Blood Pressure and the Risk of Alzheimer’s Disease

Abstract

Alzheimer disease is one of the most common neurodegenerative disorder, and the incidence is increasing. Many epidemiologic studies have considered the association between blood pressure and Alzheimer disease, yet the relationship is still controversial. The objective of this study was to validate whether or not blood pressure is indeed associated with AD. We compared different prospective studies and ultimately found that it is also a controversial issue. Large prospective double-blinded and placebo-controlled studies conducted with the use of standardized outcome measures in different levels are necessary to assess the association of blood pressure and Alzheimer disease.

Alzheimer’s disease (AD) is a very common neurodegenerative disorder with a strong vascular component, which is characterized by progressive dementia, brain atrophy, and neuronal loss. ¹ The global prevalence of dementia is estimated to amount to 24 million and has been predicted to quadruple by the year 2050, and AD is the most frequent cause of dementia, which places a considerable burden on the society. ² Although acetylcholine esterase inhibitors (donepezil and rivastigmine) and the N-Methyl-d-aspartate (NMDA-type) glutamate receptor antagonist (memantine) are widely used for the treatment of cognitive dysfunction of AD, these drugs could not stop the deterioration of AD. ¹ Therefore, the identification of new therapeutic approaches and treatments to improve the prognosis of patients with AD is required.

As we all know, hypertension (especially in middle age) is a risk factor for cardiovascular and cerebrovascular diseases as well as an important worldwide public health challenges. ³ There is a well-recognized epidemiological link between hypertension and the increased risk of AD morbidity. ^{4 -6} However, many studies have reported a higher prevalence of dementia and AD in very old individuals with low blood pressure ^7,8 as well as low diastolic pressure and high systolic pressure in elderly individuals aged 75 years, and dementia risk was higher in patients with persistently low blood pressure. ^9,10 The association between blood pressure and AD is debated. A possible explanation for the varying effects of that phenomenon could account for the different outcome measures, study size, and populations used in the different studies, which hampers the comparison of the findings.

The recent study in a mouse model of the disease indicates that hypertension accelerates the development of AD-related structural and functional alterations, ¹¹ and the effectiveness of the antihypertensive drug (angiotensin receptor blockers) against the AD pathological process is obvious in mice. ¹² But the antihypertensive drugs were not associated with a reduction in risk of AD in patients with essential hypertension. ^{13 -15} Power et al even found that there is not a causal relationship between blood pressure and AD with a system review, ¹⁶ which was the same as the conclusions of some large sample studies. ¹⁷ This recent controversial report challenges whether or not blood pressure is indeed associated with AD. It is therefore imperative to explore the attendant concerns. First of all, experimental studies that assess blood pressure in animal models of AD should preferably have a longer time window. Furthermore, the assessment of variability of blood pressure during follow-up should be considered. It is necessary to examine higher quality prospective evidence on the relationship between blood pressure and AD in different age stage.

In summary, certain recommendations should be considered for the efficacy of the antihypertensive drugs in the treatment of AD to slow the progress of AD. Large prospective, double-blinded, and placebo-controlled studies conducted with the use of standardized outcome measures as well as the blood pressure control outcomes in different levels are necessary to assess the association of blood pressure and AD.