1. ABSTRACT  Prevalence of dementia is over 10% in those > 65 years, and almost 50% in those > 85.  The fastest growing segment of the U.S. population is those age 85 years and older.  Studies have shown that hypertension in mid- life is a strong predictor for the development of dementia in late life.  Studies have been mixed about the cross- sectional and longitudinal relationships between late life blood pressure and cognition. Some studies have found a “U” shaped association, with worse cognitive function at both extremes of blood pressure.  Few have studied the association between blood pressure and cognitive decline in very old age (> 80 years). Introduction: Hypertension in mid-life is a strong predictor of subsequent dementia. The relationship between blood pressure (BP) in late life and cognitive function is less understood, especially for low BP. We studied the association between low BP and cognitive function over 6 years. Methods: The Honolulu-Asia Aging Study began in 1991-93, when 3734 Japanese-American men ages 71-93 years were administered the Cognitive Abilities Screening Instrument (CASI). CASI scores ranged from 0-100, and 3-year and 6-year cognitive decline were defined as a drop in score of >=10 or >=14 points, respectively (1 SD). BP was measured by standard manometer and mean of two readings was used. Subjects were divided into 4 groups for systolic (SBP): <120, 120-139, 140-159, and ≥160 mmHg; and 3 groups for diastolic (DBP): <80, 80-89, and ≥90 mmHg. Analyses used chi square, GLM, logistic regression, mixed models for change in CASI and Cox proportional hazards models. Results: The prevalence of dementia was 6%, and an additional 10% had cognitive impairment (CASI <74). Prevalent dementia and cognitive impairment were more common in low SBP (<120 mmHg) and low DBP (<80 mmHg) groups (p<0.0001). Multiple logistic regression analyses adjusting for age, education, apoE4, stroke, diabetes and smoking found that low SBP was significantly associated with prevalent dementia (OR=2.70, 95% CI=1.68-4.35, p<0.0001), with normal SBP (120-139) as reference. Those with low SBP were more likely to have prevalent Alzheimer ’ s Disease (OR=2.20, 95% CI=1.04-4.66, p=0.04), but not vascular or mixed/other dementias. Multivariate models found no association between low SBP or low DBP and cognitive decline or incident dementia over 6 years. Those with low SBP had significantly higher rates of prevalent CHD, stroke and functional impairment, suggesting that the association with prevalent dementia may be due to chronic disease rather than causal. Conclusion: Low SBP in late life had a significant association with prevalent dementia and Alzheimer ’ s Disease, but not cognitive decline or incident dementia. Those with low BP were significantly sicker and no longer reflected a healthy group of elderly subjects. The Honolulu Heart Program (HHP)  Began in 1965 to study cardiovascular diseases in 8,006 Japanese-American men living on Oahu, Hawaii  Ages 45 to 68 years at baseline (born 1900-1919)  42-year longitudinal follow-up with serial examinations, review of hospital and death records The Honolulu-Asia Aging Study (HAAS)  Began with the fourth HHP examination (1991-93) to study cognitive function and other diseases of aging  3,734 men ages 71-93 years examined (80% of survivors)  Follow-up at 3 years (exam 5, 1994-96) and 6 years (exam 6, 1997-99) for cognitive decline and dementia Cognitive Abilities Screening Instrument (CASI) A comprehensive measure of global intellectual function Developed for use in cross-cultural and cross-national studies to test 9 cognitive domains Scores range from 0-100, higher scores are better Outcomes:  Cognitive impairment No Dementia (CIND): CASI <74  3-Year cognitive decline (3Y CD): Drop in CASI > 10 points (1 SD); 541/2693 (20.1%)  6-Year cognitive decline (6Y CD): Drop in CASI > 14 points (1 SD); 409/1982 (20.6%)  Dementia: DSM III/R criteria  Alzheimer’s Disease (AD): NINDS-ADRDA criteria  Vascular Dementia (VD): California ADDTC criteria Blood Pressure (BP)  Mean of 2 readings measured by standard manometer  4 groups for systolic BP (SBP) and 3 groups for diastolic BP (DBP) (data not shown for DBP)  To study the cross-sectional association between low blood pressure in late life and cognitive impairment and prevalent dementia and its subtypes  To study the longitudinal association between low blood pressure in late life and 6-year cognitive decline and incident dementia and its subtypes METHODS RESULTS Gina Fujikami, MSIV; Kamal Masaki, MD; Randi Chen, MS; Irwin Schatz, MD; Danielle Laurin, PhD; Robert Abbott, PhD; G. Webster Ross, MD; Helen Petrovitch, MD; Lon White, MD, MPH; Patricia Lanoie Blanchette, MD, MPH; Lenore Launer, PhD. The research reported on this poster was supported by: The Hawaii Medical Student Aging Research National Training Center (National Institute on Aging, John A. Hartford Foundation and American Federation for Aging Research grant), Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Pacific Health Research Institute, Honolulu Department of Veteran Affairs, National Institute on Aging, National Heart, Lung, and Blood Institute. The investigators retained full independence in the conduct of this research. Association Between Low Blood Pressure and Cognitive Function in Late Life: The Honolulu-Asia Aging Study. INTRODUCTION Statistical Methods  Chi square for categorical variables, Spearman correlations and GLM models for continuous variables  Prevalent cases of dementia were excluded for all longitudinal analyses (cognitive decline and incidence)  Multiple logistic regression models for prevalence and for cognitive decline  Cox proportional hazards models for incidence  All multivariate models were adjusted for age, education, apoE4, stroke, diabetes and smoking status  Subgroup analyses were performed for those with or without Prevalent Chronic Diseases (Cancer, Coronary heart disease, Stroke, Diabetes) or Functional impairment (FI) (defined as difficulty walking ½ mile) CIND and Prevalent Dementia by SBP GroupsCognitive Decline and Incident Dementia by SBP Groups RESULTS CONCLUSIONS Multiple Logistic Regression Models for Prevalent CIND and Dementia  Prevalent dementia and cognitive impairment were more common in elderly men with low SBP in late life.  Low SBP in late life had a significant association with prevalent dementia and its subtypes.  SBP in late life did not have a significant association with cognitive decline over 3 or 6 years, incident dementia, or its subtypes with the exception of vascular dementia, which was associated with high SBP.  Low SBP was significantly associated with several chronic diseases and with functional impairment, which at least partly explained the cross- sectional association with cognitive impairment and prevalent dementia.  There were no significant associations between low DBP and cognitive function after adjustment for covariates. DISCUSSION Strengths  Large population-based study  Long follow-up period  Unique population of elderly Japanese- American men  Few previous studies available in very old ages and in minority populations Limitations  Generalizability was limited, since subjects were only Japanese-American men  Unable to infer cause and effect (observational study) Possible Mechanisms  Previous studies have hypothesized that low blood pressure may cause cognitive impairment and dementia. However, in our study, low blood pressure reflected a state of chronic disease and frailty, which may account for the association with dementia. Future Directions  Other longitudinal studies should stratify for chronic disease and frailty status  Anti-hypertensive medications may modify the association between BP and cognition and should be taken into account Late Life SBP Groups (mmHg) <120120-139140-159> 160 316/3734 (8.47%) 1029/3734 (27.59%) 1216/3734 (32.60%) 1169/3734 (31.34%) Cognitive Impairment No Dementia (CIND) Prevalent Dementia (All) Prevalent Alzheimer’s Disease Prevalent Vascular Dementia Prevalent Other Dementia OR95% CIp-valueOR95% CIp-valueOR95% CIp-valueOR95% CIp-valueOR95% CIp-value SBP<1201.410.89-2.260.152.701.68-4.35<0.00012.201.04-4.660.040.770.20-2.970.712.530.42-15.30.31 SBP 120-139111111111111111 SBP 140-1590.810.58-1.120.211.010.67-1.520.98 0.53-1.790.940.570.24-1.380.211.020.23-4.570.98 SBP>=1600.640.46-0.890.0080.620.41-0.950.030.420.21-0.840.010.640.29-1.410.270.450.07-2.780.39 6-Year Cognitive Decline Incident Dementia (All) Incident Alzheimer’s Disease Incident Vascular Dementia Other Incident Dementia OR95% CIp-valueRR95% CIp-valueRR95% CIp-valueRR95% CIp-valueRR95% CIp-value SBP<1201.210.74-1.970.451.110.60-2.050.731.480.72-3.020.290.820.10-7.100.860.570.13-2.500.45 SBP 120-139111111111111111 SBP 140-1591.020.75-1.380.901.00.69-1.440.990.870.54-1.410.320.960.48-1.950.920.960.48-1.950.92 SBP>=1601.190.88-1.610.270.830.56-1.230.350.470.27-0.840.013.631.36-9.670.010.590.27-1.300.19 METHODS Prevalent Chronic Diseases by SBP Groups CIND and Prevalent Dementia by SBP Groups, Stratified by Those WITH Chronic Disease Only p<0.0001 p=0.03 p=0.11 p=0.17 p=0.82 p=0.19 p=0.002p=0.68 p=0.88 p=0.007 p=0.01 p=0.0004 p<0.0001 p=0.03 OBJECTIVES Multiple Logistic Regression Models for Cognitive Decline and Cox Proportional Hazards Models for Incident Dementia