Coenzyme NAD+ Postpones Aging in Mice and Worms

August 7, 2017 · Posted in Potential Treatments · Comment 

mouseAging cells seem to lose their ability to repair DNA, while the mitochondria that power cells also become less reliable. A coenzyme called NAD+ may be able to postpone these changes. NAD+, which is found in all living cells, naturally decreases with age.

A 2016 article by Evandro Fei Fang and colleagues in the journal Cell Metabolism reports that giving mice and roundworms supplemental NAD+ postponed cell aging and extended the lives of these animals.

The researchers hope this research might eventually help patients with Alzheimer’s and Parkinson’s’ diseases.

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.

Statins Have Many Benefits

July 25, 2017 · Posted in Current Treatments · Comment 

box of statinsPatients with mood disorders and elevated lipids, cholesterol, or triglycerides can get several benefits by taking statin drugs. Patients with depression are at increased risk for cardiovascular disease, heart attack, and stroke, and statins can lower these risks. Statins lower cholesterol and triglycerides.

Compared to women not taking statins, women taking this class of medications have a lower risk of depression. Men taking statins have a lower incidence of depression following a heart attack than men who are not taking statins.

Several studies over the past two decades have suggested that statins can also decrease the incidence of Alzheimer’s disease, though a 2017 article by Julie M. Zissimopoulos and colleagues in the journal JAMA Neurology suggested the effectiveness of statins in preventing Alzheimer’s may depend on the race and gender of the person taking them. People with depression are at increased risk for Alzheimer’s.

Editor’s Note: Given these many benefits, it may be a good idea for patients with depression or bipolar disorder and high lipid levels to talk to their physician about whether statins would be a helpful treatment for them.

Medical Device May Treat Alzheimer’s Disease

January 17, 2017 · Posted in Potential Treatments · Comment 

NeuroAD for Alzheimer's

A recently completed clinical trial suggests that NeuroAD, a treatment system that combines transcranial magnetic stimulation and cognitive training targeted at brain regions affected by Alzheimer’s disease, may be effective at treating mild to moderate cases of the illness.

Neuronix Ltd, the company that produces the device used to deliver transcranial magnetic stimulation in the trial, plans to seek Food and Drug Administration approval for NeuroAD. It would be the first device approved for the treatment of Alzheimer’s in the US. The device is already in use in Europe and Asia.

In the clinical trial, 131 patients received six weeks of the NeuroAD treatment or a sham treatment used as a comparison. Those participants who received the real intervention performed better on an assessment of Alzheimer’s and experienced minimal side effects.

In transcranial magnetic stimulation, a non-invasive procedure, magnets placed near the skull stimulate electrical impulses in the brain. This activates neurons, releasing excitatory transmitters and brain-derived neurotrophic factor (BDNF), which is important for new synapse formation and long-term learning and memory.

Editor’s Note: This editor (Robert Post) has long advocated the use of repeated transcranial magnetic stimulation (rTMS) with simultaneous cognitive behavioral or other positive therapy to activate and enhance specific neural circuits and relieve depression. The trial of NeuroAD adds evidence of the positive effects of this approach in domains other than depression. Cognitive training enhanced by rTMS may be helpful with a variety of cognitive difficulties.

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.

Cinnamon Improves Memory in Mice

October 27, 2016 · Posted in Potential Treatments · Comment 

cinnamon improves learning in mice

A recent study found that mice that ate more cinnamon got better and faster at learning. In the study, published in the Journal of Neuroimmune Pharmacology in 2016, separated mice into good learners and poor learners based on how easily they navigated a maze to find food. After the poor learners were fed cinnamon for a month, they could find the food more than twice as quickly as before.

The benefits of cinnamon come from sodium benzoate, a chemical produced as the body breaks down the cinnamon. Sodium benzoate enters the brain and allows the hippocampus to create new neurons.

Feeding cinnamon to the poor learning mice normalized their levels of receptors for the neurotransmitter GABA, closing the gap with good learners. Sodium benzoate also improved the structural integrity of some brain cells. Cinnamon also can help sensitize insulin receptors.

Doctors hope these findings may eventually contribute to treatment research on Alzheimer’s and Parkinson’s diseases.

Cinnamon should be consumed in moderate quantities because the Chinese variety most commonly found in North American supermarkets has high levels of coumarin, a compound that can be toxic to the liver when consumed in large quantities. Ceylon (Sri Lankan) cinnamon has lower levels of coumarin.

Alzheimer’s Treatments May Work for Memory Dysfunction in Depression

April 11, 2016 · Posted in Potential Treatments · Comment 

memory problems in depression

In a recent BNN article on potential drugs for memory loss, we omitted two conventional classes of drugs used to treat Alzheimer’s Disease—acetylcholine esterase inhibitors (AChE-Is) and the blocker of glutamate NMDA receptors memantine (Namenda). This was intentional, as we hoped to suggest possible approaches prior to the use of these drugs for full-blown dementia. However, we neglected to cite a 1999 study by Fred Jacobsen in the Journal of Clinical Psychiatry that indicated that the AChE-I drug donepezil (Aricept) was effective in improving drug-induced memory dysfunction in patients without dementia. Side effects included insomnia, nausea, vomiting, and diarrhea.

Jacobsen has used AChE-Is to improve memory in over 80 patients with unipolar or bipolar depression, aged 19-85. In a 2016 personal communication to the BNN, he indicated that doses of 5mg/day are typically enough to improve memory. Higher doses of 10mg/day may be more effective, but increase the risk of switching into mania for patients with bipolar depression. Some of Jacobsen’s patients have used AChE-I drugs for 10–15 years without the drugs losing effectiveness. For some patients, Jacobsen has switched from prescribing donezepil to prescribing rivastigmine (Exelon or Exelon patch), which he finds they can more easily tolerate.

We should also remind readers of the BNN of our previous report on memantine (Namenda) for bipolar depressed patients with cognitive impairment. We wrote, “In an abstract presented at the 67th Annual Meeting of the Society of Biological Psychiatry in 2012, Dan V. Iosifescu reported that in a randomized 12-week study in which the anti-Alzheimer’s drug memantine was given to 72 euthymic bipolar subjects experiencing cognitive deficits, the drug was associated with improvement in spatial and working memory, verbal and episodic memory, and other indices that included measurements of attention and language skills. In conjunction with this treatment, a subgroup of subjects had increases in left hippocampal NAA (a measure of neuronal viability) and increases in choline in the right hippocampus. The initial improvements in these neuropsychological test results remained over 12 weeks of open follow-up.”

In an earlier proof-of-concept study published in the journal CNS Neuroscience and Therapeutics in 2009, Iosifescu had also reported that among nineteen subjects with bipolar disorder that was in remission, but who had residual cognitive deficits, open-label treatment with the AChE-I galantamine (extended release) at doses of 8–24 mg/day led to improvement in those cognitive symptoms after 4 months.

Drug Reduces Agitation in Patients with Alzheimer’s

April 8, 2016 · Posted in Potential Treatments · Comment 

agitation in Alzheimer's

Agitation is common among people with Alzheimer’s dementia. A 2015 phase 2 clinical trial by Jeffrey L. Cummings and colleagues, which was published in the journal JAMA, found that a combination of the drugs dextromethorphan hydrobromide and quinidine sulfate called Nuedexta reduced agitation significantly compared to placebo in patients with probable Alzheimer’s disease over a period of 10 weeks. Dextromethorphan-quinidine was dosed at 20mg/10mg in the morning for one week, then twice daily in weeks 2 and 3, then increased to 30mg/10mg twice daily for weeks 4 and 5. Side effects included falls, diarrhea, and urinary tract infections. Dextromethorphan-quinidine did not cause cognitive impairment, sedation, or irregularities in heart rate.

Changes in Sense of Humor May Be Warning Sign of Dementia

April 6, 2016 · Posted in Diagnosis, Risk Factors · Comment 

senior man laughingA change in a person’s sense of humor could be an early indicator of dementia, according to a 2015 article by Jason Warren and colleagues in the Journal of Alzheimer’s Disease. The changes can appear as early as 10 years before a diagnosis of dementia. Almost all participants who would go on to be diagnosed with frontotemporal dementia showed an increased preference for slapstick humor over satirical or absurdist compared with those who would not. In contrast, changes in sense of humor appeared in less than half of those who would go on to be diagnosed with Alzheimer’s disease, indicating that changes in sense of humor may allow doctors to distinguish between different types of dementia.

The study has some limitations. It was small (48 patients) and relied on patients’ memory of what kind of humor they enjoyed 15 years earlier. More research is needed to clarify the link between changes in humor preferences and dementia.

Warren suggests that changes in humor appear before other warning signs of dementia, such as memory loss. He called humor a type of “stress test” for the brain, since getting a joke can require a quick shift in perspective.

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