👤 Peer Grande

The apolipoprotein E (APOE) ε4 allele increases Alzheimer disease risk. Understanding genotype-specific dietary needs could inform more personalized prevention strategies. To test the hypothesis that higher meat consumption may be associated with cognitive health benefits in individuals with APOE genotypes ε3/ε4 and ε4/ε4 (APOE34/44) and to examine whether this association differs from that in other genotypes. This population-based cohort study used panel data analyses conducted in January 2025 to January 2026 over 15 years of follow-up in the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), using strategies aligned with causal inference principles. Recruitment was done in 2001 to 2004 among adults without dementia aged 60 years or older. The primary exposure was total meat consumption in grams per total kilocalories assessed via validated food frequency questionnaires. The secondary exposure was the ratio of processed to total meat. Global cognitive trajectory, measured as change in z score per 10 years, was analyzed by linear regression. Incident dementia was analyzed using Fine and Gray subdistribution hazard ratios (sHRs), treating nondementia death as a competing risk. Among 2157 older adults without dementia (mean [SD] age 71.2 [9.2] years; 1337 female [62.0%]), 1680 participants had longitudinal cognition data and 569 participants (26.4%) had APOE34/44 genotypes. During follow-up, 296 participants developed dementia and 690 died without dementia. Among participants with APOE34/44 genotypes, higher total meat consumption (top vs bottom quintile) was associated with better cognitive trajectories (β = 0.32; 95% CI, 0.07 to 0.56; P = .01) and reduced dementia risk (sHR, 0.45; 95% CI, 0.21 to 0.95; P = .04). No associations were found in participants with APOE22/23/24/33 genotypes (cognitive trajectory: β = -0.11; 95% CI, -0.27 to 0.06; P = .20; dementia: sHR, 0.95; 95% CI, 0.57 to 1.61; P = .86). P values for APOE interaction were .004 for cognition and .10 for dementia. In the top quintile of meat consumption, dementia risk and cognitive decline were similar between APOE strata. A higher ratio of processed to total meat was unfavorably associated with dementia (sHR, 1.14; 95% CI, 1.01 to 1.29; P = .04), showing no APOE interaction and no substantial difference between unprocessed red meat and poultry. Post hoc analyses suggested concordant APOE interaction for all-cause mortality (unprocessed meat exposure, APOE34/44: HR, 0.85; 95% CI, 0.73 to 0.99; P = 0.04; P for interaction = .03). In this study, higher meat consumption was associated with better cognitive trajectories and lower dementia risk among individuals with APOE34/44 genotypes. The expected cognitive disadvantage among individuals with APOE34/44 genotypes was not observed at high meat consumption, suggesting clinical and public health relevance. Show less

Olfactory impairment is common in older age and is a known early feature of several dementia diseases. Blood-based biomarkers of Alzheimer's disease (AD) now offer a scalable method for detecting pathophysiological mechanisms related to olfactory decline in the general population. However, few studies have examined how these biomarkers relate to long-term olfactory trajectories. Most existing work has been limited to cross-sectional settings. In this population-based study, we used biomarker data collected at baseline and followed participants for up to 15 years, enabling us to test whether early biological changes are temporally linked to subsequent olfactory decline. Data came from the ongoing Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal population-based study with baseline assessments from March 21, 2001, through August 30, 2004. We included participants without prevalent neurodegenerative diseases who completed olfactory assessment at baseline. The 15-year follow-up was finished in December 2019. Data were analysed from December 2023 to April 2024. Serum-derived biomarkers of tau phosphorylated at threonine 217 (p-tau217) and at theorine181 (p-tau181), total tau (t-tau), amyloid-β ratio (Aβ42/Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were obtained at baseline. Linear mixed models examined associations between biomarker quartiles and Sniffin' Sticks odor identification performance over 15 years, adjusting for demographics, health conditions, and semantic knowledge. We included 1868 participants (mean [SD] age 71.3 [9.9] years; 1122 females [60.1%]). In fully adjusted models, higher quartiles of p-tau217, p-tau181, NfL, and GFAP, and lower quartiles of Aβ42/Aβ40, were associated with steeper olfactory decline, with the steepest decline among participants in the highest quartiles (β for Q4 vs Q1: -0.20 [95% CI: -0.26 to -0.15] for p-tau217; -0.19 [95% CI: -0.25 to -0.13] for p-tau181; -0.23 [95% CI: -0.29 to -0.17] for NfL; β = -0.17 [95% CI: -0.23 to -0.11] for GFAP. Participants in the lowest Aβ42/Aβ40 quartile declined more steeply than those in the highest (β = -0.09 [95% CI: -0.14 to -0.04]). Associations appeared stronger in the oldest participants, in APOE ε4 carriers for p-tau181, in non-carriers for NfL and GFAP, and among former smokers for NfL. Blood-based biomarkers of AD were consistently associated with faster olfactory decline in older adults, particularly in the highest biomarker quartiles. These results provide large-scale longitudinal evidence, across up to 15 years of follow-up, that olfactory decline in the general population is linked to AD-related blood biomarkers, supporting the hypothesis that common olfactory losses in ageing partly reflect dementia-related processes. Show less

To establish typical clinical and radiological profiles of primary low-grade parotid cancers in order to tailor therapeutic strategy. Retrospective study of 57 patients operated on for primary parotid cancer between 2010 and 2021, with review of preoperative MRI and histopathology according to a standardized scoring grid. To study prognostic factors and determine the preoperative clinical and radiological profile of low-grade cancers. Good prognostic factors for specific survival were: staging ≤ cT3 (p = 0.014), absence of adenopathy on cN0 MRI (p < 0.001), superficial lobe location (p = 0.033), pN0 (p < 0.001), absence of capsular rupture (p = 0.004), as well as the absence of peri-tumoral nodules (p = 0.033), intra-parotid adenopathies (p < 0.001), vascular emboli (p < 0.001), peri-neural sheathing (p = 0.016), nuclear atypia (p = 0.031), and necrosis (p = 0.002). It was not possible to define a reliable clinical and radiological profile for low-grade cancers (sensitivity 38%, specificity 79%). Our study demonstrated multiple factors of good prognosis, but it was not possible to define a clinical and radiological profile of patients likely to benefit from more limited surgery, nor to diagnose, a priori, low-grade cancers. Show less

In patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis. We conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared. Our study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger ( The prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive. Show less

Elevated non-fasting triglycerides mark elevated levels of remnant cholesterol. Using a Mendelian randomization approach, we tested whether genetically increased remnant cholesterol in hypertriglyceridaemia due to genetic variation in the apolipoprotein A5 gene (APOA5) associates with an increased risk of myocardial infarction (MI). We resequenced the core promoter and coding regions of APOA5 in individuals with the lowest 1% (n = 95) and highest 2% (n = 190) triglyceride levels in the Copenhagen City Heart Study (CCHS, n = 10 391). Genetic variants which differed in frequency between the two extreme triglyceride groups (c.-1131T > C, S19W, and c.*31C > T; P-value: 0.06 to <0.001), thus suggesting an effect on triglyceride levels, were genotyped in the Copenhagen General Population Study (CGPS), the CCHS, and the Copenhagen Ischemic Heart Disease Study (CIHDS), comprising a total of 5705 MI cases and 54 408 controls. Genotype combinations of these common variants associated with increases in non-fasting triglycerides and calculated remnant cholesterol of, respectively, up to 68% (1.10 mmol/L) and 56% (0.40 mmol/L) (P < 0.001), and with a corresponding odds ratio for MI of 1.87 (95% confidence interval: 1.25-2.81). Using APOA5 genotypes in instrumental variable analysis, the observational hazard ratio for a doubling in non-fasting triglycerides was 1.57 (1.32-2.68) compared with a causal genetic odds ratio of 1.94 (1.40-1.85) (P for comparison = 0.28). For calculated remnant cholesterol, the corresponding values were 1.67(1.38-2.02) observational and 2.23(1.48-3.35) causal (P for comparison = 0.21). These data are consistent with a causal association between elevated levels of remnant cholesterol in hypertriglyceridaemia and an increased risk of MI. Limitations include that remnants were not measured directly, and that APOA5 genetic variants may influence other lipoprotein parameters. Show less