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1.
Neth Heart J ; 32(2): 68-69, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38112990
2.
J Cereb Blood Flow Metab ; : 271678X231214102, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37994030

RESUMO

Cerebral amyloid angiopathy (CAA) is frequently found post mortem in Alzheimer's dementia, but often undetected during life especially since in vivo hallmarks of CAA and its vascular damage become overt relatively late in the disease process. Decreased neurovascular coupling to visual stimulation has been put forward as an early MRI marker for CAA disease severity. The current study investigates the role of neurovascular coupling in AD related dementia and its early stages. We included 25 subjective cognitive impairment, 33 mild cognitive impairment and 17 dementia patients and 44 controls. All participants underwent magnetic resonance imaging of the brain and neuropsychological assessment. Univariate general linear modeling analyses were used to assess neurovascular coupling between patient groups and controls. Moreover, linear regression analyses was used to assess the associations between neurovascular coupling and cognition. Our data show that BOLD amplitude is lower in dementia (mean 0.8 ± 0.2, p = 0.001) and MCI patients (mean 0.9 ± 0.3, p = 0.004) compared with controls (mean 1.1 ± 0.2). A low BOLD amplitude was associated with low scores in multiple cognitive domains. We conclude that cerebrovascular dysfunction, most likely due CAA, is an important comorbidity in early stages of dementia and has an independent effect on cognition.

4.
Age Ageing ; 52(1)2023 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-36626325

RESUMO

OBJECTIVE: to investigate the association between variability and loss of body weight with subsequent cognitive performance and activities of daily living in older individuals. DESIGN: cross-sectional cohort study. SETTING: PROspective Study of Pravastatin in the Elderly at Risk, multicentre trial with participants from Scotland, Ireland and the Netherlands. SUBJECTS: 4,309 participants without severe cognitive dysfunction (mean age 75.1 years, standard deviation (SD) = 3.3), at higher risk for cardiovascular disease (CVD). METHODS: body weight was measured every 3 months for 2.5 years. Weight loss was defined as an average slope across all weight measurements and as ≥5% decrease in baseline body weight during follow-up. Visit-to-visit variability was defined as the SD of weight measurements (kg) between visits. Four tests of cognitive function were examined: Stroop test, letter-digit coding test (LDCT), immediate and delayed picture-word learning tests. Two measures of daily living activities: Barthel Index (BI) and instrumental activities of daily living (IADL). All tests were examined at month 30. RESULTS: both larger body weight variability and loss of ≥5% of baseline weight were independently associated with worse scores on all cognitive tests, but minimally with BI and IADL. Compared with participants with stable weight, participants with significant weight loss performed 5.83 seconds (95% CI 3.74; 7.92) slower on the Stroop test, coded 1.72 digits less (95% CI -2.21; -1.13) on the LDCT and remembered 0.71 pictures less (95% CI -0.93; -0.48) on the delayed picture-word learning test. CONCLUSION: in older people at higher risk for CVD, weight loss and variability are independent risk-factors for worse cognitive function.


Assuntos
Doenças Cardiovasculares , Disfunção Cognitiva , Humanos , Idoso , Estudos Prospectivos , Atividades Cotidianas , Estudos Transversais , Cognição , Peso Corporal , Redução de Peso
5.
J Clin Endocrinol Metab ; 107(2): e643-e652, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34514498

RESUMO

CONTEXT: Thyroid dysfunction is associated with higher anemia prevalence, although causality remains unclear. OBJECTIVE: This study aimed to investigate the association between thyroid function and anemia. METHODS: This cross-sectional and Mendelian randomization study included 445 482 European participants from the UK Biobank (mean age 56.77 years (SD 8.0); and 54.2% women). Self-reported clinical diagnosis of hypothyroidism was stated by 21 860 (4.9%); self-reported clinical diagnosis of hyperthyroidism by 3431 (0.8%). Anemia, defined as hemoglobin level of < 13 g/dL in men and < 12 g/dL in women, was present in 18 717 (4.2%) participants. RESULTS: In cross-sectional logistic regression analyses, self-reported clinical diagnoses of hypo- and hyperthyroidism were associated with higher odds of anemia (OR 1.12; 95% CI, 1.05-1.19 and OR 1.09; 95% CI, 0.91-1.30), although with wide confidence intervals for hyperthyroidism. We did not observe an association of higher or lower genetically influenced thyrotropin (TSH) with anemia (vs middle tertile: OR for lowest tertile 0.98 [95% CI, 0.95-1.02]; highest tertile 1.02 [95% CI, 0.98-1.06]), nor of genetically influenced free thyroxine (fT4) with anemia. Individuals with genetic variants in the DIO3OS gene implicated in intracellular regulation of thyroid hormones had a higher anemia risk (OR 1.05; 95% CI, 1.02-1.10); no association was observed with variants in DIO1 or DIO2 genes. CONCLUSION: While self-reported clinical diagnosis of hypothyroidism was associated with higher anemia risk, we did not find evidence supporting a causal association with variation of thyroid function within the euthyroid range. However, intracellular regulation of thyroid hormones might play a role in developing anemia.


Assuntos
Anemia/epidemiologia , Hipotireoidismo/genética , Glândula Tireoide/fisiopatologia , Idoso , Anemia/genética , Bancos de Espécimes Biológicos/estatística & dados numéricos , Causalidade , Estudos de Coortes , Estudos Transversais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/patologia , Hipotireoidismo/fisiopatologia , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Prevalência , Autorrelato , Tireotropina/sangue , Reino Unido/epidemiologia
6.
JAMA Intern Med ; 181(11): 1440-1450, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34491268

RESUMO

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.


Assuntos
Disfunção Cognitiva , Hipertireoidismo , Hipotireoidismo , Testes de Função Tireóidea , Idoso , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Correlação de Dados , Análise de Dados , Feminino , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/diagnóstico , Hipertireoidismo/psicologia , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/psicologia , Masculino , Testes de Estado Mental e Demência/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Testes de Função Tireóidea/métodos , Testes de Função Tireóidea/estatística & dados numéricos , Glândula Tireoide/fisiopatologia , Tireotropina/análise , Tiroxina/análise
7.
Aging (Albany NY) ; 13(17): 21029-21039, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491903

RESUMO

CONTEXT: Offspring from long-lived families have a different thyroid status than controls, characterised by higher circulating levels of thyroid stimulating hormone (TSH) and similar levels of thyroid hormone. Expression of the TSH receptor has previously been observed on various extrathyroidal tissues, including bone. However, potential physiological consequences of differences in circulating TSH as observed in familial longevity on bone tissue remain unclear. OBJECTIVE: Based on the hypothesis that TSH may inhibit bone resorption, we explored whether offspring of long-lived families have lower bone turnover than controls at baseline as well as following a challenge with recombinant human TSH (rhTSH). METHODS: Bone turnover markers CTX and P1NP were measured in fasted morning samples from 14 offspring and 12 controls at baseline and at 24 hour intervals following 0.1 mg rhTSH i.m. administration for four consecutive days. RESULTS: At baseline, mean (SEM) CTX was 0.32 (0.03) ng/ml in offspring and 0.50 (0.04) ng/ml in controls, p < 0.01, whereas mean (SEM) P1NP was 39.6 (3.2) ng/ml in offspring and 61.8 (6.6) ng/ml in controls, p < 0.01. Following rhTSH administration, both CTX and P1NP levels transiently increased over time and normalized towards baseline after 72 h (general linear modelling: CTX time p = 0.01, P1NP time p < 0.01); the response was similar between offspring and controls. CONCLUSIONS: Bone turnover markers were lower at baseline in offspring from long-lived families than in controls but increased similarly following an rhTSH challenge.


Assuntos
Remodelação Óssea , Reabsorção Óssea/sangue , Família , Longevidade , Glândula Tireoide , Tirotropina Alfa/farmacologia , Tireotropina/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos , Colágeno Tipo I/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Proteínas Recombinantes/farmacologia , Hormônios Tireóideos
8.
MethodsX ; 8: 101400, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34430296

RESUMO

Serial thyroid hormone measurement in blood following recombinant human thyroid stimulating hormone (rhTSH) administration has not been studied extensively in healthy, older populations. Current methods involve measurement of thyroid hormones mostly at 4 to 24 hours following rhTSH administration. We tailored existing protocols to measure thyroid hormones at high frequencies following 0.1mg rhTSH intramuscular (i.m.) administration to identify optimal measurement points in our healthy, older population. We designed a method with frequent blood sampling in the first 8 hours, followed by blood sampling at 24, 48 and 72 hours after rhTSH administration to measure TSH, thyroxine (T4), free T4 (fT4), triiodothyronine (T3), free T3 (fT3) and thyroglobulin (Tg). In total, we performed a series of 17 blood withdrawals in four consecutive days. Following 0.1mg rhTSH (i.m.) administration, mean thyroid parameters showed great inter-individual variation and variation over time. Mean TSH concentration showed the greatest variation in the first 8 hours following rhTSH administration. Mean T4, fT4, T3 and fT3 started showing variation from 2 hours after rhTSH administration, and were less variable than mean TSH concentration. Mean Tg was only variable at later time points, namely 24, 48 and 72 hours after rhTSH administration. In this novel method with high frequency blood sampling following 0.1mg rhTSH (i.m.) administration, we identify optimal time points for measuring thyroid gland output in a healthy, older population. Our methods and findings may be informative for further thyroid but also other hormonal axis studies.•Thyroid metabolism•Blood sampling frequency•Geriatrics and longevity.

9.
BMC Geriatr ; 21(1): 29, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413165

RESUMO

BACKGROUND: Treatment decisions concerning older patients can be very challenging and individualised treatment plans are often required in this very heterogeneous group. In 2015 we have implemented a routine clinical care pathway for older patients in need of intensive treatment, including a comprehensive geriatric assessment (CGA) that was used to support clinical decision making. An ongoing prospective cohort study, the Triaging Elderly Needing Treatment (TENT) study, has also been initiated in 2016 for participants in this clinical care pathway, to study associations between geriatric characteristics and outcomes of treatment that are relevant to older patients. The aim of this paper is to describe the implementation and rationale of the routine clinical care pathway and design of the TENT study. METHODS: A routine clinical care pathway has been designed and implemented in multiple hospitals in the Netherlands. Patients aged ≥70 years who are candidates for intensive treatments, such as chemotherapy, (chemo-)radiation therapy or major surgery, undergo frailty screening based on the Geriatric 8 (G-8) questionnaire and the Six-Item Cognitive Impairment Test (6CIT). If screening reveals potential frailty, a CGA is performed. All patients are invited to participate in the TENT study. Clinical data and blood samples for biomarker studies are collected at baseline. During follow-up, information about treatment complications, hospitalisations, functional decline, quality of life and mortality is collected. The primary outcome is the composite endpoint of functional decline or mortality at 1 year. DISCUSSION: Implementation of a routine clinical care pathway for older patients in need of intensive treatment provides the opportunity to study associations between determinants of frailty and outcomes of treatment. Results of the TENT study will support individualised treatment for future patients. TRIAL REGISTRATION: The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107 . Date of registration: 22-10-2019.


Assuntos
Fragilidade , Qualidade de Vida , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/terapia , Avaliação Geriátrica , Humanos , Países Baixos/epidemiologia , Estudos Prospectivos
10.
J Am Med Dir Assoc ; 22(6): 1307-1312, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32962930

RESUMO

OBJECTIVES: This study investigates the transitions of community-dwelling patients with a proximal femoral fracture towards recovery of independence using multistate modeling. The prognostic value of factors affecting the short-term rate of recovery of independence in activities of daily living was assessed for the resilient portion of the population. DESIGN: An inception cohort was recruited between 2016 and 2019. SETTING AND PARTICIPANTS: Only community-dwelling older patients admitted with a proximal femoral fracture were included. MEASURES: Follow-up was performed at 6 weeks and 3 months, when the patients' living situation and level of independence were recorded. Multistate modeling was used to study the transition rates of the population through prespecified states of the recovery process. Using this model, prognostic factors for the recovery of independence were identified for resilient patients (defined as those patients who managed to return home at any point in the follow-up after discharge). RESULTS: A total of 558 patients were included, and 218 (40.9%) recovered to prefracture levels of independence. Of the resilient patients, 20.7% were discharged home directly, and 79.3% via a rehabilitation home. In this patient group, a more favorable American Society of Anesthesiologists classification, better prefracture mobility, and the absence of a prefracture fear of falling were statistically significantly associated with a successful recovery. A low level of prefracture independence was inversely associated, meaning that patients with a low level of prefracture independence had a higher chance of successful recovery. CONCLUSIONS AND IMPLICATIONS: This study identified 4 factors with an independent prognostic value for the recovery of independence in resilient patients after a proximal femoral fracture. These factors could be used to construct clinical profiles that contribute to the assessment of the patient's post-acute care needs and recovery capacity. In addition, multistate modeling has been shown to be an effective and versatile tool in the study of recovery prognostics.


Assuntos
Atividades Cotidianas , Fraturas do Quadril , Acidentes por Quedas , Medo , Humanos , Prognóstico , Recuperação de Função Fisiológica
11.
Geriatr Orthop Surg Rehabil ; 11: 2151459320960091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194255

RESUMO

INTRODUCTION: High mortality rates of approximately 20% within 1 year after treatment are observed for patients with proximal femoral fractures. This preliminary study explores the prognostic value of a previously constructed mortality risk score based on a set of 14 metabolites for the survival and functional recovery in patients with proximal femoral fractures. MATERIALS AND METHODS: A prospective observational cohort study was conducted including patients admitted with a proximal femoral fracture. The primary outcome was patient survival, and the recovery of independence in activities of daily living was included as a secondary outcome. The mortality risk score was constructed for each patient and its prognostic value was tested for the whole population. RESULTS: Data was available form 136 patients. The mean age of all patients was 82.1 years, with a median follow-up of 6 months. Within this period, 19.0% of all patients died and 51.1% recovered to their prefracture level of independence. The mortality score was significantly associated with mortality (HR, 2.74; 95% CI, 1.61-4.66; P < 0.001), but showed only a fair prediction accuracy (AUC = 0.68) and a borderline significant comparison of the mortality score tertile groups in survival analyses (P = 0.049). No decisive associations were found in any of the analyses for the functional recovery of patients. DISCUSSION: These findings support the previously determined prognostic value of the mortality risk score. However, the independent prognostic value when adjusted for potential confounding factors is yet to be assessed. Also, a risk score constructed for this specific patient population might achieve higher accuracies for the prediction of survival and functional recovery. CONCLUSIONS: A modest prediction accuracy was observed for the mortality risk score in this population. More elaborate studies are needed to validate these findings and develop a tailored model for clinical purposes in this patient population.

12.
J Endocr Soc ; 4(10): bvaa117, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32964174

RESUMO

CONTEXT: Familial longevity is associated with higher circulating levels of thyrotropin (TSH), in the absence of differences in circulating thyroid hormones, and a lower thyroid responsivity to TSH, as previously observed in the Leiden Longevity Study (LLS). Further mechanisms underlying these observations remain unknown. OBJECTIVE: We hypothesized that members from long-lived families (offspring) have higher thyroid hormone turnover or less negative feedback effect on TSH secretion compared to controls. METHODS: In a case-control intervention study, 14 offspring and 13 similarly aged controls received 100 µg 3,5,3'-triiodothyronine (T3) orally. Their circulating T3, free T3 (fT3), and TSH levels were measured during 5 consecutive days. We compared profiles of circulating T3, fT3, and TSH between offspring and controls using general linear modeling (GLM) and calculated the percentage decline in TSH following T3 administration. RESULTS: Circulating T3 and fT3 levels increased to supraphysiologic values and normalized over the course of 5 days. There were no serious adverse events. T3 and fT3 concentration profiles over 5 days were similar between offspring and controls (T3 GLM P = .11, fT3 GLM P = .46). TSH levels decreased in a biphasic manner and started returning to baseline by day 5. The TSH concentration profile over 5 days was similar between offspring and controls (GLM P = .08), as was the relative TSH decline (%). CONCLUSIONS: Members of long-lived families have neither higher T3 turnover nor diminished negative feedback of T3 on TSH secretion. The cause and biological role of elevated TSH levels in familial longevity remain to be elucidated.

13.
Exp Gerontol ; 139: 111035, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739519

RESUMO

INTRODUCTION: The current understanding of prognostic factors of functional recovery after a proximal femoral fracture is limited, and enhancements could improve the prognostic accuracy and target subgroups for additional care strategies. This systematic review aims to identify all studied factors with an independent prognostic value for the long-term functional recovery of patients with a proximal femoral fracture. MATERIALS AND METHODS: Observational studies with multivariate analyses on prognostic factors of long-term functional outcome after proximal femoral fractures were obtained through an electronic search performed on November 9, 2018. RESULTS: In the 31 included articles, thirteen prognostic factors were studied by at least two independent studies and an additional ten by only one study. Age, comorbidity, functionality and cognition were factors for which the majority of studies indicated a significant effect. The majority of studies which included sex as a factor found no significant effect. The level of evidence for the remaining factors was deemed too low to be conclusive on their relevance for long-term functional outcome. CONCLUSION: The identified factors showed overlap with prognostic factors of short-term functional outcomes and mortality. The validity and applicability of prognostic models based on these factors may be of interest for future research.


Assuntos
Fraturas do Fêmur , Fraturas do Quadril , Comorbidade , Fraturas do Quadril/epidemiologia , Humanos , Prognóstico , Recuperação de Função Fisiológica
14.
BMC Nephrol ; 21(1): 126, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272897

RESUMO

BACKGROUND: The prevalence of impaired cognitive functioning in older patients with end stage kidney disease (ESKD) is high. We aim to describe patterns of memory, executive function or psychomotor speed and to identify nephrologic, geriatric and neuroradiologic characteristics associated with cognitive impairment in older patients approaching ESKD who have not yet started with renal replacement therapy (RRT). METHODS: The COPE-study (Cognitive Decline in Older Patients with ESRD) is a prospective cohort study including 157 participants aged 65 years and older approaching ESKD (eGFR ≤20 ml/min/1.73 m2) prior to starting with RRT. In addition to routinely collected clinical parameters related to ESKD, such as vascular disease burden and parameters of metabolic disturbance, patients received a full geriatric assessment, including extensive neuropsychological testing. In a subgroup of patients (n = 93) a brain MRI was performed. RESULTS: The median age was 75.3 years. Compared to the normative data of neuropsychological testing participants memory performance was in the 24th percentile, executive function in the 18th percentile and psychomotor speed in the 20th percentile. Independent associated characteristics of impairment in memory, executive and psychomotor speed were high age, low educational level and low functional status (all p-values < 0.003). A history of vascular disease (p = 0.007) and more white matter hyperintensities on brain MRI (p = 0.013) were associated with a lower psychomotor speed. CONCLUSION: Older patients approaching ESKD have a high prevalence of impaired memory, executive function and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potentially added value in the decision-making process concerning patients with ESKD.


Assuntos
Encéfalo/diagnóstico por imagem , Cognição , Disfunção Cognitiva , Função Executiva , Falência Renal Crônica , Desempenho Psicomotor , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Demência Vascular/diagnóstico , Feminino , Avaliação Geriátrica/métodos , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/psicologia , Imageamento por Ressonância Magnética/métodos , Masculino , Países Baixos/epidemiologia , Testes Neuropsicológicos , Estudos Prospectivos
15.
J Clin Endocrinol Metab ; 105(7)2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32303766

RESUMO

CONTEXT: Longevity is associated with higher circulating levels of TSH in the absence of differences in circulating thyroid hormones (TH), as previously observed in F2 members of long-lived families (F2-LLS) and their partners (F2-Con). The mechanism underlying this observed difference remains unknown. OBJECTIVE: We hypothesized that the thyroid gland of members from long-lived families are less responsive to TSH stimulation, thereby requiring higher circulating TSH levels to maintain adequate TH levels. METHODS: We performed a case-control intervention study with a single intramuscular (gluteal) injection with 0.1 mg recombinant human TSH in a subgroup of 14 F2-LLS and 15 similarly aged F2-Con. They were followed for 4 days. No serious adverse events were reported. For analyses, we compared time trajectories of TSH and TH, and the ratio of TH to TSH using area under the curve (AUC) calculations. RESULTS: The AUC free T4/AUC TSH ratio was significantly lower in F2-LLS than in F2-Con (estimated mean [95% confidence interval] 1.6 [1.2-1.9] and 2.2 [1.9-2.6], respectively, P = 0.01). The AUC thyroglobulin/AUC TSH ratio was also lower in F2-LLS than in F2-Con (median [interquartile range] 2.1 [1.4-3.6] and 3.2 [2.7-7.4], respectively, P = 0.04). We observed the same trend with the AUC free T3/AUC TSH ratio, although the difference was not statistically significant (estimated mean [95% confidence interval] 0.6 [0.4-0.7] and 0.7 [0.6-0.8], respectively, P = 0.07). CONCLUSIONS: The present findings show that members of long-living families have a lower thyroid responsivity to TSH compared with their partners.


Assuntos
Longevidade/genética , Proteínas Recombinantes/farmacologia , Glândula Tireoide/efeitos dos fármacos , Tireotropina/farmacologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
16.
J Clin Endocrinol Metab ; 105(4)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31853555

RESUMO

CONTEXT: Hormones of the hypothalamic-pituitary-target gland axes are mostly investigated separately, whereas the interplay between hormones might be as important as each separate hormonal axis. OBJECTIVE: Our aim is to determine the interrelationships between GH, TSH, ACTH, and cortisol in healthy older individuals. DESIGN: We made use of 24-hour hormone serum concentrations assessed with intervals of 10 minutes from 38 healthy older individuals with a mean age (SD) of 65.1 (5.1) years from the Leiden Longevity Study. Cross-correlation analyses were performed to assess the relative strength between 2 24-hour hormone serum concentration series for all possible time shifts. Cross-approximate entropy was used to assess pattern synchronicity between 2 24-hour hormone serum concentration series. RESULTS: Within an interlinked hormonal axis, ACTH and cortisol were positively correlated with a mean (95% confidence interval) correlation coefficient of 0.78 (0.74-0.81) with cortisol following ACTH concentrations with a delay of 10 minutes. Between different hormonal axes, we observed a negative correlation coefficient between cortisol and TSH of -0.30 (-0.36 to -0.25) with TSH following cortisol concentrations with a delay of 170 minutes. Furthermore, a positive mean (95% confidence interval) correlation coefficient of 0.29 (0.22-0.37) was found between TSH and GH concentrations without any delay. Moreover, cross-approximate entropy analyses showed that GH and cortisol exhibit synchronous serum concentration patterns. CONCLUSIONS: This study demonstrates that interrelations between hormones from interlinked as well as different hypothalamic-pituitary-target gland axes are observed in healthy older individuals. More research is needed to determine the biological meaning and clinical consequences of these observations.


Assuntos
Biomarcadores/sangue , Ritmo Circadiano , Hormônio do Crescimento Humano/sangue , Hidrocortisona/sangue , Longevidade , Hormônios Hipofisários/sangue , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
PLoS One ; 14(6): e0218596, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220173

RESUMO

BACKGROUND/OBJECTIVES: Cognitive impairment is a frequent problem among older patients attending the Emergency Department (ED) and can be the result of pre-existing cognitive impairment, delirium, or neurologic disorders. Another cause can also be acute disturbance of brain perfusion and oxygenation, which may be reversed by optimal resuscitation. This study aimed to assess the relationship between vital signs, as a measure of acute hemodynamic changes, and cognitive impairment in older ED patients. DESIGN: Prospective cohort study. SETTING: ED's of two tertiary care and two secondary care hospitals in the Netherlands. PARTICIPANTS: 2629 patients aged 70-years and older. MEASUREMENTS: Vital signs were measured at the moment of ED arrival as part of routine clinical care. Cognition was measured using the Six-Item Cognitive Impairment Test (6-CIT). RESULTS: The median age of patients was 78 years (IQR 74-84). Cognitive impairment was present in 738 patients (28.1%). When comparing lowest with highest quartiles, a systolic blood pressure of <129 mmHg (OR 1.30, 95% confidence interval (95%CI) 0.98-1.73)was associated with increased risk of cognitive impairment. A higher respiratory rate (>21/min) was associated with increased risk of impaired cognition (OR 2.16, 95% CI 1.58-2.95) as well as oxygen saturation of <95% (OR 1.64, 95%CI 1.24-2.19). CONCLUSION: Abnormal vital signs associated with decreased brain perfusion and oxygenation are also associated with cognitive impairment in older ED patients. This may partially be explained by the association between disease severity and delirium, but also by acute disturbance of brain perfusion and oxygenation. Future studies should establish whether normalization of vital signs will also acutely improve cognition.


Assuntos
Disfunção Cognitiva/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Sinais Vitais , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Países Baixos
18.
Head Neck ; 41(8): 2477-2483, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30816619

RESUMO

BACKGROUND: The aim is to describe the association of functional capacity and cognitive functioning with 1-year mortality in older patients with cancer in the head and neck region. METHODS: We performed a cohort study in which all patients aged 70 years and older received a geriatric screening before treatment. Main outcome was 1-year mortality. RESULTS: A total of 102 patients were included. Median age was 78.7 years (interquartile range [IQR], 72.3-84.5), 25% were cognitive impaired, 40% were malnourished, and 28.4% used a walking device. Overall, 1-year mortality was 42.3%. Male sex (hazard ratio [HR], 4.30; 95% confidence interval [CI], 1.35-13.67), malnutrition (HR, 2.55; 95% CI, 1.19-5.16), and using a walking device (HR, 2.80; 95% CI 1.13-6.93) were associated with higher mortality risk, independent of stage and comorbidities. CONCLUSION: In older patients with head and neck cancer, the mortality rates are high. Nutritional status and mobility are determinants of 1-year mortality, independent of tumor stage, age, and comorbidity.


Assuntos
Avaliação Geriátrica , Neoplasias de Cabeça e Pescoço/mortalidade , Idoso , Idoso de 80 Anos ou mais , Bengala , Estudos de Coortes , Pessoas com Deficiência/estatística & dados numéricos , Feminino , Humanos , Masculino , Desnutrição/epidemiologia , Países Baixos/epidemiologia , Estudos Retrospectivos , Fatores Sexuais , Andadores
19.
Eur J Emerg Med ; 26(6): 428-432, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30585854

RESUMO

OBJECTIVES: Delirium is a frequent problem among older patients in the emergency department (ED) and early detection is important to prevent its associated adverse outcomes. Several screening tools for delirium have been proposed for the ED, such as the 6-Item Cognitive Impairment Test (6-CIT) and the Confusion Assessment Method-ICU (CAM-ICU). Previous validation of the CAM-ICU for use in the ED showed varying results, possibly because it was administered at different or unknown time points. The aim was to study the prevalence of delirium in older ( ≥ 70 years) ED patients using the CAM-ICU and 6-CIT. PARTICIPANTS AND METHODS: A prospective cohort study was carried out in one tertiary care and one secondary care hospital in the Netherlands. Patients aged 70 years and older attending the ED were included. Delirium screening was performed within 1 h after ED registration using the CAM-ICU. The 6-CIT was determined for comparison using a cut-off point of at least 14 points indicating possible delirium. RESULTS: A total of 997 patients were included in the study, with a median age of 78 years (interquartile range 74-84). Delirium as assessed with CAM-ICU was positive in only 13 (1.3%, 95% confidence interval: 0.8-2.2) patients. Ninety-five (9.5% 95% confidence interval: 7.9-11.5) patients had 6-CIT more than or equal to 14. CONCLUSION: We found a delirium prevalence of 1.3% using the CAM-ICU, which was much lower than the expected prevalence of around 10% as being frequently reported in the literature and what we found when using the 6-CIT. On the basis of these results, caution is warranted to use the CAM-ICU for early screening in the ED.


Assuntos
Delírio/diagnóstico , Serviço Hospitalar de Emergência , Testes de Estado Mental e Demência , Idoso , Idoso de 80 Anos ou mais , Delírio/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Prevalência , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Eur J Emerg Med ; 26(4): 255-260, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29384753

RESUMO

OBJECTIVES: Self-rated health (SRH) is an important patient-reported outcome, but little is known about SRH after a visit to the emergency department (ED). We investigated the determinants of decline in SRH during 3 months after an ED visit in older patients. DESIGN: This was a multicenter prospective cohort study including acutely presenting older ( ≥ 70 years) patients in the ED (the Netherlands). Patients were asked to self-rate their health between 0 and 10. The main outcome was a decline in SRH defined as a transition of a SRH of at least 6 to a SRH of less than 6, 3 months after the patient's visit to the ED. RESULTS: Three months after the ED visit, 870 (71.4%) patients had a stable SRH and 209 (11.5%) patients declined in SRH. Independent predictors with a decline in SRH were: male gender (OR 1.83) living alone (OR 1.56), living in residential care or nursing home (OR 2.75), number of different medications (OR 1.08), using a walking device (OR 1.70), and the Katz-ADL score (OR 1.22). Patients with functional decline 3 months after an ED visit show a steeper decline in the mean SRH (0.68 points) than patients with no functional decline (0.12 points, P < 0.001). CONCLUSION: Decline in SRH after an ED visit in older patients is at least partly dependent on factors of functional capacity and functional decline. Preventive interventions to maintain functional status may be the solution to maintain SRH, but more research is needed to further improve and firmly establish the clinical usability of these findings.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Autorrelato , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Avaliação Geriátrica/métodos , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Países Baixos , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo
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