Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities

Landmark Recognition in Alzheimer’s Dementia: Spared Implicit Memory for Objects Relevant for Navigation

Contains fulltext : 97074.pdf (publisher's version ) (Open Access)BACKGROUND: In spatial navigation, landmark recognition is crucial. Specifically, memory for objects placed at decision points on a route is relevant. Previous fMRI research in healthy adults showed higher medial-temporal lobe (MTL) activation for objects placed at decision points compared to non-decision points, even at an implicit level. Since there is evidence that implicit learning is intact in amnesic patients, the current study examined memory for objects relevant for navigation in patients with Alzheimer's dementia (AD). METHODOLOGY/PRINCIPAL FINDINGS: 21 AD patients participated with MTL atrophy assessed on MRI (mean MMSE = 21.2, SD = 4.0), as well as 20 age- and education-matched non-demented controls. All participants watched a 5-min video showing a route through a virtual museum with 20 objects placed at intersections (decision points) and 20 at simple turns (non-decision points). The instruction was to pay attention to the toys (half of the objects) for which they were supposedly tested later. Subsequently, a recognition test followed with the 40 previously presented objects among 40 distracter items (both toys and non-toys). Results showed a better performance for the non-toy objects placed at decision points than non-decision points, both for AD patients and controls. CONCLUSION/SIGNIFICANCE: Our findings indicate that AD patients with MTL damage have implicit memory for object information relevant for navigation. No decision point effect was found for the attended items. Possibly, focusing attention on the items occurred at the cost of the context information in AD, whereas the controls performed at an optimal level due to intact memory function.5 p

Two emerging topics regarding long-range physical signaling in neurosystems: Membrane nanotubes and electromagnetic fields

In this review paper, an overview is given of two emerging research topics that address the importance of long-range physical signaling in living biosystems. The first topic concerns the biophysical principles and the physiological significance of long-range cell-to-cell signaling through electrical signals facilitated by membrane nanotubes (MNTs) (also called "tunneling nanotubes"), namely long membrane extensions that connect cells, discovered about 10 years ago. This review paper looks at experimental results that showed electrical signals being propagated through MNTs, and that MNT-mediated electrical coupling between brain cells involves activation of low-voltage-gated calcium channels. The significance of electrical cell-to-cell coupling through MNT for neuronal communication is discussed. The second topic deals with endogenous electromagnetic fields generated by nerve cells. The review concludes that these fields are not just an "epiphenomenon" but play a fundamental role in neuronal processes. For example, electromagnetic fields from brain cells feed back to their generating cells and to other cells (ephaptic coupling) and, for example, modulate the spiking timing of them. It is also discussed that cell membranes of neurons have specific resonance properties which possibly determine the impact of endogenous electric field fluctuations with respect to field strength and frequency. In addition, it is reviewed how traveling and standing waves of the endogenous electromagnetic field produced by neuronal and non-neuronal cells may play an integral part in global neuronal network dynamics. Finally, an outlook is given on which research questions should be addressed in the future regarding these two topics