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2 Minute Medicine Rewind March 9, 2026
Sex-Specific Associations of α-Synuclein Pathology With Tau Accumulation
1. α-synuclein pathology was associated with faster tau accumulation in women than men.
Evidence Rating Level: 2 (Good)
Sex differences play an important role in Alzheimer’s disease, as women often show greater tau burden and faster cognitive decline than men. Although misfolded α-Synuclein frequently occurs in Alzheimer’s disease, it is unclear whether this copathology is differentially associated with disease progression by sex. This study thus examined whether α-synuclein pathology is differentially associated with tau accumulation in women and men across the Alzheimer’s disease continuum. This cohort study used data from the Alzheimer’s Disease Neuroimaging Initiative collected between 2015 and 2023 and included participants who were cognitively unimpaired or cognitively impaired (mild cognitive impairment or dementia) at baseline. Cerebrospinal fluid α-synuclein status was determined by cerebrospinal fluid seed amplification assay (SAA) and dichotomized as SAA negative or SAA positive. The primary outcome was tau burden measured as standardized uptake value ratio (SUVr) in the medial temporal composite region of interest from positron emission tomography (PET) imaging. In total, 415 participants were included (mean [SD] age, 72.3 [7.6] years; 220 women [53%]; 69 SAA positive [17%] and 346 SAA negative [83%]), with a median (IQR) follow-up of 1.23 (0.00-3.84) years. A 3-way interaction was found between SAA status, sex, and time on tau accumulation (β, 0.061; 95% CI, 0.030-0.093; P < .001), indicating that the rate of tau accumulation over time differed by both SAA status and sex. Tau accumulation was fastest for women with positive SAA compared with other groups (0.066 SUVr per year; 95% CI, 0.043 to 0.089 SUVr per year). Overall, this study found that α-synuclein pathology was associated with faster tau accumulation in women than men, highlighting the importance of sex-specific interpretation of α-synuclein biomarkers in Alzheimer’s disease.
Ultraprocessed Food Consumption and Behavioural Outcomes in Canadian Children
1. Higher ultra-processed food consumption in children at age 3 was associated with adverse behavioural and emotional symptoms at age 5.
Evidence Rating Level: 2 (Good)
UPF has been linked to adverse health outcomes, behaviour, and mental health outcomes in adults and adolescents. The relationship between UPF intake and behavioural development during early childhood is unclear. This study thus examined the associations between preschool UPF intake and behavioural outcomes. This prospective cohort study analyzed data from the CHILD Cohort Study between September 2011 to April 2018. Canadian children from singleton births, gestational age of at least 34 weeks and 4 days, and who had no congenital abnormalities were included. UPF uptake was assessed at age 3 years by a 112-item food frequency questionnaire. The primary outcome, behaviour, was assessed at age 5 years using the Child Behaviour Checklist (CBCL; range 0-100; higher scores indicating more adverse symptoms). The total behaviour scale included questions from the internalizing scale that captured inward-focused behaviour (e.g., anxiety, fearfulness, and depression), and the externalizing scale that captured outward-directed behaviour (e.g., aggression, hyperactivity). In total, 2,077 participants were included (1,0921 male [52.6%]; 1,376 White [66.2%], 480 multiracial [23.1%], 221 another ethnic group [10.7%]). At age 3 years, UPF accounted for a mean (SD) of 45.5% (11.6%) of total energy intake. The main UPF subgroups contributing to energy were sweets and desserts (12.5%), breads and cereals (11.9%), animal-based products (7.9%), and ready-to-eat or ready-to-heat mixed dishes (6.1%). At age 5 years, every 10% increase in energy contribution from UPF was independently associated with higher CBCL internalizing (β = 0.81 [95% CI, 0.43 to 1.19]), externalizing (β = 0.47 [95% CI, 0.08 to 0.87]), and total (β = 0.64 [95% CI, 0.27 to 1.01]) scores. Overall, this study found that higher UPF intake at age 3 years was associated with adverse behavioural and emotional symptoms at age 5 years, highlighting the importance of early-life dietary interventions and policies to support healthy behavioural development.
1. Lower preoperative serum calcium levels were associated with a higher risk of postoperative complications in older orthopedic patients.
Evidence Rating Level: 2 (Good)
As the incidence of orthopedic diseases and demand for surgery among older adults are increasing, reducing the occurrence of orthopedic surgical complications is becoming increasingly important. Serum calcium plays a crucial role in maintaining physiological functions such as muscle contraction, nerve conduction, blood coagulation, and cell signalling. Hypocalcemia has been linked with postoperative morbidity and mortality. However, research on the use of serum calcium as a prognostic indicator in orthopedic surgery is lacking. This study thus assessed the ability of preoperative serum calcium levels to predict the occurrence of postoperative complications in geriatric orthopedic surgery. This prospective cohort study from December 20th, 2023, to April 24th, 2025, included orthopedic surgery patients aged >60 years in China, who were followed up for three months postoperatively. Serum calcium levels were classified into three groups: low (1.82–2.19 mmol/L), medium (2.19–2.32 mmol/L), and high (2.32–2.75 mmol/L). The primary outcome was postoperative complications. In total, 690 patients were included, with 230 in the low serum calcium group (mean [SD] age, 70.7 [7.3]; 116 female [50.4%]), 221 in the middle group (mean [SD] age, 70.7 [7.3]; 79 female [35.7%]), and 239 in the high group (mean [SD] age, 68.1 [6.3]; 85 female [35.6%]). Postoperative complications occurred in 101 patients (43.9%) in the low group, 74 (33.5%) in the medium group, and 64 (26.8%) in the high group. For every 1 mmol/L increase in blood preoperative serum calcium level, the odds of postoperative complications decreased by 76% (OR: 0.24, CI: 0.07–0.76). Compared to the high calcium group, patients in the low serum calcium group had a 79% higher risk of complications (OR = 1.79, 95% CI: 1.12–2.78). A nonlinear association was found between serum calcium levels and postoperative complications, with the inflection point at 2.4 mmol/L, below which lower serum calcium levels were associated with increased risk of complications. Overall, this study found that lower preoperative serum calcium levels were associated with a higher risk of postoperative complications, with levels below 2.4 mmol/L potentially indicating a poorer prognosis. These findings highlight the importance of preoperative calcium screening and correction to mitigate postoperative complications.
1. Six weeks of visual perturbation training reduced visual dependency and improved temporal gait characteristics to a greater extent than treadmill training alone in people with early-stage Parkinson’s disease.
Evidence Rating Level: 1 (Excellent)
Visual dependency is defined as a “reduced ability to disregard visual cues in complex or conflicting visual environments”. Decreased gait automaticity and increased visual dependency may increase the risk of falls in people with Parkinson’s disease (PwPD). However, there is a lack of research on rehabilitation training to decrease visual dependency and its effects on gait and fall risk in PD. This study thus assessed if visual perturbation training during treadmill walking decreases visual dependency in PwPD and improves spatiotemporal gait characteristics. This randomized controlled trial included adults aged 50-67 years with early-to-mid-stage idiopathic PD in Belgium. Participants were randomly assigned 1:1 to the visual perturbation group or the treadmill training-only control group. Both groups trained twice/week for six weeks. Visual perturbation training consisted of self-paced treadmill walking with perturbations applied as tilting (rotations around the sagittal axis) and horizon shifts (medio-lateral translations) of a virtual reality environment. The primary outcome was visual dependency. Secondary outcomes included steady-state spatiotemporal gait parameters (gait speed, step time/length/width/frequency, and cadence), and self-reported (near) falls. In total, 25 participants completed the study, with 11 in the VPT group (mean [SD] age, 60.00 [4.93], 12 male [86%]) and 14 in the control group (mean [SD] age, 61.36 [4.82], 8 male [73%]). Compared to the treadmill-only control group, the visual perturbation training group had decreased visual dependency (interaction p < 0.001) and improved temporal gait characteristics such as step time (p = 0.012), stride time (p = 0.021) and cadence (p = 0.018). No significant effects were found for step width, step length, gait speed, and (near) falls. Overall, this study found that VPT reduced visual dependency and improved temporal gait characteristics to a greater extent than treadmill training alone in people with early-stage PD. These findings highlight the potential of VPT as a rehabilitation approach to reduce fall risk in PwPD.
1. Use of glucagon-like peptide-1 (GLP-1) receptor agonists was associated with reduced risk of developing substance use disorders among US veterans with type 2 diabetes.
Evidence Rating Level: 2 (Good)
Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with reduced risks of incident substance use disorders (SUDs) such as alcohol use and incident cannabis use disorder. However, the link between GLP-1 receptor agonists and risks of other SUDs, such as opioid use disorder and stimulant use disorder are unclear. This study thus investigated the relationship between initiation of GLP-1 receptor agonists and risk of incident SUDs across a range of substances in people with no history of SUDs. This cohort study emulated a set of eight parallel, new user target trials using the US Department of Veterans Affairs electronic health records and included veterans aged >18 and a diagnosis of type 2 diabetes. Participants were assigned to one of the two protocols: people without pre-existing SUD in protocol 1 and people with pre-existing SUD in protocol 2. For both protocols, treatment strategies of initiating a GLP-1 receptor agonist versus a sodium-glucose cotransporter-2 (SGLT-2) inhibitor were compared. Patients were followed for up to three years. The main outcomes of incident SUDs were alcohol, cannabis, cocaine, nicotine, opioid, other SUDs, and a composite of these outcomes. Out of the 524,817 participants included in Protocol 1, 124,001 initiated GLP-1 receptor agonists and or 400,816 initiated SGLT-2 inhibitors. Out of the 81,617 participants included in Protocol 2, 16,768 initiated GLP-1 receptor agonists, and 64,849 initiated SGLT-2 inhibitors. Compared with initiation of SGLT-2 inhibitors, initiation of GLP-1 receptor agonists was associated with 18% lower risk of alcohol use disorders (hazard ratio [HR], 0.8295%; 95% CI, 0.78 to 0.85), 14% lower risk of cannabis use (HR, 0.86; 95% CI, 0.81 to 0.90), 20% lower risk of cocaine use (HR, 0.80; 95% CI, 0.72 to 0.88), 20% lower risk of nicotine use (HR, 0.80; 95% CI, 0.74 to 0.87), 25% lower risk of opioid use (HR, 0.75; 95% CI, 0.67 to 0.85), 13% lower risk of other SUDs (HR, 0.87; 95% CI, 0.81 to 0.94), and 14% lower risk of composite outcome of all incident SUDs (HR, 0.86; 95% CI, 0.83 to 0.88). Overall, this study found that initiating GLP-1 receptor agonists was associated with reduced risk of developing various SUDs, highlighting its potential in the prevention of SUDs.
Image: PD
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