Transcranial Direct Current Stimulation Improved Picture-Naming in People with Dementia
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
A 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.
Some Drugs for Hypertension Come with Greater Risk of Mood Disorders
Depression and bipolar disorder have been linked to atherosclerosis, the accumulation of fats, cholesterol, and plaques on the walls of the arteries. There is some evidence that drugs to treat hypertension may contribute to mood disorders. A large study published in the journal Hypertension in 2016 suggests that certain classes of anti-hypertensive drugs, calcium antagonists and beta blockers, may increase risk of mood disorders compared to other treatments for hypertension.
The study by researcher Angela H. Boal and colleagues used data from a hospital database to identify 144,066 patients between the ages of 40 and 80 who had taken anti-hypertensive drugs for more than 90 days. There was an independent linear connection between receiving a prescription for hypertenstion and being diagnosed with a mood disorder. Patients who took angiotensin-converting enzyme inhibitors or angiotensin receptor blocking drugs had the lowest rates of mood disorder admissions. Those taking calcium antagonists or beta blockers had an increased risk of a mood disorder, while those taking thiazide diuretics and those not taking anti-hypertensive drugs had no change in risk.
Statins Have Many Benefits
Patients 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.
Preventing Metformin Side Effects
Depression is a risk factor for type 2 diabetes, and the drug metformin is a common treatment for diabetes. In a 2016 article in the Journal of Clinical Psychiatry, researcher Chittaranjan Andrade suggests ways of minimizing side effects from metformin.
Gastrointestinal side effects such as nausea, vomiting, abdominal discomfort, flatulence, and diarrhea are common on metformin. In the article, Andrade writes, “These are less likely to occur with gradual dose uptitration, administration of the drug with meals, and use of a time-release formulation.”
Lactic acidosis, a buildup of lactate in the body that can result in muscle pain, burning, and other symptoms, is a rare side effect of metformin. Avoiding prescribing metformin to people with impaired kidney, liver, or cardiac functioning and other risk factors can prevent lactic acidosis.
Vitamin B12 absorption can also be affected by long-term metformin use. Andrade suggests that rather than waiting for a vitamin deficiency to be identified, a proactive approach should be taken. Long-term metformin users could be given an annual intramuscular shot of vitamin B12.
Bipolar Disorder and Diabetes Linked
A 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.
In Case Control Study, Two-Thirds of Patients With Severe Depression Had Underlying Metabolic Abnormalities
A recent study suggests that potentially treatable metabolic abnormalities in the central nervous system may underlie a large proportion of cases of severe, treatment-resistant depression. These abnormalities, such as folate deficiency in the cerebrospinal fluid, are not screened for regularly, as they require a spinal tap to diagnose.
Researchers led by Lisa A. Pan were inspired to assess metabolic function in people with treatment-resistant depression after a young patient with severe, persistent depression who had attempted suicide several times improved dramatically after being diagnosed with a tetrahydrobiopterin deficiency in his cerebrospinal fluid and treated for the deficiency. Tetrahydrobiopterin is critical to the production of monoamine neurotransmitters.
The researchers carried out a case-control study of 33 teen and young adult patients who had had treatment-resistant depression since childhood and 16 healthy control participants. Twenty-one of the 33 patients with severe depression had metabolic abnormalities in their cerebrospinal fluid. Twelve had cerebral folate deficiencies (but no folate deficiency in blood tests). Those who took folinic acid for at least six weeks (1–2 mg/kg/day) in addition to their regular medications showed sometimes dramatic improvement in their depression.
Other metabolic issues identified in the patients with severe depression included abnormal levels of acylcarnitine in five patients, low tetrahydrobiopterin intermediates in one, low guanidinoacetate in another, and unusual creatine/creatinine ratios in three patients. None of the healthy participants had any metabolic abnormality.
While the study, published in the American Journal of Psychiatry in 2017, was small, it suggests that the underlying causes of some severe depression cases are going undiagnosed and untreated. The authors suggest that assessment of metabolic function should be more common in cases of severe treatment-resistant depression.
Depression Increases Heart Disease Risk to Same Extent That Obesity, High Cholesterol Do
In men, depression seems to be equal to obesity and high cholesterol in increasing heart disease risk. A German study about heart disease risk included 3,428 men between the ages of 45 and 74 who were observed over a period of 10 years.
In an article in the journal Atherosclerosis, lead researcher Karl-Heinz Ladwig reported that while high blood pressure and smoking are the most powerful risk factors for fatal cardiovascular disease, depression is comparable to obesity and high cholesterol levels. Depression accounts for about 15% of cardiovascular deaths.
Ladwig suggests that depression screening should be standard in patients with other risk factors for heart disease.
Editor’s Note: Long-term preventive treatment for depression may have the added benefit of preventing heart attacks. In people with two prior depressions, most guidelines now recommend lifetime continuation of antidepressant treatment.
Teens with Bipolar Disorder at Increased Risk for Cardiovascular Disease
A scientific statement from the American Heart Association reported in 2015 that youth with major depressive disorder and bipolar disorder are at moderate (Tier II level) increased risk for cardiovascular disorders. The combined prevalence of these illnesses in adolescents in the US is approximately 10%.
There are many factors that contribute to this risk, including inflammation, oxidative stress (when the body falls behind neutralizing harmful substances produced during metabolism), dysfunction in the autonomic nerve system, and problems with the endothelium (the inner lining of blood vessels). Lifestyle factors include adversity in early life, sleep disturbance, sedentary lifestyle, poor nutrition, and abuse of tobacco, alcohol, or other substances.
Taking some atypical antipsychotics as treatment for bipolar disorder also contributes to the risk of cardiovascular problems by increasing weight and/or lipid levels. Among the atypicals, ziprasidone (Geodon) and lurasidone (Latuda) come with the lowest likelihood of weight gain.
The statement by Benjamin I. Goldstein and colleagues that appeared in the Heart Association-affiliated journal Circulation suggested that therapeutic interventions should address some of these risk factors to help prevent cardiovascular problems and improve life expectancy for young people with depression or bipolar disorder. These could include a good diet, regular exercise, and treatments with good long-term tolerability that are aimed at preventing episodes.
The Role of Inflammatory Markers and BDNF
Inflammation worsens the risk of cardiovascular problems, while brain-derived neurotrophic factor (BDNF), which protects neurons and plays a role in learning and memory, may improve prospects for someone with depression or bipolar disorder.
A 2017 article by Jessica K. Hatch and colleagues including Goldstein in the Journal of Clinical Psychiatry suggests that inflammation and BDNF are mediators of cardiovascular risk in youth with bipolar disorder. The study looked at 40 adolescents with bipolar disorder and 20 healthy controls.
Those with bipolar disorder had greater waist circumference, body mass index, and pulse pressure than the controls. The youth with bipolar disorder also had higher levels of the inflammatory cytokine Il-6. Participants who had lower BDNF had greater thickness of the carotid vessel internal lining (intima media).
Hatch and colleagues point to the importance of prevention strategies in adolescents with these indicators of increased cardiovascular risk. These data complement the American Heart Association’s recognition of adolescent mood disorders as a large problem that deserves wider attention both in psychiatry and in the media.
