Abstract
Background: Hypertension is an important risk factor for Alzheimer’s disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances.Objective: The aim of the present work was to investigate the differences in cognitive performances, CSF biomarkers and magnetic resonance imaging (MRI) of brain structure between normotensive, controlled hypertensive, uncontrolled hypertensive, and untreated hypertensive older adults from the Gothenburg H70 Birth Cohort Studies.Methods: As an indicator of vascular brain pathology, we measured white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, enlarged perivascular space (epvs), and fractional anisotropy (FA). To assess markers of AD pathology/neurodegeneration, we measured hippocampal volume, temporal cortical thickness on MRI, and amyloid-β42, phosphorylated tau, and neurofilament light protein (NfL) in cerebrospinal fluid. Various neuropsychological tests were used to assess performances in memory, attention/processing speed, executive function, verbal fluency, and visuospatial abilities.Results: We found more white matter pathology in hypertensive compared to normotensive participants, with the highest vascular burden in uncontrolled participants (e.g., lower FA, more WMHs, and epvs). No significant difference was found in any MRI or CSF markers of AD pathology/neurodegeneration when comparing normotensive and hypertensive participants, nor among hypertensive groups. No significant difference was found in most cognitive functions between groups.Conclusion: Our results suggest that good blood pressure control may help prevent cerebrovascular pathology. In addition, hypertension may contribute to cognitive decline through its effect on cerebrovascular pathology rather than AD-related pathology. These findings suggest that hypertension is associated with MRI markers of vascular pathology in the absence of a significant decline in cognitive functions.
Highlights
Hypertension is considered to play an important role in cognitive deficits, being mediated by microvascular dysfunction and cerebrovascular pathology (Iadecola, 2014)
Neurochemical and radiological differences between normotensives and those with controlled, uncontrolled or untreated hypertension, using MRI markers of vascular pathology (WMHs, lacunes, microbleeds, enlarged perivascular space, and fractional anisotropy (FA)), MRI and cerebrospinal fluid (CSF) markers of Alzheimer’s disease (AD) pathology/neurodegeneration, as well as cognitive tests in a cognitively healthy population-based sample of 70-year-olds
We found that uncontrolled hypertensive participants had more lacunes than normotensives, and a lower FA, suggesting that uncontrolled blood pressure leads to further microstructural damage
Summary
Hypertension is considered to play an important role in cognitive deficits, being mediated by microvascular dysfunction and cerebrovascular pathology (Iadecola, 2014). DTI metrics can capture microstructural changes related to hypertension before the appearance of irreversible white matter damage. These metrics can capture microstructural changes within WMHs that are not yet visible on standard T2 fluid attenuation inversion recovery (FLAIR) images (Maillard et al, 2014). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances
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