Hypertension has been shown to be a major risk factor for cognitive decline. It might also be a predisposing factor for early underlying brain changes in SMC (31). Therefore, hypertensive older adults with normal cognition but experiencing SMC is of main interests in this study, because this group concerns what constitute an effective antihypertensive treatment yet preserving their current cognitive function. In our study, we found that hypertension was associated with less SMC in a group of older adults free of MCI and clinical dementia. Additionally, higher MAP was significantly associated with better global cognition and executive function in hypertensive older adults. One thing to be noted is that our hypertensive group has a mean MAP value of 101.2, which is still below the range of Grade 1 hypertensive category (105.68–119 mmHg) in the MAP classification (32). This result suggest that a blood pressure control to lower than 130/80mmHg or a MAP value of 96.66mmHg is too tight and may have potential detrimental impact on cognitive function in older people.
Our interpretation lend supports from some longitudinal studies in oldest old (aged 85 and above) to advance the idea of a blood pressure higher than 130/85mmHg was associated with better global cognitive function (33, 34). Our results showed the potential role of high blood pressure, in particular MAP, on preserving cognitive function and executive function in normal older adults aged 60 and above. An explanation might be that a possible compensatory mechanism improves blood flow to the brain or profusion in older adults with SMC who might have long existing cerebral pathology, such as white matter lesion (15, 35). Previous studies have demonstrated that mean arterial pressure (MAP) is the most relevant proxy indicator that have implicated on cerebral perfusion pressure. It is also a well-established marker of cerebrovascular events, especially ischemic stroke, in both clinical and community samples (36, 37). However, more in-depth prospective studies with neuroimaging data must be needed to examine how high MAP may protect against early cognitive and executive function impairment relating to SMC.
Another possible explanation might be due to the use of different definitions and measurements of hypertension and executive function in previous studies. Previous studies on systemic arterial hypertension (SAH) reported poor performance in specific executive functioning tasks, such as inhibitory control and shifting (38), but some comparisons were made against normotensive younger adults. Other study found link with greater cognitive decline, but hypertension was computed as one of the aggregated vascular risks (39). HYVET is the only study found to examine SMC in a sample of hypertensive octogenarians, but it is primarily focused on SMC conversion to dementia in hypertensive older adults (17). Furthermore, SMC was measured with a single question drawn from the Geriatric Depression Scale. Their participants also had a high baseline age, in which the neurodegenerative process might already be developed over an extensive period affecting the representativeness of cognitive profiling. Furthermore, executive function was not examined in the study.
More importantly, unlike the SPRINT-MIND study, a merit in our study is the endorsement of a clear definition for SMC and MCI that may align future methodology for study replication, and hence result comparison. The exclusion of MCI and dementia in the analysis has strengthened the association identified and supported the view that a tight blood pressure control in hypertensive older adults could be associated with cognitive impairment or decline. We have also excluded those with major depression from the study and further adjusted for any mood symptoms in the analysis, so to ensure the association is independent of mood related factor. In addition, we have considered a comprehensive list of potential confounders and adjusted for factors that might affect cognitive performance.
However, a major limitation of the study is that the direction of associations regarding hypertension and SMC could not be determined. Indeed, recent neuroimaging study has drawn on the vascular hypothesis of cognitive decline, by which suggest that long-term exposure to hypertension may lead to hypoperfusion of the white matter predisposing early manifestation of subclinical AD (15). However, we lack direct neuroimaging data to support hypertension as a contributing factor to the association between cerebral pathology and SMC. We also lack data on the duration of hypertension, so effect of midlife hypertension on current cognitive performance was not known.