Research Article
The impact of hypertension on cerebral perfusion and cortical thickness in older adults

https://doi.org/10.1016/j.jash.2014.04.002Get rights and content

Abstract

Hypertension may increase risk for dementia possibly because of its association with decreased cortical thickness. Disturbed cerebral autoregulation is one plausible mechanism by which hypertension impacts the cerebral structure, but the associations among hypertension, brain perfusion, and cortical thickness are poorly understood. The current sample consisted of 58 older adults with varying levels of vascular disease. Diagnostic history of hypertension and antihypertensive medication status was ascertained through self-report, and when available, confirmed by medical record review. All participants underwent arterial spin labeling and T1-weighted magnetic resonance imaging to quantify total and regional cortical perfusion and thickness. Analysis of covariance adjusting for medical variables showed that participants with hypertension exhibited reduced temporal and occipital brain perfusion and total and regional cortical thickness relative to those without hypertension. The effects of hypertension on total brain perfusion remained unchanged even after adjustment for age, although no such pattern emerged for cortical thickness. Decreased total brain perfusion predicted reduced thickness of the total brain and of the frontal, temporal, and parietal lobe cortices. Antihypertensive treatment was not associated with total cerebral perfusion or cortical thickness. This study provides initial evidence for the adverse effects of a diagnostic history of hypertension on brain hypoperfusion and reduced cortical thickness. Longitudinal studies are needed to investigate the role of hypertension and its interaction with other contributing factors (eg, age) in the manifestation of cerebral hypoperfusion and reduced cortical thickness.

Introduction

Approximately one of three U.S. adults has hypertension and nearly 50% of these individuals do not have it controlled.1 This is concerning, as hypertension elevates mortality risk and leads to chronic medical conditions such as cardiovascular disease (CVD).1 Hypertension is also associated with poor neurocognitive outcomes, including increased risk for Alzheimer's disease and vascular dementia.2, 3 These adverse outcomes may in part be attributed to the negative impact of hypertension on the brain. Hypertension is linked with stroke, greater white matter hyperintensity volume, and total and regional (eg, hippocampus) brain atrophy.4, 5, 6 Although poorly understood, hypertension may also be associated with decreased cortical thickness—a sensitive risk factor for cognitive decline and Alzheimer's disease conversion.7, 8, 9, 10, 11

Hypertension is associated with reduced cerebral blood flow (CBF), which in turn, may serve as one possible etiology for adverse brain changes in hypertensive older adults. Specifically, hypertension may contribute to reduced CBF to cortical and subcortical structures.12, 13 Reduced brain perfusion has been correlated with decreased integrity of the cerebral structure, including decreased thickness of the cortex. Poorer cerebral circulation is linked with reduced cortical thickness in older adults, with specific effects found on frontal and temporal lobe cortices.14 Individuals susceptible to lower brain perfusion levels (eg, Apolipoprotein E epsilon 4 carriers) also exhibit reduced thickness of regions vulnerable to aging (eg, medial prefrontal cortex) and Alzheimer's disease (eg, occipitotemporal and basal temporal cortices).8, 15, 16, 17

The adverse effects of hypertension on the brain may be attenuated through medication therapy. Blood pressure lowering in older adults has been suggested to reduce the risk of stroke and the development of dementia.18, 19 Antihypertensive treatment is associated with better cerebral perfusion levels20 and may also reduce risk of brain atrophy and lesions.21 Nonetheless, the effects of antihypertensive drugs on the brain appear to be complicated. As an example, past work also shows antihypertensive treatment has limited effects on the brain structure and does not reduce dementia risk.22, 23 Furthermore, there is also extant evidence suggesting that antihypertensive medications may have no impact on cerebral perfusion levels.24

As reviewed previously, past studies have examined the effect of hypertension on CBF and brain morphometry, yet, no study has simultaneously investigated the associations among hypertension, brain perfusion, and cortical thickness. The purpose of the present study was to examine the associations among hypertension, CBF, and cortical thickness in a representative sample of older adults using T1-weighted magnetic resonance imaging (MRI) and arterial spin labeling (ASL), a perfusion MRI technique. We also examined whether antihypertensive treatment was associated with better cerebral perfusion and increased cortical thickness.

Section snippets

Participants

A total of 58 older adults were recruited from a larger National Institutes of Health study examining the effects of CVD on the brain. The present sample consisted of 58 participants with complete MRI, medical, and demographic data (Table 1). Participants were recruited from outpatient cardiology offices and advertisements in local papers and screened for study eligibility. The inclusion criteria included English-speaking older men and women older than 50 years. Potential participants were

Sample Medical Characteristics

On an average, the sample exhibited a cardiac index (mean [standard deviation] = 2.77 [0.56] L/min/m2) that fell in the lower end of the normative range. Of the sample, 39.7% had a diagnostic history of hypertension and 51.7% of the sample was prescribed an antihypertensive agent. Angiotensin-converting enzyme inhibitors were most prevalent (27.6%), followed by β blockers (25.9%); other antihypertensive agents (12.1%), calcium channel blockers (8.6%), diuretics (8.6%), and angiotensin II

Discussion

This is the first study to examine the interrelationships among hypertension, CBF, and cortical thickness. Hypertension was common in this representative sample of older adults with varying levels of vascular disease. This study provides preliminary findings that hypertension is associated with cerebral hypoperfusion and that of reduced cortical thickness.11, 12 We further extend the current literature by showing that antihypertensive drugs may not be associated with cortical perfusion or

Conclusion

In brief summary, the present study suggests that a diagnostic history of hypertension is associated with decreased cerebral perfusion and reduced cortical thickness. Antihypertensive use was not associated with improved CBF or cortical thickness. Prospective studies are needed to elucidate the effects of hypertension on the brain and subsequent risk for neurologic conditions such as Alzheimer's disease.

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      Counter to our hypotheses, higher BP was associated with greater cortical thickness. This finding was unexpected given that most studies have found the opposite association pattern (Alosco et al., 2014; Silbert et al., 2018; Kharabian Masouleh et al., 2018; Vuorinen et al., 2013; Gonzalez et al., 2015; Leritz et al., 2011; Shi et al., 2019). However, some studies in hypertensive older adults have observed that high BP was associated with greater cortical thickness and volume (Muller et al., 2014; Nasrallah et al., 2019; van Velsen et al., 2013; Foster-Dingley et al., 2015), with the speculation that in the presence of cerebral small vessel disease, reduced BP results in cerebral hypoperfusion and ultimately cortical atrophy (Muller et al., 2014; van Velsen et al., 2013; Foster-Dingley et al., 2015).

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    Support for this work was provided by National Institutes of Health Grant R01HL084178.

    Conflicts of interest: None.

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