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Significant reductions in the risk of mild cognitive impairment (MCI), and the combination of MCI and dementia, have been demonstrated for the first time by aggressive lowering of systolic blood pressure in new findings SPRINT MIND research study, funded by the federal government, reported at the International Alzheimer's Conference (AAIC) 2018 in Chicago
"This is the first randomized clinical trial to demonstrate a reduction in new cases of MCI alone and the combined risk of MCI plus -sausage dementia, "said Jeff D. Williamson, MD, MHS, professor of internal medicine and epidemiology and head of the department's Gerontology and Geriatric Medicine at Wake Forest School of Medicine Williamson reported these findings to AAIC 2018.
The results of this large-scale, long-term clinical trial provide the uve the strongest to date on reducing the risk of MCI and dementia by treating high blood pressure, which is one of the
"This study shows more conclusively than ever before that & dquo; There are things you can do – especially regarding risk factors for cardiovascular disease – to reduce your risk of MCI and dementia, "said Maria C. Carrillo, PhD, scientific director for head of the Alzheimer's Association. "To reduce new cases of IBD and dementia globally, we must do everything we can, both professional and individual, to reduce blood pressure to the levels outlined in this study, which we know is the best way to reduce blood pressure. it is beneficial for cardiovascular risk. "
pointed out that these results fit well with recent demographics showing reductions in new cases of dementia in developed Western cultures. These lower rates of dementia can occur when these companies begin to improve control of risk factors for cardiovascular disease through drug management, tobacco reduction, and increased awareness of healthy living
. the whole person with a combination of drugs and interventions on modifiable risk factors – as we do now in heart disease, "suggested Carrillo. "These new blood pressure data increase our level of anticipation for the US POINTER study, which includes the management of cardiovascular risk factors as part of the multi-component intervention."
Reducing Risk (US POINTER) is a two-year clinical trial funded by the Alzheimer's Association to assess whether lifestyle interventions can protect cognitive function in older people at increased risk of cognitive decline. Interventions include physical exercise, nutritional counseling and modification, cognitive and social stimulation, and improved self-management of health status.
Intensive control of blood pressure significantly reduces new cases of MCI and dementia
At AAIC 2018, Williamson and colleagues reported preliminary findings related to the risk of dementia and cognitive decline in the patient. interventional test of systolic arterial hypertension (SPRINT). SPRINT is a randomized clinical trial comparing two strategies for the management of hypertension in the elderly: an intensive strategy with a goal of systolic blood pressure less than 120 mmHg versus a standard care strategy aimed at a tension goal less systolic blood pressure. Previously, SPRINT demonstrated that more intensive blood pressure control reduced the risk of cardiovascular morbidity and mortality (NEJM, 11-26-15). SPRINT helped inform the American Heart Association 2017 and the American College of Cardiology of guidelines on hypertension
SPRINT Memory and Cognition IN Decrease of Hypertension (SPRINT MIND) examined whether treatment for hypotension decreases the risk of developing dementia and / or or MCI, and reduces the total volume of white matter lesions in the brain as shown by magnetic resonance imaging ( MRI).
The study participants were 9361 elderly hypertensive with increased cardiovascular risk (based on the Framingham score). diabetes, dementia or previous stroke. The average age of participants was 67.9 years (35.6% female) and 8,626 (92.1%) completed at least one cognitive follow-up assessment. In SPRINT MIND, the main outcome measure was the likelihood of probable dementia. Secondary endpoints included MCI and a composite outcome of MCI and / or likely dementia. Each outcome was judged by a panel of blind experts who belonged to each treatment group.
Recruitment for SPRINT began in October 2010. At one year, the mean systolic blood pressure was 121.4 mmHg in the intensive care group and 136.2 mmHg in the standard treatment group. Treatment was discontinued in August 2015 due to cardiovascular benefit (CVD) after a median follow-up of 3.26 years, but cognitive assessment continued until June 2018
Intervention – After NEJM 11-26 -15, "All major classes of antihypertensives were included in the form and were provided at no cost to participants. SPRINT researchers could also prescribe other antihypertensive drugs (not provided by the study) The protocol encouraged, but did not mandate, the use of drug classes with evidence of stronger reduction in cardiovascular outcomes, including thiazide diuretics (encouraged as a first-line agent), loop diuretics (in participants with advanced chronic renal failure) and beta-blockers ( for the "
" p articipants were seen monthly during the first three months and every three months thereafter. at a systolic blood pressure lower than 120 mm Hg. For participants in the standard treatment group, the drugs were adjusted to target systolic blood pressure of 135 to 139 mm Hg and the dose was reduced if the Systolic blood pressure was less than 130 mm Hg during a single visit or less than 135 mm Hg during two consecutive visits.
In SPRINT MIND, the researchers found a statistically significant 19% of new cases of MCI (p = 0.01) in the intensive blood pressure treatment group. The combined outcome of MCT and probable all-cause dementia was 15% lower (p = 0.02) in the intensive versus standard group, with a nonsignificant reduction in likely dementia alone (HR = 0.83, p = 0.10). Events – According to NEJM, 11-26-15, "Serious adverse events occurred in 1793 participants in the intensive treatment group (38.3%) and in 1736 participants in the standard treatment group (37.1%) ( risk ratio with intensive treatment, 1.04, P = 0.25) Serious adverse events of hypotension, syncope, electrolyte abnormalities and acute renal injury or acute renal failure , but no falls or bradycardia, occurred more frequently in the intensive-treatment group than in the standard treatment group.The orthostatic hypotension assessed at a clinical consultation was significantly less common in the group of In a total of 220 participants in the intensive treatment group (4.7%) and 118 participants in the standard treatment group (2.5%) experienced serious adverse events classified as possibly or definitively related to the intervention (hazard ratio, 1.88; <0.001) [but overall number of SAEs by group did not differ]. The magnitude and trend of differences in adverse events by treatment distribution among participants aged 75 and over were similar to those of the overall cohort.
"These results confirm the need to maintain well-controlled blood pressure, especially" A particular strength of SPRINT-MIND is that 30% of participants were African-American and 10% were Hispanic. "
"It's something that doctors and the majority of their community – patients who have high blood pressure should do the same now to keep their heart – and their brains – healthy." These new findings for Maintaining cognitive health provides another good reason to start and maintain healthy lifestyle changes in mid-life, "added Williamson
2018, Ilya Nasrallah, MD, PhD , from the University of Pennsylvania, Philadelphia, reported preliminary results from 673 participants at SPRINT MIND who were recruited for brain magnetic resonance imaging (MRI). Total brain volume and volume (TBV) ) were measured in 454 participants (67.4%) at a median of 3.98 years after randomization
In this sub-study, the volume of WML increased in both treatment groups. increase was significantly less in the intensive treatment group.There was no significant difference in the change in total brain volume.
In the intensive treatment group, the WML volume increased by 0.28 cm 3 compared with 0.92 cm 3 in the standard treatment group (mean difference = 0.64 cm 3 p = 0.004)
TBV decreased by 27.3 cm 3 in the intensive treatment group vs. 24.8 cm 3 in the standard treatment group (mean difference = 2.54 cm 3 p = 0.16).
White matter lesions are frequently indicative of small vessel disease and linked to a higher risk of stroke, dementia, and higher mortality. While white matter lesions are considered to increase the risk of vascular dementia, they can also be a risk factor for Alzheimer's disease. People with dementia can have Alzheimer's disease and white matter lesions at the same time. Research has shown that when people have more of a type of brain-related changes to the disease, the cognitive consequences are greater.
Genomic Analysis of the Alzheimer Phase 2a Study with ANAVEX ® 2-73 May Allow Precision Medicinal Approach "Precision Medicine is about giving the right therapy to the right patient at the right time, adapted to its specific biological makeup, "says Professor Harald Hampel, MD, Ph.D., MA, MSc, AXA Research Fund and Sorbonne University Excellence Chair Department of Neurology, Sorbonne University, Paris
Precision medicine favors the personalization and individualization of care, with treatments and practices adapted to the specific situation and needs of the patient, taking into account the genes, the environment and the environment. of the lifestyle. Sometimes called personalized medicine, it is a common approach in cancer and respiratory diseases.
At AAIC 2018, Hampel and his colleagues reported the results of an innovative attempt to move closer to precision medicine in Alzheimer's therapeutic trials. Anavex Life Sciences (AVXL) conducted a 57-week Phase 2a study with ANAVEX ® 2-73, a selective sigma-1 receptor agonist in 32 people with mild Alzheimer's disease to moderate and analyzed the whole genome DNA and RNA of all study participants, resulting in the analysis of 33,311 genes and 860 pathways.
The company has identified several genetic variants that affect the drug's response, including SIGMAR1, which is the target of ANAVEX®2-73 and COMT, a gene involved in the memory function. They further found that excluding those with these variants (about 20% of the study group) – about 80% of the population – resulted in improved cognitive test scores (MMSE) and activities of daily living (ADCS-ADL) (p <0.05).
Including participants with a lighter disease (MMSE reference 20) and excluding those with a variant SIGMAR1 resulted in an improvement of 1.7 MMSE and 3.9 ADCS-ADL at week 57. L & # 39; Further exclusion of the COMT variant resulted in an improvement in the score of 2.0 MMSE and 4.9 ADCS-ADL at week 57.
"This study represents an exciting step forward, far from the development of drugs" miracle , one-size-fits-all "in Alzheimer's disease, following targeted therapeutic successes in the field of oncology," said Mr. Hampel. "Our vision is that an approach Precision medicine will allow us to more accurately treat and prevent the main features of the cause and progression of Alzheimer's disease. "We are intrigued by the fact that several studies are now planned or underway."
the company, these markers of selectio n patients will be implemented in a future phase 2b / 3 study of ANAVEX ® 2-73.
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