SIMULTANEOUS CHANGES IN BLOOD PRESSURE, COGNITION AND BRAIN VOLUME IN AGEING, MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE

Abstract

Hypertension is associated with reduced brain volume, higher future dementia risk, and greater Alzheimer's disease (AD) pathology. However, average blood pressure (BP) is lower in people with AD than in controls. Understanding whether changes in BP, cognition and brain volume occur simultaneously could inform strategies for AD prevention and management. Using data from two cohorts, we investigated whether baseline BP predicted baseline and changes in cognition, and the correlation between changes in cognition, BP and brain volume change (atrophy). Alzheimer's Disease Neuroimaging Initiative 1 participants were investigated: 198 controls, 345 MCI and 154 ADs. National Alzheimer Co-ordinating Center participants were separately investigated; 1,098 controls, 1,126 mild cognitive impairment (MCI) and 5,100 AD subjects. Multivariate mixed linear regression models were fitted with outcomes of BP (systolic, diastolic and pulse pressure), MMSE and atrophy (whole brain, hippocampus). Analyses were adjusted for age, gender, APOE genotype, head-size (for atrophy) and antihypertensive use (NACC only). A random intercept (BP, MMSE) and random slope (all outcomes) were included for participant level with unstructured covariance to allow for correlations between all random effects. Likelihood ratio tests were used to examine the evidence for the correlation between baseline values of outcomes and the evidence for correlation between change in (Δ) outcomes. In ADNI, higher hippocampal atrophy was associated with greater baseline systolic ((r, p value); 0.2, p=0.004) and pulse pressure (0.2, p=0.007) in MCIs; no associations were found in controls. In NACC, higher baseline systolic BP was associated with lower baseline MMSE in MCIs (-0.23, <0.001); falling MMSE was predicted by falling systolic (0.35, p<0.001) and pulse pressure (0.34, p=0.001). Conversely, in AD patients, lower MMSEs were associated with lower systolic (0.10, p<0.001), diastolic (0.06, p=0.05), and pulse pressure (0.08, p=0.01). These results suggest whilst high BP may be associated with AD development, falling BP may be important in the mid-late AD stages; MCIs with falling BP were more likely to worsen on MMSE, and AD subjects with low systolic BP more likely to have lower baseline MMSEs. Further work is required to understand whether this could inform AD management and prevention strategies.