October 12, 2017
"Other studies have suggested that hypertension in midlife is a risk factor for dementia later in life, but these studies have mainly used blood pressure measurements when the participants were in their 50s as the midlife timepoint. We looked quite a bit earlier than this — in the 30s and 40s," first author, Paola Gilsanz, ScD, Kaiser Permanente Division of Research, Oakland, California, commented to Medscape Medical News.
They found that hypertension in a person's 30s wasn't a risk factor for later dementia in men or women. However, women with hypertension in their 40s did have a higher risk for dementia later in life, with a 73% increased risk compared with women without hypertension. No such association was seen for men, the authors note.
"This is very intriguing," Dr Gilsanz noted. "We know that women have higher rates of dementia than men. It is possible that we might need to look at sex-specific pathways when linking hypertension in midlife to later dementia, and we shouldn't assume other risk factors for dementia behave similarly in men and women.
"The fact that we have seen a link between hypertension as early as in the 40s and later dementia underscores that brain health is something to be considered right through the life course, not just in old age," she said.
Commenting on the study for Medscape Medical News was Costantino Iadecola, MD, chair of the Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York City, and lead author of an American Heart Association statement issued last year on blood pressure as a risk factor for vascular cognitive impairment.
"This study reinforces the concept that hypertension has devastating effects on the brain, also in relatively young women, who were traditionally considered to be protected in the reproductive stages of life," he said. "Public and health professionals should be mindful of the potential harm of hypertension even at a young age and particularly in women."
The study is published online in Neurology on October 4.
The researchers explain that while hypertension in midlife is a known risk factor for dementia, possible sex differences in the link between hypertension and dementia have not been evaluated, and the effect of hypertension onset before midlife on dementia also remains unknown for either sex.
"Correctly targeting at-risk populations requires a greater understanding of when the association between hypertension and dementia begins, how changes in blood pressure ... increase dementia risk, and if risk factors have different inflection points by sex," they write. "Exploration of possible sex differences in risk factors over the life course may help explain why women have higher rates of dementia than men."
For the current study, the researchers evaluated 5646 members of Kaiser Permanente Northern California, an integrated healthcare delivery system, who had clinical examinations and health survey data from 1964 to 1973 (mean age, 32.7 years; early adulthood) and 1978 to 1985 (mean age, 44.3 years; mid-adulthood) and were members as of 1996 (mean age, 59.8 years).
They looked for associations between hypertension diagnosis in the 30s and 40s and dementia diagnoses between 1996 and 2015 (identified from electronic medical records). Cox proportional hazard models were adjusted for demographic characteristics, vascular comorbidities, and hypertension treatment.
Results showed that a total of 532 individuals (9.4%) were diagnosed with dementia.
Early-adulthood hypertension was not associated with dementia, although effect estimates were elevated among women (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.95 - 1.79).
Mid-adulthood persistent hypertension was associated with a 65% increased dementia risk among women (HR, 1.65; 95% CI, 1.25 - 2.18), and onset of hypertension in mid-adulthood predicted a 73% higher dementia risk in women (HR, 1.73; 95% CI, 1.24 - 2.40) compared with stable normotensive women.
Remitted hypertension was not associated with risk for dementia, and there was no evidence that hypertension or changes in hypertension increased dementia risk among men.
The researchers say their findings are "surprising" given that previous studies examining midlife hypertension as a risk factor for dementia have found no difference by sex or a stronger association among men.
But they point out growing evidence that the harmful effect of hypertension may be stronger among women than men for some outcomes, including microalbuminuria, left ventricular hypertrophy, and baroreceptor reflex sensitivity, and greater reductions in systolic and diastolic function.
However, they also note that men were more likely to die before the end of the study, particularly if they had hypertension in early or mid-adulthood. Thus, the risk for dementia associated with hypertension could have been underestimated among men.
They conclude that: "Further research is needed to disentangle possible sex-specific pathways through which elevated BP [blood pressure] over the life course accelerates brain aging."
Dr Iadecola said that while midlife hypertension has long been tied to dementia, the current finding that relatively young women with hypertension have increased risk for dementia is both novel and surprising. "Surprising, because premenopausal women have traditionally been considered to be shielded from vascular risk factors," he said.
He added that the finding that women may be more susceptible than men to the effects of early midlife hypertension on later dementia would fit well with the evidence that late-life dementia is more common in women than men.
He suggested that the increased risk seen in this study in women in their 40s could be related to perimenopause.
"At perimenopause, there is a dramatic increase in the risk for stroke that exceeds that of men of comparable age," he said. "Therefore, the study also highlights the importance of this critical period for women's health. In this context, it would have been of interest to know the menopausal/perimenopausal state of the women and the use of estrogen replacement."
This work was supported by grants from the National Institute on Aging. Coauthor Charles DeCarli is a consultant to Novartis Pharmaceuticals. The other authors have disclosed no relevant financial relationships.