Stress and its relation to Alzheimer's disease

Stress can be the culprit of many ills in people's lives. Researchers have now determined that it could be linked with a type of memory decline that's often a prelude to Alzheimer's disease (AD).

In the new study of older adults, feeling stressed out increased the likelihood that people would go on to develop a form of mild cognitive impairment (MCI), according to scientists at Albert Einstein College of Medicine (New York) and Montefiore Health System (Bronx, N.Y.)

The researchers posit that people with MCI face a greater risk of eventually developing AD.

The researchers analyzed data from an ongoing study of adults age 70 and over from Bronx County. All were dementia-free at the start of the study.

The participants were followed for an average of 3.6 years, and over the course of the study, 71 of the 507 were diagnosed with amnesiac mild cognitive impairment (aMCI), the most common form of the condition.

The greater a participant's stress level – which was measured using standardized stress tests – the greater their risk for developing cognitive impairment, the researchers reported. An MCI diagnosis was based on standardized clinical criteria including the results of memory recall tests and reports of forgetfulness from the participants or others.

Sweet tooth is in the liver

Two separate research teams, one at the University of Texas Southwestern Medical Center and the other at the University of Iowa and the Danish University of Copenhagen, have identified fibroblast growth factor 21 (FGF21) as a factor that was produced by the liver and acted on the brain to suppress the intake of sweets, both simple sugars and alcohol, in response to dietary intake. Genetic variants in FGF21 affect the preference for sweets, and loss of FGF21 in mice increases their sugar consumption, while its overexpression decreases. In their work, on both mice and primates, the teams showed that sugar consumption increased FGF21 production by the liver.

The FGF21 then acted on neurons in the hypothalamus, a brain region responsible for regulating food intake. The U.S,/Danish team concluded in their paper that "these data raise the interesting possibility that molecular therapies could be developed to treat obesity and Type 2 diabetes by qualitatively improving diet." Their findings appeared back to back in the Dec. 24, 2015, issue of Cell Metabolism.

Geneuro initiates study of RRMS

Geneuro SA (Geneva), a maker of therapies for neurology and autoimmune disorders, has initiated its planned phase IIb study "Clinical trial assessing the HERV-W Env ANtagonist GNbAC1 for Efficacy in Multiple Sclerosis" (CHANGE-MS) with its lead antibody GNbAC1 in relapsing-remitting multiple sclerosis (RRMS).

The study plans to enroll 260 patients in 68 clinical centers in the EU and Eastern Europe. Preliminary results are expected by the end of 2017.

In conjunction with the study, development partner Servier (Neuilly-sur-Seine, France) has exercised its equity investment option, as part of an agreement signed in November 2014, to become a minority shareholder in Geneuro by purchasing shares from existing shareholder Eclosion2 (Plan-les-Ouates, Switzerland).

The terms of the partnership agreement provide for Geneuro to receive $40 million (€37.5 million) from Servier for the completion of the Phase IIb study. Subject to exercising its option for a licensing agreement, Servier has agreed to finance the global Phase III development program and pay Geneuro up to an additional $355 million (€325 million) in future development and sales related milestones, as well as royalties on future sales.

The aim of the phase IIb study is to demonstrate on RRMS patients the clinical benefit of GNbAC1 in neutralizing the MSRV-Env protein, which has been identified as a potential key factor fueling the inflammatory and neurodegenerative components of MS. Efficacy will be based on multiple brain magnetic resonance imaging scans, with an initial endpoint analysis after 6 months followed by a 6-month extension. By targeting MSRV-Env, Geneuro aims to bring to patients a safe and effective treatment for both relapsing-remitting and progressive forms of the disease without hampering the patient's immune system.

A search for better understanding of thalamic amnesia

A recent study out of Europe seeks to better understand the mechanisms behind thalamic amnesia. It seems to be unclear whether is it directly related to specific in particular to the anterior or mediodorsal nuclei, or indirectly related to lesions of the mammillothalamic tract (MTT).

In particular the scientists want to understand if direct damage to these mentioned nuclei (especially the anterior or mediodorsal nuclei) are a direct cause to this type of amnesia.

The study recruited 12 patients with a left thalamic infarction and 25 healthy matched controls. All underwent a comprehensive neuropsychological assessment of verbal and visual memory, executive functions, language and affect, and a high-resolution structural volumetric MRI scan.

Thalamic lesions were manually segmented and automatically localized with a computerized thalamic atlas. As well as comparing patients with controls, we divided patients into subgroups with intact or damaged MTT.

The researchers found only one patient had a small lesion of the anterior nucleus. Most of the lesions included the mediodorsal and intralaminar nuclei. Patients performed worse than controls on the verbal memory tasks, but the five patients with intact MTT who showed isolated lesions of the mediodorsal (MD) nucleus only displayed moderate memory impairment. The seven patients with a damaged MTT performed worse on the verbal memory tasks than those whose MTT was intact.

The lesions in the MTT and in the MD result in memory impairment, severely in the case of MTT and to a lesser extent in the case of MD. This would suggest the roles of these two structures in memory circuits.