0.4) 0.03Disability (WHODAS 2.0 score) +0.1 (+0.0 to +0.1) 0.03Care-related factorsNeeds for care +6.3 (+2.0 to +10.5) 0.004Carer age +0.1 (+0.0 to +0.2) 0.02
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DSM-IV dementia *
10/66 Dementia
Any dementia
ALL 9.00 21.04 21.17BY SEXMale 9.39 18.36 18.36Female 8.80 22.41 22.60BY AGE65-69 3.27 5.95 5.9570-74 8.97 18.18 18.6175-79 11.67 27.64 27.6480+ 16.29 48.85 48.85
* Incidence rate/ 1000 pyr
Incidence of dementia by sex and age, Cuba Cohort 65 years and over N=2728
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Risk factors for incident dementiaRisk factors for incident dementiaAge groupAge group 1.79 (1.37-2.37)1.79 (1.37-2.37)Male genderMale gender 1.27 (0.62-2.60)1.27 (0.62-2.60)Education levelEducation level 0.79 (0.67-0.98)0.79 (0.67-0.98)Leg lengthLeg length 1.02 (0.98-1.06)1.02 (0.98-1.06)Skull circSkull circ 1.06 (0.91-1.23)1.06 (0.91-1.23)SmokerSmoker 0.77 (0.40-1.48)0.77 (0.40-1.48)HypertensionHypertension 1.35 (1.02-2.37)1.35 (1.02-2.37)Parkinsonism scoreParkinsonism score 1.18 (1.05-1.33)1.18 (1.05-1.33)Fish FrequencyFish Frequency 0.40 (0.22-0.74)0.40 (0.22-0.74)Hazardous drinkerHazardous drinker 1.66 (0.54-5.06)1.66 (0.54-5.06)StrokeStroke 2.84 (1.20-6.72)2.84 (1.20-6.72)APOE 4APOE 4 2.01 (1.03-3.92)2.01 (1.03-3.92)FH DementiaFH Dementia 1.39 (0.72-2.64)1.39 (0.72-2.64)
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Population 11,6 millons
Life expectancy Men 79 years Women 80 years
Dementia´s prevalence 6.4-10.2 % (130 000 cases )
Incidence rate 21.7 per 1000/year (28 760 new cases/year)
Mortality rate in dementia people 195.5 per 1000/year
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Does African ancestry Does African ancestry protect against dementia? A protect against dementia? A population-based case-population-based case-control study in an admixed control study in an admixed Cuban populationCuban population??
Admixtures Admixtures mapping provides mapping provides information about the contribution of information about the contribution of
genetic and non genetic factors.genetic and non genetic factors.In Cuba, there is sufficient variation of In Cuba, there is sufficient variation of
admixture between individuals to admixture between individuals to detect relationships of disease risk to detect relationships of disease risk to
proportionate admixture.proportionate admixture.
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10/66 admixture studies
• Design– Populations of mixed
African and Caucasian ancestry
– Genotype to measure ancestry directly in individuals
• Hypothesis– Higher levels of African
ancestry associated with lower risk of dementia
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Main source of admixture Main source of admixture Migration , 1400–1800, Migration , 1400–1800,
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Cuba – association of APOE genotype with dementia
DementiDementiaaN 273 (%)N 273 (%)
No No dementidementiaaN 2247 N 2247 (%)(%)
Crude PR Crude PR (95% CI)(95% CI)
Adj. PR Adj. PR (95% CI)(95% CI)**
1 or 2 1 or 2 alleles alleles ApoE4ApoE4
87 (31.9)87 (31.9) 329 (14.6)329 (14.6) 2.4 (1.9-3.0)2.4 (1.9-3.0) 2.6 (2.1-3.2)2.6 (2.1-3.2)
Number of ApoE4 alellesNumber of ApoE4 alelles00 186 (68.1)186 (68.1) 1918 (85.4)1918 (85.4) 1.00 (ref.)1.00 (ref.) 1.00 (ref.)1.00 (ref.)11 79 (28.9)79 (28.9) 300 (13.4)300 (13.4) 2.35 (1.9-2.35 (1.9-
3.0)3.0)2.6 (2.0-3.2)2.6 (2.0-3.2)
22 8 (2.9)8 (2.9) 29 (1.3)29 (1.3) 2.45 (1.3-2.45 (1.3-4.6)4.6)
2.9 (1.6-5.3)2.9 (1.6-5.3)* * Adjusted age, sex and educationAdjusted age, sex and education
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APOE allele APOE allele frequencyfrequency
White White n=1677n=1677(72%) (72%)
MixedMixed n=394n=394(17%) (17%)
BlackBlack n=261n=261 (11%) (11%)
P-valueP-value test for test for trendtrend
E2 E2 0.0570.057 0.064 0.064 0.0720.072 <0.001<0.001E3E3 0.8650.865 0.8520.852 0.7800.780 E4E4 0.0780.078 0.0840.084 0.1480.148 Association Association between any E4 between any E4 and dementiaand dementia
2.84 2.84 (2.2-3.6)(2.2-3.6)
0.810.81(0.2-2.8)(0.2-2.8)
2.38 2.38 (1.4-3.9)(1.4-3.9)
Overall association Overall association between E4 and between E4 and any dementiaany dementia
2.58 2.58 (2.06- 3.22)(2.06- 3.22)
Adjusted for race 2.50 2.50 (1.91-3.21)(1.91-3.21)
APOE allele frequency by ethno-racial identity
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Mean admixture proportion by APOE allele status (case control subsample)
APOE APOE genotype genotype Admixture Admixture proportionsproportions
No APOE No APOE allelealleleN= 445N= 445
One APOE One APOE allelealleleN=119N=119
Two APOE Two APOE allelealleleN=20N=20
P valueP value
African mean African mean 95% CI95% CI
0.150.15(0.13-(0.13-0.18)0.18)
0.19 0.19 (0.15 - (0.15 - 0.23)0.23)
0.35 0.35 (0.22-(0.22-0.48)0.48)
P = 0.01P = 0.01
European European mean 95% CImean 95% CI
0.82 0.82 (0.80-(0.80-0.84)0.84)
0.780.78(0.74-0.83)(0.74-0.83)
0.620.62(0.48-(0.48-0.75)0.75)
P = 0.007P = 0.007
Native Native american american
0.03 0.03 (0.02-(0.02-0.03)0.03)
0.03 0.03 (0.02-0.04)(0.02-0.04)
0.03 0.03 (0.02-(0.02-0.05)0.05)
P = 0.65P = 0.65
* *
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Incidence of dementia according age group and APOE 4 genotype (HR). Cuba 10/66 incidence
phase.Age groupAge group 1 or 2 APOE4 1 or 2 APOE4
allelealleleNo APOE4 alleleNo APOE4 allele
65-6965-69 6.56 (2.16-19.9)6.56 (2.16-19.9) 3.673.67
70-7470-74 3.34 (1.82-3.34 (1.82-6.14)6.14)
1.871.87
75-7975-79 5.74 (3.91 5.74 (3.91 10.5)10.5)
3.213.21
80+80+ 11.3 (5.97-11.3 (5.97-21.5)21.5)
6.346.34
Interaction termInteraction term 0.56 (0.37-0.56 (0.37-0.85)0.85)
**p<0.006p<0.006
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Conclusions
• The world is facing a new epidemic of unprecedented proportions
• Its effects will be felt particularly in low and middle income countries - currently least prepared to meet the challenge
• Societal costs will rise inexorably, driven by the increasing need for long term care
• Time for action– Clinical care– Social policy– Prevention
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The next steps
• Care/ ImpactCare/ Impact– Intervention! Intervention!
• Incidence phase I (2006-2010) Incidence phase I (2006-2010) II (2010 -2014)II (2010 -2014)– AetiologyAetiology
• Cardiovascular risk (BP/ smoking/ fasting glucose/ Cardiovascular risk (BP/ smoking/ fasting glucose/ cholesterol)cholesterol)
• Diet (anaemia, B12, folate, subclinical hypothyrodism, Diet (anaemia, B12, folate, subclinical hypothyrodism, albumin, anthropometry)albumin, anthropometry)
• Developmental factorsDevelopmental factors• APOE effect modification APOE effect modification • African ancestryAfrican ancestry
– Chronic non communicabke diseasesChronic non communicabke diseases
•
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10/66 Dementia Research Group10/66 Dementia Research Group
www.alz.co.uk/1066