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Age-related macular degeneration (AMD) is a prevalent disease impeding vision. More recently, AMD has also been linked to cognitive impairment, such as deficits in language and memory skills. In order to better understand the extent of AMD-related changes in the whole brain structure and connectivity, we have conducted an MRI diffusion acquisition study on 40 participants (20 diagnosed with AMD and 20 controls). These acquisitions were then performed again in a follow up two years later. We developed novel analysis methods for diffusion based tractography and connectomes to better determine which, if any, brain region connections saw the greatest changes between the AMD and the age-matched control groups. Using voxel-based analysis, we identified atrophy in AMD participants in the cuneate gyrus, which has been associated with vision, and the left superior temporal gyrus, which has been associated with language, while later acquisitions compounded this with a deficiency in the bilateral cingulate gyrus, itself linked to higher cognition and memory. These regional atrophy findings support that people with AMD experience widespread neuronal degradation that is not limited to retinal neurons. Regions that saw drastically lowered fractional anisotropy among AMD vs. control included the visual cortex, such as the bilateral occipital lobe and the frontoparietal cortex. Tensor Network Principal Component Analysis (TN-PCA) isolated lingual and temporal connections as important differentiators of AMD connectomes compared to controls, thus supporting our morphometric and texture findings in regions related to vision, but also connectopathies of language and memory brain regions. Bundle based analyses in baseline data revealed that the lingual gyrus had greater spread of tracts overall in the AMD participants, which may be explained by prior reorganization in this area, demonstrating a connection between retinal health and lingual structure. Moreover, we noted group differences in the interhemispheric temporal connections, and lingual cerebellar connections, supporting extensive downstream effects of vision loss. Our bundle-based analyses expand the toolset available for neuroimaging-based phenotyping, and reveal widespread changes in AMD participants beyond brain regions and tractography networks directly involved in vision processing, including those involved in language and memory.

We analyzed two mid-Holocene (∼5000 years before present) individuals from North America that belong to mitochondrial DNA (mtDNA) haplogroup M, a common type found in East Asia, but one that has never before been reported in ancient or living indigenous populations in the Americas. This study provides evidence that the founding migrants of the Americas exhibited greater genetic diversity than previously recognized, prompting us to reconsider the widely accepted five-founder model that posits that the Americas were colonized by only five founding mtDNA lineages. Additional genetic studies of prehistoric remains in the Americas are likely to reveal important insights into the early population history of Native Americans. However, the usefulness of this information will be tempered by the ability of researchers to distinguish novel founding lineages from contamination and, as such, we recommend strategies to successfully accomplish this goal.

The pathophysiology of 'early' dry age-related macular degeneration (ARMD), characterized by the accumulation of lipid and protein-rich sub-retinal deposits remains largely unknown. Accumulation and dysregulated turnover of lipids as well as extracellular matrix (ECM) molecules in sub-retinal pigment epithelial (RPE) deposits and Bruch's membrane, itself an ECM, play a role in ARMD. Epidemiological studies have shown an increased risk for the disease associated with higher dietary intake of long chain poly-unsaturated fatty acids (LCPUFA) and specifically more so for n-6 versus n-3 fatty acids. PUFAs are membrane targets of lipid peroxidation and natural ligands for the nuclear receptors, peroxisome proliferator activated receptors (PPAR). Here we investigated the expression of genes involved in lipid metabolism and expression of the three isoforms of PPARs in an immortalized cell line of human RPE cells (ARPE19) in the presence or absence of fatty acids.