Major Finding: Midlife hypertension was associated with a greater than threefold higher risk of late-life cortical thinning.
Data Source: A subgroup of 63 older adults in the Cardiovascular Risk Factors, Aging, and Incidence of Dementia study (CAIDE), which comprises 1,449 residents of eastern Finland with up to 30 years of follow-up data.
Disclosures: The study group noted no potential conflicts of interest in either study. The CAIDE study is sponsored by grants from the university, and various Swedish and Finnish government grants.
BARCELONA – Uncontrolled hypertension at midlife may be related to continuous cortical thinning, a condition which has been shown to be associated with dementia in old age.
“We suggest that midlife hypertension is associated with cortical thinning in areas related to blood pressure regulation, and dementia,” Miika Vuorinen and his colleagues wrote in a poster at the conference.
“To our knowledge, this is the first study focusing on the effects of midlife hypertension on these multiple brain regions in later life,” wrote Mr. Vuorinen, a doctoral student at the University of Finland, Kuopio.
The study yielded some interesting observations that await further clarification in other populations before additional interpretations can be made, said Dr. Richard J. Caselli, who was not involved in the study.
“The general relationship of cerebrovascular risk factors with Alzheimer's disease [AD] is an area of great interest, but also some controversy, as not all studies agree with each other. In the current case, for example, some factors like hypercholesterolemia and obesity, that others have found to correlate with AD risk, did not correlate with cortical thinning,” said Dr. Caselli, professor of neurology at the Mayo Clinic in Scottsdale, Ariz.
The Cardiovascular Risk Factors, Aging, and Incidence of Dementia study (CAIDE) comprises 1,449 residents of eastern Finland who were first evaluated at midlife, in 1972, 1977, 1982, or 1987.
Now, with up to 30 years of follow-up, researchers are evaluating how midlife blood pressure, body mass index, cholesterol levels, smoking, and physical activity might relate to late-life brain health.
This substudy included all participants who were suspected of having mild cognitive impairment at their 2005–2008 visit. All of these participants (mean age 78 years) underwent magnetic resonance imaging. Of these, 63 had images sufficient to measure cortical thickness in 10 brain areas related to cognition and blood pressure regulation: the bilateral hemispheric anterior insulae cortices, bilateral orbitofrontal cortices, and bilateral posterior superior medal temporal gyri and the left intraparietal sulcus. Measurements of the right hemisphere involved only the temporal pole, entorhinal cortex, and inferior frontal gyrus.
The researchers compared participants who had midlife hypertension (blood pressure of more than 160/95 mm Hg) against normotensive subjects. Elevated midlife blood pressure was associated with cortical thinning in all of the brain regions measured.
The right hemisphere of the brain showed more thinning overall than did the left hemisphere, and the insular cortices and orbitofrontal areas were bilaterally affected, the investigators noted.
None of the associations changed in a multivariate analysis that controlled for age, gender, late-life antihypertensive medications, follow-up time, or the type of scanner used in the imaging.
“In a further analysis, systolic blood pressure and pulse pressure showed linear relationships with decreasing cortical thickness in the right insular cortex,” the investigators added.
Decreasing blood pressure in late life was also related to decreased cortical thickness, supporting previous findings that patients who develop dementia may also experience decreasing blood pressure, the investigators noted.
Dr. Caselli cautioned that subgroup analyses “get tricky and risk bias,” and he wondered “why should the insular cortex specifically show such a strong effect?” Even though it is interesting, is it “coincidence or is it meaningful?” he asked.
“Cortical thinning can certainly relate to Alzheimer's disease, but it may also relate to cerebrovascular disease, so the correlation, while of interest, need not be exclusively related to Alzheimer's disease,” Dr. Caselli said.
He added that the investigators did not mention apolipoprotein E (APOE) genotype, but “some studies have shown that CV risk factors have a greater impact on [APOE e4 allele] carriers than [do] noncarriers, at least as regards AD-related outcomes.”
The same group of investigators recently published another CAIDE substudy, which found significant associations between increased white matter lesions in late life with mid- and late-life vascular risk factors (Dement. Geriatr. Cogn. Disord. 2011;31:119–25).
This substudy comprised 112 CAIDE participants with an average follow-up of 21 years. The subjects underwent MRI scanning and were assessed for white matter lesions. White matter lesions were found to be significantly associated with other CAIDE risk factors, including being overweight at midlife (relative risk 2.5), obesity (RR 2.9), and hypertension (RR 2.7); the associations remained significant after adjustment for several factors.