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Aging is accompanied by deficits in cognitive function, which may be related to the vulnerability of myelinated nerve fibers to the normal process of aging. Loss of nerve fibers, together with agerelated alterations in myelin sheath structure, may result in the inefficient and poorly coordinated conduction of neuronal signals. Until now, the ultrastructural analysis of cerebral white matter fiber tracts associated with frontal lobe areas critical in cognitive processing has been limited. In this study we have analyzed the morphology and area number density of myelinated nerve fibers in the cingulate bundle and genu of the corpus callosum in behaviorally assessed young, middle aged, and old rhesus monkeys (Macaca mulatta). In both structures, normal aging results in a 20% decrease in the number of myelinated nerve fibers per unit area, while remaining nerve fibers exhibit an increasing frequency of degenerative changes in their myelin sheaths throughout middle and old age. Concomitantly, myelination continues in older monkeys, suggesting ongoing, albeit inadequate, reparative processes. Despite similar patterns of degeneration in both fiber tracts, only the age-related changes in the cingulate bundle correlate with declining cognitive function, underscoring its role as a critical corticocortical pathway linking the medial prefrontal, cingulate, and parahippocampal cortices in processes of working memory, recognition memory, and other higher cognitive faculties. These results further demonstrate the important role myelinated nerve fiber degeneration plays in the pathogenesis of age-related cognitive decline.

While cognitive decline is observed in the normal aging monkey, neurons are not lost with age. Instead, frontal white matter is lost as myelin degenerates and both correlate with age-related cognitive decline. As age-related myelin damage increases, there should be an increase in clearance of damaged myelin by microglial phagocytosis. In this study, brains of behaviorally tested rhesus monkeys were assessed using unbiased stereology to quantify the density of activated microglia (LN3 antibody positive) and phagocytic microglia (galectin-3 (Gal-3) antibody positive) in three white matter regions: the corpus callosum, cingulum bundle (CGB), and frontal white matter (FWM). LN3 cell density was significantly increased in the CGB, whereas Gal-3 cell density was significantly increased in all regions. Increases in Gal-3 cell density in the FWM were associated with cognitive impairment. In the FWM of old animals, Gal-3-positive microglia were classified by morphological subtype as ramified, hypertrophic, or amoeboid. The densities of hypertrophic and amoeboid microglia significantly correlated with cognitive impairment. Finally, microglia were double-labeled with LN3 and Gal-3 showing that 91% of Gal-3 cells were also LN3 positive, thus expressing an Bactivated^phenotype. Furthermore, 15% of all double-labeled cells formed phagocytic cups. Overall, these results suggest that microglia become activated in white matter with age where the majority express a phagocytic phenotype. We hypothesize that age-related phagocytic activation of microglia is a response to accumulating myelin pathology. The association of Gal-3 in the FWM with cognitive impairment may reflect regional differences in damage or dysfunction of normal clearance mechanisms.

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arental leave policies have major effects on resident well-being, gender disparities in academic medicine, 1 and maternal, child, and family health. 2 The increasing occurrence of parenthood during residency training underscores the critical importance of policies that are clear and supportive. Recent surveys have shown that approximately 40% of respondents plan to have children during residency. 3 A recent editorial in the New England Journal of Medicine recommended that parental leave during graduate medical education (GME) should include a minimum of 6 weeks of paid leave with the goal of increasing to 12 weeks, applicable to all trainees, without automatic extension of training. 4 A policy statement from the American Board of Medical Specialties (ABMS) in July 2020 issued similar recommendations. 5 Unfortunately, a majority of institutions lack consistent policies that meet these goals. 6 The successful revision of a parental leave policy requires understanding of and compliance with the relevant laws and regulations in GME. Clear, concise resources summarizing this information are lacking. In order to facilitate the creation of modern parental leave policies at all institutions, we summarize the pertinent regulations in this article (TABLE ). Specialtyand institution-specific factors are paramount. Accordingly, we use the field of neurology as an illustrative example for the creation of a residency program parental leave policy. However, most issues discussed here are relevant to all fields of medicine.

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