Midlife CV Risk Linked to Brain Atrophy, Cognitive Decline

Pauline Anderson

August 02, 2011

August 2, 2011 — Cardiovascular risk factors, such as hypertension, diabetes, and 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.

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

The study results should be a "wake-up call" not to take midlife hypertension lightly, said lead study author Charles DeCarli, MD, Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento.

"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 was published in the August 2 issue of Neurology.

The analysis included 1352 subjects from the offspring cohort of the Framingham Heart Study, a community-based, prospective study initiated in 1949. Researchers assessed vascular risk factors (hypertension, systolic blood pressure, diabetes, smoking, hypercholesterolemia, obesity, and waist to hip ratio [WHR]) in these offspring at a mean age of 54 years, 7 to 10 years before they first underwent neuropsychological testing and volumetric brain magnetic resonance imaging.

The study found that all measures of change in brain structure and cognitive function were more marked with increasing age. APOE ε4 carriers had a more rapid decline in logical memory performance compared with noncarriers.

Insidious Impact of Hypertension

Hypertension and increasing systolic blood pressure in midlife were associated with a more rapid increase in WMHV (both P < .001), even after adjusting for interim stroke, hypertension, and systolic blood pressure.

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 Dr. DeCarli. This is especially important to know because a quarter of middle-aged Americans has 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 (THV), a surrogate marker of accelerated hippocampal atrophy (P = .017).

Midlife obesity, which affected 22.6% of study subjects, was associated with increasing WHR with marked decrease in total brain volume (TBV), whereas smoking (15.0% of subjects) was associated with a greater annual increase in THV and decrease in TBV and also predicted an increased risk for prominent change in THV, TBV, and WMHV.

Cognitive Decline

For cognitive decline, both hypertension and systolic blood pressure were associated with a more marked decline in Trail-Making Test B-A performance (P = .012 and .002, respectively). These associations were unaltered after adjusting for baseline cognitive performance.

Midlife obesity, too, was associated with rapid decline in executive function. There was only a trend toward an association of midlife diabetes with decline in executive function, but the study's power was limited because of the small number of diabetic patients (only 5% had diabetes).

Vascular risk factors are highly correlated with each other, making it difficult to tease out individual mechanisms, but the study 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.

Although 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 because it found effects of most risk factors on structural brain measures, said the study authors.

'Walking Train Wrecks'

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

Dr. 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 study 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 Dr. DeCarli.

Important Supporting Role

Reached by email for a comment, David Knopman, MD, professor of neurology at the Mayo Clinic in Rochester, Minnesota, and a member of the American Academy of Neurology, said the study is "scientifically valid and informative."

The results are important because they show that cardiovascular risk factors influence brain integrity relatively early in life, said Dr. Knopman. "Although the results do not challenge the view that Alzheimer 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 that adding a neurological reason shouldn't make a very, very compelling story more so."

Dr. DeCarli serves as editor-in-chief of Alzheimer Disease and Associated Disorders, serves as a consultant for Takeda Pharmaceutical Company Limited and Avanir Pharmaceuticals, and receives research support from Merck Serono and the National Institutes of Health. For conflict information on the other authors, see the original paper. Dr. Knopman is deputy editor of Neurology Second and is affiliated with the Atherosclerosis Risk in Communities "ARIC" Study, a research group that found similar results (reference 30 in the current paper).

Neurology. 2011;77:461-468.

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