Regression-based norms for the FAS phonemic fluency test for ages 40–84 based on a Norwegian sample

The FAS phonemic fluency test is a commonly used neuropsychological test of executive function and processing speed. Although Norwegian discrete norms have been developed for the FAS test, American regression-based norms are frequently used by clinicians in Norway. However, language and cultural differences impact performance on the FAS test, and using foreign norms may not be appropriate. Moreover, while discrete norming relies on stratified subgroups of demographics, regression-based norming uses the entire sample to estimate the influence of demographics on performance and may thus improve normative estimates. Here we develop regression-based norms for the FAS phonemic fluency test based on n = 204 healthy Norwegian controls between the ages 40−84 from the Norwegian Dementia Disease Initiation cohort (DDI). We compare the proposed regression norms to published Norwegian discrete norms and American regression-based norms in an independent sample of n = 182 cognitively healthy adults reporting subjective cognitive decline (SCD). We found that years of education was the only significant predictor of FAS performance in our normative sample, accounting for 14.9% of the variance. Both the proposed regression-based norms and previously published discrete norms adequately adjusted for demographics in the independent sample. In contrast, the American norms underestimated the effect of education and overestimated the effect of age. While both the proposed Norwegian regression norms and the previously published discrete norms are suitable for use in Norway, the proposed regression norms may be less vulnerable to sub-stratification sample characteristics posed by discrete norming procedures, and thereby improve normative estimation

Regression-based norms for the FAS phonemic fluency test for ages 40–84 based on a Norwegian sample

The FAS phonemic fluency test is a commonly used neuropsychological test of executive function and processing speed. Although Norwegian discrete norms have been developed for the FAS test, American regression-based norms are frequently used by clinicians in Norway. However, language and cultural differences impact performance on the FAS test, and using foreign norms may not be appropriate. Moreover, while discrete norming relies on stratified subgroups of demographics, regression-based norming uses the entire sample to estimate the influence of demographics on performance and may thus improve normative estimates. Here we develop regression-based norms for the FAS phonemic fluency test based on n = 204 healthy Norwegian controls between the ages 40−84 from the Norwegian Dementia Disease Initiation cohort (DDI). We compare the proposed regression norms to published Norwegian discrete norms and American regression-based norms in an independent sample of n = 182 cognitively healthy adults reporting subjective cognitive decline (SCD). We found that years of education was the only significant predictor of FAS performance in our normative sample, accounting for 14.9% of the variance. Both the proposed regression-based norms and previously published discrete norms adequately adjusted for demographics in the independent sample. In contrast, the American norms underestimated the effect of education and overestimated the effect of age. While both the proposed Norwegian regression norms and the previously published discrete norms are suitable for use in Norway, the proposed regression norms may be less vulnerable to sub-stratification sample characteristics posed by discrete norming procedures, and thereby improve normative estimation

Investigating the relationship between allocentric spatial working memory and biomarker status in preclinical and prodromal Alzheimer’s disease

The 4 Mountain Test (4MT) is a test of allocentric spatial working memory and has been proposed as an earlier marker of predementia Alzheimer’s disease (AD) than episodic verbal memory. We here compare the 4MT to the CERAD word list memory recall in both cognitively normal (CN) and mild cognitive impairment (MCI) cases with or without cerebrospinal fluid markers (CSF) of Alzheimer’s disease pathology. Linear regression was used to assess the influence of CSF determined Aβ-plaque (Aβ-/+) or neurofibrillary tau tangles (Tau-/+) on 4MT and CERAD recall performance. Analyses were performed in the full sample and the CN and MCI sub-samples. Pearson correlations were calculated to examine the relationship between 4MT and tests of psychomotor speed, verbal memory, cognitive flexibility, verbal fluency, and visuo-spatial perception. Analyses showed no significant differences in 4MT scores between Aβ-/Aβ+, nor Tau-/Tau + participants, irrespective of cognitive status. In contrast, CERAD recall scores were lower in both Aβ+ compared to Aβ- (p<.01), and Tau + compared to Tau- participants (p<.01) in the full sample analyses. There were no significant differences in CERAD recall performance between Aβ- vs. Aβ+ and Tau- vs. to Tau + in the in CN/MCI sub-samples. 4MT scores were significantly correlated with tests of psychomotor speed, cognitive flexibility, and visuo-spatial perception in the full sample analyses. In conclusion, the CERAD recall outperformed the 4MT as a cognitive marker of CSF determined AD pathology. This suggests that allocentric working memory, as measured by the 4MT, may not be used as an early marker of predementia AD.publishedVersio

Demographically adjusted Rey–Osterrieth Complex Figure Test norms in a Swedish and Norwegian cohort aged 49–77 years and comparison with North American norms

Introduction The Rey–Osterrieth Complex Figure Test (RCFT) is one of the most commonly used neuropsychological tests in Sweden and Norway. However, no publications provide normative data for this population. The objective of this study was to present demographically adjusted norms for a Swedish and Norwegian population and to evaluate these in an independent comparison group. Methods The RCFT was administrated to 344 healthy controls recruited from the Swedish Gothenburg MCI study, the Norwegian Dementia Disease Initiation study, and the Swedish Cardiopulmonary Bioimage Study. Age ranged from 49 to 77 years (mean = 62.4 years, SD = 5.0 years), and education ranged from 6 to 24 years (mean = 13.3 years, SD = 3.0 years). Using a regression-based procedure, we investigated the effects of age, sex, and years of education on test performance. We compared and evaluated our Swedish and Norwegian norms with North American norms in an independent comparison group of 145 individuals. Results In healthy controls, age and education were associated with performance on the RCFT. When comparing normative RCFT performance in an independent comparison group, North American norms generally overestimated immediate and delayed recall performance. In contrast, our Swedish and Norwegian norms appear to better take into account factors of age and education. Conclusions We presented demographically adjusted norms for the RCFT in a Swedish and Norwegian sample. This is the first normative study of the RCFT that presents normative data for this population. In addition, we showed that North American norms might produce inaccurate normative estimations in an independent comparison group

Regression-based normative data for the D-KEFS Color-Word Interference Test in Norwegian adults ages 20–85

Objective: The Delis-Kaplan Executive Function System (D-KEFS) Color-Word-Interference Test (CWIT; AKA Stroop test) is a widely used measure of processing speed and executive function. While test materials and instructions have been translated to Norwegian, only American age-adjusted norms from D-KEFS are available in Norway. We here develop norms in a sample of 1011 Norwegians between 20 and 85 years. We provide indexes for stability over time and assess demographic adjustments applying the D-KEFS norms. Method: Participants were healthy Norwegian adults from Center for Lifespan Changes in Brain and Cognition (LCBC) (n = 899), the Dementia Disease Initiation (n = 77), and Oslo MCI (n = 35). Using regression-based norming, we estimated linear and non-linear effects of age, education, and sex on the CWIT 1-4 subtests. Stability over time was assessed with intraclass correlation coefficients (ICC). The normative adjustment of the D-KEFS norms was assessed with linear regression models. Results: Increasing age was associated with slower completion on all CWIT subtests in a non-linear fashion (accelerated lowering of performance with older age). Women performed better on CWIT-1&3. Higher education predicted faster completion time on CWIT-3&4. The original age-adjusted norms from D-KEFS did not adjust for sex or education. Furthermore, we observed significant, albeit small effects of age on all CWIT subtests. ICC analyses indicated moderate to good stability over time. Conclusion: We present demographically adjusted regression-based norms and stability indexes for the D-KEFS CWIT subtests. US D-KEFS norms may be inaccurate for Norwegians with high or low educational attainment, especially women

Regression‐based normative data for the Rey Auditory Verbal Learning Test in Norwegian and Swedish adults aged 49–79 and comparison with published norms

Objective: The Rey Auditory Verbal Learning Test (RAVLT) is a widely used measure of episodic verbal memory. To our knowledge, culturally adapted and demographically adjusted norms for the RAVLT are currently not available for Norwegian and Swedish adults, and imported North American norms are often used. We here develop regression-based norms for Norwegian and Swedish adults and compare our norms to North American norms in an independent sample of cognitively healthy adults. Method: Participants were 244 healthy adults from Norway and Sweden between the aged 49 and 79years, with between 6 and 24years of education. Using a multiple multivariate regression-based norming procedure, we estimated effects of age, sex, and years of education on basic and derived RAVLT test scores. The newly developed norms were assessed in an independent comparison group of cognitively healthy adults (n=145) and compared to recently published North American regression-based norms. Results: Lower age, female sex and more years of education predicted higher performance on the RAVLT. The new norms adequately adjusted for age, education, and sex in the independent comparison group. The American norms corrected for demographics on all RAVLT trials except trials 4, 7, list B, and trials 1–5 total. Test-retest (M=2.55 years) reliability varied from poor to good. Conclusion: We propose regression-based norms for the RAVLT adjusting for pertinent demographics. The norms may be used for assessment of Norwegian and Swedish adults between the aged of 49 and 79years, with between 6 and 24years of education

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

International audienceAbstract Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 )