This study is a population-based case-control study with a strict training process and quality assurance programs. The risk of developing MCI in hypertensive patients in this study appears to be influenced by various factors. And after adjusting for confounding factors, we found that controlling patients' hypertension to target levels (no matter the type of hypertensive drugs used) reduced the incidence of MCI, particularly in the younger elderly population in an urban community in Nanjing China.
Research on hypertension and cognitive impairment first began in the 1960s with the study of pilots. Until now, there has been controversy about studying the effects of hypertension on cognitive impairment in the middle-aged and elderly population. Several observational studies have found that chronic hypertension, especially high SBP in middle age (40-65 years), was associated with an increased risk of cognitive impairment or dementia in later life.[2, 14, 15] However, studies on the relationship between blood pressure levels and cognitive decline and dementia at older ages have reached inconsistent conclusions. An observational study in Italy has shown that hypertension in the elderly was not related to cognitive impairment. Some studies have even suggested that higher blood pressure levels are associated with better cognitive function scores. In the present study, MCI occurred in about 44.8% of hypertensive patients, and we found no significant difference in the prevalence of MCI between 50-57, 58-65, and >65 age groups. However, the prevalence of MCI among adults aged ≥60 years in China was 15.5% in 2020, significantly lower than that of hypertensive patients in this study. Our findings suggest an effect of hypertension on the onset of MCI in middle-aged and older adults, and grade 3 hypertension was more likely to have cognitive impairment than grade 1 hypertension. But the further expansion of the sample size is needed to confirm the findings.
Currently recognized research concluded that structural changes in the cerebral vasculature secondary to long-term hypertension, with endothelial damage, leading to altered cerebral perfusion was thought to be the main biological pathway linking hypertension to cognitive impairment. Therefore, antihypertensive treatment is crucial. There is controversy about whether lowering blood pressure helps prevent cognitive impairment in patients with hypertension. This year, a cohort study in Brazil showed that effective treatment of hypertension at any age could prevent or slow cognitive decline.  In 2020, a meta-analysis that included six prospective studies (containing 31,090 participants) showed that receiving antihypertensive therapy reduced the risk of cognitive impairment by 12% and the risk of Alzheimer's disease by 16% compared with not receiving antihypertensive therapy, and this effect was independent of the type of antihypertensive drugs. Also, there was meta-analyze that held the opposite view. Chang et al. evaluated the association between antihypertensive medication use and the risk of cognitive decline but showed that antihypertensive treatment did not decrease the risk of cognitive decline.
The present study found that the two key ORs for the prevention of MCI (patients on regular hypertension medication compared with that not on regular hypertension medication and patients with controlled hypertension compared with those uncontrolled hypertension) were similar in the univariate analysis. However, in multivariate regression analysis, we found that the prevalence of MCI was significantly lower in patients with hypertension who reached the treatment target than in those who did not, although they were taking antihypertensive drugs regularly. The results suggest that hypertension treatment has a protective effect on MCI, but treatment targets (blood pressure level) need to be met, and this effect was not statistically significant across different classes of antihypertensive agents (ACEI, ARB, β-blockers, CCB, and else).
In addition, many complex factors may be involved in the poorer cognitive performance of hypertensive patients. Hypertension was always accompanied by other risk factors, such as diabetes and hyperlipidemia. Diabetes can lead to abnormal cerebral angiogenesis and increased capillary density in the central nervous system. This change would accelerate the damage and leakage of blood vessels in the process of neurodegeneration. Ryuno and his colleagues found that hypertension combined with diabetes was more likely to have future cognitive decline than hypertension or diabetes alone,which is similar to the results of the current study. Hyperlipidemia can cause chronic inflammation of the nervous system, damage nerve cells and impair the function of vascular endothelial cells, and affect the brain's cognitive function. The prevalence of MCI in patients with hyperlipidemia was 1.49 times higher than in patients without hyperlipidemia in the current study. But research on the relationship between blood lipids and MCI is still divided, with some researchers suggesting that elevated blood lipids have beneficial effects on cognitive function in the elderly population.[26, 27] Future studies should focus on the interaction of multiple risk factors with a more extended follow-up period.
In terms of personal life, we also identified factors associated with the development of MCI in patients with hypertension in the current study. For instance, education, dietary preferences, and physical exercise. A study by Langa et al. found that as education levels increased, the prevalence of cognitive impairment among those aged 70 and older decreased from 12.2% in 1993 to 8.7% in 2002. This study suggests that the cognitive reserve generated by early education and cognitive stimulation can prevent MC that the cognitive reserve generated by early education and cognitive stimulation can prevent MCI. Therefore, further strengthening children’s education will help reduce the burden of dementia and cognitive impairment. The salt intake of Chinese residents is one of the highest globally. The average daily intake of salt for adults has been above 10 grams for the past 40 years, more than twice the recommended amount. Excessive salt intake can directly cause hypertension, which could lead to cognitive decline, and reduces blood flow to the brain and lead to dementia. Khater et al.  confirmed that good dietary status maintains good cognitive health, the Mediterranean dietary pattern has been shown to have a cognitive protective effect,  but the further research evidence is needed for its use in patients with hypertension. Whether physical exercise affects cognitive impairment in hypertensive patients has not been confirmed by authoritative studies. However, a meta-analysis demonstrated that maintaining physical activity in hypertensive patients helped improve cognitive function scores, and brisk walking for 40 minutes three times per week reduces brain atrophy and improves memory and other cognitive functions. More research is needed in the future to individualize the type, frequency, and duration of physical exercise.
There are limitations to this study. First, there may be recall bias in the collection of patients data (e.g., disease histories), as each piece of information was self-reported by the patient. To avoid such problems, we asked participants to bring historical medical paperwork and let their relatives join in the conversation if possible. Second, changes in MoCA scores over time were not studied. If differences in MoCA were not related to hypertension, the ability to identify specific risk factors (e.g., treatment for hypertension) would be reduced. Third, specific dietary and blood pressure variances were not collected from participants. The factors may be essential covariates in the analysis of the study. Fourth, the relationship between hypertension and cognitive function is complicated, which the middle-aged and elderly often have an exceptionally high number of risk factors, such as coronary heart disease, depression, and insomnia. And although we adjusted for confounding variables in our analysis, we cannot guarantee the effect of other undetected covariates on the current study results. Fifth, the present study may have been subject to misclassification bias. Some patients may not have taken their antihypertensive medication on the morning of the study because some participants may have been required to fast on the day of the blood test. Their blood pressure may have been elevated on the study day, so the investigators would have misclassified them as patients with irregular medication or uncontrolled hypertension. Finally, Nanjing is a developed area in eastern China and the study results may not be generalizable to less economically developed areas in northwestern China. Further prospective studies with large nationwide sample sizes are needed to explore practical measures to prevent and treat MCI in China's middle-aged and elderly hypertensive population.