1. Is anxiety a risk factor for dementia? John Gallacher Tony Bayer Mark Fish Yoav Ben-Shlomo Frank Dunstan Active ageing research group: www.activeageing.co.uk

7. CaPS: Methods Total cohort –2,959 men aged 45-59 at recruitment Measures at C2 (2 nd examination: C1 + 5 years) –Trait anxiety (STAI) –Vascular risk factors –CHD –Demographics Measures at C3 (C2 + 5 years) –NART (pre-morbid cognitive function) Measures at C5 (C2 + 17 years: men aged 67-81 years) –Cognitive impairment: CIND, Dementia

8. Statistical analysis Logistic regression Outcomes: –Overall impairment (CIND + Dementia) –CIND –Dementia Adjustment for covariates: – age, sbp, cholesterol, alcohol consumption –social class, marital status, smoking, diabetes, leisure activity Adjustment for pre-morbid cognitive function –NART at C3

10. Available data: Sample size main analysis men with complete covariate data Cog. healthyVascularNon vascular Total Cog. healthy78300 CIND02999128 Dementia0333871 Total78362137982

11. Available data: Sample size 2 0 analysis men with complete covariate data and no evidence of decline at baseline Cog. healthyVascularNon vascular Total Cog. healthy65500 CIND0166581 Dementia071219 Total6552377755

12. Distribution of Trait Anxiety

13. Anxiety and cognitive impairment 31 st -95 th centile in 982 men with complete data Severity of impairment Adjusted for ageAdjusted for age + vascular risk Adjusted for age +vascular risk +pre-morbid CF All impairment 2.87 (1.68, 4.88) p<0.001 2.60 (1.50, 4.51) p=0.001 2.19 (1.24, 3.88) p=0.007 CIND only 2.85 (1.55, 5.26) p=0.001 2.62 (1.39, 4.94) p=0.003 2.31 (1.20, 4.44) p=0.012 Dementia only 2.89 (1.28, 6.54) p=0.11 2.73 (1.16, 6.45) p=0.022 2.37 (0.98, 5.71) p=0.056

14. Anxiety and all cognitive impairment 31 st -95 th centile in 755 men with complete data Type of impairment Adjusted for ageAdjusted for age + vascular risk Adjusted for age +vascular risk +pre-morbid CF Non Vascular 3.81 (2.17, 6.70) p<0.001 3.38 (1.89, 6.05) p<0.001 2.45 (1.28, 4.68) p=0.007 Vascular 2.21 (1.01, 4.84) p=0.047 1.95 (0.85, 4.49) p=0.117 1.94 (0.77, 4.89) p=0.160

15. Anxiety and CIND 31 st -95 th centile in 755 men with complete data Type of impairment Adjusted for ageAdjusted for age + vascular risk Adjusted for age +vascular risk +pre-morbid CF Non Vascular 4.00 (2.16, 7.42) p<0.001 3.56 (1.88, 6.74) p<0.001 2.70 (1.33, 5.51) p=0.006 Vascular 2.00 (0.67, 5.97) p=0.214 1.80 (0.57, 5.70) p=0.321 1.18 (0.31, 4.56) p=0.807

16. Anxiety and Dementia 31 st -95 th centile in 755 men with complete data Type of impairment Adjusted for ageAdjusted for age + vascular risk Adjusted for age +vascular risk +pre-morbid CF Non Vascular 3.12 (1.12, 8.70) p<0.030 2.83 (0.97, 8.221) P=0.056 1.97 (0.60, 6.50) p=0.267 Vascular 2.69 (0.96, 7.59) p=0.061 2.28 (0.75, 6.96) p=0.147 3.38 (1.02, 11.2) p=0.046

17. Anxiety and cognitive impairment 31 st -95 th centile in 755 men with complete data and no evidence of decline at baseline Severity of impairment Adjusted for ageAdjusted for age + vascular risk Adjusted for age +vascular risk +pre-morbid CF All impairment 4.02 (2.05, 7.91) p<0.001 3.76 (1.84, 7.69) p<0.001 3.36 (1.61, 7.01) p=0.001 CIND only 3.75 (1.82, 7.76) p<0.001 3.60 (1.67, 7.79) p=0.001 3.32 (1.51, 7.31) p=0.003 Dementia only 5.03 (1.24, 20.5) p=0.024 4.24 (0.92, 20.0) p=0.065 3.60 (0.74, 17.4) p=0.112

18. Conclusion Anxiety is associated with cognitive impairment –Duration of follow-up (17 yrs) suggests causal association –Insidious nature of cognitive decline means reverse causality cannot be ruled out –No control for depression: association may not be independent –Analyses for dementia likely to be conservative due to survivor effect –Some evidence that effect is stronger for non- vascular dementia

19. Further work: “Age well, feel good” Pilot Study: –October 2008-March 2009 –3,000 older persons: 60+ years 15,000 mailed invitations Web links from interest groups –Remote Recruitment (web) Consent(web) Assessment(web) Bio-sampling(mail) Follow-up(record linkage)

20. www.activeageing.co.uk

21. Anxiety and all cognitive impairment 31 st -95 th centile in 755 men with complete data and no evidence of decline at baseline Type of impairment Adjusted for ageAdjusted for age + vascular risk Adjusted for age +vascular risk +pre-morbid CF Non Vascular 4.32 (2.08, 8.95) p<0.001 4.13 (1.91, 8.96) p<0.001 3.65 (1.61, 8.28) p=0.002 Vascular 3.17 (0.90, 11.2) p=0.073 2.81 (0.71, 11.1) p=0.141 2.76 (0.68, 11.1) p=0.155

22. Anxiety and CIND 31 st -95 th centile in 755 men with complete data and no evidence of decline at baseline Type of impairment Adjusted for ageAdjusted for age + vascular risk Adjusted for age +vascular risk +pre-morbid CF Non Vascular 4.78 (2.24, 10.2) p<0.001 4.73 (2.10, 10.7) p<0.001 4.23 (1.78, 10.0) p=0.001 Vascular 1.24 (0.23, 6.72) p=0.806 1.05 (0.17, 6.47) p=0.957 1.08 (0.17, 6.73) p=0.935

23. Anxiety and dementia 31 st -95 th centile in 755 men with complete data and no evidence of decline at baseline Type of impairment Adjusted for ageAdjusted for age + vascular risk Adjusted for age +vascular risk +pre-morbid CF Non Vascular 1.83 (0.25, 13.4) P=0.549 1.42 (0.17, 12.0) P=0.750 1.23 (0.14, 11.1) p=0.851 Vascular 15.6 (2.00, 121) p=0.009 20.8 (1.71, 253) p=0.017 19.2 (1.41, 751) p=0.063