Neurovascular coupling (NVC) links neuronal activity to haemodynamic responses. Altered NVC may contribute to cognitive impairment in vascular pathology, but evidence is limited by inconsistent definitions and by the conflation of paired neuronal–haemodynamic NVC measures with haemodynamic-only, model-derived, or imaging-derived proxy measures.
The primary aim is to evaluate the association between paired neuronal–haemodynamic NVC measures and cognitive performance in middle-aged and older adults with vascular pathology. Secondarily, we will compare paired neuronal–haemodynamic NVC measures between patients with vascular pathology and age-matched controls without vascular pathology, determine whether predefined pathology strata show distinct impairment profiles, and examine whether the NVC–cognition association varies across cognitive domains. As an exploratory objective, we will synthesise evidence on the prognostic utility of paired neuronal–haemodynamic NVC measures in predicting future cognitive decline. Collectively, these objectives address critical gaps in a fragmented literature characterised by heterogeneous methodologies, populations, and assessment techniques, as well as methodological limitations including small samples, cross-sectional designs, and inadequate confounder control. This review will systematically synthesise existing findings, identify remaining knowledge gaps, and outline priorities for future research.
This protocol follows PRISMA-P guidance and is registered with PROSPERO (CRD420261351976). We searched five electronic databases from inception to 28 July 2026 for peer-reviewed English-language studies. Eligible studies include middle-aged and older adults with vascular pathology and/or participants from relevant comparator groups and report paired neuronal–haemodynamic NVC measures based on independently acquired neuronal and haemodynamic or vascular signals. The primary synthesis will evaluate associations between paired neuronal–haemodynamic NVC measures and cognitive performance, with meta-analysis conducted only for synthesis strata that meet prespecified feasibility criteria.
V. Abramova, Marta Estrada, Veronica Egovtseva et al.· Systematic Reviews· 0 citations
Summary Alzheimer’s disease (AD) has a higher prevalence in women than men and is more frequently inherited from mothers than fathers. Yet, while neuroimaging and biomarker studies link maternal family history to stronger AD-related alterations, epidemiological studies suggest that paternal history confers comparable or even greater risk. Here, we leverage the deeply profiled PREVENT-AD cohort to derive three intermediate phenotypes of AD susceptibility. Drawing on nearly 1,000 individual study visits, we quantify how these intermediate phenotypes vary as a function of maternal versus paternal AD lineage. We show that lineage-specific differentiation, including both maternal and paternal biases, is reflected in the brain structure and phenome of adult children of AD patients. Cognitive and cardiovascular risk markers, together with associated genetic variants, show the strongest differentiation along the parental-lineage spectrum of disease susceptibility relative to other correlates of AD burden. Our cross-generational analysis ultimately delineates multidimensional parent-of-origin effects in AD genealogy.
Chloé Savignac, Frédéric St-Onge, S. Villeneuve et al.· Cell Reports Medicine· 0 citations
In Alzheimer’s disease (AD), misfolded proteins emerge across the entire brain in structured, yet not rigid, spatiotemporal patterns. Yet, a systematic bias of single-cell genomics toward sampling mostly cortical tissue limits our understanding of the whole-brain transcriptomic vulnerability to AD. Here, we develop a machine learning method to extrapolate local AD neuropathology signatures to the whole brain. By analyzing gene expression profiles of over two million cortical cells from 427 humans spanning the AD-pathology spectrum, we derive transcriptomic estimators of AD neuropathology. After extensive validations on datasets with known ground truth, we apply this framework to three million cells from 108 brain regions in the Siletti whole human brain atlas and derive an anticipated brain map of transcriptomic signatures indexing AD neuropathology. This interrogation of regions spanning the cortical, subcortical, and brainstem structures uncovers transcriptomic signatures associated with hyperphosphorylated tau in the medulla oblongata, dorsal raphe nucleus, and the tuberal and mammillary regions of the hypothalamus. At the cellular level, assessments of these signatures across 31 cell populations identify VGLUT1/2 expressing neurons, astrocytes, and microglia as key neuropathology-resembling populations. Within the hippocampus, pathology signatures surface in the rostral cornu ammonis (CA) subfields, particularly in the CA1 pyramidal neurons and dentate granule cells. β-amyloid-like signatures localize to the neocortex with laminar selectivity — most prominently in upper layer somatostatin+ intratelencephalic neurons (L2-L3), but also in deep layer intratelencephalic and corticothalamic neurons (L5-L6). Neocortical astrocytes and microglia exhibiting disease associated signatures similarly demonstrate a unique laminar preference. Together, this study provides the first whole human brain map of AD pathology-associated transcriptomic signals, and exposes cell type, region, and cortex layer specific vulnerabilities.
