Lithium inhibits the enzyme glycogen synthase kinase 3, which has been implicated in dementia. To study whether lithium may prevent cognitive decline, researchers led by Tobias Gerhard looked at the medication histories of patients with bipolar disorder who were 50 years of age or older. In their article published in the British Journal of Psychiatry, those patients who had taken lithium 301–365 days out of the previous year had substantially lower risk of dementia than those who had not taken lithium during that time. Patients who had 300 or fewer days of lithium use did not have a significant reduction in dementia risk, nor did patients who were prescribed anticonvulsant drugs.
Editor’s Note: These data are consistent with those of Lars Kessing and colleagues, which suggest that patients in Denmark who renewed their lithium prescriptions were less likely to receive a diagnosis of dementia in old age.
In 2011, Orestes V. Forlenza and colleagues also reported in the British Journal of Psychiatry that compared to placebo, a very small dose of lithium, 150 mg/day, slowed the progression of mild cognitive impairment over one year.
We’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.
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.
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.