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With the rapid expansion of aging biology research, the identification and evaluation of longevity interventions in humans have become key goals of this field. Biomarkers of aging are critically important tools in achieving these objectives over realistic time frames. However, the current lack of standards and consensus on the properties of a reliable aging biomarker hinders their further development and validation for clinical applications. Here, we advance a framework for the terminology and characterization of biomarkers of aging, including classification and potential clinical use cases. We discuss validation steps and highlight ongoing challenges as potential areas in need of future research. This framework sets the stage for the development of valid biomarkers of aging and their ultimate utilization in clinical trials and practice.
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Aging , Longevity , Humans , BiomarkersABSTRACT
Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential. Here, we present a consensus from the International Cell Senescence Association (ICSA), defining and discussing key cellular and molecular features of senescence and offering recommendations on how to use them as biomarkers. We also present a resource tool to facilitate the identification of genes linked with senescence, SeneQuest (available at http://Senequest.net). Lastly, we propose an algorithm to accurately assess and quantify senescence, both in cultured cells and in vivo.
Subject(s)
Aging/genetics , Biomarkers , Cellular Senescence/genetics , Genetic Diseases, Inborn/genetics , Cell Cycle Checkpoints/genetics , Chromatin/genetics , Gene Expression Regulation/genetics , Genetic Diseases, Inborn/therapy , HumansABSTRACT
PPFIA3 encodes the protein-tyrosine phosphatase, receptor-type, F-polypeptide-interacting-protein-alpha-3 (PPFIA3), which is a member of the LAR-protein-tyrosine phosphatase-interacting-protein (liprin) family involved in synapse formation and function, synaptic vesicle transport, and presynaptic active zone assembly. The protein structure and function are evolutionarily well conserved, but human diseases related to PPFIA3 dysfunction are not yet reported in OMIM. Here, we report 20 individuals with rare PPFIA3 variants (19 heterozygous and 1 compound heterozygous) presenting with developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, autistic features, and epilepsy with reduced penetrance. Seventeen unique PPFIA3 variants were detected in 18 families. To determine the pathogenicity of PPFIA3 variants in vivo, we generated transgenic fruit flies producing either human wild-type (WT) PPFIA3 or five missense variants using GAL4-UAS targeted gene expression systems. In the fly overexpression assays, we found that the PPFIA3 variants in the region encoding the N-terminal coiled-coil domain exhibited stronger phenotypes compared to those affecting the C-terminal region. In the loss-of-function fly assay, we show that the homozygous loss of fly Liprin-α leads to embryonic lethality. This lethality is partially rescued by the expression of human PPFIA3 WT, suggesting human PPFIA3 function is partially conserved in the fly. However, two of the tested variants failed to rescue the lethality at the larval stage and one variant failed to rescue lethality at the adult stage. Altogether, the human and fruit fly data reveal that the rare PPFIA3 variants are dominant-negative loss-of-function alleles that perturb multiple developmental processes and synapse formation.
Subject(s)
Drosophila Proteins , Intellectual Disability , Neurodevelopmental Disorders , Adult , Animals , Humans , Alleles , Animals, Genetically Modified , Drosophila , Drosophila Proteins/genetics , Intellectual Disability/genetics , Intracellular Signaling Peptides and Proteins , Neurodevelopmental Disorders/genetics , Protein Tyrosine PhosphatasesABSTRACT
BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.
Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Aged , Meningioma/pathology , Meningeal Neoplasms/pathology , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Risk AssessmentABSTRACT
BACKGROUND AND PURPOSE: This study investigated the effects of deep abdominal breathing on cardiovascular parameters and symptoms in patients with postural orthostatic tachycardia syndrome (POTS) during head-up tilt-table (HUT) challenge. METHODS: Thirty POTS patients completed two consecutive rounds of 10-min HUT in a crossover design. One round was HUT without intervention, and one round combined the HUT with deep breathing at a rate of 6 breaths/min. Cardiovascular parameters, including mean blood pressure and maximum and mean heart rate (HR), were measured supine and standing. Symptoms were assessed using the Vanderbilt Orthostatic Symptom Score (VOSS). RESULTS: During the breathing technique, the mean HR increase was -7.35 bpm (95% confidence interval [CI] = -11.71 to -2.98), and the maximum HR increase was -6.27 bpm (95% CI = -11.85 to -0.68, p = 0.041), significantly lower compared to normal breathing. Additionally, improvements were observed in all absolute cardiovascular parameters during standing, with VOSS symptoms simultaneously and significantly decreasing by -5.38 (95% CI = -10.43 to -0.36). CONCLUSIONS: Slow deep abdominal breathing can act as a simple technique to reduce the standing HR increase upon HUT in patients with POTS. This suggests that modulation of the cardiopulmonary neurocircuits and the respiratory pump may reduce HR increase and symptoms in patients with POTS. The findings of this study highlight the use of a safe, zero-cost, and simple behavioral tool to suggest to POTS patients for symptom relief apart from standard treatment. The observed improvements in cardiovascular parameters and symptoms offer a promising therapeutic approach for patients in times of inadequate treatment options.
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BACKGROUND: Contradictory findings link trait conscientiousness in mid- and late life to increased healthspan and lifespan, as well as to death by suicide. It remains unclear whether conscientiousness is associated with higher odds of attempting suicide or with more severe suicidal behavior among attempters, and whether its relationship to suicide risk varies with aging-related stressors, such as declining health. METHODS: In this cross-sectional study comprising 313 depressed adults aged ≥40 years and participating in the Longitudinal Research Program in Late-Life Suicide (Pittsburgh, USA), we employed logistic and linear regression to test whether conscientiousness was associated with the presence of recent suicidal behavior (≤2 years) and with intent severity in recent attempters (n = 84). We further tested whether the above relationships varied based on mental, cognitive, and physical health status, measured as depression severity, cognitive functioning, and the presence/absence of severe physical illness. RESULTS: Participants were 62.1 years old on average (SD = 7.6), 85% White, and 53% female. Recent attempters had a mean age of 61.8 years at their most recent attempt (SD = 8.5), had lower cognitive functioning and were more likely severely physically ill than comparisons. Conscientiousness was positively associated with a higher likelihood of recent suicidal behavior overall (adjusted OR = 1.44, 95% CI = 1.09, 1.90, p = .010), but not in case of co-occurring severe physical illness (interaction OR = 0.54, 95% CI = 0.30, 0.97, p = .039). Conscientiousness was also positively associated with suicidal intent at the most recent attempt (adjusted ß = 1.60, SE = 0.62, p = .012), explaining 7% of its variance, although this association lost significance after adjusting for other personality dimensions. CONCLUSIONS: Highly conscientious middle-aged and older adults may be at increased risk of resolute suicidal behavior, although conscientiousness may not confer additional suicide risk among those severely physically ill.
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INTRODUCTION: Foot problems, including musculoskeletal problems, peripheral neuropathy, peripheral arterial disease and dermatologic pathology are common in older adults and are associated with an increased risk of falling. Multicomponent podiatry interventions have been shown to reduce the incidence of falls. This paper aimed to identify older adults requiring podiatry input in a Falls and Balance clinic; to describe the model of foot health care they receive; to explore cross-sectional associations between foot problems and function and ultimately demonstrate the role of podiatry input in the multidisciplinary management of falls risk. METHODS: Cohort study of patients attending a Falls and Balance Clinic for Comprehensive Geriatric Assessment. Demographic information was collected and functional independence, mobility, foot problems, and footwear were assessed in the clinic. RESULTS: One-hundred and two patients were included; median age 79.3 (73-84.3) years, 68.6% female, 93.1% residing independently, 62.7% used a gait aid. Podiatry referrals were made in 80.4% of cases, with muscle weakness being the most common problem identified (90.2%); 74.8% were found to be wearing inappropriate footwear. Most patients received footwear education and half were prescribed foot and ankle strengthening exercises. Hallux and lesser toe weakness were associated with lower Short Physical Performance Battery scores (p < 0.001). CONCLUSION: The majority of older adults in the Falls and Balance Clinic required podiatry input, with foot weakness and inappropriate footwear being common reasons for referral. Those with weakness of the hallux and lesser toes had poorer balance and mobility, which is known to be associated with greater falls risk. This highlights the need for podiatry assessment and interventions as part of the multidisciplinary approach to the management of falls risk in older adults.
Subject(s)
Accidental Falls , Foot Diseases , Geriatric Assessment , Podiatry , Postural Balance , Humans , Aged , Female , Male , Accidental Falls/prevention & control , Accidental Falls/statistics & numerical data , Aged, 80 and over , Geriatric Assessment/methods , Foot Diseases/epidemiology , Foot Diseases/therapy , Foot Diseases/etiology , Podiatry/methods , Cross-Sectional Studies , Shoes , Cohort Studies , Referral and ConsultationABSTRACT
OBJECTIVE: To determine the prevalence and co-occurrence of common geriatric syndromes in geriatric rehabilitation inpatients. DESIGN: Restoring Health of Acutely Unwell Adults (RESORT) and Enhancing Muscle Power in Geriatric Rehabilitation (EMPOWER-GR) are observational, longitudinal cohorts. SETTING: Geriatric rehabilitation. PARTICIPANTS: Geriatric rehabilitation inpatients (N=1890 and N=200). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Geriatric syndromes included polypharmacy, multimorbidity (Cumulative Illness Rating Scale), cognitive impairment, depression (Hospital Anxiety and Depression Scale/Geriatric Depression Scale), malnutrition (Global Leadership Initiative on Malnutrition), functional limitation (Katz index), falls, physical frailty (Fried), and sarcopenia (European Working Group on Sarcopenia in Older People 2). RESULTS: Inpatients in RESORT (R) (N=1890, 56% females) had a median age of 83.4 years (interquartile range [IQR], 77.6-88.4) and in EMPOWER-GR (E) (N=200, 57% females) of 79.8 years (IQR, 75.0-85.9). Polypharmacy (R, 82.2%; E, 84.0%), multimorbidity (R, 90.4%; E, 85.5%), functional limitation (R, 96.0%; E, 76.5%), and frailty (R, 91.8%; E, 92.2%) were most prevalent. Most inpatients had ≥5 geriatric syndromes at admission in both cohorts (R, 70.0%; E, 72.4%); few inpatients had only 1 (R, 0.4%; E, 1.5%) or no geriatric syndrome (R, 0.2%; E, 0.0%). Geriatric syndromes did not occur in isolation (without other syndromes), except for multimorbidity (R, 1%; E, 5%), functional limitation (R, 3%; E, 2%), falls (R, 0%; E, 4%), and frailty (R, 2%; E, 5%), which occurred in isolation in some inpatients; sarcopenia did not. CONCLUSIONS: Geriatric syndromes are highly prevalent at admission to geriatric rehabilitation, with a median of 5 co-occurring syndromes. Implications for diagnosis and intervention potential should be further addressed.
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INTRODUCTION: China has the world's largest number of older adults with cognitive impairment (CI). We aimed to examine secular trends in the prevalence of CI in China from 2002 to 2018. METHODS: Generalized estimating equations (GEE) was used to assess changes in CI trend in 44,154 individuals (72,027 observations) aged 65 to 105 years old. RESULTS: The prevalence of CI increased from 2002 to 2008 and then decreased until 2018. The age-standardized prevalence increased from 25.7% in 2002, 26.1% in 2005, to 28.2% in 2008, then decreased to 26.0% in 2011, 25.3% in 2014, and 24.9% in 2018. Females and those ≥ 80 years old had greater CI prevalence. DISCUSSION: The prevalence of CI showed an inverted U shape from early 2000s to late 2010s with a peak in 2008. Follow-up studies are needed to confirm the decreasing trend after 2008 and examine the contributing factors and underlying mechanisms of this trend. HIGHLIGHTS: Generalized estimating equations (GEE) were used to assess trends of changes in cognitive impairment (CI). CI prevalence in China increased from 2002 to 2008 and then decreased until 2018. Females and those ≥ 80 years old had greater CI prevalence. Stroke, diabetes, and cigarette smoking were risk factors for CI.
Subject(s)
Cognitive Dysfunction , Stroke , Female , Humans , Aged , Aged, 80 and over , Prevalence , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Risk Factors , China/epidemiologyABSTRACT
INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-ß1-42 (Aß42)-positive status. METHODS: Individual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume. RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p < 0.001), external capsule (B = 0.052, p < 0.001), and middle cerebellar peduncle (B = 0.067, p < 0.001), and Aß42-positive status with WMH in posterior thalamic radiation (B = 0.097, p < 0.001) and splenium (B = 0.103, p < 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. HIGHLIGHTS: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aß42 status in 11 memory clinic cohorts. Aß42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.
Subject(s)
Arteriolosclerosis , Dementia , White Matter , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Male , White Matter/pathology , Arteriolosclerosis/pathology , Amyloid beta-Peptides/metabolism , Dementia/pathology , Magnetic Resonance ImagingABSTRACT
BACKGROUND: The clinical picture of people with Ehlers-Danlos syndromes (EDS) is complex and involves a variety of potential causes of pain. This poses major challenges to patients and healthcare professionals alike in terms of diagnosis and management of the condition. OBJECTIVES: The aim of the article was to provide an overview of the specific pain management needs of patients with EDS and address their background. MATERIAL AND METHODS: A selective literature search was performed to highlight the current state of research on pain management in EDS patients. RESULTS: Affected patients require multimodal pain management considering their individual needs, disease-specific features, and comorbidities. CONCLUSION: Medical awareness and evidence need to be further improved to enhance the medical care situation of these patients with complex needs.
Subject(s)
Ehlers-Danlos Syndrome , Joint Instability , Humans , Joint Instability/diagnosis , Ehlers-Danlos Syndrome/complications , Ehlers-Danlos Syndrome/diagnosis , Ehlers-Danlos Syndrome/therapy , Pain , Comorbidity , Pain ManagementABSTRACT
BACKGROUND: Neuropathic pain is difficult to diagnose and treat. Small fiber neuropathy (SFN) flies under the radar of nerve conduction studies. OBJECTIVES: The importance of a structured patient history and physical examination in the context of neuropathic pain is emphasized. Describing SFN as an important cause, the authors consider rare but partially treatable differential diagnoses. They conclude that autonomic symptoms are frequently associated, often presenting with diverse symptoms. METHODS: A selective literature research to present SFN symptoms as well as differential diagnostic and therapeutic steps in the context of SFN and rare diseases focusing on the autonomic nervous system. RESULTS: Neuropathic pain significantly reduces quality of life. To shorten the time until diagnosis and to initiate therapy, the authors recommend a structured patient history including sensory plus and minus symptoms and non-specific autonomic signs. If the initial search for the cause is not successful, rare causes such as treatable transthyretin (ATTR) amyloidosis and Fabry's disease or autoimmune causes should be considered, particularly in the case of progressive and/or autonomic symptoms. CONCLUSION: The diagnosis and therapy of rare SFN requires interdisciplinary collaboration and, in many cases, a referral to specialized centers to achieve the best patient care.
Subject(s)
Neuralgia , Small Fiber Neuropathy , Humans , Small Fiber Neuropathy/diagnosis , Small Fiber Neuropathy/therapy , Quality of Life , Rare Diseases/complications , Neuralgia/diagnosis , Neuralgia/etiology , Neuralgia/therapy , Autonomic Nervous SystemABSTRACT
OBJECTIVES: Meningiomas are the most common, primary intracranial tumor and most are benign. Little is known of the rare patient group living with a malignant meningioma, comprising 1-3% of all meningiomas. Our aim was to explore how patients perceived quality of daily life after a malignant meningioma diagnosis. METHODS: This qualitative explorative study was composed of individual semi-structured interviews. Eligible patients (n = 12) were selected based on ability to participate in an interview, from a background population of 23 patients diagnosed with malignant meningioma at Rigshospitalet from 2000 to 2021. We performed an inductive thematic analysis following Braun and Clarke's guidelines. RESULTS: Eight patients were interviewed. The analysis revealed 4 overarching themes: (1) perceived illness and cause of symptoms, (2) identity, roles, and interaction, (3) threat and uncertainty of the future, and (4) belief in authority. The perceived quality of daily life is negatively impacted by the disease. Patients experience a shift in self-concept and close interactions, and some struggle with accepting a new everyday life. Patients have a high risk of discordant prognostic awareness in relation to health-care professionals. SIGNIFICANCE OF RESULTS: We provide a much-needed patient-centered perspective of living with malignant meningioma: quality of life was affected by perception of threat and an uncertainty of the future. Perception of illness and the interpretation of the cause of symptoms varied between subjects, but a common trait was that patients' identity, roles, and interactions were affected. Shared decision-making and a strengthened continuity during follow-up could aid this rare patient group.
Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Meningioma/complications , Meningioma/epidemiology , Meningioma/pathology , Quality of Life , Prognosis , Qualitative Research , Meningeal Neoplasms/complications , Meningeal Neoplasms/epidemiology , Meningeal Neoplasms/pathologyABSTRACT
Chronological age is the most important risk factor for the incidence of age-related diseases. The pace of ageing determines the magnitude of that risk and can be expressed as biological age. Targeting fundamental pathways of human aging with geroprotectors has the potential to lower the biological age and therewith prolong the healthspan, the period of life one spends in good health. Target populations for geroprotective interventions should be chosen based on the ageing mechanisms being addressed and the expected effect of the geroprotector on the primary outcome. Biomarkers of ageing, such as DNA methylation age, can be used to select populations for geroprotective interventions and as a surrogate outcome. Here, the use of DNA methylation clocks for selecting target populations for geroprotective intervention is explored.
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BACKGROUND AND PURPOSE: Ehlers-Danlos syndromes are hereditary disorders of connective tissue that are characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The most common subtype is the hypermobile type. In addition to symptoms of small fibre neuropathy (SFN) due to damage to the small peripheral nerve fibres, with degeneration of the distal nerve endings, autonomic disorders such as postural tachycardia syndrome (PoTS) are frequently reported features in patients with hypermobile Ehlers-Danlos syndrome (hEDS). To date, the underlying pathophysiological mechanisms are still not completely understood. STUDY PURPOSE: To better understand pathophysiological mechanisms of small fiber neuropathy and autonomic neuropathy in hypermobile Ehlers-Danlos Syndromes. METHODS: We prospectively investigated 31 patients with hEDS compared to 31 healthy controls by using skin biopsy, quantitative sensory testing, tilt-table testing, the painDetect, Small Fibre Neuropathy Screening List and the COMPASS-31 (Composite Autonomic Symptom Score 31) questionnaire. RESULTS: Nineteen (61%) patients with hEDS were diagnosed with SFN, and 10 (32%) fulfilled the criteria for PoTS. Patients with hEDS had significantly higher heart rates than controls. According to quantitative sensory testing, these patients had generalized thermal and tactile hypesthesia. Skin biopsy revealed significantly reduced intraepithelial nerve fibre density proximally (thigh) and distally (lower leg) in patients compared to controls. This was consistent with various complaints of pain and sensory disturbances in both the proximal and distal body regions. CONCLUSION: These results confirm histologically proven SFN as a common feature in patients with hEDS, revealing a generalized distribution of nerve fibre loss. Regarding the frequently reported autonomic and neuropathic dysfunctions, the findings support SFN as an important, but not the only, underlying pathomechanism.
Subject(s)
Ehlers-Danlos Syndrome , Small Fiber Neuropathy , Humans , Small Fiber Neuropathy/etiology , Ehlers-Danlos Syndrome/complications , Ehlers-Danlos Syndrome/diagnosis , Ehlers-Danlos Syndrome/pathology , Skin/pathology , BiopsyABSTRACT
AIMS: Older adults are vulnerable to medication-related harm mainly due to high use of medications and inappropriate prescribing. This study aimed to investigate the associations between inappropriate prescribing and number of medications identified at discharge from geriatric rehabilitation with subsequent postdischarge health outcomes. METHOD: RESORT (REStORing health of acutely unwell adulTs) is an observational, longitudinal cohort study of geriatric rehabilitation inpatients. Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) were measured at acute admission, and at admission and discharge from geriatric rehabilitation, using Version 2 of the STOPP/START criteria. RESULTS: In total, 1890 (mean age 82.6 ± 8.1 years, 56.3% female) were included. The use of at least 1 PIM or PPO at geriatric rehabilitation discharge was not associated with 30-day and 90-day readmission and 3-month and 12-month mortality. Central nervous system/psychotropics and fall risk PIMs were significantly associated with 30-day hospital readmission (adjusted odds ratio [AOR] 1.53; 95% confidence interval [CI] 1.09-2.15), and cardiovascular PPOs with 12-month mortality (AOR 1.34; 95% CI 1.00-1.78). Increased number of discharge medications was significantly associated with 30-day (AOR 1.03; 95% CI 1.00-1.07) and 90-day (AOR 1.06; 95% CI 1.03-1.09) hospital readmissions. The use and number of PPOs (including vaccine omissions) were associated with reduced independence in instrumental activities of daily living scores at 90-days after geriatric rehabilitation discharge. CONCLUSION: The number of discharge medications, central nervous system/psychotropics and fall risk PIMs were significantly associated with readmission, and cardiovascular PPOs with mortality. Interventions are needed to improve appropriate prescribing in geriatric rehabilitation patients to prevent hospital readmission and mortality.
Subject(s)
Inappropriate Prescribing , Patient Discharge , Aged , Aged, 80 and over , Female , Humans , Male , Activities of Daily Living , Aftercare , Inappropriate Prescribing/prevention & control , Inpatients , Longitudinal Studies , Outcome Assessment, Health CareABSTRACT
PURPOSE: Approximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired during sitting and active standing in 30 patients with PoTS compared with 30 healthy controls (HCs) and whether it will improve with the counter manoeuvre of leg crossing. METHODS: In this prospective pilot study, patients with PoTS were compared to HCs matched for age, sex, and educational level. Baseline data included norepinephrine plasma levels, autonomic testing and baseline cognitive function in a seated position [the Montreal Cognitive Assessment, the Leistungsprüfsystem (LPS) subtests 1 and 2, and the Test of Attentional Performance (TAP)]. Cognitive functioning was examined in a randomized order in supine, upright and upright legs crossed position. The primary outcomes were the cognitive test scores between HCs and patients with PoTS at baseline testing, and among the different body positions. RESULTS: Patients with PoTS had impaired attention (TAP median reaction time) in the seated position and impaired executive functioning (Stroop) while standing compared with HC. Stroop was influenced by position (supine versus upright versus upright legs crossed) only in the PoTS group. Leg crossing did not result in an improvement in executive function. In patients with PoTS, there was a negative correlation of Stroop with norepinephrine plasma levels while standing. CONCLUSION: Compared with HCs, PoTS participants showed impaired cognitive attention and executive function in the upright position that did not improve in the legs crossed position. Data provide further evidence for orthostatic cognitive deterioration in patients with PoTS. TRIAL REGISTRATION INFORMATION: The study was registered at ClinicalTrials.gov (NCT03681080).
Subject(s)
Postural Orthostatic Tachycardia Syndrome , Humans , Pilot Projects , Prospective Studies , Norepinephrine , Cognition , Heart Rate , Blood PressureABSTRACT
Rapamycin (sirolimus) is an immunosuppressive drug approved by the Food and Drug Administration (FDA). It is also a leading candidate for targeting aging. Rapamycin and its analogs (everolimus, temsirolimus, ridaforolimus) inhibit the mammalian target of rapamycin (mTOR) kinase by binding to FK506-binding proteins (FKBP) and have a similar chemical structure that only differs in the functional group present at carbon-40. Analogs of rapamycin were developed to improve its pharmacological properties, such as low oral bioavailability and a long half-life. The analogs of rapamycin are referred to as "rapalogs." Rapamycin is the parent compound and should therewith not be called a "rapalog."
Subject(s)
MTOR Inhibitors , Sirolimus , Humans , Sirolimus/pharmacology , Immunosuppressive Agents/pharmacology , EverolimusABSTRACT
BACKGROUND: Effective post-pandemic telehealth (TH) requires understanding patients' characteristics and perceptions, which have not been established in broader clinical services and are independent of TH appointments. AIMS: To understand medical patients' characteristics and perspectives on using TH. METHODS: General medical patients in a statewide tertiary hospital in Victoria, Australia received a de-identified survey independent of TH appointments during visits between July and November 2020. Patients' characteristics, access to devices enabling TH, knowledge of TH and willingness to use TH were analysed with descriptive statistics. RESULTS: Of 1600 patients, 754 (46.4% female, aged 72.0 years [59.0-83.0]) were able to complete the survey. The majority lived in metropolitan areas (74.4%), owned at least one TH device (98.1%) and had internet access at home (55.6%). About 52.7% of patients were comfortable with their devices, and 43.5% had successfully used TH. Although patients preferred face-to-face appointments (80.8%) and 41.4% agreed TH would be as good as in-person appointments, 63.9% were interested in future TH appointments. Patients preferring face-to-face appointments were older (P = 0.008) and had lower education levels (P = 0.010), whereas patients preferring TH had video TH devices (P < 0.05), were comfortable with their devices (P = 0.002) and were willing to use TH (P < 0.05). TH cost saving was parking AU$10.0 [0.0-15.0], driving AU$5.8 [4.5-19.9], public transport AU$8.00 [5.0-10.0], taxis AU$30.00 [15.0-50.0] and time AU$153.2 [76.6-153.2]. CONCLUSION: From predominantly middle-aged to older, metropolitan-based general medical patients completing the survey, most patienpreferred face-to-face appointments to TH. Health services should subsidise those in need of TH and target the patients' barriers to effective TH use.
Subject(s)
Telemedicine , Middle Aged , Humans , Female , Male , Delivery of Health Care , Pandemics , Surveys and Questionnaires , Victoria/epidemiologyABSTRACT
BACKGROUND: Research assessing the relationship of physical activity and dementia is usually based on studies with individuals younger than 90 years of age. The primary aim of this study was to determine physical activity levels of cognitively normal and cognitively impaired adults older than 90 years of age (oldest-old). Our secondary aim was to assess if physical activity is associated with risk factors for dementia and brain pathology biomarkers. METHODS: Physical activity was assessed in cognitively normal (N = 49) and cognitively impaired (N = 12) oldest-old by trunk accelerometry for a 7-day period. We tested physical performance parameters and nutritional status as dementia risk factors, and brain pathology biomarkers. Linear regression models were used to examine the associations, correcting for age, sex and years of education. RESULTS: Cognitively normal oldest-old were on average active for a total duration of 45 (SD 27) minutes per day, while cognitively impaired oldest-old seemed less physically active with 33 (SD 21) minutes per day with a lower movement intensity. Higher active duration and lower sedentary duration were related to better nutritional status and better physical performance. Higher movement intensities were related to better nutritional status, better physical performance and less white matter hyperintensities. Longer maximum walking bout duration associated with more amyloid binding. CONCLUSION: We found that cognitively impaired oldest-old are active at a lower movement intensity than cognitively normal oldest-old individuals. In the oldest-old, physical activity is related to physical parameters, nutritional status, and moderately to brain pathology biomarkers.