Hypertension, Target Organ Injury, and the Brain

Do elevated blood pressures lead to cognitive dysfunction?

If there ever was, there is no longer any argument that hypertension is a critical risk factor for stroke and its consequent disabilities. But there is more to the unhealthy relationship between elevated blood pressures and brain injury. More recent data address a new and disturbing question: Is hypertension a risk factor for cognitive dysfunction and dementia? With the epidemic of Alzheimer disease and other dementias a fact of contemporary aging, finding the answer--and doing something about it--is critical.

Are you current on the recent literature? Let’s find out with a short quiz.

1. Which of the following statements are true?

A. In a French study of 1,373 persons aged 59 to 71 years, the risk of cognitive impairment on 4-year follow-up was increased slightly in those individuals with hypertension.

B. In the same study, among those individuals with hypertension, there was a greater increase in the risk of cognitive impairment in those patients who were not treated for their hypertension.

C. At 3-year follow up in another study of persons aged ≥ 75 years (n=1301), with and without dementia, those with hypertension who were treated had a 30% lower incidence of dementia than those with hypertension who were untreated.

Please click here for answer, discussion, and next question

Answers: Options B and C are true.

Results from the study in option A¹ found the risk of cognitive impairment at 4 years was not slightly but rather was substantially increased-2.8 times-in those participants with hypertension. Also in that study, the risk of cognitive impairment was increased 4.3 times in the those with hypertension who were untreated versus 1.9 times in those individuals who were treated (option B).¹

Results of the study referenced in option C² show an equally remarkable difference in the incidence of dementia between older persons with hypertension treated and untreated for the disease.²

The bottom line: cognitive regions of the brain do indeed appear to be susceptible to injury from elevated blood pressure.

The follow-on question to be explored is what specific injury is incurred by cognitive centers in the brain as a consequence of hypertension?

The answer is not known at this time, but research is ongoing and has scientific direction. The primary suspicion is that hypertension, manifested as a variety of small-vessel diseases, damages the cerebral microcirculation.³ Theories about the specific mechanism of the injury include disruption of the blood brain barrier, interference in the connections between neurons and their blood supply, as well as direct capillary damage.³ Other studies have identified that specific small vessel injuries –senile plaques and neurofibrillary tangles-are increased in persons with hypertension.⁴

Although there is conflicting evidence on the impact of antihypertensive therapy on the prevention of dementia, there are some promising studies. How familiar are you with the data?

2. Of the following statements, which is/are true and which false?  

A. The use of antihypertensive agents significantly reduced the risk of Alzheimer disease in persons with higher baseline blood pressures than controls.

B. Regarding specific agents used to treat hypertension in older adults, the use of diuretics at baseline in patients age ≥ 75 years reduced the prevalence of dementia on follow up more than in those individuals not taking diuretics.

C. Patients with dementia at baseline who were not taking diuretics experienced a 2-fold faster rate of dementia progression as assessed by Mini-Mental State Examination than those taking diuretics.

Please click here for answer and discussion.

Answer: All 3 statements are true.²

Although clinical data are preliminary, evidence is accumulating for an association between small vessel pathology/dementia and hypertension and also for a protective effect for select drugs to treat hypertension, ie, thiazide diuretics.²

The benefits of antihypertensive therapy to help prevent cognitive decline is a work in progress. It appears based on the current evidence that lowering blood pressure may decrease the incidence of new-onset dementia. In addition, preliminary data suggest that agents such as thiazide diuretics may slow the progressive debility of dementia. 

The brain pathology that results from stroke is a result of large vessel injury. The presumed smaller size of the vessel injured in dementia will make research more complex, but the early returns suggest that hypertension is a “player.”  That is a solid foundation to build on!

References

Tzourio C, Dufouil C, Ducimetiere P, et al. Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of Vascular Aging. Neurology 1999;53: 1948-52.

Guo Z, Fratiglioni L, Zhu L, et al. Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use. Arch. Neurol. 1999; 56:991-996.

Csiszar A, Tarantini S, Fulop GA, et al. Hypertension impairs neurovascular coupling and promotes microvascular injury: role in exacerbation of Alzheimer’s Disease. Geroscience 2017; Aug. 29 doi: 10.1007/s11357-017-9991-9, Epub ahead of print.

Sparks DL,  Scheff W, Liu H, et al. Increased incidence of neurofibrillary tangles in non-demented individuals with hypertension. J Neurol. Sci. 1995;131:162-169.