Caffeine One of Several Compounds That May Protect Against Dementia

August 2, 2017 · Posted in Risk Factors · Comment 

cup of coffee

A 2017 article by Yousuf O. Ali and colleagues in the journal Scientific Reports finds that 24 different compounds may boost a brain enzyme that protects against dementia. The enzyme, NMNAT2, protects neurons from stress and combats misfolded proteins called tau that form plaques in the brain as people age.

Ali and colleagues screened 1280 compounds to identify those that might increase NMNAT2 production. Twenty-four of these looked promising, including caffeine and rolipram, an “orphaned drug” once studied as an antidepressant but discontinued in the 1990s. Others with weaker effects on NMNAT2 production included the atypical antipsychotic ziprasidone, cantharidin (a wart-removing substance secreted by blister beetles), fungal metabolite wortmannin, and retinoic acid, a vitamin A derivative. Thirteen of the compounds tested decreased NMNAT2 production.

The researchers followed up the caffeine finding by testing caffeine in mice genetically engineered to produce less NMNAT2. The caffeine administration normalized NMNAT2 production levels in these mice.

Senior researcher Hui-Chen Lu hopes this research will lead to the development of new drugs that can create a chemical blockade against the effects of neurodegenerative illnesses.

Antipsychotic Drug Pimavanserin Seems to Reduce Psychosis in People with Alzheimer’s

August 1, 2017 · Posted in Potential Treatments · Comment 

elderly womanThe antipsychotic drug pimavanserin was approved by the US Food and Drug Administration last year as a treatment for hallucinations and delusions in Parkinson’s disease. Now it looks as though it may also help people with Alzheimer’s disease. Pimavanserin works differently than other antipsychotic medications—a selective serotonin inverse agonist, it acts at serotonin HT2A receptors to produce effects opposite to those that serotonin would produce at the same receptor.

In a trial of 181 patients with Alzheimer’s and psychotic symptoms, those who received 34 mg/day of pimavanserin had a significant improvement in psychotic symptoms in six weeks compared to those who received placebo.

Over 12 weeks of treatment, pimavanserin did not impair cognition, as atypical antipsychotics can do.

Pimavanserin was well tolerated. The most common side effects were falls, urinary tract infections, and agitation. Like other atypical antipsychotics, the drug carries a box warning from the FDA that there is an increased risk of death when the drug is used to treat older people with dementia-related psychosis.

The FDA has designated pimavanserin a breakthrough therapy and is giving it priority review. These designations can speed up the development and review of a drug and are granted when a drug looks like it will be substantially better or safer than existing treatments for a serious condition.

Transcranial Direct Current Stimulation Improved Picture-Naming in People with Dementia

July 31, 2017 · Posted in Potential Treatments · Comment 
picture naming activity

Picture-naming activity

In a study of 12 people with mild Alzheimer’s disease or frontotemporal dementia, transcranial direct current stimulation (tDCS) improved the participants’ abilities to name an object in a picture more than did a sham stimulation. TDCS is a treatment in which an anode and a cathode electrode placed on the skull are used to deliver a steady low level of electrical current to the brain. There is currently no treatment available to specifically target symptoms of dementia such as forgetting words.

The research by Howard Chertkow and colleagues was presented at the 2017 meeting of the American Academy of Neurology. In the study, participants received either 30 minutes of anodal tDCS targeting the parietal lobe of the brain or a sham stimulation.

They also received training in picture-naming. The participants were evaluated before stimulation, at the final stimulation session, two weeks after stimulation, and two months after stimulation. Compared to those who received the sham stimulation, those who received real tDCS improved at picture-naming, and maintained that improvement for two months.

Those who received tDCS also performed better at naming new pictures not included in the training, and were better able to remember a string of digits than those who got the sham stimulation.

Marker of Heart Failure May Predict Brain Deterioration

July 27, 2017 · Posted in Diagnosis · Comment 

heartA protein released into the blood in response to heart failure may be able to predict brain deterioration before clinical symptoms appear. The protein, N-terminal pro-B-type natriuretic peptide (NT-proBNP), is released when cardiac walls are under stress. High levels of NT-proBNP in the blood are a sign of heart disease. A 2016 Dutch study indicated that high levels of NT-proBNP in the blood are also linked to smaller brain volume, particularly small gray matter volume, and to poorer organization of the brain’s white matter. The study by researcher Hazel I. Zonneveld and colleagues, published in the journal Neuroradiology, assessed heart and brain health in 2,397 middle-aged and elderly people with no diagnosed heart or cognitive problems.

Researchers are working to clarify the relationship between cardiac dysfunction and preliminary brain disease, but researcher Meike Vernooij says it is likely cardiac dysfunction comes first and leads to brain damage. Measuring biomarkers such as NT-proBNP may help identify brain diseases such as stroke and dementia earlier and allow for earlier treatment and lifestyle changes that can slow or reverse the course of disease.

Bipolar Disorder and Diabetes Linked

July 19, 2017 · Posted in Risk Factors · Comment 

diabetes linked to bipolar disorderA systematic literature review in 2016 showed a definitive link between bipolar disorder and diabetes. Bipolar disorder almost doubles the risk of diabetes while diabetes more than triples the risk of bipolar disorder. The article by Ellen F. Charles and colleagues was published in the International Journal of Bipolar Disorders.

The review included seven large cohort studies. The studies, based on elderly populations only, examined bipolar disorder and diabetes rates. Charles and colleagues suggested that shared mechanisms could cause both illnesses. New disease models that explain the link between bipolar disorder and diabetes could lead to better treatments.

The review also reported that both bipolar disorder and diabetes were independently associated with risk of cognitive decline and dementia in these elderly individuals. People with diabetes had more brain atrophy on average than others who share their age and gender but did not have diabetes. People with bipolar disorder who also had diabetes and either insulin resistance or glucose intolerance had neurochemical changes in the prefrontal cortex that indicated poor neuronal health. In some cases, these patients also had reduced brain volume in the hippocampus and cortex.

Microdoses of Lithium May Stabilize Cognition in People with Alzheimer’s

January 13, 2017 · Posted in Potential Treatments · Comment 

lithium for Alzheimer's

Several researchers have found that lithium has some value in fighting dementia. The researcher Lars Kessing has published several studies showing that people taking clinical doses of lithium for bipolar disorder have a lower incidence of dementia in old age.

In 2011, another researcher, Oreste Vicentes Forlenza, reported that a year of low-dose lithium (typically around 300mg/day) slowed deterioration in people with mild cognitive impairment compared to placebo.

In an article published in the journal Current Alzheimer Research in 2013, researchers led by Marielza Andrade Nunes reported that very small doses of lithium (more than a thousand times lower than doses used to treat mood disorders) also improved mild cognitive impairment in people with Alzheimer’s disease.

In Nunes’ study, participants with Alzheimer’s disease were randomly assigned to receive either 300 micrograms of lithium daily or a placebo. Beginning at three months of treatment, those receiving the microdoses of lithium showed stable performance on a common Alzheimer’s evaluation tool that measures how well patients remember, recall information, and follow directions; while those taking placebo got worse.

This continued over the 15 months of the study, with the difference between the two groups intensifying over time—those taking placebo got worse, while those getting the microdoses of lithium remained stable.
There were no complaints of side effects from the microdoses of lithium, and participants showed no sign of impairment to their kidney or thyroid function (a risk with the higher doses of lithium used to treat bipolar disorder).

In 2015, Nunes and colleagues reported in the journal PLOS ONE that in a mouse model of Alzheimer’s disease, mice treated with chronic low doses of lithium in their water had less memory disruption, fewer plaques in the brain, and fewer reductions in cortex and hippocampus size compared to mice given plain water.

These studies suggest that low or micro doses of lithium may be a promising treatment for Alzheimer’s disease. Much more research is needed to determine appropriate lithium dosing for the treatment of dementia or cognition problems.

Galantamine Did Not Improve Cognitive Deficits in People with Bipolar Disorder

November 18, 2016 · Posted in Current Treatments · Comment 

cognitive deficits

In a recent study by researcher Dan V. Iosifescu and colleagues, the drug galantamine, which is used to treat dementia, did not improve cognitive function in euthymic people with bipolar disorder. The drug had done so in earlier studies. Seventy-two participants with bipolar disorder that was in remission were randomized to receive either a placebo or galantamine extended release for a period of two weeks. Doses of galantamine ranged from 8 to 24 mg/day.

The participants took several tests of attention and memory over the course of the study. After 16 weeks of treatment, those taking galantamine did not show significant improvements in functioning compared to those who received placebo.

This research was presented at the 2016 meeting of the Society of Biological Psychiatry.

Bad Habits May Reduce Brain Volumes, May Cause Dementia

September 26, 2016 · Posted in Risk Factors · Comment 

bad habits can reduce brain volumes

Smoking, alcohol use, obesity, and diabetes aren’t just harmful to the body. They may actually lead to dementia.

Behavioral risk factors for cardiovascular disease like those listed above have been linked to reduced volume in the brain as a whole and several brain regions,  including the hippocampus, precuneous, and posterior cingulate cortex. A 2015 study by researcher Kevin King and colleagues found that these reduced brain volumes are early indicators of cognitive decline.

King and colleagues analyzed data on 1,629 participants in the long-term Dallas Heart Study. Their cardiovascular risk factors were assessed when they began the study, and their brain volume and cognitive function were measured seven years later.

Alcohol use and diabetes were associated with lower total brain volumes, while smoking and obesity were linked to low volumes in the posterior cingulate cortex.

Low hippocampal volume was linked to past alcohol use and smoking, while lower precuneous volume was linked to alcohol use, obesity, and blood glucose levels.King and colleagues suggested that subtle differences in brain volumes  in midlife are the first sign of developing dementia in participants who were still younger than 50 years of age.

Inactivity in Young Adulthood May Worsen Cognition Later in Life

September 22, 2016 · Posted in Risk Factors · Comment 

inactivity can worsen cognition later in life

The couch potato lifestyle common in the US may have consequences later, in the form of deficits in memory, executive functioning (including planning and execution) and processing speed.

At the 2015 Alzheimer’s Association International Conference, researcher Kristine Yaffe and colleagues reported that low levels of physical activity and high rates of television viewing in young adulthood may reduce cognitive capabilities in midlife.

The Centers for Disease Control report that less than 50% of adults aged 18–64 get the recommended minimum of physical activity each week. The guidelines recommend at least 150 minutes of moderate intensity aerobic activity (such as walking briskly) and two or more days of muscle-strengthening activities that work all major muscle groups.

Yaffe says that physical activity can protect against cognitive decline or dementia later on.
Participants in the long-term study who reported burning fewer than 300 calories per 50-minute session three times per week during two-thirds of their followup visits had worse cognition at year 25 than those participants who were more active. Those who watched more than four hours of television per day also had reduced cognition in midlife.

Yaffe stresses that exercising regularly is not just important in keeping weight down and protecting the heart, but also in protecting the brain. Regular physical activity may even prevent illnesses such as Alzheimer’s disease.

Lithium Improves Medical Outcomes

May 27, 2016 · Posted in Current Treatments · Comment 

lithium improves medical outcomes

Lithium is one of the most effective medications for bipolar disorder, but it has other benefits as well. At a 2015 scientific meeting, Ronald Fieve reported that among 1021 psychiatric outpatients, 570 who received long-term lithium treatment for their psychiatric illnesses had a significantly lower likelihood of certain medical conditions compared to the other outpatients who did not receive lithium therapy. The medical conditions that lithium made less likely were seizures, amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, dementia, and heart attack.

It is not yet know how lithium decreases these medical conditions. It may be by increasing the length of telomeres. Telomeres are repeated DNA sequences that sit at the end of chromosomes and protect them during cell replication. Telomeres get shorter with aging and with stressors or psychiatric illnesses. Lithium directly increases the enzyme telomerase, which maintains telomere length. This may be one reason lithium use provides some protection from seizures, heart attacks, and other conditions.

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