Alex Becker

TL;DR: There is direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA.

Abstract: Background: Aging is characterized by retraction of neocortical dendrites, traditionally captured only on histology. Recent MRI advances demonstrate that multi-shell diffusion can be applied to grey matter (GM) in vivo, allowing for assessment of neurite complexity and dispersion. Cognitive aging has been associated with decrements in working memory. Prior studies indicate that alterations in GM may underlie these changes; however, few studies have examined the association between working memory (WM) and neurite dispersion. In this pilot study, we hypothesized that reduced neuritic dispersion in GMwould be associated with worseWMperformance. Methods: 10 healthy older adults (mean age1⁄469, range: 61-80) underwent cognitive testing, neurological exam, and informant interview. WM was assessed with measures from the Spanish and English Neuropsychological Assessment Scale (SENAS) and a dot counting WM measure from the NIH EXAMINER. Subjects underwent brain MRI including isotropic T1 images and a twoshell diffusion imaging protocol known as neurite orientation dispersion and density imaging (NODDI). This technique allows quantification of orientation dispersion index (ODI), a measure of angular variation of neurite orientation. Mean ODI values were calculated in frontal, parietal, and whole brain GM. FreeSurfer was used to calculate mean cortical thickness in the same regions. Spearman correlations were used to examine the association between WM measures and ODI measures. Results: ODI was negatively associated with age in frontal GM (rs1⁄4-0.63, p1⁄40.05), and moderate effects were noted when examining parietal (rs1⁄4-0.45) and total GM (rs1⁄4-0.54). Worse performance on dot counting WM trended with lower ODI in frontal (rs1⁄40.45, p1⁄40.19, figure), parietal (rs1⁄40.41, p1⁄40.24), and total GM ODI (rs1⁄40.50, p1⁄40.14). Smaller effects were noted between the SENAS WM composite and ODI, but still demonstrated an association with frontal GM (rs1⁄40.27). All effect sizes remained comparable when controlling for whole brain mean cortical thickness. Conclusions: In this pilot study, we note inverse correlations between age and neuritic dispersion in greymatter. Furthermore, we found positive correlations between neuritic dispersion and working memory. Effects were not explained by cortical thickness. These results support further investigation into in vivo imaging evidence of retraction of dendritic arbors in aging and cognitive domain vulnerability.

TL;DR: Preliminary findings suggest that T807 PET is a promising new biomarker that relates to both clinical and cognitive status.

TL;DR: This research presents a novel and scalable approach called “Smart MRI” that allows for real-time assessment of the dynamic response of the immune system to treat Alzheimer’s disease.