Cholinergic white matter pathways make a stronger contribution to attention and memory in normal aging than cerebrovascular health and nucleus basalis of Meynert Abstract   The integrity of the cholinergic system plays a central role in cognitive decline both in normal aging and neurological disorders including Alzheimerxe2x80x99s disease and vascular cognitive impairment. Most of the previous neuroimaging research has focused on the integrity of the cholinergic basal forebrain, or its subregion the nucleus basalis of Meynert (NBM). Tractography using diffusion tensor imaging data may enable modelling of the NBM white matter projections. We investigated the contribution of NBM volume, NBM white matter projections, small vessel disease (SVD), and age to performance in attention and memory in 262 cognitively normal individuals (39xe2x80x9377 years of age, 53% female). We developed a multimodal MRI pipeline for NBM segmentation and diffusionbased tracking of NBM white matter projections, and computed white matter hypointensities (WMhypo) as a marker of SVD. We successfully tracked pathways that closely resemble the spatial layout of the cholinergic system as seen in previous postmortem and DTI tractography studies. We found that high WMhypo load was associated with older age, male sex, and lower performance in attention and memory. A high WMhypo load was also associated with lower integrity of the cholinergic system above and beyond the effect of age. In a multivariate model, age and integrity of NBM white matter projections were stronger contributors than WMhypo load and NBM volume to performance in attention and memory. We conclude that the integrity of NBM white matter projections plays a fundamental role in cognitive aging. This and other modern neuroimaging methods offer new opportunities to reevaluate the cholinergic hypothesis of cognitive aging.

Temporolimbic cortical volume is associated with semantic odor memory performance in aging Abstract   Olfactory function, and specifically semantic olfactory memory (i.e., odor identification), has frequently been shown to predict cognitive functioning across multiple domains in old age. This observation suggests that olfactory function can serve as a marker for the integrity of temporolimbic cortical networks, but a clear delineation of this association is still missing. To address this issue, the present study employed voxelbased morphometry in a region of interestbased design to determine the extent to which gray matter volumes of core olfactory and memory areas are associated with olfactory memory performance in an aging population free from neurodegenerative disease. We further aimed to determine potential overlap in structural anatomical correlates, and differences in association strength, for semantic and episodic olfactory memory. Structural magnetic resonance imaging (MRI), episodic and semantic odor memory and episodic and semantic verbal memory data were collected in 422 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNACK), all agedxe2x80xafxe2x89xa5xe2x80xaf60 years. Controlling for age and education, semantic, but not episodic, olfactory memory was positively related to gray matter volume in a cluster extending from the anterior hippocampus and amygdala into the posterior piriform cortex. The observed associations remained even when verbal memory performance was controlled for, supporting a link between the olfactory memory domain and cortical volume over and above more generalized memory abilities. As such, our data provide evidence for distinct functionalstructural associations for semantic odor memory, supporting the idea of temporolimbic integrity as a neurobiological substrate linking olfactory function to cognitive health in old age.