- Email: [email protected]
The epidemiological study of cognitive function among chinese community-dwelling elderly people, 1998-2011: The chinese longitudinal healthy longevity survey
Podium Presentations: Sunday, July 19, 2015
construct representative indicators (e.g. level of income, education, rate of unemployment, urbanization, access to services...). All variables estimated at community level were transformed into tertiles (T1-T2-T3). The dementia cases were actively diagnosed according to the DSM-IV criteria and validated by an independent expert committee. Associations between dementia and community factors were assessed with the marginal Cox model with delayed entry and age as the time scale, including sex and individual education as confounding factors. Results: During the follow-up, 934 dementia cases were identified. Risk of dementia is increased in participants living in neighborhoods with a higher proportion of laborers (T3/T1 HR¼1.20[1.01; 1.43], p¼0.04), or unemployed (T3/T1 HR¼1.22 [1.03; 1.44], p¼0.02). On the opposite, living in high income neighborhoods is associated with lower risk (T3/T1 HR¼0.81[0.68; 0.95], p¼0.01). In neighborhoods with intermediate proportion of elderly, risk of dementia is decreased (T2/T1 HR¼0.79[0.67; 0.95], p¼0.01) while there is no significant difference for those with highest proportion of elderly (T3/T1 HR ¼0.87 [0.73-1.04], p¼0.12). Conclusions: Independently of age, sex and individual level of education, some factors reflecting socioeconomic disadvantage of the area where subjects are living are associated with dementia risk. Understanding how environmental factors may
P151
influence this risk is a challenge as they can be a proxy for the quality of social environment or related to deprivation of basic activities including cognitive stimulation.
O1-09-05
THE EPIDEMIOLOGICAL STUDY OF COGNITIVE FUNCTION AMONG CHINESE COMMUNITYDWELLING ELDERLY PEOPLE, 1998-2011: THE CHINESE LONGITUDINAL HEALTHY LONGEVITY SURVEY
Mingyue Gao1, Min Yang2, Peiyuan Qiu2, Weihong Kuang3, 1West China School of Public Health, Sichuan University, Chengdu, China; 2School of Public Health, West China Research Center for Rural Health Development, Sichuan University, Chengdu, China; 3Mental Health Center of West China of Sichuan University, Chengdu, China. Contact e-mail: [email protected] Background: The prevalence of cognitive impairment in western
countries decreased in past twenty years. It is still unclear how the index changes over time in China. Methods: The study examined Mini-Mental State Examination (MMSE) status of 33,043 participants aged at 60 years or older in the Chinese Longitudinal Healthy Longevity Surveys (CLHLS) in 1998, 2000, 2002, 2005, 2008, 2011, and Activities of Daily Living (ADLs) of 23,537 participants
Table 1 Demographic characteristics of individuals participating in CLHLS Year Gender Male Female Age group 60w69 years 70w79 years 80w89 years 90w99 years 100w109 years 110years Resident Urban Rural Total
1998 N (%)
2000 N (%)
2002 N (%)
2005 N (%)
2008 N (%)
2011 N (%)
Total N (%)
2465 (49.3) 2537 (50.7)
2459 (54.6) 2045 (45.4)
3941 (57.8) 2879 (42.4)
3735 (58.1) 2696 (41.9)
3815 (58.9) 2666 (41.1)
2351 (61.8) 1454 (38.2)
18766 (56.8) 14277 (43.2)
-
-
107 (2.1) 2585 (51.7) 1549 (31.0) 755 (15.1) 6 (0.1)
24 (0.5) 2759 (61.3) 1330 (29.5) 387 (8.6) 4 (0.1)
1218 (17.9) 2043 (30.0) 2033 (29.8) 1055 (15.5) 469 (6.9) 2 (0.0)
1279 (19.9) 2096 (32.6) 1709 (26.6) 1032 (16.0) 314 (4.9) 1 (0.0)
1287 (19.9) 1858 (28.7) 1820 (28.1) 1139 (17.6) 375 (5.8) 2 (0.0)
548 (14.4) 1525 (40.1) 1030 (27.1) 546 (14.3) 154 (4.0) 2 (0.1)
4332 (13.1) 7653 (23.2) 11936 (36.1) 6651 (20.1) 2454 (7.4) 17 (0.1)
2115 (42.3) 2887 (57.7) 5002 (100.0)
2961 (65.7) 1543 (34.3) 4504 (100.0)
3523 (51.7) 3297 (48.3) 6820 (100.0)
3189 (49.6) 3242 (50.4) 6431 (100.0)
2856 (44.1) 3625 (55.9) 6481 (100.0)
1915 (50.3) 1890 (49.7) 3805 (100.0)
16559 (50.1) 16484 (49.9) 33043 (100.0)
Table 2 Prevalence of Ml, PD and CI over time by gender Year
1998 Cases (%) 2000 Cases (%) 2002 Cases (%) 2005 Cases (%) 2008 Cases (%) 2011 Cases (%) Total Cases (%) P value 1 P value 2
Mental Impairment Male 449(18.2) Female 560(22.1) Total 1009(20.2) Physical disability Male Female Total Cognitive impairment Male Female Total
348(14.2) 294(14.4) 642(14.3)
615(15.6) 464(16.1) 1079(15.8)
496(13.3) 336(12.5) 832(12.9)
671(17.6) 475(17.8) 1146(17.7)
288(12.3) 128(8.8) 416(10.9)
2867(15.3) 2257(15.8) 5124(15.5)
0.005 0.000 0.000
0.096
951(24.1) 1107(38.5) 2058(30.2)
847(22.7) 863(32.0) 1710(26.6)
861(22.6) 853(32.0) 1714(26.4)
446(19.0) 442(30.4) 888(23.3)
3105(22.4) 3265(33.7) 6370(27.1)
0.000 0.000 0.000
0.000
320(8.1) 344(11.9) 664(9.7)
225(6.0) 209(7.8) 434(6.7)
288(7.5) 291(10.9) 579(8.9)
103(4.4) 65(4.5) 168(4.4)
936(6.8) 909(9.4) 1845(7.8)
0.000 0.000 0.000
0.000
Note: Mental impairment (MI) was defined by the MMSE criteria of SHANG HAI mental health center. Physical disability (PD) was defined as a need for assistance in two or more ADL activities. Cognitive impairment (CI) was defined when both MI and PDwere met the prior criteria. P value 1 was the result of Chi-square test for linear trend, which means the secular trends over time. P value 2 was the result of Pearson Chi-Square test which means the difference of prevalence between male and female.
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Podium Presentations: Sunday, July 19, 2015
Table 3 Trends of prevalence of MI, PD and CI overtime by resident area Year
1998 Cases (%) 2000 Cases (%) 2002 Cases (%) 2005 Cases (%) 2008 Cases (%) 2011 Cases (%) Total Cases (%) P value 1 P value 2
Mental Impairment Urban 419(19.85) Rural 590(20.4) Total 1009(20.2) Physical disability Urban Rural Total Cognitive impairment Urban Rural Total
435(14.7) 207(13.4) 642(14.3)
552(15.7) 527(16.0) 1079(15.8)
388(12.2) 444(13.7) 832(12.9)
497(17.4) 649(17.9) 1146(17.7)
207(10.8) 209(11.1) 416(10.9)
2498(15.1) 2626(15.9) 5124(15.5)
0.000 0.000 0.000
0.018
1061(30.1) 997(30.2) 2058(30.2)
894(28.0) 816(25.2) 1710(26.6)
776(27.2) 938(25.9) 1714(26.4)
463(24.2) 425(22.5) 888(23.3)
3194(27.8) 3176(26.3) 6370(27.1)
0.000 0.000 0.000
0.006
345(9.8) 319(9.7) 664(9.7)
197(6.2) 237(7.3) 434(6.7)
233(8.2) 346(9.5) 579(8.9)
99(5.2) 69(3.7) 168(4.4)
874(7.6) 971(8.1) 1845(7.8)
0.000 0.000 0.000
0.107
Note: Mental impairment (MI) was defined by the MMSE criteria of SHANG HAI mental health center. Physical disability (PD) was defined as a need for assistance in two or more ADL activities. Cognitive impairment (CI) was defined when both MI and PDwere met the prior criteria. P value 1 was the result of Chi-square test for linear trend, which means the secular trends over time. P value 2 was the result of Pearson Chi-Square test which means the difference of prevalence between urban and rural.
Figure 1. Trends of the prevalence of MI over time by different age groups.
Figure 3. Trends of the prevalence of CI over time by different age groups.
Figure 2. Trends of the prevalence of PD over time by different age groups
in the same age range in the CLHLS in 2002, 2005, 2008, 2011. The clinical screening for cognitive impairment (CI) was positive when both mental impairment (MI) by MMSE and physical disability (PD) by ADL score were met [“notes” in “Tables and Figures”]. Prevalence of MI, PD and CI was described to find their trends over time and differences between genders, age groups and urban/rural. Results: The prevalence of MI was 20.2%, 14.3%, 15.8%, 12.9%, 17.7%, 10.9% in 1998, 2000, 2002, 2005, 2008, 2011 respectively, that of PD was 30.2%, 26.6%, 26.4%, 23.3% and that of CI was 9.7%, 6.7%, 8.9%, 4.4% in 2002, 2005, 2008, 2011 respectively. In general, the three indexes were higher in female than in male, with the decline more evident in female than male, in rural than urban residents. The three indexes ascended as age grows older. Furthermore, rural residents had higher prevalence of MI and CI than urban residents, but lower prevalence of PD. Differentiated by age groups, the prevalence of MI fluctuated steadily in a small range over time; the prevalence of PD increased slightly in young-olds (60-69 years old) and decreased slowly in older-olds (80-109 years old), and the prevalence of CI decreased more evident in older-olds than in young-olds. Conclusions:
Podium Presentations: Sunday, July 19, 2015
The prevalence of MI, PD and CI among Chinese elderly in communities were deceasing during the last decade, consistence to existing literatures, with variation between male and female, urban/ rural residence and age groups. The decline in the three indexes over time was partly attributed to the confounding of age effects. Other possible factors associated the decline in prevalence are under investigation.
O1-09-06
HERPES SIMPLEX VIRUS, ANTI-HERPETIC MEDICATION, AND DEMENTIA: RESULTS FROM THE THREE-CITY POPULATION-BASED COHORT
Catherine Helmer1,2, Melanie Le Goff1,2, Catherine Feart1,2, Isabelle Garrigue3,4, Herve Fleury3,4, Claudine Berr5, Christophe Tzourio2,6, Luc Letenneur1,2, Jean-Franc¸ois Dartigues1,2,7, 1 INSERM U897, Bordeaux, France; 2Bordeaux University, Bordeaux, France; 3Laboratory of Virology, Bordeaux University, Bordeaux, France; 4 Laboratory of Virology, CHU Bordeaux, Bordeaux, France; 5INSERM U1061, Montpellier, France; 6INSERM U897, Bordeaux, France; 7Memory Consultation, CHU Bordeaux, Bordeaux, France. Contact e-mail: [email protected] Background: Herpes simplex virus (HSV) remains latent in sensitive
ganglia and could enhance the two main pathological lesions of AD, aß and hyperphosphorylated tau. Two previous cohorts have found a delayed increased risk of AD associated with a marker of HSV reactivation, the anti-HSV immunoglobulin M (IgM). Our objective was to replicate these results and to test if anti-herpetic medications could have a protective effect. Methods: Within the Three-City French population-based prospective cohort, we analyzed the occurrence of incident dementia over a 12-year period. Two subsamples of initially non-demented participants were considered: 1) 2341 participants with anti-HSV-IgM status available at baseline. 2) 3789 participants with available reimbursement claim data after the second follow-up; anti-herpetic medications were identified according to the ATC classification. The dementia cases were actively screened and diagnosed according to the DSM-IV criteria over the follow-up. Associations between anti-HSV-IgM status, anti-herpetic medications and dementia were assessed using Cox models adjusted on age, sex, ApoE4 and cardio-vascular factors. Because of the potential delayed increased risk, associations between anti-HSV-IgM status and dementia were analyzed both over the total follow-up period and specifically for long-term risk. Results: Participants with available anti-HSV-IgM status were 74y old, 60% were women, and 3.2% were IgM positive. Over the follow-up 513 incident demented were diagnosed. The risk of dementia associated with positive anti-HSV-IgM was not increased over the total 12-year period (HR¼1.1, p¼0.81), but increased progressively when analyzing long-term risk: HR¼1.4, p¼0.31 for dementia at or after the 7-year follow-up; HR¼2.1, p¼0.03 for dementia at or after the 10-year follow-up. Participants with available reimbursement claim data were 75y old, 66% were women, and 11.7% have at least one reimbursement for anti-herpetic medication. Over the follow-up 407 incident demented were diagnosed. Risk of dementia associated with anti-herpetic medications tended to decrease although not significantly (HR¼0.75, p¼0.14). Conclusions: Our data confirm the results observed in two previous cohorts, with an increased long-term risk of dementia for people with positive anti-HSV-IgM, possibly related to a viral reactivation. The results regarding anti-herpetic
P153
medications, although not significant, could represent a future strategy for the prevention of dementia.
SUNDAY, JULY 19, 2015 ORAL SESSIONS O1-10 CLINICAL: CLINICAL TRIAL DESIGN AND OUTCOME MEASURES O1-10-01
ESTIMATING EFFECT SIZE OF APOE GENOTYPE ON ALZHEIMER’S DISEASE PROGRESSION TO DETERMINE THE LIKELY IMPACT ON CLINICAL TRIAL DESIGN
Sheng Feng, Biogen, Cambridge, MA, USA. Contact e-mail: sheng.feng@ biogenidec.com Background: APOE has shown consistent association with Alzheimer’s Disease with an increased risk of disease of approximately 5 fold per ε4 allele. We wanted to better understand the relationship between APOE genotype and various parameters that are measured in AD clinical trials to determine whether APOE genotype might influence outcomes and whether this might inform recruitment strategy into clinical trials. Methods: Using ADNI data (demographic, clinical, neurological, imaging, protein/CSF, genetics),
Figure 1. Over six years, cognitive decline rates are different by ApoE status in MCI population, but the magnitude of change is small at year 2 or 3 (two vertical lines). No difference in Normal and AD population.
Figure 2. Over six years, cognitive decline rates are different by ApoE status in MCI population, but the magnitude of change is small at year 2 or 3 (two vertical lines). No difference in Normal and AD population.
construct representative indicators (e.g. level of income, education, rate of unemployment, urbanization, access to services...). All variables estimated at community level were transformed into tertiles (T1-T2-T3). The dementia cases were actively diagnosed according to the DSM-IV criteria and validated by an independent expert committee. Associations between dementia and community factors were assessed with the marginal Cox model with delayed entry and age as the time scale, including sex and individual education as confounding factors. Results: During the follow-up, 934 dementia cases were identified. Risk of dementia is increased in participants living in neighborhoods with a higher proportion of laborers (T3/T1 HR¼1.20[1.01; 1.43], p¼0.04), or unemployed (T3/T1 HR¼1.22 [1.03; 1.44], p¼0.02). On the opposite, living in high income neighborhoods is associated with lower risk (T3/T1 HR¼0.81[0.68; 0.95], p¼0.01). In neighborhoods with intermediate proportion of elderly, risk of dementia is decreased (T2/T1 HR¼0.79[0.67; 0.95], p¼0.01) while there is no significant difference for those with highest proportion of elderly (T3/T1 HR ¼0.87 [0.73-1.04], p¼0.12). Conclusions: Independently of age, sex and individual level of education, some factors reflecting socioeconomic disadvantage of the area where subjects are living are associated with dementia risk. Understanding how environmental factors may
P151
influence this risk is a challenge as they can be a proxy for the quality of social environment or related to deprivation of basic activities including cognitive stimulation.
O1-09-05
THE EPIDEMIOLOGICAL STUDY OF COGNITIVE FUNCTION AMONG CHINESE COMMUNITYDWELLING ELDERLY PEOPLE, 1998-2011: THE CHINESE LONGITUDINAL HEALTHY LONGEVITY SURVEY
Mingyue Gao1, Min Yang2, Peiyuan Qiu2, Weihong Kuang3, 1West China School of Public Health, Sichuan University, Chengdu, China; 2School of Public Health, West China Research Center for Rural Health Development, Sichuan University, Chengdu, China; 3Mental Health Center of West China of Sichuan University, Chengdu, China. Contact e-mail: [email protected] Background: The prevalence of cognitive impairment in western
countries decreased in past twenty years. It is still unclear how the index changes over time in China. Methods: The study examined Mini-Mental State Examination (MMSE) status of 33,043 participants aged at 60 years or older in the Chinese Longitudinal Healthy Longevity Surveys (CLHLS) in 1998, 2000, 2002, 2005, 2008, 2011, and Activities of Daily Living (ADLs) of 23,537 participants
Table 1 Demographic characteristics of individuals participating in CLHLS Year Gender Male Female Age group 60w69 years 70w79 years 80w89 years 90w99 years 100w109 years 110years Resident Urban Rural Total
1998 N (%)
2000 N (%)
2002 N (%)
2005 N (%)
2008 N (%)
2011 N (%)
Total N (%)
2465 (49.3) 2537 (50.7)
2459 (54.6) 2045 (45.4)
3941 (57.8) 2879 (42.4)
3735 (58.1) 2696 (41.9)
3815 (58.9) 2666 (41.1)
2351 (61.8) 1454 (38.2)
18766 (56.8) 14277 (43.2)
-
-
107 (2.1) 2585 (51.7) 1549 (31.0) 755 (15.1) 6 (0.1)
24 (0.5) 2759 (61.3) 1330 (29.5) 387 (8.6) 4 (0.1)
1218 (17.9) 2043 (30.0) 2033 (29.8) 1055 (15.5) 469 (6.9) 2 (0.0)
1279 (19.9) 2096 (32.6) 1709 (26.6) 1032 (16.0) 314 (4.9) 1 (0.0)
1287 (19.9) 1858 (28.7) 1820 (28.1) 1139 (17.6) 375 (5.8) 2 (0.0)
548 (14.4) 1525 (40.1) 1030 (27.1) 546 (14.3) 154 (4.0) 2 (0.1)
4332 (13.1) 7653 (23.2) 11936 (36.1) 6651 (20.1) 2454 (7.4) 17 (0.1)
2115 (42.3) 2887 (57.7) 5002 (100.0)
2961 (65.7) 1543 (34.3) 4504 (100.0)
3523 (51.7) 3297 (48.3) 6820 (100.0)
3189 (49.6) 3242 (50.4) 6431 (100.0)
2856 (44.1) 3625 (55.9) 6481 (100.0)
1915 (50.3) 1890 (49.7) 3805 (100.0)
16559 (50.1) 16484 (49.9) 33043 (100.0)
Table 2 Prevalence of Ml, PD and CI over time by gender Year
1998 Cases (%) 2000 Cases (%) 2002 Cases (%) 2005 Cases (%) 2008 Cases (%) 2011 Cases (%) Total Cases (%) P value 1 P value 2
Mental Impairment Male 449(18.2) Female 560(22.1) Total 1009(20.2) Physical disability Male Female Total Cognitive impairment Male Female Total
348(14.2) 294(14.4) 642(14.3)
615(15.6) 464(16.1) 1079(15.8)
496(13.3) 336(12.5) 832(12.9)
671(17.6) 475(17.8) 1146(17.7)
288(12.3) 128(8.8) 416(10.9)
2867(15.3) 2257(15.8) 5124(15.5)
0.005 0.000 0.000
0.096
951(24.1) 1107(38.5) 2058(30.2)
847(22.7) 863(32.0) 1710(26.6)
861(22.6) 853(32.0) 1714(26.4)
446(19.0) 442(30.4) 888(23.3)
3105(22.4) 3265(33.7) 6370(27.1)
0.000 0.000 0.000
0.000
320(8.1) 344(11.9) 664(9.7)
225(6.0) 209(7.8) 434(6.7)
288(7.5) 291(10.9) 579(8.9)
103(4.4) 65(4.5) 168(4.4)
936(6.8) 909(9.4) 1845(7.8)
0.000 0.000 0.000
0.000
Note: Mental impairment (MI) was defined by the MMSE criteria of SHANG HAI mental health center. Physical disability (PD) was defined as a need for assistance in two or more ADL activities. Cognitive impairment (CI) was defined when both MI and PDwere met the prior criteria. P value 1 was the result of Chi-square test for linear trend, which means the secular trends over time. P value 2 was the result of Pearson Chi-Square test which means the difference of prevalence between male and female.
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Podium Presentations: Sunday, July 19, 2015
Table 3 Trends of prevalence of MI, PD and CI overtime by resident area Year
1998 Cases (%) 2000 Cases (%) 2002 Cases (%) 2005 Cases (%) 2008 Cases (%) 2011 Cases (%) Total Cases (%) P value 1 P value 2
Mental Impairment Urban 419(19.85) Rural 590(20.4) Total 1009(20.2) Physical disability Urban Rural Total Cognitive impairment Urban Rural Total
435(14.7) 207(13.4) 642(14.3)
552(15.7) 527(16.0) 1079(15.8)
388(12.2) 444(13.7) 832(12.9)
497(17.4) 649(17.9) 1146(17.7)
207(10.8) 209(11.1) 416(10.9)
2498(15.1) 2626(15.9) 5124(15.5)
0.000 0.000 0.000
0.018
1061(30.1) 997(30.2) 2058(30.2)
894(28.0) 816(25.2) 1710(26.6)
776(27.2) 938(25.9) 1714(26.4)
463(24.2) 425(22.5) 888(23.3)
3194(27.8) 3176(26.3) 6370(27.1)
0.000 0.000 0.000
0.006
345(9.8) 319(9.7) 664(9.7)
197(6.2) 237(7.3) 434(6.7)
233(8.2) 346(9.5) 579(8.9)
99(5.2) 69(3.7) 168(4.4)
874(7.6) 971(8.1) 1845(7.8)
0.000 0.000 0.000
0.107
Note: Mental impairment (MI) was defined by the MMSE criteria of SHANG HAI mental health center. Physical disability (PD) was defined as a need for assistance in two or more ADL activities. Cognitive impairment (CI) was defined when both MI and PDwere met the prior criteria. P value 1 was the result of Chi-square test for linear trend, which means the secular trends over time. P value 2 was the result of Pearson Chi-Square test which means the difference of prevalence between urban and rural.
Figure 1. Trends of the prevalence of MI over time by different age groups.
Figure 3. Trends of the prevalence of CI over time by different age groups.
Figure 2. Trends of the prevalence of PD over time by different age groups
in the same age range in the CLHLS in 2002, 2005, 2008, 2011. The clinical screening for cognitive impairment (CI) was positive when both mental impairment (MI) by MMSE and physical disability (PD) by ADL score were met [“notes” in “Tables and Figures”]. Prevalence of MI, PD and CI was described to find their trends over time and differences between genders, age groups and urban/rural. Results: The prevalence of MI was 20.2%, 14.3%, 15.8%, 12.9%, 17.7%, 10.9% in 1998, 2000, 2002, 2005, 2008, 2011 respectively, that of PD was 30.2%, 26.6%, 26.4%, 23.3% and that of CI was 9.7%, 6.7%, 8.9%, 4.4% in 2002, 2005, 2008, 2011 respectively. In general, the three indexes were higher in female than in male, with the decline more evident in female than male, in rural than urban residents. The three indexes ascended as age grows older. Furthermore, rural residents had higher prevalence of MI and CI than urban residents, but lower prevalence of PD. Differentiated by age groups, the prevalence of MI fluctuated steadily in a small range over time; the prevalence of PD increased slightly in young-olds (60-69 years old) and decreased slowly in older-olds (80-109 years old), and the prevalence of CI decreased more evident in older-olds than in young-olds. Conclusions:
Podium Presentations: Sunday, July 19, 2015
The prevalence of MI, PD and CI among Chinese elderly in communities were deceasing during the last decade, consistence to existing literatures, with variation between male and female, urban/ rural residence and age groups. The decline in the three indexes over time was partly attributed to the confounding of age effects. Other possible factors associated the decline in prevalence are under investigation.
O1-09-06
HERPES SIMPLEX VIRUS, ANTI-HERPETIC MEDICATION, AND DEMENTIA: RESULTS FROM THE THREE-CITY POPULATION-BASED COHORT
Catherine Helmer1,2, Melanie Le Goff1,2, Catherine Feart1,2, Isabelle Garrigue3,4, Herve Fleury3,4, Claudine Berr5, Christophe Tzourio2,6, Luc Letenneur1,2, Jean-Franc¸ois Dartigues1,2,7, 1 INSERM U897, Bordeaux, France; 2Bordeaux University, Bordeaux, France; 3Laboratory of Virology, Bordeaux University, Bordeaux, France; 4 Laboratory of Virology, CHU Bordeaux, Bordeaux, France; 5INSERM U1061, Montpellier, France; 6INSERM U897, Bordeaux, France; 7Memory Consultation, CHU Bordeaux, Bordeaux, France. Contact e-mail: [email protected] Background: Herpes simplex virus (HSV) remains latent in sensitive
ganglia and could enhance the two main pathological lesions of AD, aß and hyperphosphorylated tau. Two previous cohorts have found a delayed increased risk of AD associated with a marker of HSV reactivation, the anti-HSV immunoglobulin M (IgM). Our objective was to replicate these results and to test if anti-herpetic medications could have a protective effect. Methods: Within the Three-City French population-based prospective cohort, we analyzed the occurrence of incident dementia over a 12-year period. Two subsamples of initially non-demented participants were considered: 1) 2341 participants with anti-HSV-IgM status available at baseline. 2) 3789 participants with available reimbursement claim data after the second follow-up; anti-herpetic medications were identified according to the ATC classification. The dementia cases were actively screened and diagnosed according to the DSM-IV criteria over the follow-up. Associations between anti-HSV-IgM status, anti-herpetic medications and dementia were assessed using Cox models adjusted on age, sex, ApoE4 and cardio-vascular factors. Because of the potential delayed increased risk, associations between anti-HSV-IgM status and dementia were analyzed both over the total follow-up period and specifically for long-term risk. Results: Participants with available anti-HSV-IgM status were 74y old, 60% were women, and 3.2% were IgM positive. Over the follow-up 513 incident demented were diagnosed. The risk of dementia associated with positive anti-HSV-IgM was not increased over the total 12-year period (HR¼1.1, p¼0.81), but increased progressively when analyzing long-term risk: HR¼1.4, p¼0.31 for dementia at or after the 7-year follow-up; HR¼2.1, p¼0.03 for dementia at or after the 10-year follow-up. Participants with available reimbursement claim data were 75y old, 66% were women, and 11.7% have at least one reimbursement for anti-herpetic medication. Over the follow-up 407 incident demented were diagnosed. Risk of dementia associated with anti-herpetic medications tended to decrease although not significantly (HR¼0.75, p¼0.14). Conclusions: Our data confirm the results observed in two previous cohorts, with an increased long-term risk of dementia for people with positive anti-HSV-IgM, possibly related to a viral reactivation. The results regarding anti-herpetic
P153
medications, although not significant, could represent a future strategy for the prevention of dementia.
SUNDAY, JULY 19, 2015 ORAL SESSIONS O1-10 CLINICAL: CLINICAL TRIAL DESIGN AND OUTCOME MEASURES O1-10-01
ESTIMATING EFFECT SIZE OF APOE GENOTYPE ON ALZHEIMER’S DISEASE PROGRESSION TO DETERMINE THE LIKELY IMPACT ON CLINICAL TRIAL DESIGN
Sheng Feng, Biogen, Cambridge, MA, USA. Contact e-mail: sheng.feng@ biogenidec.com Background: APOE has shown consistent association with Alzheimer’s Disease with an increased risk of disease of approximately 5 fold per ε4 allele. We wanted to better understand the relationship between APOE genotype and various parameters that are measured in AD clinical trials to determine whether APOE genotype might influence outcomes and whether this might inform recruitment strategy into clinical trials. Methods: Using ADNI data (demographic, clinical, neurological, imaging, protein/CSF, genetics),
Figure 1. Over six years, cognitive decline rates are different by ApoE status in MCI population, but the magnitude of change is small at year 2 or 3 (two vertical lines). No difference in Normal and AD population.
Figure 2. Over six years, cognitive decline rates are different by ApoE status in MCI population, but the magnitude of change is small at year 2 or 3 (two vertical lines). No difference in Normal and AD population.