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It is estimated that by 2050, about 30-40 million elderly people worldwide will suffer from cognitive impairment [1]
.
Among the many risk factors that lead to cognitive impairment, hypertension is an important pathological state that has the widest impact (nearly 1 billion patients worldwide) and can be early intervention
.
Therefore, exploring the complex relationship between hypertension and cognitive impairment is of great significance for improving cognitive impairment
.
In fact, in previous studies, scientists have confirmed through long-term clinical follow-up that middle-aged patients with hypertension are more prone to cognitive impairment [2]
.
However, in the elderly, the relationship between hypertension and cognitive impairment is still unclear
.
In addition, how high blood pressure causes cognitive impairment is currently poorly understood
.
Recently, a research team led by Professor Yu Jintai from Huashan Hospital Affiliated to Fudan University published important research results on the correlation between blood pressure and cognitive impairment in hypertensive patients in China in Alzheimer's & Dementia, an international mainstream cognitive impairment research journal [3]
.
They found that hypertension patients, especially those with high blood pressure fluctuations, are more likely to develop cognitive dysfunction, and the underlying molecular mechanism may be mediated by Tau protein
.
It is understood that this project is currently the largest systematic analysis of the correlation between blood pressure, cognitive function and AD core pathological biomarkers, providing new clues for clarifying the correlation between hypertension and cognitive impairment
.
Screenshot of the paper's homepage Alzheimer's disease (AD) is the most common type of cognitive impairment with extracellular amyloid plaques and intracellular neurofibrillary tangles in the brain as the main pathological manifestations
.
As early as the preclinical stage, amyloid β protein (Aβ42), phosphorylated Tau protein (p-Tau), total Tau protein (t-Tau) and other proteins suggesting the above pathological changes can be detected in the cerebrospinal fluid (CSF) of AD patients Index [1]
.
And do these core pathological changes related to AD participate in the impact of blood pressure on cognitive impairment? In order to clarify the above problems, the Yujintai team conducted their research with the Chinese Alzheimer's Biomarker and LifestylE (CABLE) as the research object
.
Since 2017, the CABLE database has collected biological samples of peripheral blood and cerebrospinal fluid from people aged 40-90 in northern China, and conducted an overall clinical neuropsychiatric evaluation of the included persons
.
The Yujintai team selected data from 1,546 people in the database without cognitive impairment, anxiety and depression and other emotional disorders
.
From the baseline data of the subjects, the average age of hypertension patients and the proportion of male patients were significantly higher than those of other populations
.
At the same time, the proportion of hypertension patients suffering from diabetes, chronic heart disease, hyperlipidemia and atrial fibrillation is also significantly higher than that of other populations
.
On this basis, the researchers further comprehensively analyzed the subjects' blood pressure indicators, cognitive function indicators and AD-related core pathological changes
.
In general, in terms of cognitive function, the MOCA cognitive function score of people with hypertension is significantly lower than that of people without hypertension
.
At the same time, the levels of Tau and p-Tau in the cerebrospinal fluid of hypertensive patients were significantly higher than those of the control population
.
Further subgroup analysis found that the above phenomenon was more significant in patients diagnosed with hypertension in the middle age; while the MOCA score and Tau-related biomarker levels of patients with hypertension in later life were not significantly different from those in the control population
.
This result suggests that hypertension is not only one of the risk factors for cognitive impairment, but also may be involved in the regulation of Tau-related neuropathological manifestations
.
Based on this, the researchers further analyzed and found that the correlation between hypertension and cognitive impairment may be mediated by Tau protein, and the proportion of it mediated is about 11% to 17%
.
The correlation between hypertension and cognitive function and Tau-related biomarkers.
Subsequently, Yu Jintai's team analyzed the correlation between a variety of blood pressure indicators and cognitive function
.
They found that the increase in systolic blood pressure and the decrease in diastolic blood pressure were significantly negatively correlated with cognitive function
.
This reminds us that pulse pressure, which represents the difference between systolic and diastolic blood pressure, may be a better indicator associated with cognitive function
.
Based on this, the researchers analyzed the correlation between pulse pressure and cognitive function and found that the correlation between this indicator and cognitive function is stronger
.
In order to clarify the causality and internal mechanism of cognitive impairment caused by hypertension, the Yujintai team did further analysis.
On this basis, they found that Tau-related pathological changes were partially mediated (approximately 15% to 24%).
Blood pressure-related cognitive dysfunction
.
This effect is more pronounced in middle-aged patients with hypertension diagnosed.
Tau protein-mediated cognitive dysfunction accounts for about 14% to 30%
.
Correlation analysis between pulse pressure and cognitive function and Tau-related biomarkers Based on the correlation analysis between pulse pressure and cognitive function mentioned above, the researchers guessed the blood pressure variability (BPV), that is, the degree of blood pressure fluctuation within a certain period of time.
An important factor leading to hypertension patients' susceptibility to cognitive impairment
.
Correlation analysis further confirms this conjecture, and the pattern diagram is shown below
.
The pattern diagram of cognitive impairment caused by hypertension considers that in addition to Tau protein, amyloid Aβ42 is also the core pathological indicator of AD
.
After analyzing the mediating effects of Aβ42, blood pressure indicators, and cognitive function, Yujintai Group found that Aβ42 is not involved in mediating the cognitive decline caused by hypertension
.
In general, this study shows that high systolic blood pressure in middle age, low diastolic blood pressure and high pulse pressure in old age are closely related to the occurrence of cognitive impairment and Tau-related pathological manifestations; and this blood pressure is closely related to The link between cognitive impairments is partly mediated by Tau protein and has nothing to do with amyloidosis
.
It is worth mentioning that the above research results also have important implications for the clinical treatment of cognitive impairment
.
It reminds clinicians that in clinical screening of AD, they should not only focus on the diagnosis of hypertension itself or a single blood pressure indicator, but doctors need to pay attention to more blood pressure testing indicators
.
In addition, antihypertensive treatment can not only monitor the lowering of blood pressure, but also pay attention to pulse pressure and blood pressure variability
.
Finally, we would like to remind all hypertensive patients: it is very important to control your blood pressure to take the medicine on time and in accordance with the doctor's advice! References: 1.
Scheltens, P.
et al.
Alzheimer's disease.
Lancet 388, 505-517, doi:10.
1016/S0140-6736(15)01124-1 (2016).
2.
Ou, YN et al.
Blood Pressure and Risks of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of 209 Prospective Studies.
Hypertension 76, 217-225, doi:10.
1161/HYPERTENSIONAHA.
120.
14993 (2020).
3, Hu, H.
et al.
Tau pathologies mediate the association of blood pressure with cognitive impairment in adults without dementia: The CABLE study.
Alzheimers Dement, doi:10.
1002/alz.
12377 (2021).
Editor in chargeBioTalker
.
Among the many risk factors that lead to cognitive impairment, hypertension is an important pathological state that has the widest impact (nearly 1 billion patients worldwide) and can be early intervention
.
Therefore, exploring the complex relationship between hypertension and cognitive impairment is of great significance for improving cognitive impairment
.
In fact, in previous studies, scientists have confirmed through long-term clinical follow-up that middle-aged patients with hypertension are more prone to cognitive impairment [2]
.
However, in the elderly, the relationship between hypertension and cognitive impairment is still unclear
.
In addition, how high blood pressure causes cognitive impairment is currently poorly understood
.
Recently, a research team led by Professor Yu Jintai from Huashan Hospital Affiliated to Fudan University published important research results on the correlation between blood pressure and cognitive impairment in hypertensive patients in China in Alzheimer's & Dementia, an international mainstream cognitive impairment research journal [3]
.
They found that hypertension patients, especially those with high blood pressure fluctuations, are more likely to develop cognitive dysfunction, and the underlying molecular mechanism may be mediated by Tau protein
.
It is understood that this project is currently the largest systematic analysis of the correlation between blood pressure, cognitive function and AD core pathological biomarkers, providing new clues for clarifying the correlation between hypertension and cognitive impairment
.
Screenshot of the paper's homepage Alzheimer's disease (AD) is the most common type of cognitive impairment with extracellular amyloid plaques and intracellular neurofibrillary tangles in the brain as the main pathological manifestations
.
As early as the preclinical stage, amyloid β protein (Aβ42), phosphorylated Tau protein (p-Tau), total Tau protein (t-Tau) and other proteins suggesting the above pathological changes can be detected in the cerebrospinal fluid (CSF) of AD patients Index [1]
.
And do these core pathological changes related to AD participate in the impact of blood pressure on cognitive impairment? In order to clarify the above problems, the Yujintai team conducted their research with the Chinese Alzheimer's Biomarker and LifestylE (CABLE) as the research object
.
Since 2017, the CABLE database has collected biological samples of peripheral blood and cerebrospinal fluid from people aged 40-90 in northern China, and conducted an overall clinical neuropsychiatric evaluation of the included persons
.
The Yujintai team selected data from 1,546 people in the database without cognitive impairment, anxiety and depression and other emotional disorders
.
From the baseline data of the subjects, the average age of hypertension patients and the proportion of male patients were significantly higher than those of other populations
.
At the same time, the proportion of hypertension patients suffering from diabetes, chronic heart disease, hyperlipidemia and atrial fibrillation is also significantly higher than that of other populations
.
On this basis, the researchers further comprehensively analyzed the subjects' blood pressure indicators, cognitive function indicators and AD-related core pathological changes
.
In general, in terms of cognitive function, the MOCA cognitive function score of people with hypertension is significantly lower than that of people without hypertension
.
At the same time, the levels of Tau and p-Tau in the cerebrospinal fluid of hypertensive patients were significantly higher than those of the control population
.
Further subgroup analysis found that the above phenomenon was more significant in patients diagnosed with hypertension in the middle age; while the MOCA score and Tau-related biomarker levels of patients with hypertension in later life were not significantly different from those in the control population
.
This result suggests that hypertension is not only one of the risk factors for cognitive impairment, but also may be involved in the regulation of Tau-related neuropathological manifestations
.
Based on this, the researchers further analyzed and found that the correlation between hypertension and cognitive impairment may be mediated by Tau protein, and the proportion of it mediated is about 11% to 17%
.
The correlation between hypertension and cognitive function and Tau-related biomarkers.
Subsequently, Yu Jintai's team analyzed the correlation between a variety of blood pressure indicators and cognitive function
.
They found that the increase in systolic blood pressure and the decrease in diastolic blood pressure were significantly negatively correlated with cognitive function
.
This reminds us that pulse pressure, which represents the difference between systolic and diastolic blood pressure, may be a better indicator associated with cognitive function
.
Based on this, the researchers analyzed the correlation between pulse pressure and cognitive function and found that the correlation between this indicator and cognitive function is stronger
.
In order to clarify the causality and internal mechanism of cognitive impairment caused by hypertension, the Yujintai team did further analysis.
On this basis, they found that Tau-related pathological changes were partially mediated (approximately 15% to 24%).
Blood pressure-related cognitive dysfunction
.
This effect is more pronounced in middle-aged patients with hypertension diagnosed.
Tau protein-mediated cognitive dysfunction accounts for about 14% to 30%
.
Correlation analysis between pulse pressure and cognitive function and Tau-related biomarkers Based on the correlation analysis between pulse pressure and cognitive function mentioned above, the researchers guessed the blood pressure variability (BPV), that is, the degree of blood pressure fluctuation within a certain period of time.
An important factor leading to hypertension patients' susceptibility to cognitive impairment
.
Correlation analysis further confirms this conjecture, and the pattern diagram is shown below
.
The pattern diagram of cognitive impairment caused by hypertension considers that in addition to Tau protein, amyloid Aβ42 is also the core pathological indicator of AD
.
After analyzing the mediating effects of Aβ42, blood pressure indicators, and cognitive function, Yujintai Group found that Aβ42 is not involved in mediating the cognitive decline caused by hypertension
.
In general, this study shows that high systolic blood pressure in middle age, low diastolic blood pressure and high pulse pressure in old age are closely related to the occurrence of cognitive impairment and Tau-related pathological manifestations; and this blood pressure is closely related to The link between cognitive impairments is partly mediated by Tau protein and has nothing to do with amyloidosis
.
It is worth mentioning that the above research results also have important implications for the clinical treatment of cognitive impairment
.
It reminds clinicians that in clinical screening of AD, they should not only focus on the diagnosis of hypertension itself or a single blood pressure indicator, but doctors need to pay attention to more blood pressure testing indicators
.
In addition, antihypertensive treatment can not only monitor the lowering of blood pressure, but also pay attention to pulse pressure and blood pressure variability
.
Finally, we would like to remind all hypertensive patients: it is very important to control your blood pressure to take the medicine on time and in accordance with the doctor's advice! References: 1.
Scheltens, P.
et al.
Alzheimer's disease.
Lancet 388, 505-517, doi:10.
1016/S0140-6736(15)01124-1 (2016).
2.
Ou, YN et al.
Blood Pressure and Risks of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of 209 Prospective Studies.
Hypertension 76, 217-225, doi:10.
1161/HYPERTENSIONAHA.
120.
14993 (2020).
3, Hu, H.
et al.
Tau pathologies mediate the association of blood pressure with cognitive impairment in adults without dementia: The CABLE study.
Alzheimers Dement, doi:10.
1002/alz.
12377 (2021).
Editor in chargeBioTalker
