Blood Pressure, Microinfarcts, and Dementia: A Pathway for Alzheimer's Disease Management

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Project Summary Blood pressure, Microinfarcts, and Dementia: A Pathway for Alzheimer’s Disease Management Maintaining optimal cognitive function is one of the important components of successful aging. Alzheimer’s disease (AD) is the leading cause of dementia in older adults and it is projected to increase every year. Hypertension is the most powerful risk factor for cerebrovascular pathology, leading to dementia. Both hypertension and decreased blood pressure (BP) from antihypertensives as well as cerebral vasculopathies (e.g., cerebral amyloid angiopathy, arteriolosclerosis) are significant factors influencing microinfarcts (MIFs) formation and neurodegenerative changes prior to dementia. Thus, MIFs might play an important role in the relationship between BP and dementia. Cortical MIFs have significant association with cognitive impairment. Considering its significant effect in aging brain outcomes, preventing the formation of MIFs through proper monitoring and treatment of BP are essential. Since long-term hypertension for at least 5 years is an especially significant contributor for the MIFs formation, the relationship between BP profile and aging brain outcomes can be better understood through a rich longitudinal community-based dataset of older adults like the Adult Changes in Thought (ACT) autopsy data (n=800). Fundamental gaps in knowledge exist with regard to the determinants of regional microvascular vulnerability and resilience and mechanisms of potential interactions between pathologic processes of microvascular injury and AD. Thus, we will fill the gaps by examining the complex interplay between hypertension, vasculopathies, MIFs, and dementia through the following specific aims: 1) To examine the relationships between late-life BP (systolic BP, diastolic BP, pulse pressure) and region- specific quantified MIFs in cortical (frontal, temporal, parietal, and occipital) and subcortical (caudate nucleus, putamen, internal capsule, and thalamus) MIFs, controlling for APOE genotype, age, BRAAK stage (III - VI), and antihypertensive medication use. 2) To examine the relationships between vasculopathies (cerebral amyloid angiopathy, arteriolosclerosis) and region-specific MIFs. 3) To examine the relationship between MIFs and the risk of dementia by sex. We will conduct our project with the well-characterized group of individuals from the ACT (U01 AG 06781) autopsy cohort (age ≥ 65) (n=800) study funded by NIA. The study will fill fundamental gaps in pathophysiologic mechanisms of vascular injury and cognitive impairment. Innovations of this study include longitudinal, prospectively collected community-based research data; assessment of systemic and central determinants of MIFs; and assessment of determinants of regional microvascular vulnerability and resilience and its association with dementia.