Walking energetics and white matter hyperintensities in mid-to-late adulthood.

Introduction: White matter hyperintensities (WMHs) increase with age and contribute to cognitive and motor function decline. Energy costs for mobility worsen with age, as the energetic cost of walking increases and energetic capacity declines. We examined the cross-sectional associations of multiple measures of walking energetics with WMHs in mid- to late-aged adults.

Probabilistic estimation for across-batch compatibility enhancement for amyloid PET.

Introduction: It is necessary to accurately account for systematic differences due to variability in scanners, radiotracers, and acquisition protocols in multisite studies combining amyloid imaging data.

Methods: We propose Probabilistic Estimation for Across-batch Compatibility Enhancement (PEACE), a fully Bayesian multimodal extension of the widely used ComBat harmonization model, and we apply it to harmonize regional amyloid positron emission tomography data from two scanners.

Results: Simulations show that PEACE recovers true harmonized values better than ComBat, even for unimodal data.

The role of peripheral inflammatory insults in Alzheimer's disease: a review and research roadmap.

Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon that has been identified as a risk factor for Alzheimer's disease. While the role of chronic peripheral inflammation has been well characterized in the context of dementia and other age-related conditions, less is known about the neurologic contribution of acute inflammatory insults that take place outside the central nervous system. Herein, we define acute inflammatory insults as an immune challenge in the form of pathogen exposure (e.

Sensory impairment and beta-amyloid deposition in the Baltimore longitudinal study of aging.

Introduction: Beta-amyloid (Aβ) plaque deposition is a biomarker of preclinical Alzheimer's disease (AD). Impairments in sensory function are associated with cognitive decline. We sought to investigate the relationship between PET-indicated Aβ deposition and sensory impairment.

Sensory impairment and algorithmic classification of early cognitive impairment.

Introduction: Sensory impairment (SI) is linked to cognitive decline, but its association with early cognitive impairment (ECI) is unclear.

Methods: Sensory functions (vision, hearing, vestibular function, proprioception, and olfaction) were measured between 2012 and 2018 in 414 Baltimore Longitudinal Study of Aging (BLSA) participants (age 74 ± 9 years; 55% women). ECI was defined as 1 standard deviation below age-, sex-, race-, and education-specific mean performance in Card Rotations or California Verbal Learning Test immediate recall.

Association of Accelerometer-Measured Physical Activity and Sedentary Behavior With Incident Cardiovascular Disease, Myocardial Infarction, and Ischemic Stroke: The Women's Health Study.

Background Few studies have investigated associations of acclerometer-based assessments of physical activity (PA) and sedentary behavior (SB) with incidence of cardiovascular disease (CVD) and its components. This prospective cohort study assessed the associations of accelerometer-measured PA and SB with total CVD, myocardial infarction, and ischemic stroke (IS). Methods and Results The authors included 16 031 women aged 62 years and older, free of CVD, with adherent accelerometer wear (≥10 hours/day for ≥4 days) from the Women's Health Study (mean age, 71.

Dysregulated Genes, MicroRNAs, Biological Pathways, and Gastrocnemius Muscle Fiber Types Associated With Progression of Peripheral Artery Disease: A Preliminary Analysis.

Background Peripheral artery disease (PAD) is associated with gastrocnemius muscle abnormalities. However, the biological pathways associated with gastrocnemius muscle dysfunction and their associations with progression of PAD are largely unknown. This study characterized differential gene and microRNA (miRNA) expression in gastrocnemius biopsies from people without PAD compared with those with PAD.

Ankle-Brachial Index and Energy Production in People Without Peripheral Artery Disease: The BLSA.

Background Lower ankle-brachial index (ABI) values within the 0.90 to 1.40 range are associated with poorer mitochondrial oxidative capacity of thigh muscles in cross-sectional analyses.

Association of walking energetics with amyloid beta status: Findings from the Baltimore Longitudinal Study of Aging.

Introduction: Higher energetic costs for mobility predict gait speed decline. Slow gait is linked to cognitive decline and Alzheimer's disease (AD). Whether the energetic cost of walking is linked to AD pathology is unknown.

Perceived Versus Objective Change in Walking Ability in Peripheral Artery Disease: Results from 3 Randomized Clinical Trials of Exercise Therapy.

Background In people with lower-extremity peripheral artery disease, the effects of exercise on patient-reported outcomes remain unclear. Methods and Results Four hundred four people with peripheral artery disease in 3 clinical trials were randomized to exercise (N=205) or a control group (N=199) and completed the 6-minute walk and the Walking Impairment Questionnaire distance score (score 0-100, 100=best) at baseline and 6-month follow-up. Compared with the control group, exercise improved 6-minute walk distance by +39.

Astrocytes deliver CK1 to neurons via extracellular vesicles in response to inflammation promoting the translation and amyloidogenic processing of APP.

Chronic inflammation is thought to contribute to the early pathogenesis of Alzheimer's disease (AD). However, the precise mechanism by which inflammatory cytokines promote the formation and deposition of Aβ remains unclear. Available data suggest that applications of inflammatory cytokines onto isolated neurons do not promote the formation of Aβ, suggesting an indirect mechanism of action.

Targeting abnormal metabolism in Alzheimer's disease: The Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study.

Drug discovery for disease-modifying therapies for Alzheimer's disease and related dementias (ADRD) based on the traditional paradigm of experimental animal models has been disappointing. We describe the rationale and design of the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study, an innovative multidisciplinary alternative to traditional drug discovery. First, we use a systems biology perspective in the "hypothesis generation" phase to identify metabolic abnormalities that may either precede or interact with the accumulation of ADRD neuropathology, accelerating the expression of clinical symptoms of the disease.

Parsimonious discretization for characterizing multi-exponential decay in magnetic resonance.

We address the problem of analyzing noise-corrupted magnetic resonance transverse decay signals as a superposition of underlying independently decaying monoexponentials of positive amplitude. First, we indicate the manner in which this is an ill-conditioned inverse problem, rendering the analysis unstable with respect to noise. Second, we define an approach to this analysis, stabilized solely by the nonnegativity constraint without regularization.

Shared mechanisms for cognitive impairment and physical frailty: A model for complex systems.

Introduction: We describe findings from a large study that provide empirical support for the emerging construct of cognitive frailty and put forth a theoretical framework that may advance the future study of complex aging conditions. While cognitive impairment and physical frailty have long been studied as separate constructs, recent studies suggest they share common etiologies. We aimed to create a population predictive model to gain an understanding of the underlying biological mechanisms for the relationship between physical frailty and cognitive impairment.

Correlations of Calf Muscle Macrophage Content With Muscle Properties and Walking Performance in Peripheral Artery Disease.

Background Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy.

Background Patients with peripheral artery disease (PAD) undergo frequent episodes of ischemia-reperfusion in lower extremity muscles that may negatively affect mitochondrial health and are associated with impaired mobility. We hypothesized that skeletal muscle from PAD patients will show high mitochondrial DNA heteroplasmy, especially in regions more susceptible to oxidative damage, such as the displacement loop, and that the degree of heteroplasmy will be correlated with the severity of ischemia and mobility impairment. Methods and Results Mitochondrial mutations and deletions and their relative abundance were identified by targeted mitochondrial DNA sequencing in biopsy specimens of gastrocnemius muscle from 33 PAD (ankle brachial index <0.

Association Between Cardiovascular Risk and Perceived Fatigability in Mid-to-Late Life.

Background Cardiovascular disease (CVD) and fatigue commonly co-occur in older adults, yet the subjective nature of fatigue and its situational dependence leave the true magnitude of this association undefined. Methods and Results Six-hundred and twenty-five participants with no history of CVD (aged 68.1+12.

Subclinical Longitudinal Change in Ankle-Brachial Index With Aging in a Community-Dwelling Population Is Associated With Central Arterial Stiffening.

Background Aging is associated with a modest decline in ankle-brachial index (ABI); however, the underpinnings of this decline are not fully understood. The greater systolic ankle than brachial blood pressure, a normal ABI implies, is partially attributed to lower central than peripheral arterial stiffness. Hence, we examined the hypothesis that the age-associated decline in ABI is associated with central arterial stiffening with aging, assessed by pulse wave velocity.

Associations of Weight Change With Changes in Calf Muscle Characteristics and Functional Decline in Peripheral Artery Disease.

Background Among people with lower extremity peripheral artery disease, obesity is associated with faster functional decline than normal weight. The association of weight loss with functional decline in peripheral artery disease is unknown. Methods and Results Adults with an ankle-brachial index <0.

Racial Differences in the Effect of Granulocyte Macrophage Colony-Stimulating Factor on Improved Walking Distance in Peripheral Artery Disease: The PROPEL Randomized Clinical Trial.

Background The effects of race on response to medical therapy in people with peripheral artery disease ( PAD ) are unknown. Methods and Results In the PROPEL (Progenitor Cell Release Plus Exercise to Improve Functional Performance in PAD) Trial, PAD participants were randomized to 1 of 4 groups for 6 months: supervised treadmill exercise+granulocyte-macrophage colony-stimulating factor ( GM - CSF ) (Group 1), exercise+placebo (Group 2), attention control+ GM - CSF (Group 3), or attention control+placebo (Group 4). Change in 6-minute walk distance was measured at 12- and 26-week follow-up.

Durability of Benefits From Supervised Treadmill Exercise in People With Peripheral Artery Disease.

Background It is currently unknown whether 6 months of supervised treadmill exercise has a durable benefit on 6-minute walk performance, even after exercise is completed, in people with peripheral artery disease. Methods and Results A total of 156 participants with peripheral artery disease were randomized to 1 of 3 groups: supervised treadmill exercise, supervised resistance training, or attention control. Participants received supervised sessions during months 1 to 6 and telephone contact during months 6 to 12.

VOR Gain Is Related to Compensatory Saccades in Healthy Older Adults.

Objective: Vestibulo-ocular reflex (VOR) gain is well-suited for identifying rotational vestibular dysfunction, but may miss partial progressive decline in age-related vestibular function. Since compensatory saccades might provide an alternative method for identifying subtle vestibular decline, we describe the relationship between VOR gain and compensatory saccades in healthy older adults.

Methods: Horizontal VOR gain was measured in 243 subjects age 60 and older from the Baltimore Longitudinal Study of Aging using video head impulse testing (HIT).

Low neural exosomal levels of cellular survival factors in Alzheimer's disease.

Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001).