Latest Research News
A clinical trial involving 9361 older adults (50+) with hypertension but without diabetes or history of stroke has found that intensive control of blood pressure significantly reduced the risk of developing mild cognitive impairment.
While there was also a 15% reduction in dementia, this result did not reach statistical significance. This may have been due to the small number of new cases of dementia in the study groups.
Participants were randomly assigned to a systolic blood pressure goal of either less than 120 mm HG (intensive treatment) or less than 140 mm HG (standard treatment). They were then classified after five years as having no cognitive impairment, MCI or probable dementia.
The trial was stopped early due to its success in reducing cardiovascular disease. As a result, participants were on intensive blood pressure lowering treatment for a shorter period than originally planned. This impacted the number of cases of dementia occurring.
Hypertension affects more than half of Americans over age 50 and more than 75% of those older than 65.
The SPRINT MIND Investigators for the SPRINT Research Group. (2019). Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA, 321(6), 553–561.
A large study using data from the famous Framingham Heart Study has compared changes in dementia onset over the last three decades. The study found that over time the age of onset has increased while the length of time spent with dementia has decreased.
The study involved 5,205 participants from the Framingham Original and Offspring cohorts. Four 5-year periods anchored to different baseline examinations (participants have been examined every four years) were compared. These baseline years are (on average, because participants’ schedules are different): 1978, 1989, 1996, 2006. Participants were those who were aged 60 or older and dementia-free at the start of a time period. There were at least 2000 participants in each time period. In total, there were 371 cases of dementia, and 43% of dementia cases survived more than 5 years after diagnosis.
It was found that the mean age of dementia onset increased by around two years per time period, while age at death increased by around one year. Length of survival after diagnosis decreased over time for everyone, taken as a whole, and also for each gender and education level, taken separately. Survival was almost 6 years in the first time period, and only three years in the last. But the mean age of onset was 80 in the first period, compared to over 86 in the last.
However, the changes haven’t been steady over the 30 years, but rather occurred mostly in those with dementia in 1986–1991 compared to 1977–1983.
Part of the reason for the changes is thought to be because of the reduced risk of stroke (largely because of better blood pressure management), and the better stroke treatments available. Stroke is a major risk factor for dementia. Other reasons might include lower burdens of multiple infections, better education, and better nutrition.
A long-running study comparing African-Americans and Nigerians has found the incidence of dementia has fallen significantly over two decades among the African-Americans, but remained the same for the Nigerians (for whom it was lower anyway).
The study enrolled two cohorts, one in 1992 and one in 2001, who were evaluated every 2–3 years until 2009. The 1992 cohort included 1440 older African-Americans (70+) and 1774 Nigerian Yoruba; the 2001 cohort included 1835 African-Americans and 1895 Yoruba. None of the participants had dementia at study beginning.
The overall standardized annual incidence rate was 3.6% for the 1992 African-American cohort, and 1.4% for the 2001 cohort. For the Yoruba, it was 1.7% and 1.4%, respectively.
It's suggested that one reason for the improvement among African-Americans may be medications for cardiovascular conditions. Although both groups had similar rates of high blood pressure, this was recognized and treated in the American group but not in the Nigerian.
As you can see, African-Americans in the earlier cohort were more than twice as likely as Africans to develop dementia. Their decrease has brought them into line with the African rate.
Although the rate of new cases of dementia decreased, the African-Americans enrolling in 2001 had significantly higher rates of diabetes, hypertension and stroke, but also higher treatment rates, than the African-Americans who enrolled in 1992.
The finding offers hope that treatment can offset the expected increase in dementia resulting from the rise in lifestyle diseases.
A large meta-analysis has concluded that having diabetes increases the chance that a person with mild cognitive impairment will progress to dementia by 65%.
There was no consistent evidence that hypertension or cholesterol levels increased the risk of someone with MCI progressing to dementia. Smoking was similarly not associated with increased risk, although the reason for this probably lies in mortality: smokers tend to die before developing dementia.
There was some evidence that having symptoms of psychiatric conditions, including depression, increased the risk of progressing to dementia.
There was some evidence that following a Mediterranean diet decreased the risk of an individual with amnestic MCI progressing to Alzheimer's, and that higher folate levels decrease the risk of progressing from MCI to dementia. The evidence regarding homocysteine levels was inconsistent.
The evidence indicates that level of education does not affect the risk of someone with MCI progressing to dementia.
Do note that all this is solely about progression from MCI to dementia, not about overall risk of developing dementia. Risk factors are complex. For example, cholesterol levels in mid-life are associated with the later development of dementia, but cholesterol levels later in life are not. This is consistent with cholesterol levels not predicting progression from MCI to dementia. Level of education is a known risk factor for dementia, but it acts by masking the damage in the brain, not preventing it. It is not surprising, therefore, that it doesn't affect progression from MCI to dementia, because higher education helps delay the start, it doesn't slow the rate of decline.
Do note also that a meta-analysis is only as good as the studies it's reviewing! Some factors couldn't be investigated because they haven't been sufficiently studied in this particular population (those with MCI).
The long-running Cache County study has previously found that 46% of those with MCI progressed to dementia within three years; this compared with 3% of those (age-matched) with no cognitive impairment at the beginning of the study.
More recently, data from the long-running, population-based Rotterdam study revealed that those diagnosed with MCI were four times more likely to develop dementia, over seven years. compared with those without MCI. Of those with MCI (10% of the 4,198 study participants), 40% had amnestic MCI — the form of MCI that is more closely associated with Alzheimer's disease.
The 2014 study also found that older age, positive APOE-ɛ4 status, low total cholesterol levels, and stroke, were all risk factors for MCI. Having the APOE-ɛ4 genotype and smoking were related only to amnestic MCI. Waist circumference, hypertension, and diabetes were not significantly associated with MCI. This may be related to medical treatment — research has suggested that hypertension and diabetes may be significant risk factors only when untreated or managed poorly.
de Bruijn, R.F.A.G. et al. Determinants, MRI Correlates, and Prognosis of Mild Cognitive Impairment: The Rotterdam Study. Journal of Alzheimer’s Disease, Volume 42/Supplement 3 (August 2014): 2013 International Congress on Vascular Dementia (Guest Editor: Amos D. Korczyn), DOI: 10.3233/JAD-132558.
The jugular venous reflux (JVR) occurs when the pressure gradient reverses the direction of blood flow in the veins, causing blood to leak backwards into the brain. A small pilot study has found an association between JVR and white matter changes in the brains of patients with Alzheimer’s disease and those with mild cognitive impairment. This suggests that cerebral venous outflow impairment might play a role in the development of white matter changes in those with Alzheimer’s.
JVR occurs when the internal jugular vein valves don’t open and close properly, which occurs more frequently in the elderly. The study involved 12 patients with Alzheimer’s disease, 24 with MCI, and 17 age-matched controls. Those with severe JVR were more likely to have hypertension, more and more severe white matter changes, and tended to have higher cerebrospinal fluid volumes.
Further research is needed to validate these preliminary findings.
Chung, C-P. et al. 2013. Jugular Venous Reflux and White Matter Abnormalities in Alzheimer’s Disease: A Pilot Study. Journal of Alzheimer’s Disease, 39 (3), 601-609.
A study following 837 people with MCI, of whom 414 (49.5%) had at least one vascular risk factor, has found that those with risk factors such as high blood pressure, diabetes, cerebrovascular disease and high cholesterol were twice as likely to develop Alzheimer's disease. Over five years, 52% of those with risk factors developed Alzheimer's, compared to 36% of those with no risk factors In total, 298 people (35.6%) developed Alzheimer's.
However, of those with vascular risk factors, those receiving full treatment for their vascular problems were 39% less likely to develop Alzheimer's disease than those receiving no treatment, and those receiving some treatments were 26% less likely to develop the disease.
Treatment of risk factors included using high blood pressure medicines, insulin, cholesterol-lowering drugs and diet control. Smoking and drinking were considered treated if the person stopped smoking or drinking at the start of the study.
Part of the Women's Health Initiative study looking at the effect of hormone therapy on thinking and memory in postmenopausal women, involving over 1400 women, has found those who had high blood pressure at the start of the study (eight years earlier) had significantly higher amounts of white matter lesions. Damage to white matter seems to be an independent risk factor for dementia. The finding adds to evidence suggesting that preventing hypertension helps protect against dementia. High blood pressure is common in the U.S. — of the nearly 99,000 women enrolled in the WHI study, 37.8% had hypertension. You can watch the researcher discussing the findings at http://www.eurekalert.org/multimedia/pub/19494.php?from=152110
Kuller, L. H., Margolis, K. L., Gaussoin, S. A., Bryan, N. R., Kerwin, D., Limacher, M., et al. (2009). Relationship of Hypertension, Blood Pressure, and Blood Pressure Control With White Matter Abnormalities in the Women's Health Initiative Memory Study (WHIMS) MRI Trial. The Journal of Clinical Hypertension, 9999(9999). doi: 10.1111/j.1751-7176.2009.00234.x.
Midlife hypertension has been confirmed as a risk factor for the development of dementia in late life, but there have been conflicting findings about the role of late-life hypertension. Now a five-year study involving 990 older adults (average age 83) with cognitive impairment but no dementia, has found that dementia developed at around the same rate among participants with and without hypertension, among those with memory dysfunction alone and those with both memory and executive dysfunction. However, among patients with executive dysfunction only, presence of hypertension was associated with double the risk of developing dementia (57.7 percent of those with high blood pressure progressed to dementia, vs. 28 percent of those without). The findings suggest that efforts to control to hypertension should be especially targeted to this group.
Two mouse experiments have found that the drug carvedilol, prescribed for the treatment of hypertension, significantly improved synaptic transmission in Alzheimer's disease-type brains, and at a behavioral level significantly improved learning and memory.
Arrieta-Cruz, I. et al. 2010. Carvedilol Reestablishes Long-Term Potentiation in a Mouse Model of Alzheimer’s Disease. Journal of Alzheimer's Disease, 21 (2), in press.
Older news items (pre-2010) brought over from the old website
Why sufferers from Alzheimer's disease might have lower blood pressure
A review of studies relating to dementia and blood pressure suggests that rather than low blood pressure being a causative factor for cognitive impairment, it is the failing memory that reduces blood pressure — by allowing the patient to forget the anxieties that cause stress. If confirmed, the finding also suggests that heart disease could be substantially reduced in old people simply by making them happier about themselves and their lives.
Sven, K. et al. 2008. Is sympathetic activation by stressful memories linked to the occurrence of hypertension and metabolic syndrome? Bioscience Hypotheses, 1 (4), 179-184.
Full text available at http://dx.doi.org/10.1016/j.bihy.2008.04.006
High blood pressure or irregular heartbeat linked to Alzheimer's disease progression
A study of 135 men and women newly diagnosed with Alzheimer’s found that those with high blood pressure at the time of diagnosis showed a rate of memory loss roughly 100% faster than those with normal blood pressure, and those with atrial fibrillation (an irregular heartbeat) showed a rate of memory decline that was 75% faster than those with normal heartbeats. The findings suggest that treating these conditions may also slow memory loss in Alzheimer’s sufferers.
Mielke, M.M. et al. 2007. Vascular factors predict rate of progression in Alzheimer disease. Neurology, 69, 1850-1858
Low blood pressure risk factor for Alzheimer's
A long-term study of 488 adults over 75 (the Bronx Aging Study) found that 122 participants developed dementia (65 Alzheimer’s, 28 vascular dementia, 29 other), and that the relative risk of dementia increased as a function of decreases in blood pressure (diastolic and mean arterial). Low diastolic BP significantly increased the risk of developing Alzheimer’s, but not vascular dementia. Those with mildly to moderately raised systolic BP had a reduced risk of developing Alzheimer’s. The risk of developing dementia was higher in those who had persistently low BP over 2 years.
Verghese, J., Lipton, R.B., Hall, C.B., Kuslansky, G. & Katz, M.J. 2003. Low blood pressure and the risk of dementia in very old individuals. Neurology, 61, 1667-1672.
High blood pressure and cholesterol are risk factors for Alzheimer's disease
A large-scale Finnish study following 1449 men and women over 21 years found that raised systolic blood pressure and high serum cholesterol concentration, particularly in combination, in midlife, increase the risk of Alzheimer's disease in later life. Raised diastolic blood pressure had no significant effect.
The study was reported in the British Medical Journal.