Band 5, Heft 2

Diabetes type 2, caused mainly by insulin resistance, is growing in incidence worldwide. In addition to being a major public health concern, type 2 diabetes is also a risk factor for dementia, including Alzheimer’s disease type dementia. Coffee consumption is reported to have protective effects in both diabetes and Alzheimer’s disease. We review here the reported beneficial effects of coffee in both disease conditions and the previously identified active ingredients of coffee. Furthermore, we revisit our recent findings of improved glucose utilization in the periphery and in the brain in a mouse model of high-fat diet induced type 2 diabetes after treatment with a decaffeinated green coffee preparation. Overall, consumption of coffee appears to improve diabetes and reduce the risk of dementia, although future studies are required to further identify the active components and the type of coffee that is most effective in addressing these conditions.

Previous reports revealed that middle cerebral artery occlusion (MCAO) models in rats were very diverse in nature, and experimental stroke of a more homogenous nature had not been previously documented. This paper aims to present our novel observations of experimental stroke in rats with similar MRI characteristics after MCAO. Immediately after MCAO, 19 rats were placed into a 4.7 T MRI scanner, and diffusion weighted imaging (DWI) of axial and coronal planes was repeated every 10 minutes up to post-occlusion 115 minutes. Apparent diffusion coefficient (ADC) values of the ischemic lesions were calculated and compared to those of the unaffected contra-lateral hemispheres. Successful MCAO was defined when the whole left MCA territory showed ADC abnormality on DWI. Percentage of hemispheric lesion volume (% HLV), relative ADC value (rADC), and relative DWI signal intensity (rDWI) were serially evaluated for quantitative analysis of ADC-derived lesion characteristics. Successful MCA territorial infarction was induced in nine rats (9/19, 47.4%). In quantitative analysis of ADC-derived lesion characteristics, lesion volumes of seven rats (group 1) were very similar, but larger than those of the other two rats (group 2): % HLV of initial MRI = 45.4 ± 2.5 / 19.1 ± 6.6. rADCs and rDWIs of group 1 showed similar patterns of temporal change, which was different from those of group 2. Using prospective diffusion MRI after MCAO in rats, we identified territorial hyperacute ischemic lesions with similar MRI characteristics. This observation would contribute to the establishment of more homogenous rodent models for ischemic stroke translational research.

“Anxiety disorders” are extremely common; and are a major source of health costs and lost work days. Their diagnosis is currently based on clinical symptom check lists and there are no biological markers to diagnose specific syndromal causes. This paper describes: 1) a detailed theory of the brain systems controlling anxiolytic-insensitive threat-avoidance and anxiolytic-sensitive threat-approach — where, in specific brain structures, activity generates specific normal behaviours, hyperactivity generates abnormal behaviours, and hyper-reactivity (hypersensitivity to input) generates specific clinical syndromes; 2) a rodent model of systemic anxiolytic action (rhythmical slow activity), linked to the theory, that over a period of 40 years has shown predictive validity with no false positives or false negatives — and which is likely to assay the sensitivity of endogenous systems that control anxiety; and, 3) derivation from this rodent-based theory of a specific non-invasive biomarker (goal-conflict-specific rhythmicity) for the threat-approach system in humans. This new biomarker should allow division of untreated “anxiety” patients, with superficially similar clusters of symptoms, into distinct high scoring (syndromal) and low scoring groups with different treatment-responses. This would be the first theoretically-derived biomarker for any mental disorder and should: 1) predict treatment efficacy better than current symptom-based diagnoses; 2) provide a human single dose test of novel anxiolytics; 3) provide a starting point for developing biomarkers for other “anxiety” syndromes; and so, 4) greatly improve treatment outcomes and cost-effectiveness.

The ability to remember the destination to whom a piece of information has been addressed (e.g., did I tell you about the weekend?) has been labelled destination memory. Although this topic has been relatively scarcely studied, recent studies support the notion that destination recall can be the subject of important distortions in healthy younger and older adults and in individuals with Alzheimer’s disease. This research also links destination recall to several cognitive domains such as episodic memory, executive function, and self-referential processes (e.g., did I tell you about the weekend?). The present review aims to assemble these findings into a comprehensive framework and shed light onto potential neuroanatomical underpinnings of destination memory, thus providing a promising venue for future exploration and research.

A growing body of evidence indicates that neurodegenerative motor disorders involved high-order cognitive dysfunctions. Crucially, evidence obtained in multiple behavioral, neuroimaging, and electrophysiological studies points to selective impairments of action language -that is, processing of linguistic stimuli denoting motor actions, including idioms (e.g., cut a rug) and action verbs (e.g., clap). Action-verb deficits (with relative preservation of noun processing) have been repeatedly documented in Parkinson’s disease (PD). However, research on relevant biomarkers is still scant, and clinical implications of these findings have not yet been formally discussed. Relevant insights may be obtained through the assessment of motor-language coupling (i.e., the behavioral and neural integration of action-verb processing and ongoing motor actions). We propose that motorlanguage coupling deficits, as indexed by a cortical-subcortical network, may constitute an early neurocognitive marker of PD. Specifically, deficits in this domain at the prodromal stage may be detected through the actionsentence compatibility (ACE) paradigm, which induces a contextual coupling of ongoing motor actions and action-verb processing. Our translational proposal is supported and illustrated by recent studies demonstrating the sensitivity of the ACE technique as well as its potential to assist in differential diagnosis and interventionprogram design.

Cerebral microbleeds are considered an imaging marker of cerebral small vessel disease. The location of microbleeds is thought to reflect the underlying pathology. Microbleeds in the deep and infratentorial region are thought to reflect hypertensive arteriopathy whereas lobar microbleeds are associated clinically with cerebral amyloid angiopathy (CAA). Aside from patient populations, microbleeds are frequently observed in seemingly asymptomatic populations. Moreover, many elderly, both in clinical and preclinical populations, have multiple coexisting pathologies in their brains, which complicates the interpretation of cerebral microbleeds, especially early in the clinical course. In this commentary, we discuss the influence of the strongest genetic risk factor for CAA, Apolipoprotein E (APOE), in the spatial distribution of microbleeds, and we additionally address issues in interpretation and implication of the location of microbleeds in clinical and asymptomatic populations.