High Blood Pressure in Younger Adults: Dementia Risk Only in Women?
It is known that high blood pressure in one’s 50s puts a person at risk for dementia in later life. What about in younger people? In the October 31 Neurology, scientists led by Rachel Whitmer of the Kaiser Permanente Division of Research, Oakland, California, report that hypertension in the 30s and 40s has a similar effect, but only in women. Same-age men with hypertension developed dementia at the same rate as their normotensive peers, according to the data. The findings come as a surprise, since many prior epidemiological studies concluded that midlife high blood pressure increased everyone’s risk of getting dementia. Whitmer and colleagues caution that their finding could result from a survival effect, meaning that some men with hypertension may have died before follow-up could have detected incident dementia.
- Midlife high blood pressure increased risk for dementia in women.
- A survival effect could obscure an effect in men.
“Our findings emphasize how important it is to look at the timing of risk factors,” said first author Paula Gilsanz.
Prior work has established high blood pressure in late middle age—usually the 50s—as a risk factor for developing late-life dementia in both men and women (Whitmer et al., 2005; Kimm et al., 2011; Apr 2017 news). Whitmer and colleagues wondered if hypertension in younger people might have the same effect.
To find out, Gilsanz and colleagues reviewed the medical records of 5,646 members of the Kaiser Permanente Northern California integrated health care delivery system. Each had voluntarily seen a doctor for a routine checkup between 1964 and 1973, when they were 30–35 years old, and filled out a health survey. Between 1978 and 1985, when they were over 40, they had a second checkup. Both times doctors tested for hypertension, defined as a systolic blood pressure at or above 140 mm Hg or a diastolic blood pressure of 90 mm Hg or more. The researchers then checked records from 1996–2015 to see who had been diagnosed with dementia.
In total, 532 people had been—298 women and 234 men. Though midlife hypertension was more common in the men, it didn’t appear to increase their chances of developing dementia. In the women, by contrast, hypertension in their 30s or 40s carried 63 and 73 more risk, respectively, of being diagnosed with dementia compared with their normotensive peers.
The results suggest that hypertension in early to midlife poses a dementia risk for women, not men, wrote the authors. This could be explained by a greater risk for organ damage and cardiovascular disease from hypertension that has been reported for women (Palatini et al., 2011; Cheng et al., 2014).
However, the authors caution that more men in their sample died before follow-up. Having hypertension might have contributed to their early deaths, hence a link between hypertension and dementia in men could have gone undetected. The authors also note that screening and treatment for high blood pressure has evolved considerably since the 1960s, which might limit the generalizability of these findings.
Lewis Kuller, University of Pittsburgh, noted that using hospital records may have underestimated dementia in men while overestimating it in women, since women are hospitalized more frequently, raising the chances that dementia would be detected. In addition, since most men die younger than women do, and there is a delay between diagnosis of dementia and its inclusion in records, the diagnosis may have gone unrecorded in some men. While Kuller considered these the most likely reasons for the reported sex difference, he noted that hormone replacement therapy in this cohort may also have increased women’s risk for hypertension and dementia (see full comment below).—Gwyneth Dickey Zakaib
- Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology. 2005 Jan 25;64(2):277-81. PubMed.
- Kimm H, Lee PH, Shin YJ, Park KS, Jo J, Lee Y, Kang HC, Jee SH. Mid-life and late-life vascular risk factors and dementia in Korean men and women. Arch Gerontol Geriatr. 2011 May-Jun;52(3):e117-22. PubMed.
- Palatini P, Mos L, Santonastaso M, Saladini F, Benetti E, Mormino P, Bortolazzi A, Cozzio S. Premenopausal women have increased risk of hypertensive target organ damage compared with men of similar age. J Womens Health (Larchmt). 2011 Aug;20(8):1175-81. Epub 2011 Jun 24 PubMed.
- Cheng S, Claggett B, Correia AW, Shah AM, Gupta DK, Skali H, Ni H, Rosamond WD, Heiss G, Folsom AR, Coresh J, Solomon SD. Temporal trends in the population attributable risk for cardiovascular disease: the Atherosclerosis Risk in Communities Study. Circulation. 2014 Sep 2;130(10):820-8. Epub 2014 Aug 11 PubMed.
- Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000 Jan-Feb;21(1):49-55. PubMed.
- Alonso A, Mosley TH Jr, Gottesman RF, Catellier D, Sharrett AR, Coresh J. Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) study. J Neurol Neurosurg Psychiatry. 2009 Nov;80(11):1194-201. Epub 2009 Aug 19 PubMed.
- Gilsanz P, Mayeda ER, Glymour MM, Quesenberry CP, Mungas DM, DeCarli C, Dean A, Whitmer RA. Female sex, early-onset hypertension, and risk of dementia. Neurology. 2017 Oct 4; PubMed.
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University of Pittsburgh
This is an interesting paper. There are several reasons why there might be a sex difference in the relationship between midlife hypertension and risk of dementia, i.e., higher rates in women. First, the paper purports to document that their method of ascertainment of dementia has been validated. However, the reference provided in the paper (#19) has no relationship to the current study using the Kaiser Permanente database and refers to a personal communication as the validation for the evaluation of dementia in a study done in members of a health program in Seattle. A further reference from that paper is to a publication on the accuracy of Medicare claims data to identify Alzheimer's disease in the Journal of Clinical Epidemiology by Taylor, et al. That paper shows that Medicare claims data, using all types of Medicare claims records, including hospital records, physician records, and so-called institutional records over a three- to five-year period, identified about 80 percent of all of the dementia cases that were in the CERAD registry. However, the CERAD registry by definition was a registry of patients seen and evaluated in tertiary care facilities at major teaching hospitals and AD centers in the late 1990s, and these patients were most likely to have been referred from clinical services within these centers and therefore much more likely to have dementia diagnoses on their hospital records. Furthermore, CERAD likely reported their diagnoses of dementia to the primary care physician. Thus, there still may be a substantial underreporting of dementia in this paper. The likelihood of a dementia diagnosis being on a hospital record is a function of the number of times an individual is seen by a physician or in hospital care. Women have a higher level of morbidity and hospitalizations than men and it is possible, therefore, that the diagnosis of dementia was more likely identified among women as compared to men. Therefore, there may be a substantial bias in using the database for their study.
Men have a higher mortality, especially in relationship to hypertension and atherosclerosis, and may have died prior to the diagnosis of dementia appearing on their hospital record or other records. The time between the dementia diagnosis and death after the diagnosis of dementia will, in part, determine the likelihood that the dementia diagnosis will appear on a medical record and be included in this study, and since men have a higher mortality or possibly shorter length of time with their dementia, the diagnosis may not be included in their records. I would suspect that this is the most likely explanation for this sex difference, i.e., a bias associated with likelihood of dementia appearing on the medical records.
The second and interesting possibility is that the association may be a function of use of sex steroid hormones, i.e., estrogens and progesterone, in women. The cohort that they describe probably included large numbers of women who were using estrogen or estrogen plus progesterone prior to the results of the Women's Health Initiative (WHI), etc. In the WHI, the use of estrogens or estrogen plus progesterone was associated with an increased risk of stroke and also with an increased risk of dementia. Furthermore, studies have shown that estrogen and progesterone therapy, as well as estrogens alone, are associated with an increased risk of hypertension. Thus, it is possible that the midlife hypertension plus the use of estrogens or estrogens plus progesterone may have been associated with a further increase in the risk of dementia. It would be very interesting for the group to analyze their data among the women in relationship to prior use of estrogens and progesterone, midlife hypertension, and risk of dementia. Was the higher risk of dementia primarily found among women who were estrogen and estrogen plus progesterone users and those who were nonusers had a lower risk of dementia or risk similar to that of men?
A third and final possibility is that they have previously reported from this same cohort (Whitmer et al., 2008) that central obesity in midlife is associated with an increased risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity. Central obesity is a major risk factor for hypertension and is also a risk factor for diabetes, and previous studies from the group have also suggested that diabetes is related to dementia. Older women tend to be more obese than men, although men generally have more central obesity at younger ages while women tend to get more central obesity postmenopausally. It is possible that the interaction between obesity, development of hypertension, and diabetes may have differential effects in men and women and account for the observed association of dementia with hypertension only primarily in the women.
Unfortunately, there are no solid clinical trial data substantiating that reduction of blood pressure, especially in middle age or even in older ages, is associated with any substantial decrease in the risk of dementia, and certainly no data on whether there is a differential effect between men and women. Such data from clinical trials as well as better evaluation of the underlying pathology, i.e., amount of vascular disease in the brain, small vessel disease, etc., would be critically important to further understand the relationship between midlife blood pressure and dementia risk, and especially the sex difference.
Whitmer RA, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson EP, Yaffe K. Central obesity and increased risk of dementia more than three decades later. Neurology. 2008 Sep 30;71(14):1057-64. Epub 2008 Mar 26 PubMed.
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