Middle-life hypertension may shrink the brain in later life

A long-running study which ha been following up people into their seventies concludes that high blood pressure between the age of 36 and 53 years is associated with brain pathology such as white matter lesions and brain shrinkage in later life. To prevent this, blood pressure should be monitored beginning at or before 40 years, suggest the researchers.

The study titled, 'Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study', is published in the Lancet Neurology.

Blood pressure gauge show Hypertension or High Blood Pressure. Image Credit: Voraorn Ratanakorn / Shutterstock
Blood pressure gauge show Hypertension or High Blood Pressure. Image Credit: Voraorn Ratanakorn / Shutterstock

The motivation for the current study was to reduce the prevalence of dementia, which affects 44 million people globally. It is estimated that the number of victims could be cut to half by simply delaying the disease for 5 years. In order to do this, the risk factors must be identified and addressed.

One well-known risk factor for dementia resulting from damaged blood supply to the brain is high blood pressure during middle age. Since this covers a fairly broad period, it is necessary to identify the time at which high blood pressure is most injurious to the brain, if any, and to find out how it acts.  This study helped to elucidate the timing and nature of the additional risk. The surprise is that the risk begins to operate much younger than previously thought.

To arrive at this conclusion, the researchers used the Insight 46 study, which includes about 500 people who have been followed up since their birth in the same week in 1946. At 70, this group shows no evidence of cognitive impairment or of beta-amyloid plaques. Despite the normal cognition, this group shows brain lesions apparent on MRI scanning.

The researchers used blood pressure measurements carried out at the ages of 36, 43, 53, 60-64, and 69 years. In addition, the rise in blood pressure between consecutive readings was found. The criterion for hypertension was standard: 140/90 mm Hg or higher, either measured or reported by the subject.

Around the age of 70 years, the overall brain volume and hippocampal volume was measured using 3D T1 MRI. Simultaneously, white matter lesions were assessed for extent, as well as the amount of beta-amyloid plaques, using multimodal MRI. The Preclinical Alzheimer Cognitive Composite (PACC) test was also administered to detect cognitive loss. This data was then analyzed to detect any linkage between absolute blood pressure values and blood pressure variations during this period, with the outcomes described earlier. Adjustments were made for factors like high cholesterol, smoking, diabetes, and body mass index, which could influence the result. The genetic marker called APOE was also tested for.

What were the results?

While higher blood pressure levels were always linked to more white matter lesions at all ages, the association became significant only at 53 years, and a steeper slope of blood pressure over the ten preceding years, were key factors in determining an increased number of white matter lesions at age 70. For instance, when the systolic or diastolic blood pressure was 10 mm higher over these ten years, the white matter lesions at age 70 were more frequent by 7% and 10% respectively. There was a 15% increase in both outcomes with each standard deviation increase in either systolic or diastolic blood pressure.

Another finding was that when the blood pressure was higher at the age of 43 and 53 years, or when the blood pressure rose significantly after the age of 36 years, there was a non-linear decrease in brain volume. The cut-off of 140 mm Hg appears to be crucial for systolic blood pressure at age 53 onwards.

The study also confirmed that systolic and diastolic blood pressure change in different directions over time. While systolic blood pressure shows an upward trend with age, diastolic blood pressure goes down after the age of 50 or 60 years. Hypotension may thus be more harmful to the small vessels in the brain and for the brain volume, and this may be accentuated if the person was hypertensive before.

For a 10 mm increase in systolic or diastolic pressure at age 43, the brain is about 6.5 ml and 7 ml smaller, respectively, by age 70. Hippocampal volume is also reduced by about 0.02 ml with a 10 mm rise in systolic blood pressure, but no link was found with diastolic blood pressure.

Other associations that were observed in this group included smaller brain volume and fewer white matter lesions in men compared to women. Diabetics had smaller brain volumes, while amyloid was more frequently found in APOE-positive individuals. Cognitive performance was lower in males, in those with a lower socioeconomic status, and in those whose childhood cognition scores were lower.

The lack of association with beta-amyloid or cognitive changes implies that the deterioration in brain health often seen in later life in hypertensive people is not related to this physical change. The accumulation of beta-amyloid plaques in the brain is among the first signs of the degenerative dementia called Alzheimer’s disease.

The researchers found that the greatest damage to the brain occurs in individuals who had high blood pressure between about 36 and 53 years. Thus they recommend that regular blood pressure checks begin before the age of 40, and that a sharply rising blood pressure during this period should be treated carefully, to prevent age-related brain lesions.

The study has several limitations. For one, it follows a birth cohort, and all the participants therefore belong to the same life phase, have the same blood pressure targets, and will have undergone one of the same set of blood pressure treatments. Thus the findings may not be easily extrapolated to broader groups. Secondly, all participants were white Britons, and the number of people in ill health is a little lower than the average in such a group. This again limits its broader applicability. All individuals showed normal cognition, which is expected of a group in its early 70s. And finally, the study looked at only one of several possible processes which can culminate in dementia.

The association between blood pressure and disease processes affecting the brain is probably significant, according to an aging expert, Lenore J. Launer (National Institute on Ageing, NIH), who says, “Millions of individuals have unhealthy blood pressure. Immediate attention should be given to efforts to control blood pressure through clinical services and public health interventions, and to alleviate the barriers to delivery and uptake of these messages.”

Journal reference:

Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study
Lane, Christopher A et al., The Lancet Neurology, https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(19)30228-5/fulltext

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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