The interactive effect of intra-beat and inter-beat blood pressure variability on neurodegeneration in older adults.

Blood pressure variability (BPV) and arterial stiffness are age-related hemodynamic risk factors for neurodegenerative disease, but it remains unclear whether they exert independent or interactive effects on brain health. When combined with high inter-beat BPV, increased intra-beat BPV indicative of arterial stiffness could convey greater pressure wave fluctuations deeper into the cerebrovasculature, exacerbating neurodegeneration. This interactive effect was studied in older adults using multiple markers of neurodegeneration, including medial temporal lobe (MTL) volume, plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Older adults (N=105) without major neurological or systemic disease were recruited and underwent brain MRI and continuous BP monitoring to quantify inter-beat BPV through systolic average real variability (ARV) and intra-beat variability through arterial stiffness index (ASI). Plasma NfL and GFAP were assessed. The interactive effect of ARV and ASI on MTL atrophy, plasma NfL, and GFAP was studied using hierarchical linear regression. Voxel-based morphometry (VBM) was used to confirm region-of-interest analysis findings. The interaction between higher ARV and higher ASI was significantly associated with left-sided MTL atrophy in both the region-of-interest and false discovery rate-corrected VBM analysis. The interactive effect was also significantly associated with increased plasma NfL, but not GFAP. The interaction between higher ARV and higher ASI is independently associated with increased neurodegenerative markers, including MTL atrophy and plasma NfL, in independently living older adults. Findings could suggest the increased risk for neurodegeneration associated with higher inter-beat BPV may be compounded by increased intra-beat variability due to arterial stiffness.

Reliability of beat-to-beat blood pressure variability in older adults.

Blood pressure variability (BPV) is emerging as an important risk factor across numerous disease states, including cerebrovascular and neurodegenerative disease in older adults. However, there is no current consensus regarding specific use cases for the numerous available BPV metrics. There is also little published data supporting the ability to reliably measure BPV across metrics in older adults. BPV metrics were derived from continuous beat-to-beat blood pressure monitoring data. Two sequential 7-minute waveforms were analyzed. Absolute and relative reliability testing was performed. Differences between antihypertensive medication users and non-users on BPV metric reliability was also assessed. All sequence and dispersion based BPV metrics displayed good test-retest reliability. A measure of BP instability displayed only moderate reliability. Systolic and diastolic average real variability displayed the highest levels of reliability at ICC= .87 and .82 respectively. Additionally, systolic average real variability was the most reliable metric in both the antihypertensive use group, and the no antihypertensive use group. Beat-to-beat dispersion and sequence-based metrics of BPV can be reliably obtained from older adults using noninvasive continuous blood pressure monitoring. Average real variability may be the most reliable and specific beat-to-beat blood pressure variability metric due to its decreased susceptibility to outliers and low frequency blood pressure oscillations.

High-Intensity interval training reduces transcriptomic age: A randomized controlled trial.

While the relationship between exercise and life span is well-documented, little is known about the effects of specific exercise protocols on modern measures of biological age. Transcriptomic age (TA) predictors provide an opportunity to test the effects of high-intensity interval training (HIIT) on biological age utilizing whole-genome expression data. A single-site, single-blinded, randomized controlled clinical trial design was utilized. Thirty sedentary participants (aged 40-65) were assigned to either a HIIT group or a no-exercise control group. After collecting baseline measures, HIIT participants performed three 10 × 1 HIIT sessions per week for 4 weeks. Each session lasted 23 min, and total exercise duration was 276 min over the course of the 1-month exercise protocol. TA, PSS-10 score, PSQI score, PHQ-9 score, and various measures of body composition were all measured at baseline and again following the conclusion of exercise/control protocols. Transcriptomic age reduction of 3.59 years was observed in the exercise group while a 3.29-years increase was observed in the control group. Also, PHQ-9, PSQI, BMI, body fat mass, and visceral fat measures were all improved in the exercise group. A hypothesis-generation gene expression analysis suggested exercise may modify autophagy, mTOR, AMPK, PI3K, neurotrophin signaling, insulin signaling, and other age-related pathways. A low dose of HIIT can reduce an mRNA-based measure of biological age in sedentary adults between the ages of 40 and 65 years old. Other changes in gene expression were relatively modest, which may indicate a focal effect of exercise on age-related biological processes.

Blood pressure variability, central autonomic network dysfunction and cerebral small vessel disease in APOE4 carriers.

Background: Increased blood pressure variability (BPV) is a risk factor for cerebral small vessel disease (CSVD) and neurodegeneration, independent of age and average blood pressure, particularly in apolipoprotein E4 (APOE4) carriers. However, it remains uncertain whether BPV elevation is a cause or a consequence of vascular brain injury, or to what degree injury to the central autonomic network (CAN) may contribute to BPV-associated risk in APOE4 carriers. Methods: Independently living older adults (n=70) with no history of stroke or dementia were recruited from the community and underwent 5 minutes of resting beat-to-beat blood pressure monitoring, genetic testing, and brain MRI. Resting BPV, APOE genotype, CSVD burden on brain MRI, and resting state CAN connectivity by fMRI were analyzed. Causal mediation and moderation analysis evaluated BPV and CAN effects on CSVD in APOE4 carriers (n=37) and non-carriers (n=33). Results: Higher BPV was associated with the presence and extent of CSVD in APOE4 carriers, but not non-carriers, independent of CAN connectivity (B= 18.92, P= .02), and CAN connectivity did not mediate the relationship between BPV and CSVD. In APOE4 carriers, CAN connectivity moderated the relationship between BPV and CSVD, whereby BPV effects on CSVD were greater in those with lower CAN connectivity (B= 36.43, P= .02). Conclusions: Older APOE4 carriers with higher beat-to-beat BPV exhibit more extensive CSVD, independent of average blood pressure, and the strength of CAN connectivity does not mediate these effects. Findings suggest increased BPV is more likely a cause, not a consequence, of CSVD. BPV is more strongly associated with CSVD in APOE4 carriers with lower rsCAN connectivity, suggesting CAN dysfunction and BPV elevation may have synergistic effects on CSVD. Further studies are warranted to understand the interplay between BPV and CAN function in APOE4 carriers.

Predictors of Biological Age: The Implications for Wellness and Aging Research.

As healthspan and lifespan research breakthroughs have become more commonplace, the need for valid, practical markers of biological age is becoming increasingly paramount. The accessibility and affordability of biological age predictors that can reveal information about mortality and morbidity risk, as well as remaining years of life, has profound clinical and research implications. In this review, we examine 5 groups of aging biomarkers capable of providing accurate biological age estimations. The unique capabilities of these biomarkers have far reaching implications for the testing of both pharmaceutical and non-pharmaceutical interventions designed to slow or reverse biological aging. Additionally, the enhanced validity and availability of these tools may have increasingly relevant clinical value. The authors of this review explore those implications, with an emphasis on lifestyle modification research, and provide an overview of the current evidence regarding 5 biological age predictor categories: Telomere length, composite biomarkers, DNA methylation "epigenetic clocks," transcriptional predictors of biological age, and functional age predictors.

A comparison of the effect of a variety of thermal and vibratory modalities on skin temperature and blood flow in healthy volunteers.

BACKGROUND: Circulation plays an essential role in tissue healing. Moist heat and warm water immersion have been shown to increase skin circulation; however, these heating modalities can cause burns. Recent research has shown that passive vibration can also increase circulation but without the risk of burns. MATERIAL/METHODS: The aim of this study is to compare the effects of short-duration vibration, moist heat, and a combination of the two on skin blood flow (SBF) and skin temperature (ST). Ten (10) subjects, 5 female and 5 male, aged 20-30 years of age, received two interventions a day for 3 consecutive days: Intervention 1--Active vibration only (vibration exercise), Intervention 2--passive vibration only, Intervention 3--moist heat only, Intervention 4--passive vibration combined with moist heat, Intervention 5--a commercial massaging heating pad, and Intervention 6--no intervention, resting in supine only (control). SBF and ST were measured using a laser Doppler imager during the 10 minute intervention and then throughout the nine minute recovery period. RESULTS: The mean skin blood flow following a ten-minute intervention of the combination of passive vibration and moist heat was significantly different from the control, active vibration, and the commercial massaging heating pad. Skin temperature following the ten-minute interventions of moist heat alone and passive vibration alone were both significantly different from the commercial massaging heating pad and active vibration interventions. CONCLUSIONS: The combination of passive vibration and moist heat produced the greatest increase in skin blood flow and the second highest increase in skin blood flow nine minutes post application.

A device to evaluate motor and autonomic impairment.

Various devices have been developed to assess impairment of the autonomic nervous system, while other devices have been developed to evaluate the motor system. However, no devices have been developed to examine the interaction between the autonomic and somatic nervous systems. Therefore, the device described here, a square platform which was 0.7x0.7 m in length and 0.1m thick, was developed to examine somatic-autonomic interaction. The device can be used by placing it directly on the floor or on 1 of 2 pivots; one that allowed the platform to move 0.2m (+/-44.1 degrees) in the front to back or side to side direction and one that allowed both movements together. Strain gauge load cells in the platform measured sway and tremor during the subjects attempt to balance and a continuous blood pressure monitor and the ECG were used to assess the response of the autonomic nervous system (heart rate variability). The device was tested on 5 normal subjects and the following was evaluated: (1) sway during standing, (2) weight shift during standing, (3) frequency of sway and extent of sway during standing, (4) sympathetic and parasympathetic alterations in the ANS during attempted balance, and (5) phase delays between motor and autonomic responses. The results showed that, with increasing balance challenge, sway increased, tremor increased, the sway angle increased and sway was positively correlated with heart rate and negatively correlated with blood pressure. A balance challenge significantly increased sympathetic activity but not parasympathetic activity. This device should have useful applications in assessing motor impairments and sensory and autonomic impairments in a variety of conditions.