Midlife CV risk linked to brain atrophy, cognitive decline

Pauline Anderson

August 02, 2011

Davis, CA -Cardiovascular risk factors such as hypertension, diabetes, or obesity in midlife are associated with an increase in the rate of brain changes linked to dementia just 10 years down the road, a new study has found [1].

For example, the study showed that being hypertensive at about age 54 years was a significant predictor of white-matter hyperintensity volume (WMHV) progression and worsening performance in executive function at about age 61.

The study results should be a "wake-up call" not to take midlife hypertension lightly, said lead author Dr Charles DeCarli (University of California, Davis).

"We should be very, very clear about the insidious impact of hypertension and be more wary about just saying, 'your blood pressure is 140 over 90; that's no big deal, we'll just watch it,' " he said. "That's a common mistake."

The study is published in the August 2, 2011 issue of Neurology.

The analysis included 1352 subjects from the offspring cohort of the Framing ham Heart Study. Researchers assessed vascular risk factors (hypertension, systolic blood pressure, diabetes, smoking, hypercholesterolemia, obesity, waist-to-hip ratio) in these offspring at a mean age of 54 years, seven to 10 years before they first underwent neuropsychological testing and volumetric brain MRI.

The study found that all measures of change in brain structure and cognitive function were more marked with increasing age.

Hypertension and increasing systolic blood pressure in midlife were associated with a more rapid increase in WMHV (both p<0.001), even after adjustment for interim stroke, hypertension, and systolic blood pressure.

Insidious impact of hypertension

It's not surprising that the study linked hypertension to brain aging; what was a surprise was that this association starts so early in life, said DeCarli. This is especially important to know, since a quarter of middle-aged Americans have hypertension. In this study, hypertension affected 26.5% of study subjects, making it one of the "big players" when it comes to brain aging, he said.

The study found that diabetes was significantly associated with a greater annual increase in temporal horn volume, a surrogate marker of accelerated hippocampal atrophy (p=0.017).

Midlife obesity, which affected 22.6% of study subjects, was associated with increasing waist-to-hip ratio, with a marked decrease in total brain volume, while smoking (15.0% of subjects) was associated with a greater annual increase in temporal horn volume and decrease in total brain volume and also predicted an increased risk of prominent change in temporal horn volume, total brain volume, and WMHV.

Cognitive decline

Hypertension was associated with a more marked decline in cognition regardless of baseline cognitive performance, while midlife obesity and diabetes were associated with declines in executive function, although this link was not statistically significant for diabetes, potentially due to the small number of diabetics in the study (5%).

Vascular risk factors are highly correlated with each other, making it difficult to tease out individual mechanisms, but the authors speculated that hypertension could increase small vessel disease load, leading to an accelerated rate of WMHV progression and decline in executive function. Diabetes could have a neurodegenerative effect that accelerates hippocampal atrophy, and smoking could lead to both vascular and neurodegenerative lesions, they said.

While the study didn't uncover a significant association between midlife vascular risk factors and decline in memory, it did suggest at least an indirect association, since it found effects of most risk factors on structural brain measures, said the authors.

"Walking train wrecks"

Having vascular risk factors in middle age means "you're not at the top of your game" as a person moves into their 70s and 80s, when Alzheimer's disease begins to be an issue, said DeCarli.

"People get to age 80, and they've got these brain injuries from the hypertension they've had for 50 years; they might have had a stroke or a heart attack, and maybe their kidneys aren't working," he said. "They're walking train wrecks."

DeCarli pointed out that vascular risk factors are additive, "so if you have all of these things, you're in much worse shape," he said.

The study suggests that vascular risk factors in midlife should be targeted for primary-prevention trials of dementia, said the authors. Identifying these risk factors in middle-aged people could be useful in screening those who may be at risk for dementia and encouraging them to make crucial lifestyle changes, added DeCarli.

Important supporting role

Reached by email for a comment, Dr David Knopman (Mayo Clinic, Rochester, MN) said that the study results are important because they show that cardiovascular risk factors influence brain integrity relatively early in life. "Although the results do not challenge the view that Alzheimer's pathology is still the dominant one in late-life dementia, the current results emphasize that vascular risk factors play an important supporting role."

But the results, he said, will probably not change clinical practice. "After all, it is no mystery that attention to vascular risk factors in midlife is critically important from a cardiovascular point of view, so adding a neurological reason shouldn't make a very, very compelling story more so."

DeCarli serves as e ditor in c hief of Alzheimer Disease and Associated Disorders; serves as a consultant for Takeda Pharmaceutical s and Avanir Pharmaceuticals; and receives research support from Merc k Serono and the N ational I nstitutes of H ealth . Disclosures for the coauthors are listed in the paper. Knopman is d eputy e ditor of Neurology 2nd ed and is affiliated with the Ather osclerosis Risk in Communities s tudy, a research group that found similar results .


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