Despite the association of regular coffee consumption with fewer neurodegenerative diseases, it remains unclear how coffee is associated with pre-clinical brain pathologies such as lesions in the white matter, degeneration of the cortex, or alterations of the microstructural integrity. White matter hyperintensities (WMH) are hyperintense lesions on T2-weighted images and are associated with an increased risk for stroke and depression, cognitive deterioration, and gait disorders [13,14,15]. As a marker of cerebral small vessel disease (CSVD) and vascular brain damage, WMH can vary in the degree of expression, depending on the age and the presence of cardiovascular risk factors, e.g., smoking or hypertension [16,17,18]. Previous studies have reported diverging results on the association of consumed coffee with imaging markers of CSVD. They found either beneficial associations of coffee with lacunar infarcts [7], beneficial [19] or detrimental [20] associations with WMH volume, or no significant associations at all [21,22].

A recently developed and valid imaging marker of microstructural integrity is the peak width of skeletonized mean diffusivity (PSMD), calculated as the distribution of the mean diffusivity (MD) between the 5th and 95th percentile in the white matter skeleton [23]. Only one study analyzed the association of coffee consumption with microstructural integrity, as quantified by fractional anisotropy, with a higher coffee consumption being associated with higher integrity of the white matter microstructure [24].

Damage to the brain structure is not restricted to white matter, but also extents to the cortex, e.g., in the form of atrophy. Except for one study focusing on the quantification of cortical thickness in regions susceptible for Alzheimer’s Disease [22], the link between coffee consumption and cortical thickness was only indirectly examined by measuring total brain volume or grey matter volume, with incongruent results between studies [7, 21,25,26]. This study aimed at investigating whether coffee consumption is associated with multiple brain MRI markers of vascular brain damage and neurodegeneration, including WMH, PSMD, and cortical thickness in a large, population-based cohort.

The hippocampus is an important brain region known to support various cognitive (i.e., mental) processes, including the encoding and retrieval of memories, learning, decision-making and the regulation of emotional states. While extensive research has tried to delineate the structure, functions and organization of the hippocampus, the cell types contained within it and their connections with other neurons have not yet been fully mapped out.

Over the past decades, available methods for studying cell subpopulations, the expressions of genes within them and their connectivity have become increasingly advanced. One of these methods, known as spatially resolved transcriptomics, works by measuring the expression of genes in cells while preserving their arrangement in space. Another called single-nucleus RNA-sequencing (snRNA-seq), allows scientists to examine RNA molecules inside individual cell nuclei to detect differences between them and categorize cells into different subtypes.

Researchers at Johns Hopkins Bloomberg School of Public Health, the Lieber Institute for Brain Development and Johns Hopkins School of Medicine recently used a combination of these two experimental techniques to examine cells in tissue extracted from the hippocampus. Their paper, published in Nature Neuroscience, introduces a comprehensive molecular atlas of the hippocampus that maps different cell subtypes and their organization.