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

Chiari malformation: CSF flow dynamics in the craniocervical junction and syrinx

Background. A CSF flow study in patients with Chiari malformation (ChM) who undergo craniocervical junction decompression (CCJD). Methods. Using spatial modulation of magnetization (SPAMM), cerebrospinal fluid (CSF) flow velocities were measured at the prepontine (PP), anterior cervical (AC), and posterior cervical (PC) subarachnoid spaces (SAS) in healthy subjects (n = 11) and patients with Chiari malformation (ChM) before and/or after CCJD (n = 15). In the syringes, the intrasyrigeal pulsatile CSF motion was estimated qualitatively as present or absent. Findings. In normal subjects, the mean CSF velocities were 2.4 +/- 0.2 cm/s (PP), 2.8 +/- 0.3 cm/s (AC), and 2.4 +/- 0.2 cm/s (PC). Velocities were significantly lower than normal in patients with ChM prior to CCJD, reduced by 38%, 25%, and 79% in the 3 regions, respectively (P < 0.001). Post-CCJD, velocities were 20% (PP), 100% (AC), and 40% (PC) greater than preoperatively (P < 0.001). Conclusions. In ChM, the posterior cervical CSF flow velocity was low, increased minimally after CCJD and, by itself, had limited predictive value. Post-CCJD, an increase of the sum of anterior and posterior cervical CSF flow velocities by more than 20% consistently preceded or coincided with marked headache improvement. After CCJD, the finding that the intrasyringeal CSF pulsatile motion had become absent was an earlier and more sensitive predictor of motor or sensory improvement than a reduction in syrinx’s size. SPAMM can be used to assess whether CCJD has restored CSF flow, predict outcome and provide pathophysiological insights in ChM and syringomyelia