RESUMO
Visit-to-visit blood pressure variability (BPV) predicts age-related hippocampal atrophy, neurodegeneration, and memory decline in older adults. Beat-to-beat BPV may represent a more reliable and efficient tool for prospective risk assessment, but it is unknown whether beat-to-beat BPV is similarly associated with hippocampal neurodegeneration, or with plasma markers of neuroaxonal/neuroglial injury. Independently living older adults without a history of dementia, stroke, or other major neurological disorders were recruited from the community (N = 104; age = 69.5 ± 6.7 (range 55-89); 63% female). Participants underwent continuous blood pressure monitoring, brain MRI, venipuncture, and cognitive testing over two visits. Hippocampal volumes, plasma neurofilament light, and glial fibrillary acidic protein levels were assessed. Beat-to-beat BPV was quantified as systolic blood pressure average real variability during 7-min of supine continuous blood pressure monitoring. The cross-sectional relationship between beat-to-beat BPV and hippocampal volumes, cognitive domain measures, and plasma biomarkers was assessed using multiple linear regression with adjustment for demographic covariates, vascular risk factors, and average systolic blood pressure. Elevated beat-to-beat BPV was associated with decreased left hippocampal volume (P = .008), increased plasma concentration of glial fibrillary acidic protein (P = .006), and decreased memory composite score (P = .02), independent of age, sex, average systolic blood pressure, total intracranial volume, and vascular risk factor burden. In summary, beat-to-beat BPV is independently associated with decreased left hippocampal volume, increased neuroglial injury, and worse memory ability. Findings are consistent with prior studies examining visit-to-visit BPV and suggest beat-to-beat BPV may be a useful marker of hemodynamic brain injury in older adults.
RESUMO
Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment. Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest. Results: Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors. Conclusion: Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.
RESUMO
BACKGROUND: Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. METHODS: Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aß42, Aß40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed. RESULTS: All autonomic networks were positively associated with Aß42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. CONCLUSION: The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aß42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Imageamento por Ressonância Magnética , Humanos , Feminino , Doença de Alzheimer/sangue , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/diagnóstico por imagem , Idoso , Masculino , Biomarcadores/sangue , Peptídeos beta-Amiloides/sangue , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Fragmentos de Peptídeos/sangue , Sistema Nervoso Autônomo/fisiopatologia , Proteína Glial Fibrilar Ácida/sangue , Idoso de 80 Anos ou mais , Proteínas de Neurofilamentos/sangue , Doenças do Sistema Nervoso Autônomo/sangue , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/etiologiaRESUMO
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.
RESUMO
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.
Assuntos
Apolipoproteína E4 , Pressão Sanguínea , Doenças de Pequenos Vasos Cerebrais , Humanos , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Doenças de Pequenos Vasos Cerebrais/genética , Feminino , Pressão Sanguínea/fisiologia , Apolipoproteína E4/genética , Masculino , Pessoa de Meia-Idade , Idoso , Sistema Nervoso Autônomo/fisiopatologia , HeterozigotoRESUMO
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.
Assuntos
Treinamento Intervalado de Alta Intensidade , Resistência à Insulina , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Transcriptoma/genética , Treinamento Intervalado de Alta Intensidade/métodos , Exercício Físico , Perfilação da Expressão GênicaRESUMO
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.
RESUMO
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.
RESUMO
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.
Assuntos
Saúde , Temperatura Alta , Fluxo Sanguíneo Regional/fisiologia , Temperatura Cutânea/fisiologia , Pele/irrigação sanguínea , Vibração , Adulto , Feminino , Humanos , Fluxometria por Laser-Doppler , Masculino , Fatores de Tempo , Adulto JovemRESUMO
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.