RESUMEN
Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data ( N = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity. By applying a novel piecewise regression approach to our cross-sectional sample to support Granger-like causality inferences, we show that, on average, a precipitous decline in cerebral arterial elasticity (measured with diffuse optical imaging of the cerebral arterial pulse; pulse-DOT) temporally precedes an acceleration in the development of white matter lesions by nearly a decade, with women protected from these deleterious effects until approximately age 50, the average onset of menopause. By employing multiple-mediator path analyses while controlling for sex, we show that age may impair cognition via the sequential indirect effects of arteriosclerosis and white matter atrophy on fluid, but not crystallized, abilities. Importantly, we replicate these results using pulse pressure, an independent index of arterial health, thereby providing converging evidence for the central role of arteriosclerosis as an accelerating factor in normal and pathological aging and identifying robust sex-related differences in the progression of cerebral arteriosclerosis and white matter degradation.
RESUMEN
In this review we start from the assumption that, to fully understand cognitive aging, it is important to embrace a holistic view, integrating changes in bodily, brain, and cognitive functions. This broad view can help explain individual differences in aging trajectories and could ultimately enable prevention and remediation strategies. As the title of this review suggests, we claim that there are not only indirect but also direct effects of various organ systems on the brain, creating cascades of phenomena that strongly contribute to age-related cognitive decline. Here we focus primarily on the cerebrovascular system, because of its direct effects on brain health and close connections with the development and progression of Alzheimer's Disease and other types of dementia. We start by reviewing the main cognitive changes that are often observed in normally aging older adults, as well as the brain systems that support them. Second, we provide a brief overview of the cerebrovascular system and its known effects on brain anatomy and function, with a focus on aging. Third, we review genetic and lifestyle risk factors that may affect the cerebrovascular system and ultimately contribute to cognitive decline. Lastly, we discuss this evidence, review limitations, and point out avenues for additional research and clinical intervention.
