The number of people with dementia worldwide is expected to rise to 150 million in 2050. Prevention of dementia is a major public health challenge and a research priority has been the identification of potentially modifiable risk factors. Among them, hypertension (HTN) in midlife is associated with higher risk of cognitive decline and dementia in later life but data on late-life HTN and cognitive health remain inconsistent. HTN may be protective on dementia risk among the oldest old, possibly due to higher brain perfusion. Whether high blood pressure (BP) prior to midlife affects risk of late-onset dementia is unclear. In addition, young patients with early-onset HTN are paradoxically less likely to receive aggressive BP treatment. Studies with a life-course approach are needed to characterize the effects of HTN and BP lowering strategies, which optimal timing to optimize cognitive health is still under investigation. Identifying optimal BP levels in patients with HTN to preserve brain health is an added challenge. Independently of cognitive impairment and dementia prevention, controversies exist regarding HTN treatment guidelines for optimal BP targets, including in older adults where American guidelines recommend a systolic BP (SBP) goal < 130 mmHg and European guidelines 130-139 mmHg. These controversies might influence primary prevention of a large group of HTN-related diseases, including cognitive impairment and dementia. The question of whether BP lowering strategies could benefit cognitive health has been tested in randomized controlled trials (RCT) with inconclusive results. Although the SPRINT-MIND trial has suggested that intensive (SBP goal < 120 mmHg) compared to standard treatment (SBP goal < 140 mmHg), could significantly reduce the risk of mild cognitive impairment (MCI), a recent meta-analysis of RCT was unable to identify an optimal BP range for dementia prevention. Further research is also needed to assess whether age-specific BP thresholds and treatment effects differ across population subgroups and comorbidities, and which individuals could benefit most from BP lowering. Higher midlife SBP could be associated with greater risk of dementia in women, compared to men. Similar to dementia, HTN disproportionally affects Black individuals, whose higher cumulative BP levels could contribute to racial differences in later-life cognitive decline. To date, target SBP guidelines have not addressed the potential that Black patients may have greater morbidity from HTN, especially with regard to cognitive outcomes. ApoE ε4 genotype may potentiate cognitive decline in individuals with HTN; whether ApoE ε4 carriers would benefit more for cognitive health from an intensive BP control is unknown. As patients with high enough cardiovascular risk were excluded from SPRINT-MIND, whether individualized SBP targets in patients with cardiometabolic comorbidities impacts cognitive health needs further investigation. Finally, clinical guidelines on HTN recommend considering frailty in individual HTN management; however, to what extent BP lowering treatment benefits very frail patients remains to be determined. Our research aims to (1) investigate the association of age-specific SBP targets across the life-course with domain-specific cognitive trajectories and incident dementia in treated hypertensive patients and (2) to investigate whether these associations differ by (a) sex, race, ApoE ε4 genotype and (b) diabetes, chronic kidney disease, cardiovascular disease, and frailty. We will use data from 3 longitudinal cohort studies, each one focusing on specific life stages (CARDIA: early to midlife, Whitehall II Study: mid to latelife, Health ABC: latelife) and covering the entire adult lifespan. Our project will fill an important gap in the literature and be innovative with an age-specific and life-course approach, inclusion of mid-to-latelife transition often underestimated, and a personalized medicine approach.