Utilizing venous occlusion plethysmography to assess vascular effects: A study with buloxibutid, an angiotensin II type 2 receptor agonist.

Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open-label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra-arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 µg/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8-3.2 µg/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra-arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3-200 µg/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230-320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra-arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.

Editor's Choice - Short Term Cost Effectiveness of Radiofrequency Ablation and High Ligation and Stripping for Great Saphenous Vein Incompetence.

OBJECTIVE: Superficial venous incompetence (SVI) is a common disease that causes significant quality of life (QoL) impairment. There is a need for more health economic evaluations of SVI treatment. The aim of this study was to perform a cost effectiveness analysis in patients with great saphenous vein (GSV) incompetence comparing radiofrequency ablation (RFA), high ligation and stripping (HL/S), and no treatment or conservative treatment with one year follow up. METHODS: Randomised controlled trial economic analysis from an ongoing trial; 143 patients (156 limbs) with GSV incompetence (CEAP clinical class 2 - 6) were included. Treatment was performed with RFA or HL/S. Follow up was performed up to one year using duplex ultrasound, revised venous clinical severity score (r-VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), and EuroQol-5D-3L (EQ-5D-3L). RESULTS: Seventy-eight limbs were treated with RFA and HL/S respectively. No treatment or conservative treatment was assumed to have zero in treatment cost and no treatment benefit. In the RFA group, one limb had reflux in the GSV after one month and three limbs after one year. In HL/S, two limbs had remaining reflux in the treated area at one month and one year. Both disease severity (r-VCSS, p = .004) and QoL (AVVQ, p = .021 and EQ-5D-3L, p = .028) were significantly improved over time. The QALY gain was 0.21 for RFA and 0.17 for HL/S. The cost per patient was calculated as €1 292 for RFA and €2 303 for HL/S. The cost per QALY (compared with no treatment or conservative treatment) was €6 155 for RFA and €13 549 for HL/S. With added cost for days absent from work the cost per QALY was €7 358 for RFA and €24 197 for HL/S. The cost per QALY for both methods was well below the threshold suggested by Swedish National Board of Health. CONCLUSION: RFA is more cost effective than HL/S and no treatment or conservative treatment at one year follow up.

The natural history of lifetime psychiatric disorders in patients with obsessive-compulsive disorder followed over half a century.

OBJECTIVE: Few long-term studies have examined the life-time prevalence of comorbid psychiatric conditions in patients with obsessive-compulsive disorder (OCD). We therefore studied the frequency of comorbid psychiatric disorders, and their relation to onset and prognosis, in patients with OCD who were followed for almost half a century. METHODS: During 1947-1953, 285 OCD patients were admitted as inpatients to a university hospital in Gothenburg, Sweden. Among those, 251 (88%) accepted a structured comprehensive psychiatric examination in 1954-1956. In 1989-1993, 176 survivors were eligible and 144 (response rate 82%) were re-examined. The same psychiatrist performed both examinations. OCD was diagnosed according to the Schneider criteria, and other mental disorders according to DSM-IV. Mean follow-up since onset was 47 years. RESULTS: The lifetime frequency of depressive disorders was 84.7% (major depression 43.8%), generalized anxiety disorder (GAD) 71.5%, panic anxiety disorder 47.9%, agoraphobia 52.1%, specific phobias 64.6%, social phobia 47.9%, paranoid conditions 40.3% (29.1% paranoid ideation), psychotic disorders 15.3%, alcohol abuse 13.2% (men 39%, women 3%) and substance abuse 17.4%. Specific phobia most often started before OCD, while depression had a varied onset in relation to OCD. Social phobia, agoraphobia, GAD, alcohol and substance abuse, psychotic disorders and paranoid conditions most often started after OCD. Presence of GAD, psychotic disorder and substance abuse worsened prognosis of OCD. CONCLUSION: Comorbid psychiatric conditions are common in OCD patients, and have onset throughout the course. OCD signals vulnerability for other psychiatric conditions, which are important to detect in clinical practice as they negatively affect the outcome.

Sleep disturbances and change in multiple cognitive domains among older adults: a multicenter study of five Nordic cohorts.

STUDY OBJECTIVES: We examined and compared cross-sectional and longitudinal associations between self-reported sleep disturbances and various cognitive domains in five separate Nordic European longitudinal aging studies (baseline N = 5631, mean age = 77.7, mean follow-up = 4.16 years). METHODS: Comparable sleep parameters across studies included reduced sleep duration/quality, insomnia symptoms (sleep latency, waking up at night, and early awakenings), short and long sleep duration, and daytime napping. The cognitive domains were episodic memory, verbal fluency, perceptual speed, executive functioning, and global cognition (aggregated measure). A series of mixed linear models were run separately in each study and then compared to assess the level and rate of change in cognitive functioning across each sleep disturbance parameter. Models were adjusted for age, sex, education, hypnotic usage, depressive symptoms, lifestyle factors, cardiovascular, and metabolic conditions. By using a coordinated analytic approach, comparable construct-level measurements were generated, and results from identical statistical models were qualitatively compared across studies. RESULTS: While the pattern of statistically significant results varied across studies, subjective sleep disturbances were consistently associated with worse cognition and steeper cognitive decline. Insomnia symptoms were associated with poorer episodic memory and participants sleeping less or more than 7-8 hours had a steeper decline in perceptual speed. In addition, daytime napping (>2 hours) was cross-sectionally and longitudinally associated with all examined cognitive domains. Most observed associations were study-specific (except for daytime napping), and a majority of association estimates remained significant after adjusting for covariates. CONCLUSION: This rigorous multicenter investigation further supports the importance of sleep disturbance, including insomnia, long and short sleep duration, and daytime napping on baseline cognitive functioning and rate of change among older adults. These sleep factors may be targeted in future lifestyle interventions to reduce cognitive decline.

Polygenic risk scores for Alzheimer's disease in relation to cognitive change: A representative sample from the general population followed over 16 years.

BACKGROUND: Polygenic risk scores for Alzheimer's disease (AD-PRSs) have been associated with cognition. However, few studies have examined the effect of AD-PRS beyond the APOE gene, and the influence of genetic variants related to level of cognitive ability (COG-PRS) on cognitive performance over time in the general older population. METHOD: A population-based sample of 965 individuals born in 1930, with genetic and standardized cognitive data on six psychometric tests (Thurstone's picture memory, immediate recall of 10 words, Block design, word fluency, figure identification, delayed recall of 12 items), were examined at age 70, 75, 79, and 85 years. Non-APOE AD-PRSs and COG-PRSs (P < 5e-8, P < 1e-5, P < 1e-3, P < 1e-1) were generated from recent genome-wide association studies. Linear mixed effect models with random intercepts and slope were used to analyze the effect of APOE ε4 allele, AD-PRSs, and COG-PRSs, on cognitive performance and rate of change. Analyses were repeated in samples excluding dementia. RESULTS: APOE ε4 and AD-PRS predicted change in cognitive performance (APOE ε4*age: ß = -0.03, P < 0.0001 and AD-PRS *age: ß = -0.01, P = 0.02). The results remained similar in the sample excluding those with dementia. COG-PRS predicted level of cognitive performance, while APOE ε4 and AD-PRS did not. COG-PRSs did not predict change in cognitive performance. CONCLUSION: We found that genetic predisposition of AD predicted cognitive decline among 70-year-olds followed over 16 years, regardless of dementia status, while polygenic risk for general cognitive performance did not.

Dissociating memory and executive function impairment through temporal features in a word list verbal learning task.

The Rey Auditory Verbal Learning Test (RAVLT) is an established verbal learning test commonly used to quantify memory impairments due to Alzheimer's Disease (AD) both at a clinical dementia stage or prodromal stage of mild cognitive impairment (MCI). Focal memory impairment-as quantified e.g. by the RAVLT-at an MCI stage is referred to as amnestic MCI (aMCI) and is often regarded as the cognitive phenotype of prodromal AD. However, recent findings suggest that not only learning and memory but also other cognitive domains, especially executive functions (EF) and processing speed (PS), influence verbal learning performance. This research investigates whether additional temporal features extracted from audio recordings from a participant's RAVLT response can better dissociate memory and EF in such tasks and eventually help to better describe MCI subtypes. 675 age-matched participants from the H70 Swedish birth cohort were included in this analysis; 68 participants were classified as MCI (33 aMCI and 35 due to executive impairment). RAVLT performances were recorded and temporal features extracted. Novel temporal features were correlated with established neuropsychological tests measuring EF and PS. Lastly, the downstream diagnostic potential of temporal features was estimated using group differences and a machine learning (ML) classification scenario. Temporal features correlated moderately with measures of EF and PS. Performance of an ML classifier could be improved by adding temporal features to traditional counts. We conclude that RAVLT temporal features are in general related to EF and that they might be capable of dissociating memory and EF in a word list learning task.

Quantifiable remaining reflux 1 year after treatment of superficial venous incompetence is associated with impaired clinical outcome.

OBJECTIVE: Remaining symptoms after treatment of superficial venous incompetence is a common problem. Duplex ultrasound is often used during follow-up, but does not permit an overall quantification of venous function. We have developed a plethysmographic method using occlusion cuffs for separation of superficial and deep venous reflux. By assessing the superficial component it is possible to quantify a potential suboptimal hemodynamic treatment in patients with superficial venous incompetence. The aim was to examine whether patients with hemodynamically quantifiable remaining reflux after treatment experience impaired clinical outcomes. METHODS: This single-center prospective cohort study evaluated 156 limbs with great saphenous vein incompetence treated with radiofrequency ablation or high ligation and stripping. Duplex ultrasound and strain-gauge plethysmography (SGP) with and without selective superficial occlusion were performed before and one-year after treatment. Time taken (seconds) to reach 50% of the venous volume (T50) was evaluated. A difference in the T50of >5 seconds between postoperative strain-gauge plethysmography with and without superficial occlusion was defined as remaining reflux. The Venous Clinical Severity Score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ) were evaluated and compared between patients with and without remaining reflux. Multivariable logistic regression was used to evaluate risk factors for remaining plethysmographic reflux. RESULTS: In all patients, median (25th, 75th percentile) T50 increased preoperatively from 7 seconds (3, 12 seconds) to 17 seconds (11, 28 seconds) (P < .001) 1 year after treatment. The VCSS and AVVQ were reduced (VCSS, 8.0 [6.0, 10.0] vs 3.0 [1.0, 5.0] [P < .001]; AVVQ, 21.8 [15.8, 32.1] vs 6.4 [2.2, 11.0] [P < .001]). Of the 156 limbs, 87 (56%) demonstrated remaining reflux 1 year after treatment. Patients with remaining plethysmographic reflux displayed higher median (25th, 75th percentile) VCSS (3.0 [2.0, 5.0] vs 2.0 [1.0, 4.0]; P = .012) and AVVQ (7.5 [2.7, 14.9] vs 4.7 [1.6, 9.2]; P = .025). Multivariate logistic regression showed that higher preoperative C in the Clinical Etiology Anatomy Pathophysiology classification (CEAP) (odds ratio [OR], 2.9 [95% confidence interval [CI], 1.34-6.46), age (OR, 1.03; 95% CI, 1.001-1.065), small saphenous vein incompetence (OR, 4.2; 95% CI, 1.30-13.73) and postoperative great saphenous vein reflux below the treated area (OR, 2.16; 95% CI, 1.02-4.56) were significant risk factors for remaining plethysmographic reflux. CONCLUSIONS: A majority of treated limbs showed quantifiable reflux 1 year after intervention and these patients displayed worse patient related outcomes assessed with the VCSS and AVVQ. Remaining plethysmographic reflux was associated with preoperative small saphenous vein incompetence and reflux below the treated area as well as advanced age and higher C in CEAP.

Subtle Differences in Cognition in 70-Year-Olds with Elevated Cerebrospinal Fluid Neurofilament Light and Neurogranin: A H70 Cross-Sectional Study.

BACKGROUND: Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. OBJECTIVE: We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. METHODS: The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid ß1 - 42, total tau, and phosphorylated tau, were measured. RESULTS: Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and Aß42 concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic Aß42 concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological Aß42 concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. CONCLUSION: Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.

Hearing Loss and Cognitive Function in Early Old Age: Comparing Subjective and Objective Hearing Measures.

INTRODUCTION: Population-based research has consistently shown that people with hearing loss are at greater risk of cognitive impairment. We aimed to explore the cross-sectional association of both subjective and objective hearing measures with global and domain-specific cognitive function. We also examined the influence of hearing aid use on the relationship. METHODS: A population-based sample (n = 1,105, 52% women) of 70-year-olds that were representative of the inhabitants of the city of Gothenburg, Sweden completed a detailed cognitive examination, pure-tone audiometry, and a questionnaire regarding perceived hearing problems. A subsample (n = 247, 52% women) also completed a test of speech-recognition-in-noise (SPRIN). Multiple linear regression analyses were conducted to explore the association of hearing with cognitive function, adjusting for sex, education, cardiovascular factors, and tinnitus. RESULTS: Global cognitive function was independently associated with the better ear pure-tone average across 0.5-4 kHz (PTA4, ß = -0.13, 95% CI, -0.18, -0.07), the better ear SPRIN score (ß = 0.30, 95% CI, 0.19, 0.40), but not with the self-reported hearing measure (ß = -0.02, 95% CI, -0.07, 0.03). Both verbally loaded and nonverbally loaded tasks, testing a variety of cognitive domains, contributed to the association. Hearing aid users had better global cognitive function than nonusers with equivalent hearing ability. The difference was only significant in the mild hearing loss category. DISCUSSION: In a population-based sample of 70-year-old persons without dementia, poorer hearing was associated with poorer global and domain-specific cognitive function, but only when hearing function was measured objectively and not when self-reported. The speech-in-noise measure showed the strongest association. This highlights the importance of including standardized hearing tests and controlling for hearing status in epidemiological geriatric research. More research is needed on the role that hearing aid use plays in relation to age-related cognitive declines.

Screening for Mild Cognitive Impairment Using a Machine Learning Classifier and the Remote Speech Biomarker for Cognition: Evidence from Two Clinically Relevant Cohorts.

BACKGROUND: Modern prodromal Alzheimer's disease (AD) clinical trials might extend outreach to a general population, causing high screen-out rates and thereby increasing study time and costs. Thus, screening tools that cost-effectively detect mild cognitive impairment (MCI) at scale are needed. OBJECTIVE: Develop a screening algorithm that can differentiate between healthy and MCI participants in different clinically relevant populations. METHODS: Two screening algorithms based on the remote ki:e speech biomarker for cognition (ki:e SB-C) were designed on a Dutch memory clinic cohort (N = 121) and a Swedish birth cohort (N = 404). MCI classification was each evaluated on the training cohort as well as on the unrelated validation cohort. RESULTS: The algorithms achieved a performance of AUC  0.73 and AUC  0.77 in the respective training cohorts and AUC  0.81 in the unseen validation cohorts. CONCLUSION: The results indicate that a ki:e SB-C based algorithm robustly detects MCI across different cohorts and languages, which has the potential to make current trials more efficient and improve future primary health care.

Attrition in the Gothenburg H70 birth cohort studies, an 18-year follow-up of the 1930 cohort.

Background: Longitudinal studies are essential to understand the ageing process, and risk factors and consequences for disorders, but attrition may cause selection bias and impact generalizability. We describe the 1930 cohort of the Gothenburg H70 Birth Cohort Studies, followed from age 70 to 88, and compare baseline characteristics for those who continue participation with those who die, refuse, and drop out for any reason during follow-up. Methods: A population-based sample born 1930 was examined with comprehensive assessments at age 70 (N = 524). The sample was followed up and extended to increase sample size at age 75 (N = 767). Subsequent follow-ups were conducted at ages 79, 85, and 88. Logistic regression was used to analyze baseline characteristics in relation to participation status at follow-up. Results: Refusal to participate in subsequent examinations was related to lower educational level, higher blood pressure, and lower scores on cognitive tests. Both attrition due to death and total attrition were associated with male sex, lower educational level, smoking, ADL dependency, several diseases, poorer lung function, slower gait speed, lower scores on cognitive tests, depressive symptoms, and a larger number of medications. Attrition due to death was also associated with not having a partner. Conclusions: It is important to consider different types of attrition when interpreting results from longitudinal studies, as representativeness and results may be differently affected by different types of attrition. Besides reducing barriers to participation, methods such as imputation and weighted analyses can be used to handle selection bias.

Representativeness in population-based studies of older adults: five waves of cross-sectional examinations in the Gothenburg H70 Birth Cohort Study.

OBJECTIVES: To describe representativeness in the Gothenburg H70 1930 Birth Cohort Study. DESIGN: Repeated cross-sectional examinations of a population-based study. SETTING: Gothenburg, Sweden. PARTICIPANTS: All residents of Gothenburg, Sweden, born on specific birth dates in 1930 were invited to a comprehensive health examination at ages 70, 75, 79, 85 and 88. The number of participants at each examination was 524 at age 70, 767 at age 75, 580 at age 79, 416 at age 85, and 258 at age 88. PRIMARY OUTCOME MEASURES: We compared register data on sociodemographic characteristics and hospital discharge diagnoses between participants and (1) refusals, (2) all same-aged individuals in Gothenburg and (3) all same-aged individuals in Sweden. We also compared mortality rates between participants and refusals. RESULTS: Refusal rate increased with age. At two or more examination waves, participants compared with refusals had higher educational level, more often had osteoarthritis, had lower mortality rates, had lower prevalence of neuropsychiatric, alcohol-related and cardiovascular disorders, and were more often married. At two examination waves, participants compared with same-aged individuals in Gothenburg had higher education and were more often born in Sweden. At two examination waves or more, participants compared with same-aged individuals in Sweden had higher education, had higher average income, less often had ischaemic heart disease, were less often born in Sweden and were more often divorced. CONCLUSIONS: Participants were more similar to the target population in Gothenburg than to refusals and same-aged individuals in Sweden. Our study shows the importance of having different comparison groups when assessing representativeness of population studies, which is important in evaluating generalisability of results. The study also contributes unique and up-to-date knowledge about participation bias in these high age groups.

Unsupervised mobile app-based cognitive testing in a population-based study of older adults born 1944.

Background: Mobile app-based tools have the potential to yield rapid, cost-effective, and sensitive measures for detecting dementia-related cognitive impairment in clinical and research settings. At the same time, there is a substantial need to validate these tools in real-life settings. The primary aim of this study was thus to evaluate the feasibility, validity, and reliability of mobile app-based tasks for assessing cognitive function in a population-based sample of older adults. Method: A total of 172 non-demented (Clinical Dementia Rating 0 and 0.5) older participants (aged 76-77) completed two mobile app-based memory tasks-the Mnemonic Discrimination Task for Objects and Scenes (MDT-OS) and the long-term (24 h) delayed Object-In-Room Recall Task (ORR-LDR). To determine the validity of the tasks for measuring relevant cognitive functions in this population, we assessed relationships with conventional cognitive tests. In addition, psychometric properties, including test-retest reliability, and the participants' self-rated experience with mobile app-based cognitive tasks were assessed. Result: MDT-OS and ORR-LDR were weakly-to-moderately correlated with the Preclinical Alzheimer's Cognitive Composite (PACC5) (r = 0.3-0.44, p < .001) and with several other measures of episodic memory, processing speed, and executive function. Test-retest reliability was poor-to-moderate for one single session but improved to moderate-to-good when using the average of two sessions. We observed no significant floor or ceiling effects nor effects of education or gender on task performance. Contextual factors such as distractions and screen size did not significantly affect task performance. Most participants deemed the tasks interesting, but many rated them as highly challenging. While several participants reported distractions during tasks, most could concentrate well. However, there were difficulties in completing delayed recall tasks on time in this unsupervised and remote setting. Conclusion: Our study proves the feasibility of mobile app-based cognitive assessments in a community sample of older adults, demonstrating its validity in relation to conventional cognitive measures and its reliability for repeated measurements over time. To further strengthen study adherence, future studies should implement additional measures to improve task completion on time.

Relationship between clinical severity and hemodynamic impact of great saphenous vein incompetence using strain gauge plethysmography and duplex ultrasound.

OBJECTIVES: To evaluate the relation of quantitative Duplex ultrasound (DUS) and strain gauge plethysmography (SGP) parameters with clinical severity and quality of life in patients with superficial venous incompetence. METHODS: DUS volume flow and distal SGP refilling times (T50 and T90) were evaluated in 152 patients (164 Limbs) with superficial incompetence. Clinical severity and quality of life were evaluated with C of the CEAP classification, venous clinical severity score (VCSS), Aberdeen varicose vein questionnaire (AVVQ), and EuroQol 5D-3L. RESULTS: Higher DUS volume flow was associated with higher C in CEAP scores. Volume flow was also related to T50 and T90. Shorter T50 and T90 were associated with higher C in CEAP and VCSS. T50 was also associated with EQ-5DVAS. Reflux extension to the foot wase associated with shorter T50 and T90 and higher DUS volume flow. CONCLUSIONS: DUS volume flow and SGP refilling times are related with clinical severity and provide quantitative information regarding venous function in patients with superficial incompetence.

Prediction of Postoperative Delirium After Cardiac Surgery with A Quick Test of Cognitive Speed, Mini-Mental State Examination and Hospital Anxiety and Depression Scale.

Purpose: To evaluate if preoperative assessment with A Quick Test of Cognitive Speed (AQT) could increase the accuracy of predicting delirium after cardiac surgery compared to Mini-Mental State Examination (MMSE), and examine if a composite of variables, including cognitive function and depressive symptoms, could be useful to predict delirium. Patients and Methods: Cardiac surgery was performed in 218 patients (mean age 72 years). Preoperative evaluation involved AQT, MMSE and Hospital Anxiety And Depression Scale (HADS). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) and Confusion Assessment Method-ICU (CAM-ICU). Logistic regression was performed to detect predictors of postoperative delirium and receiver operator characteristic curves (ROC) with area under the curve (AUC) to determine the accuracy. Results: Postoperative delirium occurred in 47 patients (22%) who had lower MMSE scores (median (range), 27 (19-30) vs 28 (20-30), p=0.009) and slower AQT (median (range), 76 (48-181) vs 70 (40-182) seconds, p=0.030) than patients without delirium. Predictive power measured as AUC (95% CI) was 0.605 (0.51-0.70) for AQT and 0.623 (0.53-0.72) for MMSE. Logistic regression (OR, 95% CI) showed MMSE <27 points (2.72, 1.27-5.86), AQT >70 sec (2.26, 1.03-4.95), HADS-D >4 points (2.60, 1.21-5.58) and longer cardiopulmonary bypass-time (1.007, 1.002-1.013) to be associated with postoperative delirium. Combining these parameters yielded an AUC of 0.736 (0.65-0.82). Conclusion: The ability of predicting delirium using AQT was similar to MMSE, and only slightly higher by combining AQT and MMSE. Adding HADS-D and cardiopulmonary bypass-time to MMSE and AQT increased the predictive power to a borderline acceptable discriminatory value. Preoperative cognitive tests and screening for depressive symptoms may help identify patients at risk of postoperative delirium. Yet, there is still a need to establish useful preoperative tests.

Slowing gait speed precedes cognitive decline by several years.

INTRODUCTION: In this longitudinal study, we aimed to examine if slowing gait speed preceded cognitive decline and correlated with brain amyloidosis. METHODS: The sample (n = 287) was derived from the Gothenburg H70 Birth Cohort Studies, with follow-ups between 2000 and 2015. Gait speed was measured by indoor walk, and cognition using the Clinical Dementia Rating (CDR) score. All participants had CDR = 0 at baseline. Some participants had data on cerebrospinal fluid (CSF) amyloid beta (Aß)1-42 concentrations at the 2009 examination. RESULTS: Gait speed for participants who worsened in CDR score during follow-up was slower at most examinations. Baseline gait speed could significantly predict CDR change from baseline to follow-up. Subjects with pathological CSF Aß1- 42 concentrations at the 2009 visit had lost more gait speed compared to previous examinations. DISCUSSION: Our results indicate that gait speed decline precedes cognitive decline, is linked to Alzheimer's pathology, and might be used for early detection of increased risk for dementia development.

Sex differences in dementia and response to a lifestyle intervention: Evidence from Nordic population-based studies and a prevention trial.

INTRODUCTION: Evidence on sex differences in the risk for dementia has been mixed. The goal was to assess sex differences in the development of dementia, and in the effects of a lifestyle intervention. METHODS: Two strategies were adopted, one using combined data from three large Nordic population-based cohort studies (n = 2289), adopting dementia as outcome, and 2-year multidomain lifestyle intervention (n = 1260), adopting cognitive change as outcome. RESULTS: There was higher risk for dementia after age 80 years in women. The positive effects of the lifestyle intervention on cognition did not significantly differ between men and women. Sex-specific analyses suggested that different vascular, lifestyle, and psychosocial risk factors are important for women and men in mid- and late-life. CONCLUSION: Women had higher risk for dementia among the oldest individuals. Lifestyle interventions may be effectively implemented among older men and women.

Metabolic Syndrome Is Associated With Poor Cognition: A Population-Based Study of 70-Year-Old Adults Without Dementia.

BACKGROUND: Individual conditions of metabolic syndrome (MetS) have been related to dementia; however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors. METHODS: Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014-2016. MetS (central obesity plus at least 2 factors [reduced HDL-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from 10 neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein genotype were ascertained by trained staff. Data were analyzed with linear regression models. RESULTS: Overall, 618 participants (55%) had MetS. In multiadjusted linear regressions, MetS was related to poorer performance in attention/perceptual speed (ß -0.14 [95% CI -0.25, -0.02]), executive function (ß -0.12 [95% CI -0.23, -0.01]), and verbal fluency (ß -0.19 [95% CI -0.30, -0.08]). These associations were present only among individuals who did not carry any APOE-ε4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone. CONCLUSIONS: MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, apolipoprotein E-ε4 allele, and comorbid cardiovascular disease influenced the observed associations.

Effects of amyloid pathology and the APOE ε4 allele on the association between cerebrospinal fluid Aß38 and Aß40 and brain morphology in cognitively normal 70-years-olds.

The association between cerebrospinal fluid (CSF) amyloid beta (Aß) Aß38 or Aß40 and brain grey- and white matter integrity is poorly understood. We studied this in 213 cognitively normal 70-year-olds, and in subgroups defined by presence/absence of the APOE ε4 allele and Aß pathology: Aß-/APOE-, Aß+/APOE-, Aß-/APOE+ and Aß+/APOE+. CSF Aß was quantified using ELISA and genotyping for APOE was performed. Low CSF Aß42 defined Aß plaque pathology. Brain volumes were assessed using Freesurfer-5.3, and white matter integrity using tract-based statistics in FSL. Aß38 and Aß40 were positively correlated with cortical thickness, some subcortical volumes and white matter integrity in the total sample, and in 3 of the subgroups: Aß-/APOE-, Aß+/APOE- and Aß-/APOE+. In Aß+/APOE+ subjects, higher Aß38 and Aß40 were linked to reduced cortical thickness and subcortical volumes. We hypothesize that production of all Aß species decrease in brain regions with atrophy. In Aß+/APOE+, Aß-dysregulation may be linked to cortical atrophy in which high Aß levels is causing pathological changes in the gray matter of the brain.

The Diagnostic Performance of an Extended Ultrasound Protocol in Patients With Clinically Suspected Giant Cell Arteritis.

OBJECTIVE: To evaluate the diagnostic performance of an extended ultrasound protocol in patients referred under the suspicion of giant cell arteritis (GCA). METHODS: Consecutive patients with suspected GCA were examined with an extended color duplex ultrasound (CDU) protocol during a period of 2 years. The extended CDU protocol included temporal, axillary, subclavian, brachiocephalic, and carotid arteries. The reference was clinically diagnosed GCA, confirmed after ≥6-month follow-up. Hypo- or medium-echogenic, circumferential, homogenous wall thickening, and/or a positive compression sign in temporal arteries, were regarded as typical signs of arteritis. RESULTS: Of the eligible 201 patients, 83 (41%) received a clinical GCA diagnosis at follow-up ≥6 months post CDU examination. Among these cases, 48 (58%) demonstrated inflammation solely in temporal arteries, 8 (10%) showed abnormalities restricted to extra-cranial vessels, and 23 (28%) patients displayed inflammatory changes in both temporal and extra-cranial arteries. Color duplex ultrasound of temporal arteries yielded a diagnostic sensitivity and specificity [95% confidence intervals (CI)] of 86% (76-92%) and 99% (95-99%), respectively. By adding axillary artery examination, the sensitivity increased to 92% (83-97%) while the specificity remained unchanged. Further, inclusion of subclavian artery marginally increased the sensitivity by 1%. Finally, by also including brachiocephalic and common carotid arteries resulted in a sensitivity of 95% (88-99%) and a specificity of 98% (94-99%). CONCLUSIONS: Color duplex ultrasound examination demonstrated a high accuracy in diagnosing patients both with cranial and extra-cranial GCA. Further examination of brachiocephalic and common carotid arteries can increase the sensitivity without affecting the specificity when temporal and axillary findings are indecisive. Finally, the extended CDU protocol allows measurement of the general burden of inflammation, which could be relevant for future monitoring purposes.