👤 Lars Palmqvist

Dementia is a growing public health concern, and although diet is a modifiable potential risk factor, the role of free sugar intake remains unclear. Excess sugar has been linked to metabolic and cardiovascular dysfunction, both associated with cognitive decline, but evidence regarding specific sugar sources is limited. This study aimed to investigate the associations between free sugar intake, its dietary sources, and the risk of all-cause dementia, Alzheimer's disease, and vascular dementia, and to assess potential modification by apolipoprotein E (APOE) ε4 status. We included 27,786 participants without dementia at baseline (mean age: 58 y; 61% females) from the Malmö Diet and Cancer Study, a population-based prospective cohort. Dietary intake was assessed using a validated diet history method. Dementia diagnoses were obtained from national registers and validated by memory clinic physicians. During a median follow-up of 25 y, 3224 participants (11.6%) were diagnosed with dementia. Free sugar intake was not significantly associated with all-cause dementia or Alzheimer's disease. However, a U-shaped association was observed for vascular dementia, with moderate intake (10%-12.5% of energy) associated with lower risk [hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.52, 0.95]. Sugar-sweetened beverage intake showed no association with dementia risk. High chocolate intake was associated with lower risks of all-cause [HR for quintile 5 (Q5) compared with Q1: 0.81; 95% CI: 0.72, 0.91] and vascular dementia (HR for Q5 compared with Q1: 0.68; 95% CI: 0.50, 0.92), whereas high jam/marmalade intake was linked to a lower risk of all-cause dementia (HR: 0.86; 95% CI: 0.77, 0.97 for >10 servings per week compared with <0.5 servings per week). No significant interactions with APOE ε4 status were observed. Free sugar intake was not associated with overall dementia risk, but moderate intake may reduce the risk of vascular dementia. These findings suggest that future dietary guidelines for cognitive health should consider not only sugar quantity but also its food source. Show less

The global prevalence of dementia is rapidly expanding and is expected to triple by 2050. Approximately 45 % of dementia cases are estimated to be attributable to potentially modifiable risk factors. Identifying how these factors contribute to specific brain pathologies may improve strategies to reduce dementia incidence. The aim of this study was to identify both non-modifiable and modifiable risk factors associated with longitudinal changes in white matter hyperintensities (WMH), amyloid-beta (Aβ) and tau. Data were acquired in the prospective observational Swedish BioFINDER-2 study between May 2017-January 2025. All participants underwent clinical assessments, questionnaires and at least two magnetic resonance imaging (MRI), Aβ Positron Emission Tomography (PET) and tau PET scans, respectively. Mixed-effects models were used to assess the associations between non-modifiable and modifiable risk factors and WMH (MRI), Aβ (PET) and tau (PET). A total of 494 cognitively unimpaired participants were included, of whom 365 were amyloid-negative (CU Aβ-) and 129 were amyloid-positive (CU Aβ+). Non-modifiable (age, apolipoprotein E (APOE) ɛ4 genotype and sex) and modifiable risk factors (co-morbidities at baseline, such as hypertension and cardiovascular disease, BMI, and sleep duration) were analyzed with mixed-effects models, adjusted for age and sex, to predict longitudinal measurements of WMH, Aβ and tau. Mean age was 64.8 (SD 13.3) years and mean follow-up was 3.9 (SD 1.5) years. Predictors represent baseline data, both predictors and outcomes are on standardized scales. Linear mixed-effects models, adjusted for age and sex, showed that higher blood pressure (β = 0.02, 95 % CI :0.01-0.02), presence of hyperlipidemia (β = 0.03, 0.01-0.05), ischemic heart disease (β = 0.06, 0.03-0.09), smoking (β = 0.02, 0.00-0.03) and lower education (β = -0.01, -0.02- -0.01) were associated with a longitudinal increase in WMH. Presence of the APOE ε4 allele was linked to faster Aβ accumulation (β = 0.03, 0.02-0.04) and tau (β = 0.01, 0.00-0.03), but only to Aβ among Aβ+ positive participants. Higher depression score (β = 0.01, 0.00-0.01) and diabetes (β = 0.02, 0.00-0.04) were associated with faster Aβ accumulation. Lower BMI was associated with faster accumulation of tau (β = -0.01, -0.02- -0.01). Modifiable risk factors of future dementia primarily affect accumulation of cerebral vascular pathology, although lower BMI was associated with tau accumulation and diabetes with Aβ accumulation. Show less

The association between dairy intake and dementia risk remains uncertain, especially for dairy products with varying fat contents. The aim of this study was to investigate the association between high-fat and low-fat dairy intake and dementia risk. This study used data from a prospective cohort in Sweden, the Malmö Diet and Cancer cohort, which consisted of community-based participants who underwent dietary assessment at baseline (1991-1996). Dietary intake was evaluated using a comprehensive diet history method that combined a 7-day food diary, a food frequency questionnaire, and a dietary interview. Dementia cases were identified through the Swedish National Patient Register until December 31, 2020, and cases diagnosed until 2014 were further validated. The primary outcome of the study was all-cause dementia, and the secondary outcomes were Alzheimer disease (AD) and vascular dementia (VaD). Cox proportional hazard regression models were used to estimate hazard ratio (HR) and 95% CI. This study included 27,670 participants (mean baseline age 58.1 years, SD 7.6; 61% female). During a median of 25 years of follow-up, 3,208 incident dementia cases were recorded. Consumption of ≥50 g/d of high-fat cheese (>20% fat) was associated with a reduced risk of all-cause dementia (HR 0.87; 95% CI, 0.78-0.97) and VaD (HR 0.71, 95% CI 0.52-0.96) compared with lower intake (<15 g/d). An inverse association between high-fat cheese and AD was found among Higher intake of high-fat cheese and high-fat cream was associated with a lower risk of all-cause dementia, whereas low-fat cheese, low-fat cream, and other dairy products showed no significant association. Show less

Minimal residual disease (MRD) in acute myeloid leukemia (AML) is of major prognostic importance. The genetic landscape of AML is characterized by numerous somatic mutations, which constitute potential MRD markers. Leukemia-specific mutations can be identified with exome sequencing at diagnosis and assessed during follow-up at low frequencies by using targeted deep sequencing. Our aim was to further validate this patient-tailored assay for substitution mutations. By applying a statistical model, which corrects for position-specific errors, a limit of detection for single nucleotide variations of variant allele frequency (VAF) of 0.02% was achieved. The assay was linear in MRD range (0.03% to 1%) with good precision [CV, 4.1% (2.2% to 5.7%) at VAF 1% and 13.3% (8.8% to 19.4%) at VAF 0.1%], and low relative bias [7.9% (2.5% to 15.3%) at VAF 1%]. When applied to six childhood AML cases and compared with multiparameter flow cytometry for MRD analysis, deep sequencing showed concordance and superior sensitivity. Further high concordance was found with expression of fusion transcripts RUNX1-RUNX1T1 and KMT2A-MLLT10. The deep sequencing assay also detected mutations in blood when VAF in bone marrow exceeded 0.1% (n = 19). In conclusion, deep sequencing enables reliable detection of low levels of residual leukemic cells. Introduction of this method in patient care will allow for highly sensitive MRD surveillance in virtually every patient with AML. Show less