To examine the relationship between blood pressure change and amyloid- and tau-PET abnormalities in cognitively healthy adults.

There is an increasing awareness of the role of BP variability in risk of clinical dementia. Prior studies have reported associations between greater lifetime SBP variability, greater DBP variability (at both mid- and late-life), and a steep decline in SBP (between mid- and late-life), and an increased risk of incident dementia. However, whether BP variation is associated with neuroimaging markers of preclinical dementia, namely amyloid and tau burden on brain PET, is less well explored.

Dementia-free Framingham Heart Study Offspring (Gen 2) and 3^rd generation (Gen 3) cohort participants with available data on remote (Gen 2, 2005-2008; Gen 3, 2002-2005) and recent (Gen 2, 2019-2022; Gen 3, 2016-2019) BP who participated in ¹¹C-Pittsburgh Compound-B (PiB)-PET and/or ¹⁸F-Flortaucipir (FTP)-PET brain scans between 2016 to 2022. Multivariable linear regression was performed to examine the relationship between blood pressure and radiological changes.

The sample included 397 participants, including 41 Gen 2 participants (49% female, mean age 71+/- SD [standard deviation)) and 356 Gen 3 participants (51% female, mean age 55+/- SD 8). The median time between initial BP measurement and PET was 15 years. On multivariable linear regression analysis, a steep decline in DBP was associated with increased tau and amyloid deposition in the entorhinal cortex (p=0.04) but not any other brain regions. BP trajectories were not associated were amyloid deposition in any brain region.

In cognitively healthy adults, the development of hypertension in previously normotensive individuals and a steep decline in DBP over a median of 15 years were associated with preclinical entorhinal tau deposition, one of the earliest affected regions in Alzheimer’s disease. Maintenance of normotension in mid to late-life may reflect an important target for reducing the risk of preclinical tau deposition.