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.

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.

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.

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.

Assessment of Upper Extremity Venous Compliance in Patients With Abdominal Aortic Aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is associated with morphological and functional changes in both aneurysmal and non-aneurysmal arteries. However, it remains uncertain whether similar changes also exist in the venous vasculature. The aim of this study was to evaluate global venous function in patients with AAA and controls. METHODS: This experimental study comprised 31 men with AAA (mean ± standard deviation age 70.0 ± 2.8 years) and 29 male controls (aged 70.6 ± 3.4 years). Venous occlusion plethysmography (VOP) was used to evaluate arm venous compliance at venous pressures between 10 and 60 mmHg in steps of 5 mmHg. Compensatory mobilisation of venous capacitance blood (capacitance response) was measured with a volumetric technique during experimental hypovolaemia induced by lower body negative pressure (LBNP). RESULTS: The VOP induced pressure-volume curve was significantly less steep in patients with AAA (interaction, p < .001), indicating lower venous compliance. Accordingly, the corresponding pressure-compliance curves displayed reduced venous compliance at lower venous pressures in patients with AAA vs. controls (interaction, p < .001; AAA vs. control, p = .018). After adjusting for arterial hypertension, diabetes mellitus, hyperlipidaemia, chronic obstructive pulmonary disease, and smoking, VOP detected differences in venous compliance remained significant at low venous pressures, that is, at 10 mmHg (p = .008), 15 mmHg (p = .013), and 20 mmHg (p = .026). Mean venous compliance was negatively correlated with aortic diameter (r = -.332, p = .010). Mobilisation of venous capacitance response during LBNP was reduced by approximately 25% in patients with AAA (p = .030), and the redistribution of venous blood during LBNP was negatively correlated with aortic diameter (r = -.417, p = .007). CONCLUSION: Men with AAA demonstrated reduced venous compliance and, as a result, a lesser capacity to mobilise peripheral venous blood to the central circulation during hypovolaemic stress. These findings imply that the AAA disease may be accompanied by functional changes in the venous vascular wall.

Cardiovascular biomarkers and echocardiographic findings at rest and during graded hypovolemic stress in women with recurrent vasovagal syncope.

INTRODUCTION: Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope. METHODS: Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope. RESULTS: Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P < .05), smaller left atrium (36 ± 2 vs 47 ± 3 cm3 , P < .01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P < .05) and during graded hypovolemia (P < .05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P < .05) and increased more in women with vasovagal syncope during progression of LBNP (P < .01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P < .05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P < .01) were seen in women with vasovagal syncope. CONCLUSION: Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope.

The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.

To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n = 1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5 years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.

Sleep disturbances and dementia risk: A multicenter study.

INTRODUCTION: Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk. METHODS: Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project [Sweden]; Cardiovascular Risk Factors, Aging and Dementia study [Finland]). Late-life baseline analyses (3-10 years follow-up) used all three studies (N = 1446). Baseline ages ≈ 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and ≈84 years (Kungsholmen Project). Midlife baseline (age ≈ 50 years) analyses used Cardiovascular Risk Factors, Aging and Dementia (21 and 32 years follow-up) (N = 1407). RESULTS: Midlife insomnia (fully adjusted hazard ratio = 1.24, 95% confidence interval = 1.02-1.50) and late-life terminal insomnia (fully adjusted odds ratio = 1.94, 95% confidence interval = 1.08-3.49) were associated with a higher dementia risk. Late-life long sleep duration (>9 hours) was also associated with an increased dementia risk (adjusted odds ratio = 3.98, 95% confidence interval = 1.87-8.48). DISCUSSION: Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk.

Transitions across cognitive states and death among older adults in relation to education: A multistate survival model using data from six longitudinal studies.

INTRODUCTION: This study examines the role of educational attainment, an indicator of cognitive reserve, on transitions in later life between cognitive states (normal Mini-Mental State Examination (MMSE), mild MMSE impairment, and severe MMSE impairment) and death. METHODS: Analysis of six international longitudinal studies was performed using a coordinated approach. Multistate survival models were used to estimate the transition patterns via different cognitive states. Life expectancies were estimated. RESULTS: Across most studies, a higher level of education was associated with a lower risk of transitioning from normal MMSE to mild MMSE impairment but was not associated with other transitions. Those with higher levels of education and socioeconomic status had longer nonimpaired life expectancies. DISCUSSION: This study highlights the importance of education in later life and that early life experiences can delay later compromised cognitive health. This study also demonstrates the feasibility and benefit in conducting coordinated analysis across multiple studies to validate findings.

Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope.

Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 ± 5.0 yr) and 15 matched controls (22.8 ± 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P < 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P < 0.01) and the maximal percent increase in total peripheral resistance was reduced (P < 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P < 0.05) and reduced in VVS women at higher levels of LBNP (P < 0.05). Capillary fluid absorption from extra- to intravascular space was reduced by ∼40% in VVS women (P < 0.05). Accordingly, the reduction in cardiac output was more pronounced (P < 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.

Reduced venous compliance: an important determinant for orthostatic intolerance in women with vasovagal syncope.

The influence of lower limb venous compliance on orthostatic vasovagal syncope (VVS) is uncertain. The most widespread technique to calculate venous compliance uses a nonphysiological quadratic regression equation. Our aim was therefore to construct a physiologically derived venous wall model (VWM) for calculation of calf venous compliance and to determine the effect of venous compliance on tolerance to maximal lower body negative pressure (LBNP). Venous occlusion plethysmography was used to study calf volume changes in 15 women with VVS (25.5 ± 1.3 yr of age) and 15 controls (22.8 ± 0.8 yr of age). The fit of the VWM and the regression equation to the experimentally induced pressure-volume curve was examined. Venous compliance was calculated as the derivative of the modeled pressure-volume relationship. Graded LBNP to presyncope was used to determine the LBNP tolerance index (LTI). The VWM displayed a better fit to the experimentally induced pressure-volume curve (P < 0.0001). Calf blood pooling was similar in the groups and was not correlated to the LTI (r = 0.204, P = 0.30). Venous compliance was significantly reduced at low venous pressures in women with VVS (P = 0.042) and correlated to the LTI (r = 0.459, P = 0.014) in the low pressure range. No correlation was found between venous compliance at high venous pressures and the LTI. In conclusion, the new VWM accurately adopted the curvilinear pressure-volume curve, providing a valid characterization of venous compliance. Reduced venous compliance at low venous pressures may adversely affect mobilization of peripheral venous blood to the central circulation during hypovolemic circulatory stress in women with VVS.

Calf venous compliance measured by venous occlusion plethysmography: methodological aspects.

PURPOSE: Calf venous compliance (C calf) is commonly evaluated with venous occlusion plethysmography (VOP) during a standard cuff deflation protocol. However, the technique relies on two not previously validated assumptions concerning thigh cuff pressure (P cuff) transmission and the impact of net fluid filtration (F filt) on C calf. The aim was to validate VOP in the lower limb and to develop a model to correct for F filt during VOP. METHODS: Strain-gauge technique was used to study calf volume changes in 15 women and 10 age-matched men. A thigh cuff was inflated to 60 mmHg for 4 and 8 min with a subsequent decrease of 1 mmHg s(-1). Intravenous pressure (P iv) was measured simultaneously. C calf was determined with the commonly used equation [Compliance = ß 1 + 2ß 2 × P cuff] describing the pressure-compliance relationship. A model was developed to identify and correct for F filt. RESULTS: Transmission of P cuff to P iv was 100 %. The decrease in P cuff correlated well with P iv reduction (r = 0.99, P < 0.001). Overall, our model showed that C calf was underestimated when F filt was not accounted for (all P < 0.01). F filt was higher in women (P < 0.01) and showed a more pronounced effect on C calf compared to men (P < 0.05). The impact of F filt was similar during 4- and 8-min VOP. CONCLUSIONS: P cuff is an adequate substitute for P iv in the lower limb. F filt is associated with an underestimation of C calf and differences in the effect of F filt during VOP can be accounted for with the correction model. Thus, our model seems to be a valuable tool in future studies of venous wall function.

Impact of stroke on cognition in old age: Comparison of two population-based cohorts, born up to 30 years apart and followed from age 70 to 85.

Little is known about birth cohort differences in the impact of stroke on cognitive aging. Given improved poststroke rehabilitation and better treatments for vascular health risk, we may expect a reduction in the stroke impact in later-born cohorts. We tested this prediction using data from two cohorts, born in 1901-1907 (n = 1,155) and 1930 (n = 919), identified from the same city population at the same age of 70 and subsequently measured on the same cognitive outcomes (i.e., spatial ability, perceptual-motor speed, and reasoning) at ages 70, 75, 79, and 85. We fitted multiple-group second-order latent growth curve models to the data, regressing the first-order cognitive factor on the time-varying stroke variable and controlling for relevant covariates. Findings revealed moderate to large average cognitive decline (d = -.45) following stroke, and the impact was relatively similar across cohorts (1901-1907: d = -.52; 1930: d = -.39). However, there was a stroke by age by cohort interaction, implying that the stroke impact increased with age in the 1901-1907 cohort (dage ≤ 75 = -.42; dage ≥ 79 = -.70) but decreased in the 1930 cohort (dage ≤ 75 = -.53; dage ≥ 79 = -.17). We found no evidence for lagged effect of stroke beyond the impact on measures following the incidence. Our hypothesis was only partially supported, as the impact of stroke was reduced in the later-born cohort but solely at higher ages. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

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.

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.

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.

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.