Citicoline Might Improve Memory

September 16, 2013 · Posted in Potential Treatments · Comment 

older man thinkingWe’ve written before that the dietary supplement citicoline improved depression in both unipolar and bipolar patients with methamphetamine dependence, reduced cocaine use in bipolar depressed patients with cocaine dependence, and improved cognition in healthy middle-aged women. Findings from a 2013 Italian study by Gareri et al. published in Clinical Interventions in Aging suggests that citicoline improves mild vascular cognitive impairment in older adults, though the study was not randomized, so its results may not be reliable. Citicoline is a natural substance found in the brain and the liver that can also be taken as a nutritional supplement.

The study examined 349 patients over age 64 (mean age 79.9) who had memory impairment and evidence of vascular lesions in the brain (but not Alzheimer’s disease). Participants who received citicoline (500mg twice daily for 9 months) scored better on a memory examination at 3 months and at the completion of the study, while participants who did not receive citicoline performed worse on the exam. Those who received citicoline also saw some statistically non-significant improvement in mood.

The researchers believe that citicoline’s effects may also extend to Alzheimer’s dementia because citicoline contributes to the synthesis of acetylcholine. (Most Alzheimer’s drugs inhibit the breakdown of acetylcholine).

Side effects were minimal, and included occasional excitability or restlessness, digestive intolerance, and headaches.

Higher Levels of Caffeine in Blood May Be Associated With Lower Likelihood of Dementia

July 19, 2013 · Posted in Potential Treatments, Risk Factors · Comment 

older men drinking coffee

Alzheimer’s disease and other kinds of dementia can be devastating. Researchers are looking for treatments and lifestyle choices that may prevent, slow, or lessen the likelihood of serious dementia. Some epidemiological research in humans and other studies of animals has suggested that consumption of coffee or caffeine may help protect against the development of Alzheimer’s disease. A 2012 study by Arendash et al. published in the Journal of Alzheimer’s Disease sought to clarify the connection between coffee and cognitive status. The researchers also collected data on biomarkers in blood.

In patients with mild cognitive impairment, those patients whose blood levels of caffeine were 1200 ng/mL or higher (an amount that would result from drinking 3–5 cups of coffee daily) did not develop dementia during the following two to four years, while half of those whose blood levels of caffeine were below this threshold did. Moreover, those patients who had mild cognitive impairment at the beginning of the study had lower levels of caffeine than those who had normal cognitive functioning at that time.

Patients with mild cognitive impairment who later developed dementia had low levels of three biomarkers in their blood—the neurotrophic factor granulocyte colony-stimulating factor (G-CSF), the anti-inflammatory cytokine IL-10, and the pro-inflammatory cytokine IL-6. This suggests that low levels of these biomarkers may be an indicator of impending Alzheimer’s disease. G-CSF, in particular, has shown beneficial effects on cognition in mice.

Since half of patients with lower levels of caffeine did not develop dementia, it is clear that caffeine is far from being the only factor that could affect cognitive functioning. Arendash suggested that other factors may include levels of cognitive and physical activity, hypertension (high blood pressure), and antioxidant intake, especially from fruits and vegetables.

Editor’s Note: This study of caffeine was not randomized and is subject to other interpretations. For example, people who drink less coffee may have more hypertension, which is associated with dementia risk. However, the study does raise the possibility that caffeine could have positive effects on the brain (especially if it does not make a patient anxious or insomniac).

The caffeine findings are also supported by studies of dementia in mice. Long-term administration of caffeine to these animals resulted in a similar biomarker profile and prevented cognitive impairment.

Other treatments may also be useful in preventing cognitive decline. In BNN Volume 16, Issue 5 from 2012, we wrote about a one-year prospective study published by Forlenza et al. in the British Journal of Psychiatry in 2011 that showed that lithium at the small dose of 150mg per day reduced the rate of cognitive decline in those with mild cognitive impairment compared to placebo.

Immune Therapy Studied in Alzheimer’s Disease Fails

July 18, 2013 · Posted in Potential Treatments · Comment 

confused older man

Following some research that inflammatory changes occur in patients with Alzheimer’s disease, immunotherapy with intravenous immunoglobin (IVIG), a treatment typically used to treat autoimmune diseases and neurological problems, was investigated in Alzheimer’s. The treatment consists of a mix of antibodies derived from the blood plasma of thousands of young, healthy blood donors, which are then delivered in a slow intravenous infusion. IVIG not only includes antibodies to particular proteins implicated in Alzheimer’s disease, but it also has general anti-inflammatory effects.

A particular dosage of IVIG (0.4g/kg every two weeks) seemed to completely stop progression of Alzheimer’s in the four patients who received it consistently for three years as part of a small open study. (Twenty other patients received other doses of IVIG or received placebo for part of the time, and the cognitive functioning of these patients deteriorated.) However, a large, double-blind, randomized study of IVIG did not show that the treatment had greater efficacy than placebo.

Dopamine D2 and D3 Agonist Pramipexole May Enhance Cognitive Function in Bipolar I Disorder

September 7, 2011 · Posted in Potential Treatments · Comment 

Cognitive Functioning

Anil Malhotra from the Zucker Hillside Hospital found that pramipexole (Mirapex), a dopamine D2 and D3 agonist used in the treatment of Parkinson’s disease, improved measures of processing speed and working memory in euthymic bipolar patients (whose average age was 42) when compared with placebo in an adjunctive clinical trial.

Editor’s Note: Bipolar patients in a euthymic phase have consistently been shown to have some degree of cognitive dysfunction that is typically correlated with the number of prior depressive and/or manic episodes they have experienced. This is one of the first studies to directly target this cognitive dysfunction with a pharmacotherapeutic agent.

Pramipexole may be of additional value among depressed patients, because in two small, placebo-controlled studies, one led by Carlos Zarate at the National Institute of Mental Health and one led by Joseph F. Goldberg in New York, pramipexole has been shown to exert acute antidepressant effects in bipolar patients in the depressive phase of the illness. The new data from Malhotra raise the possibility that there could be a two-for-one benefit when pramipexole is used in the depressive phase of bipolar illness—improvement in both depression and cognition.

Other approaches to improving cognition in patients with bipolar disorder

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Anti-Alzheimers’s Drug Memantine (Namenda) May Augment the Antidepressant Effects of Lamotrigine

January 17, 2011 · Posted in Potential Treatments · Comment 

memantineAt the 65th Annual Scientific Convention of the Society of Biological Psychiatry in May, Amit Anand reported that the anti-Alzheimer’s drug memantine (20 mg/day) was superior to placebo in augmenting the acute antidepressant effects of lamotrigine. These data are of particular interest since one of the assumed mechanisms of action of lamotrigine is to decrease the release of glutamate.

Memantine is a drug approved for the treatment of Alzheimer’s disease and is a partial antagonist (blocker) of glutamate NMDA receptors. This suggests that the dual actions of inhibiting glutamate’s release pre-synaptically (with lamotrigine) and blocking glutamate receptor activity post-synaptically (with memantine) combine to produce a better effect than that of lamotrigine alone.

Dual Drug Treatment for Alzheimer’s

June 17, 2010 · Posted in Current Treatments · Comment 

The two main classes of drugs for the treatment of Alzheimer’s disease currently include cholinesterase inhibitors, which increase brain acetylcholine levels, and memantine (Namenda), which is a partial blocker of glutamate receptors. Treating patients with both types of drugs in combination may help their cognitive functioning.

The brains of patients with Alzheimer’s are deficient in acetylcholine. Acetylcholinesterase breaks down acetylcholine, so the first class of Alzheimer’s drugs inhibits these esterases and makes more acetylcholine available.

Memantine works a different way. Glutamate is the major excitatory neurotransmitter in the brain. Excesses of glutamate may be toxic to cells, so memantine’s ability to partially block glutamate receptors may explain the drug’s effectiveness in Alzheimer’s.
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