Medico-legal assessment of personal damage in older people: report from a multidisciplinary consensus conference.

Ageing of the global population represents a challenge for national healthcare systems and healthcare professionals, including medico-legal experts, who assess personal damage in an increasing number of older people. Personal damage evaluation in older people is complex, and the scarcity of evidence is hindering the development of formal guidelines on the subject. The main objectives of the first multidisciplinary Consensus Conference on Medico-Legal Assessment of Personal Damage in Older People were to increase knowledge on the subject and establish standard procedures in this field. The conference, organized according to the guidelines issued by the Italian National Institute of Health (ISS), was held in Bologna (Italy) on June 8, 2019 with the support of national scientific societies, professional organizations, and stakeholders. The Scientific Technical Committee prepared 16 questions on 4 thematic areas: (1) differences in injury outcomes in older people compared to younger people and their relevance in personal damage assessment; (2) pre-existing status reconstruction and evaluation; (3) medico-legal examination procedures; (4) multidimensional assessment and scales. The Scientific Secretariat reviewed relevant literature and documents, rated their quality, and summarized evidence. During conference plenary public sessions, 4 pairs of experts reported on each thematic area. After the last session, a multidisciplinary Jury Panel (15 members) drafted the consensus statements. The present report describes Conference methods and results, including a summary of evidence supporting each statement, and areas requiring further investigation. The methodological recommendations issued during the Conference may be useful in several contexts of damage assessment, or to other medico-legal evaluation fields.

Prognostic role of nutritional status in elderly patients hospitalized for COVID-19: a monocentric study.

BACKGROUND: Symptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection incidence is higher in the elderly patients. Pre-existing geriatric conditions such as comorbidity and frailty seem related to worse hospital outcomes. AIMS: To assess the role of nutritional status as an independent prognostic factor for in-hospital death in elderly patients. METHODS: Consecutive elderly patients (age > 65 years) hospitalized for novel coronavirus disease (COVID-19) were enrolled. Demographics, laboratory and comorbidity data were collected. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). Uni- and multivariate Cox regression analyses to evaluate predictors for in-hospital death were performed. RESULTS: One hundred and nine hospitalized elderly patients (54 male) were consecutively enrolled. At univariate analysis, age (HR 1.045 [CI 1.008-1.082]), cognitive impairment (HR 1.949 [CI 1.045-3.364]), C-reactive protein (HR 1.004 [CI 1.011-1.078]), lactate dehydrogenases (HR 1.003 [CI 1.001-1.004]) and GNRI moderate-severe risk category (HR 8.571 [CI 1.096-67.031]) were risk factors for in-hospital death, while albumin (HR 0.809 [CI 0.822-0.964]), PaO2/FiO2 ratio (HR 0.996 [CI 0.993-0.999]) and body mass index (HR 0.875 [CI 0.782-0.979]) were protective factors. Kaplan-Meier survival curves showed a significative higher survival in patients without GNRI moderate or severe risk category (p = 0.0013). At multivariate analysis, PaO2/FiO2 ratio (HR 0.993 [CI 0.987-0.999], p = 0.046) and GNRI moderate-severe risk category (HR 9.285 [1.183-72.879], p = 0.034) were independently associated with in-hospital death. CONCLUSION: Nutritional status assessed by GNRI is a significative predictor of survival in elderly patients hospitalized for COVID-19. The association between GNRI and PaO2/FiO2 ratio is a good prognostic model these patients.

Inverse Association Between Neck Pain and All-Cause Mortality in Community-Dwelling Older Adults.

Objective: In a previous study, we found an apparent protective effect of neck pain on all-cause mortality in subjects older than age 85 years. The present longitudinal investigation was performed to verify this unexpected finding in a larger sample and to establish its significance. Design: Population follow-up study. Setting: Three towns of Northern Italy. Subjects: We examined 5,253 community-dwelling residents age 65-102 years (55% female). Methods: Through a postal questionnaire, baseline information was obtained concerning cardiovascular risk factors, self-rated health, physical activity, cardiovascular events, medical therapy, and presence of pain in the main joints. Seven-year all-cause mortality was the end point. Results: During follow-up, 1,250 people died. After adjustment for age, sex, anti-inflammatory drugs, physical activity, and main risk factors, neck pain was inversely associated with mortality (hazard ratio = 0.74, 95% confidence interval = 0.64-0.86, P < 0.001). This association was present, with high significance, in each of the eight following subgroups: men, women, age 65-74 years, age 75-84 years, age ≥85 years and residents of each of the three towns. The subjects without neck pain (N = 3,158) were older, more often men, less often hypercholesterolemic, less physically active, and had more frequently had a stroke than the subjects with neck pain (N = 2,095). There were no differences in the causes of death between subjects with or without neck pain. Conclusion: This study has confirmed the existence of an independent inverse association between neck pain and mortality in the elderly, suggesting that reduced sensitivity to neck pain may be a new marker of frailty.

Risk of Exclusion From Stroke Rehabilitation in the Oldest Old.

OBJECTIVE: To investigate whether oldest-old age (≥85y) is an independent predictor of exclusion from stroke rehabilitation. DESIGN: Retrospective cohort study. SETTING: Stroke unit (SU) of a tertiary hospital. PARTICIPANTS: Elderly patients (N=1055; aged 65-74y, n=230; aged 75-84y, n=432; aged ≥85y, n=393) who, between 2009 and 2012, were admitted to the SU with acute stroke and evaluated by a multiprofessional team for access to rehabilitation. The study excluded patients for whom rehabilitation was unnecessary or inappropriate. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Access to an early mobilization (EM) protocol during SU stay and subsequent access to postacute rehabilitation after SU discharge. Analyses were adjusted for prestroke and stroke-related characteristics. RESULTS: 32.2% of patients were excluded from EM. Multivariable-adjusted odds ratios (ORs) of EM exclusion were 1.30 (95% confidence interval [CI], .76-2.21) for ages 75 to 84 years and 2.07 (95% CI, 1.19-3.59) for ages ≥85 years compared with ages 65 to 74 years. Of 656 patients admitted to EM and who, at SU discharge, had not yet fully recovered their prestroke functional status, 18.4% were excluded from postacute rehabilitation. For patients able to walk unassisted at SU discharge, the probability of exclusion did not change across age groups. For patients unable to walk unassisted at SU discharge, ORs of exclusion from postacute rehabilitation were 3.74 (95% CI, 1.26-11.13) for ages 75 to 84 years and 9.15 (95% CI, 3.05-27.46) for ages ≥85 years compared with ages 65 to 74 years. CONCLUSIONS: Oldest-old age is an independent predictor of exclusion from stroke rehabilitation.

Integrated Use of Lung Ultrasound and Chest X-Ray in the Detection of Interstitial Lung Disease.

BACKGROUND: Current data have shown that lung ultrasound (LUS) may be useful in the detection of interstitial lung disease (ILD) by the evaluation of B-lines, the sonographic marker of pulmonary interstitial syndrome. Nevertheless, no prospective study has compared LUS to chest X-ray (CXR) for ILD assessment, and there is no general agreement on the specific echographic diagnostic criteria for defining ILD. OBJECTIVES: The aims of this study were (1) to compare the accuracy of LUS and CXR in the detection of ILD using high-resolution CT (HRCT) as the gold standard and (2) to compare the accuracy of different echographic diagnostic criteria for ILD diagnosis. METHODS: LUS was performed on 104 patients undergoing HRCT for suspected ILD. In 49 patients, a CXR scan performed within 3 months of HRCT was analyzed. ILD was defined as the presence of ≥5 B-lines in ≥3 chest areas. A total B-line score (TBLS) was also calculated, as in previous studies. The observers evaluating LUS and CXR were blinded to the HRCT results and clinical data. RESULTS: On HRCT, ILD was assessed in 50 patients. CXR was specific (91%; 95% CI 80-100) but not sensitive (48%; 95% CI 28-67). Conversely, LUS showed high sensitivity (92%; 95% CI 84-99) and low specificity (79%; 95% CI 69-90). Using a TBLS, sensitivity did not change, while specificity decreased. CONCLUSIONS: LUS could be a sensitive tool for ILD detection. CXR and LUS have different but complementary features, and their combined use could reduce the need for HRCT. The use of different diagnostic criteria for defining ILD does not affect sensitivity but influences specificity.

The Effect of Age on Characteristics and Mortality of Intracerebral Hemorrhage in the Oldest-Old.

BACKGROUND: Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (<65 years), young-old (65-74 years) and old-old (75-84 years) subjects. We also investigated whether age is an independent mortality predictor in elderly (age ≥65 years) subjects with acute ICH. METHODS: We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. RESULTS: Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had the highest admission hematoma volume (p < 0.01). Age was unrelated to all other ICH characteristics including HE. In elderly patients, multivariable adjusted risk of in-SU and 1-year mortality did not vary across age categories. CONCLUSIONS: Oldest-old subjects with acute supratentorial ICH have higher admission hematoma volume than young and young-old subjects but do not differ for other ICH characteristics. When taking into account confounding from ICH characteristics, risk of in-SU and 1-year mortality in elderly subjects with acute supratentorial ICH does not differ across age categories. Our findings question use of age as an independent criterion for stratification of mortality risk in elderly subjects with acute ICH.

Does age modify the relationship between adherence to secondary prevention medications and mortality after acute myocardial infarction? A nested case-control study.

PURPOSE: Clinical trials have shown that evidence-based secondary prevention medications reduce mortality after acute myocardial infarction (AMI). Yet, these medications are generally underused in daily practice, and older people are often excluded from drug trials. The purpose of this study was to examine whether the relationship between adherence to evidence-based drugs and post-AMI mortality varies with increasing age. METHODS: The study population was defined as all residents in the Local Health Authority of Bologna (Italy) hospitalized for AMI between January 1, 2008 and June 30, 2011, and followed up until December 31, 2012. Medication adherence was calculated as the proportion of days covered (PDC) for filled prescriptions of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, antiplatelet drugs, and statins; patients were classified as adherent (PDC ≥75 %) or nonadherent (PDC <75 %). We used incidence density sampling, and the moderating effect of age on the relationship between adherence and mortality was investigated through conditional multiple logistic regression analysis. RESULTS: The study population comprised 3963 patients. During the 5-year study period, 1085 deaths (27.4 %) were observed. For both younger and older patients, adherence to polytherapy (three or four medications) was associated with lower mortality (adj. rate ratio = 0.41; P < 0.001). A significant inverse relationship was found between adherence to each of the four medications and mortality, although the risk reduction associated with antiplatelet therapy declined after the age of 70-75. CONCLUSIONS: The beneficial effect of evidence-based polytherapy on mortality following AMI is observed also in older populations. Nevertheless, the risk-benefit ratio associated with antiplatelet therapy is less favorable with increasing age.

The Senile Lung as a Possible Source of Pitfalls on Chest Ultrasonography and Computed Tomography.

BACKGROUND: Age-associated changes in the pulmonary system could be detected with imaging techniques. Widespread use of lung ultrasonography (US) requires characterization of a normal pattern. OBJECTIVES: To compare US and computed tomography (CT) findings in healthy subjects undergoing both techniques (with CT as the gold standard). METHODS: We prospectively selected 59 subjects undergoing chest CT and US on the same day, without a history of smoking, respiratory symptoms, or known pulmonary pathologies. There were 44 patients in group 1 (age ≥60 years - elderly) and 15 patients in group 2 (age ≤50 years - young). Lung US was performed with a convex and a linear probe, and 10 chest areas per patient were analyzed. Convex and linear probe agreement was evaluated by means of the Cohen κ statistic; Fisher's exact test was used to compare categorical variables between groups. RESULTS: Isolated B-lines were frequent in both group 1 (54.5%) and group 2 (40.0%); the number of chest areas positive for B-lines increased with age (16.1% in group 1 vs. 5.3% in group 2, p = 0.0028). In group 2, we found that 37.5% of subjects with B-lines had at least 1 chest area with multiple B-lines, but only 2 subjects had 2 or more. Moreover, in group 1 the chest CT documented a reticular pattern (2.3%), areas of increased density (9.1%), ground glass (6.8%), cysts (2.3%), bronchiectasis (22.7%), and bronchial thickening (6.8%); in group 2, only cysts (6.7%) and bronchiectasis (6.7%) were found. CONCLUSIONS: The senile lung is characterized by mild changes on CT and US. Chest areas positive for B-lines increase with age, and focal multiple B-lines can be found. However, diffuse patterns, especially in symptomatic subjects, suggest a different diagnosis.

Combination of the clock drawing test with the physical phenotype of frailty for the prediction of mortality and other adverse outcomes in older community dwellers without dementia.

BACKGROUND: Cognitive assessment is thought to increase the ability of the physical phenotype of frailty to identify older persons at a higher risk for adverse outcomes. OBJECTIVE: Data from a cohort of dementia-free community dwellers were used to investigate whether the clock drawing test (CDT), a quick and easy cognitive screening test, is associated with adverse health outcomes independently of the physical phenotype of frailty. METHODS: This was a prospective population-based cohort study of 766 dementia-free Italian community dwellers aged 65 years or older. Baseline assessment included the physical phenotype of frailty, 3 different CDT protocols [Sunderland, Shulman, and the clock drawing interpretation scale (CDIS)], and several health confounders. Hazard ratios (HR) and odds ratio (OR) along with their corresponding 95% confidence intervals (CI) from models adjusted for frailty and sociodemographic and health confounders were used to estimate the independent association of the CDT with the 7-year risk of all-cause mortality and the 3-year risk of new and worsening disability, hospitalization, and fractures. RESULTS: After adjustment for confounders, the Sunderland CDT was significantly associated with all-cause mortality independently of the physical phenotype of frailty (HR = 1.44, 95% CI 1.03-2.01, p = 0.031). However, compared to all nonfrail participants with a normal Sunderland CDT, the HR was 1.57 (95% CI 1.09-2.26, p = 0.016) for those with impairment on the Sunderland CDT only, 2.48 (95% CI 1.46-4.20, p = 0.001) for those with frailty only, and 2.52 (95% CI 1.34-4.77, p = 0.004) for those with both frailty and impairment on the Sunderland CDT. Mortality was unrelated to the CDIS CDT (p = 0.359) and the Shulman CDT (p = 0.281). No statistically significant relationship was found between nonlethal outcomes and any CDT protocol, although trends were found for an association of both the Sunderland CDT (p = 0.118) and the CDIS CDT with worsening disability (p = 0.154). CONCLUSIONS: In older persons, depending on the scoring system, the CDT may predict the mortality risk independently of the physical phenotype of frailty. However, combining the two measurements does not improve their individual prognostic abilities.

Adipocyte-fatty acid binding protein and non-alcoholic fatty liver disease in the elderly.

BACKGROUND: Adipocyte-fatty acid binding protein (A-FABP) is an intracellular lipid transporter that mediates metabolically triggered inflammation, and it is associated with insulin resistance, atherogenic dyslipidemia, and cardiovascular risk. AIMS: The aim of this study was to evaluate A-FABP behavior in elderly people, and especially its association with liver steatosis at abdominal ultrasound. METHOD: Cross-sectional study of two cohort of individuals with and without steatosis, with assessment of several clinical and laboratory variables. Prospective evaluation of liver steatosis remodeling after six years of follow-up. One hundred and fifty-six subjects aged over 65 years were enrolled. RESULTS: Serum A-FABP positively correlated with body fat percentage, total cholesterol, serum triglycerides and erythrocyte sedimentation rate. Unlike expected, high A-FABP levels were associated with absence of liver steatosis, while there was no evidence of association with steatosis grade changes after 6 years of follow-up. CONCLUSION: Among individuals aging more than 65 years included in the study, A-FABP was inversely associated with liver steatosis. It can be argued, that still uncovered mechanisms modify A-FABP behavior in elderly people, especially its association with multifactorial diseases.

The Prognostic Significance of Early Glycemic Profile in Acute Ischemic Stroke Depends on Stroke Subtype.

It is still unclear whether early glycemic profile after admission for acute ischemic stroke (IS) has the same prognostic significance in patients with lacunar and non-lacunar infarction. Data from 4011 IS patients admitted to a Stroke Unit (SU) were retrospectively analyzed. Lacunar IS was diagnosed by clinical criteria. A continuous indicator of early glycemic profile was calculated as the difference of fasting serum glucose (FSG) measured within 48 h after admission and random serum glucose (RSG) measured on admission. Logistic regression was used to estimate the association with a combined poor outcome defined as early neurological deterioration, severe stroke at SU discharge, or 1-month mortality. Among patients without hypoglycemia (RSG and FSG > 3.9 mmol/L), an increasing glycemic profile increased the likelihood of a poor outcome for non-lacunar (OR, 1.38, 95%CI, 1.24-1.52 in those without diabetes; 1.11, 95%CI, 1.05-1.18 in those with diabetes) but not for lacunar IS. Among patients without sustained or delayed hyperglycemia (FSG < 7.8 mmol/L), an increasing glycemic profile was unrelated to outcome for non-lacunar IS but decreased the likelihood of poor outcome for lacunar IS (OR, 0.63, 95%CI, 0.41-0.98). Early glycemic profile after acute IS has a different prognostic significance in non-lacunar and lacunar patients.

Probability of Cardioembolic vs. Atherothrombotic Pathogenesis of Cryptogenic Strokes in Older Patients.

Some clinical, laboratory, ECG, and echocardiographic parameters could provide useful indications to assess the probability of cardioembolism or atherothrombosis in cryptogenic strokes. We retrospectively examined 290 patients with ischemic stroke aged ≥60 years, divided into 3 groups: strokes originating from large artery atherothrombosis (n = 92), cardioembolic strokes caused by paroxysmal atrial fibrillation (n = 88) and cryptogenic strokes (n = 110). In addition to echocardiographic and routine clinical-laboratory variables, neutrophil:lymphocyte ratio, red blood cell distribution width, mean platelet volume, P wave and PR interval duration and biphasic inferior P waves, both on admission and after 7 to 10 days, were also considered. By multiple logistic regression, cardioembolic strokes were compared with large artery atherothrombosis strokes, and beta coefficients were rounded to produce a scoring system. Late PR interval ≥188 ms, left atrium ≥4 cm, left ventricular end-diastolic volume <65 ml, and posterior circulation syndrome were associated with paroxysmal atrial fibrillation (positive scores). In contrast, male gender, hypercholesterolemia, and initial platelet count ≥290 × 109/L were associated with atherothrombosis of large arteries (negative scores). The algebraic sum of these scores produced values indicative of cardioembolism if >0 (positive predictive value 89.1%), or of atherothrombosis, if ≤0 (positive predictive value 72.5%). The area under the receiver operating characteristic curve was 0.85. Among cryptogenic strokes, 41.5% had a score >0 (probable atrial fibrillation) and 58.5% had a score ≤0 (possible atherothrombosis). In conclusion, a scoring system based on electrocardiogram, laboratory, clinical and echocardiographic parameters can provide useful guidance for further investigations and secondary prevention in older patients with cryptogenic stroke.

Can We Slow Down Biological Age Progression? Study Protocol for the proBNPage Reduction (PBAR) Randomized, Double-Blind, Placebo-Controlled Trial (Effects of 4 "Anti-Aging" Food Supplements in Healthy Older Adults).

Purpose: The availability of a simple and reliable marker of biological age might allow an acceleration of the research in the field of longevity extension. Previous studies suggest that this marker might be the N-terminal of B-type natriuretic peptide precursor (NT-proBNP), from which proBNPage, a biological age surrogate, can be calculated. Objectives of the study: 1) To fine-tune the method of proBNPage progression assessment and 2) To establish whether 4 "anti-aging" treatments, which provided promising results in previous studies, can modify proBNPage progression. Patients and Methods: This is a double-blind randomized placebo-controlled clinical trial on 120 adults aged 65-80 years, free of cardiovascular diseases. Participants will be randomized into 3 groups: A) Coenzyme Q10 100 mg bid + Selenium 100 mcg; B) Resveratrol 350 mg bid + TA-65 (Astragalus Membranaceus extract) 100U; C) Placebo-1 bid + Placebo-2. They will be followed for 2 years and checked 8 times, to assess both proBNPage progression and treatment safety. Secondary variables (handgrip strength, aerobic capacity at the step test and quality of life) will also be assessed. Primary outcome will be the demonstration of significant changes of proBNPage, compared to baseline, in the 3 groups at 6, 12, 18 and 24 months. Secondary outcome will be the demonstration of similar changes of secondary variables. Statistical analyses will be mainly performed by repeated measures ANOVA (both according to intention to treat and per protocol) and paired t tests. The study was approved by the Ethics Committee Area Vasta Emilia Centro, Emilia-Romagna Region, ID: 64/2022/Sper/AOUBo. Trial registration: ClinicalTrials.gov, NCT05500742. Conclusion: The use of proBNPage as a surrogate of biological age may prove an easy method to select anti-aging treatments worthy of further, more complex assessments.

Metabolic syndrome and all-cause mortality in older men and women.

BACKGROUND: Prevalence of metabolic syndrome (MetS) increases with age, but its association with all-cause mortality in older persons remains uncertain. This study investigated the association of all-cause mortality with MetS and its individual components in older men and women. METHODS: A total of 917 men and 1043 women aged 65 years and older from two Italian population-based cohorts were included in the study. MetS was defined according to four different definitions: National Cholesterol Education Program (NCEP), NCEP revised according to the American Heart Association and National Heart Lung Blood Institute (NCEP-R), International Diabetes Organization (IDF) and Joint Interim Statement (JIS). All of these definitions include abdominal obesity, hyperglycaemia, hypertriglyceridaemia, low high-density lipoprotein cholesterol and hypertension. Hazard Ratios (HR) and their corresponding 95% confidence interval (95%CI) estimated from multivariable-adjusted Cox regression models were used to investigate the associations of all-cause mortality with baseline MetS status and individual MetS components. RESULTS: After 6·5 ± 1·8 years of follow-up, there were 179 deaths among women and 193 among men. Mortality risk was increased in women with MetS by any definition, regardless of individual components, but limited to age 70-79 years (NCEP, HR = 2·02, 95%CI, 1·16-3·53; NCEP-R, HR = 2·51, 95%CI, 1·45-4·34; IDF, HR = 2·16, 95%CI, 1·26-3·72; JIS, HR = 2·16, 95%CI, 1·26-3·72). Mortality risk of men was associated with hypertriglyceridaemia below age 70 years (HR = 2·50, 95%CI, 1·19-5·25), but unrelated to MetS status. CONCLUSIONS: Metabolic Syndrome is associated with all-cause mortality in older women but not in men. The association, however, is limited to a narrow age range.

Serum thyroid-stimulating hormone as a predictor of cognitive impairment in an elderly cohort.

BACKGROUND: It is unclear whether in late life serum thyroid-stimulating hormone (TSH) predicts risk of developing cognitive impairment. OBJECTIVE: This study investigated the prospective relationship of serum TSH with the risk of developing mild cognitive impairment (MCI), Alzheimer's disease (AD) and vascular dementia (VaD) in an elderly cohort with a 4-year follow-up. METHODS: Data are for 660 subjects aged 65 years and older from an Italian population-based cohort who were cognitively normal at an extensive assessment in 1999/2000 and underwent follow-up assessment in 2003/2004. Serum TSH was measured at baseline. Multinomial logistic models adjusted for sociodemographic and cardiovascular risk factors were used to investigate the association of serum TSH (both as a tertile and continuous log-transformed variable) with risk of incident MCI, AD and VaD diagnosed according to international criteria. RESULTS: Over 3.8 ± 0.7 years of follow-up, there were 149 incident MCI cases (77 with impairment of memory and 72 with impairment of nonmemory domains) and 86 incident dementia cases (53 with AD, 28 with VaD). No association between baseline TSH and risk of developing any MCI subtype or AD was found. The highest TSH tertile had a threefold higher increased risk of VaD (OR: 3.25, 95% CI: 1.01-10.77, p = 0.048) compared to the lowest tertile. Risk of VaD increased about 60% for each 1 SD increase in log-transformed TSH (OR: 1.61, 95% CI: 1.06-2.44, p = 0.025). CONCLUSIONS: In this elderly cohort, baseline TSH was not related to the risk of developing MCI or AD, but high TSH was associated with an increased risk of VaD. These results suggest further need for research using larger samples to examine the role of TSH as a predictor of VaD and the role of thyroid autoimmunity in vascular cognitive impairment.

Prognostic significance of diabetes and stress hyperglycemia in acute stroke patients.

BACKGROUND: Hyperglycemic non-diabetic stroke patients have a worse prognosis than both normoglycemic and diabetic patients. Aim of this study was to assess whether hyperglycemia is an aggravating factor or just an epiphenomenon of most severe strokes. METHODS: In this retrospective study, 1219 ischemic or hemorrhagic stroke patients (73.7 ± 13.1 years) were divided into 4 groups: 0 = non-hyperglycemic non-diabetic, 1 = hyperglycemic non-diabetic, 2 = non-hyperglycemic diabetic and 3 = hyperglycemic diabetic. Hyperglycemia was defined as fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/l) measured the morning after admission, while the diagnosis of diabetes was based on a history of diabetes mellitus or on a glycated hemoglobin ≥ 6.5% (≥ 48 mmol/mol), independently of blood glucose levels. All diabetic patients, except 3, had Type 2 diabetes. The 4 groups were compared according to clinical history, stroke severity indicators, acute phase markers and main short term stroke outcomes (modified Rankin scale ≥ 3, death, cerebral edema, hemorrhagic transformation of ischemic lesions, fever, oxygen administration, pneumonia, sepsis, urinary infection and heart failure). RESULTS: Group 1 patients had more severe strokes, with larger cerebral lesions and higher inflammatory markers, compared to the other groups. They also had a high prevalence of atrial fibrillation, prediabetes, previous stroke and previous arterial revascularizations. In this group, the highest frequencies of cerebral edema, hemorrhagic transformation, pneumonia and oxygen administration were obtained. The prevalence of dependency at discharge and in-hospital mortality were equally high in Group 1 and Group 3. However, in multivariate analyses including stroke severity, cerebral lesion diameter, leukocytes and C-reactive protein, Group 1 was only independently associated with hemorrhagic transformation (OR 2.01, 95% CI 0.99-4.07), while Group 3 was independently associated with mortality (OR 2.19, 95% CI 1.32-3.64) and disability (OR 1.70, 95% CI 1.01-2.88). CONCLUSIONS: Hyperglycemic non-diabetic stroke patients had a worse prognosis than non-hyperglycemic or diabetic patients, but this group was not independently associated with mortality or disability when size, severity and inflammatory component of the stroke were accounted for.

Association of early glycemic change with short-term mortality in lobar and non-lobar intracerebral hemorrhage.

The association between early glycemic change and short-term mortality in non-diabetic patients with acute intracerebral hemorrhage (ICH) is unclear. We retrospectively investigated non-diabetic patients with lobar (n = 262) and non-lobar ICH (n = 370). Each patient had a random serum glucose test on hospital admission and a fasting serum glucose test within the following 48 h. Hyperglycemia was defined as serum glucose ≥ 7.8 mmol/l. Four patterns were determined: no hyperglycemia (reference category), persistent hyperglycemia, delayed hyperglycemia, and decreasing hyperglycemia. Associations with 30-day mortality were estimated using Cox models adjusted for major features of ICH severity. Persistent hyperglycemia was associated with 30-day mortality in both lobar (HR 3.00; 95% CI 1.28-7.02) and non-lobar ICH (HR 4.95; 95% CI 2.20-11.09). In lobar ICH, 30-day mortality was also associated with delayed (HR 4.10; 95% CI 1.77-9.49) and decreasing hyperglycemia (HR 2.01, 95% CI 1.09-3.70). These findings were confirmed in Cox models using glycemic change (fasting minus random serum glucose) as a continuous variable. Our study shows that, in non-diabetic patients with ICH, early persistent hyperglycemia is an independent predictor of short-term mortality regardless of hematoma location. Moreover, in non-diabetic patients with lobar ICH, both a positive and a negative glycemic change are associated with short-term mortality.

The association of proBNPage with manifestations of age-related cardiovascular, physical, and psychological impairment in community-dwelling older adults.

NT-proB-type natriuretic peptide (NT-proBNP) serum concentration can be transformed by simple formulas into proBNPage, a surrogate of biological age strongly associated with chronological age, all-cause mortality, and disease count. This cross-sectional study aimed to assess whether proBNPage is also associated with other manifestations of the aging process in comparison with other variables. The study included 1117 noninstitutionalized older adults (73.1 ± 5.6 years, 537 men). Baseline measurements of serum NT-proBNP, erythrocyte sedimentation rate, hemoglobin, lymphocytes, and creatinine, which have previously been shown to be highly associated with both age and all-cause mortality, were performed. These variables were compared between subjects with and without manifestations of cardiovascular impairment (myocardial infarction (MI), stroke, peripheral artery disease (PAD), arterial revascularizations (AR)), physical impairment (long step test duration (LSTD), walking problems, falls, deficit in one or more activities of daily living), and psychological impairment (poor self-rating of health (PSRH), anxiety/depression, Mini Mental State Examination (MMSE) score < 24). ProBNPage (years) was independently associated (OR, 95% CI) with MI (1.08, 1.07-1.10), stroke (1.02, 1.00-1.05), PAD (1.04, 1.01-1.06), AR (1.06, 1.04-1.08), LSTD (1.03, 1.02-1.04), walking problems (1.02, 1.01-1.03), and PSRH (1.02, 1.01-1.02). For 5 of these 7 associations, the relationship was stronger than that of chronological age. In addition, proBNPage was univariately associated with MMSE score < 24, anxiety/depression, and falls. None of the other variables provided comparable performances. Thus, in addition to the known associations with mortality and disease count, proBNPage is also associated with cardiovascular manifestations as well as noncardiovascular manifestations of the aging process.

N-terminal pro B-type natriuretic peptide (NT-proBNP): a possible surrogate of biological age in the elderly people.

NT-proB-type natriuretic peptide (NT-proBNP) increases with age and is associated with all-cause mortality. With this study, we assessed its possible utilization as a marker of biological age in comparison with other variables. The study included 1079 non-institutionalized elderly subjects (mean age 72.8 ± 5.5 years, 561 women). Baseline measurements were performed of serum NT-proBNP and of some laboratory variables previously utilized to estimate biological age (creatinine, albumin, C-reactive protein, cholesterol, blood glucose, leukocytes, lymphocytes, hemoglobin, mean cell volume). During 7 years of follow-up, 114 all-cause deaths occurred. The logarithm of NT-proBNP was the most age-related parameter (r = 0.35, P < 0.0001). Its relationship with mortality, according to Cox regression and ROC curve (AUC = 0.707, 95% CI 0.654-0.759), was stronger than that of all other variables, including age. In multivariate analysis, only NT-proBNP and age remained independently associated with mortality. The regression lines between age and NT-proBNP (pg/ml) allowed a separate estimation of biological age ("proBNPage") for men (= [log(NT-proBNP) + 1.2068]/0.0827) and for women (= [log(NT-proBNP) - 1.5258]/0.0478). The hazard ratio of all-cause mortality for the fifth quintile of proBNP age (≥ 85 years) compared with the first quintile (< 61 years) was 7.9 (95% CI 3.6-17.5). Similarly, the difference between pro-BNPage and chronological age was associated with a hazard ratio of 3.5 in the fifth quintile (95% CI 1.9-6.4) and was associated with disease count (P for trend = 0.0002). In conclusion, NT-proBNP was the best indicator of biological age, which can be estimated by simple formulas and might be used for prognostic purposes or as a surrogate end point in epidemiological and intervention studies.

Diagnostic performance of an Executive Clock Drawing Task (CLOX) as a screening test for mild cognitive impairment in elderly persons with cognitive complaints.

BACKGROUND: CLOX, a clock drawing test protocol uniquely sensitive to impairment of executive functions, has been proposed as a screening tool for mild cognitive impairment (MCI), but data about its diagnostic efficiency are lacking. METHODS: There are data for 196 subjects, age >or=60 years, referred to a memory clinic for cognitive complaints. After extensive neuropsychological testing, 64 were diagnosed as cognitively normal and 132 with MCI. RESULTS: At standard cutoffs, both CLOX subtests had a fair specificity (CLOX1 72%, CLOX2 92%) but unacceptably low values of sensitivity (CLOX1 54%, CLOX2 28%) and likelihood ratio (CLOX1 1.91, CLOX2 3.59) for MCI. The use of different cutoffs or the combination of CLOX with the Mini-Mental State Examination (MMSE) did not statistically increase diagnostic efficiency. CONCLUSION: CLOX, either alone or in combination with MMSE, is not a useful screening test for MCI in a clinical setting.