Neurovascular mechanisms of cognitive aging: Sex-related differences in the average progression of arteriosclerosis, white matter atrophy, and cognitive decline.

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 temporal 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) 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.

Neurovascular Mechanisms of Cognitive Aging: Sex-Related Differences in the Average Progression of Arteriosclerosis, White Matter Atrophy, and Cognitive Decline.

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.

MaPPeRTrac: A Massively Parallel, Portable, and Reproducible Tractography Pipeline.

Large-scale diffusion MRI tractography remains a significant challenge. Users must orchestrate a complex sequence of instructions that requires many software packages with complex dependencies and high computational costs. We developed MaPPeRTrac, an edge-centric tractography pipeline that simplifies and accelerates this process in a wide range of high-performance computing (HPC) environments. It fully automates either probabilistic or deterministic tractography, starting from a subject's magnetic resonance imaging (MRI) data, including structural and diffusion MRI images, to the edge density image (EDI) of their structural connectomes. Dependencies are containerized with Singularity (now called Apptainer) and decoupled from code to enable rapid prototyping and modification. Data derivatives are organized with the Brain Imaging Data Structure (BIDS) to ensure that they are findable, accessible, interoperable, and reusable following FAIR principles. The pipeline takes full advantage of HPC resources using the Parsl parallel programming framework, resulting in the creation of connectome datasets of unprecedented size. MaPPeRTrac is publicly available and tested on commercial and scientific hardware, so it can accelerate brain connectome research for a broader user community. MaPPeRTrac is available at: https://github.com/LLNL/mappertrac .

Yoga, aerobic and stretching exercise effects on neurocognition: Randomized controlled trial protocol.

As the global population ages, the prevalence of cognitive decline and dementia is expected to rise, creating a significant health and economic burden. The purpose of this trial is to rigorously test, for the first time, the efficacy of yoga training as a physical activity intervention to mitigate age-related cognitive decline and impairment. We are conducting a 6-month randomized controlled trial (RCT) of exercise among 168 middle aged and older adults to compare the efficacy of yoga vs. aerobic exercise on cognitive function, brain structure and function, cardiorespiratory fitness, and circulating inflammatory and molecular markers. Using a single-blind, three arm RCT, 168 older adults ages 55-79 will be assigned to either: a Hatha yoga group, an aerobic exercise group or a stretching-toning active control group. Participants will engage in hour long group exercise 3x/week for 6-months. A comprehensive neurocognitive test battery, brain imaging, cardiovascular fitness test, and a blood draw will take place at baseline; end of the 6-month intervention, and at 12-month follow-up. Our primary outcomes of interest are brain regions, such as hippocampal volume and prefrontal cortex, and cognitive functions, such as episodic memory, working memory and executive functions, that are typically affected by aging and Alzheimer's disease. Not only will this RCT test whether yoga is a means to mitigate age-related cognitive decline, but it may also offer an alternative to aerobic exercise, which could be particularly appealing to older adults with compromised physical functioning. ClinicalTrials.gov Identifier: NCT04323163.

Voluntary Saccade Training Protocol in Persons With Parkinson's Disease and Healthy Adults.

Background: Voluntary saccade function gradually decreases during both the progression of Parkinson's disease (PD) and neurologically healthy adult aging. Voluntary saccades display decreased length and increased saccade latency, duration, and the number of compensatory saccades in aging and PD. Saccades serve as the key eye movement for maintaining salient features of the visual environment on the high visual acuity fovea of the retina. Abnormal saccade behavior has been associated with freezing of gait in PD. We have not identified any studies that have investigated improvement in voluntary saccade function using voluntary saccade training. Objective: We report an experimental protocol that tests a training paradigm following the principle of specificity to improve voluntary saccade velocity and amplitude, while decreasing latency and the number of compensatory saccades. Methods: Persons with PD (n = 22) and persons with no known neurological disorders (n = 22) between the ages of 40 and 65 years will be recruited. In a randomized-block study design, all participants will perform voluntary saccades to targets in eight cardinal and intercardinal directions. In each of the eight sessions during the four-week intervention period, participants will train at three target amplitudes. Participants will perform 40 trials for each amplitude block, consisting of five randomly presented repetitions for each direction. Voluntary and reflexive saccades will be recorded pre- and post-intervention, along with clinical mobility assessment using the Movement Disorder Society Unified Parkinson's Disease Rating Scale. Mobility scores, the amplitude, latency, and duration of the first saccade, and the number of saccades to reach the fixation target will be analyzed using an ANOVA of mixed effects. Discussion: This protocol holds promise as a potential method to improve voluntary saccade function in persons with PD. Should persons with PD not improve on any outcome following the intervention, this lack of response may support the use of saccade assessment as a response biomarker for the diagnosis of PD. Trial Registration: This protocol was retrospectively registered at ISRCTN (ISRCTN.com) since July 25, 2018. The first participant was recruited March 12, 2016. The protocol identifier is 17784042. Descriptive Title: A two-arm, pre/post-protocol to compare the effects of a four-week voluntary saccade training intervention in persons with Parkinson's disease and healthy adults aged forty years or older.