Hyperlipidemia: Bad for the Heart, Good for the Brain?

Megan Brooks

May 17, 2015

TORONTO, Canada — Hyperlipidemia may be bad for the heart but good for the brain in patients with schizophrenia.

Elevated cholesterol and triglyceride levels were associated with better cognitive function in patients with schizophrenia in the Clinical Antipsychotic Trial of Interventional Effectiveness (CATIE) study.

"These counterintuitive data put us in a bind; how much do we attack high lipids in patients with schizophrenia? There are no easy answers," said Henry A. Nasrallah, MD, in a presentation here on opening day of the American Psychiatric Association (APA) 2015 Annual Meeting.

Neurocognitive impairment, particularly in memory and executive function, is a core feature of schizophrenia, one that causes functional disability, said Dr Nasrallah, chair of the Department of Neurology & Psychiatry, Saint Louis University School of Medicine in Missouri. At this time, there is no treatment for cognitive problems in schizophrenia. "It's a huge unmet need," he told attendees.

He also noted that second-generation antipsychotics are associated with metabolic dysregulation such as weight gain, dyslipidemia, and hyperglycemia, which raise cardiovascular risk. However, there are reports suggesting that antipsychotic-induced hypercholesterolemia may be associated with cognitive improvement.

To investigate further, Dr Nasrallah and a colleague examined the relationship between high total cholesterol, high triglyceride levels, and low high-density lipoprotein levels, with neurocognition, using data from 1460 patients with schizophrenia in the CATIE study. Their mean age was 40 years.

In analyses adjusted for potential confounding variables, patients with schizophrenia with high total cholesterol had significantly better composite neurocognitive scores (P = .002) than their peers with low total cholesterol levels, Dr Nasrallah reported.

Those with high triglycerides also had better neurocognitive scores (P = .02) relative to those with low triglyceride levels. Patients with low high-density lipoprotein levels had significantly worse cognitive scores (P = .04) than those with high high-density lipoprotein levels.

"The brain is 85% lipids, so lipids may be good for circuitry in the brain," Dr Nasrallah commented.

Actionable Data? Not So Fast

Commenting on the findings for Medscape Medical News, Maria A. Oquendo, MD, professor of psychiatry, New York-Presbyterian/Columbia University Medical Center, and APA president-elect, who starts her term in May 2016, said "while very interesting, I don't think these data are actionable yet."

"We need work to uncover the biological bases of disease. It is important to note that while there may be an association of cholesterol and triglycerides with better cognitive function, we still need to know if this is causal or whether increasing levels of these lipids improves cognitive function," she said by email.

"I would suggest that until we have data showing that hyperlipidemia causes better cognition, clinicians should still follow the usual medical strategies for managing hyperlipidemia," said Dr Oquendo.

"Although we need more information, it is certainly the case that the brain is chock-a-bloc with lipids. Neuronal cell membranes as well as myelin, so critical to nerve conduction, are comprised of both cholesterol and other lipids. We do not yet know if higher peripheral lipid levels are linked to a higher proportion of lipids in cell membranes and myelin. If this is the case, and this leads to better conduction of signals in the nervous system, then it is plausible for hyperlipidemia to lead to better cognition," she added.

Dr Nasrallah reports serving as a consultant/advisor to Boehringer Ingelheim Pharmaceuticals, Genentech, Janssen, Merck & Co, Otsuka Pharmaceuticals, Sunovion Pharmaceuticals Inc, Teva Pharmaceuticals, Alkermes, and Lundbeck and is on the speakers bureau of Genentech, Janssen, Otsuka Pharmaceuticals, Sunovion Pharmaceuticals Inc, and Alkermes.

American Psychiatric Association (APA) 2015 Annual Meeting. Presented May 16, 2015.

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