Canadian Journal of Neurological Sciences最新文献

Background: Emerging evidence suggests that metabolic and hormonal disturbances in polycystic ovary syndrome (PCOS) may increase vulnerability to neurodegenerative disorders. However, the link between PCOS and Alzheimer's disease (AD)-related pathology remains unclear.

Methods: In this cross-sectional study, plasma levels of β-amyloid (Aβ₄₀, Aβ₄₂), phosphorylated tau (p-tau181), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified in women with PCOS and age-matched controls. Homeostasis model assessment of insulin resistance (HOMA-IR), inflammatory cytokines (IL-6, TNF-α) and hormonal parameters were assessed. Mediation and moderation analyses were conducted to explore metabolic and hormonal pathways underlying biomarker alterations.

Results: Among 400 women (200 PCOS, 200 controls), age and BMI were comparable (P > 0.05). Compared with controls, PCOS participants had increased Aβ₄₀, p-tau181, NfL and GFAP, a slightly higher Aβ₄₂, and a lower Aβ₄₂/₄₀ ratio (all P < 0.05). p-tau181 correlated positively with HOMA-IR (r = 0.41) and IL-6 (r = 0.36), while Aβ₄₂/₄₀ ratio correlated negatively with HOMA-IR (r = -0.27). In multivariable analysis, p-tau181 (aOR = 1.34, 95% CI 1.05-1.71), IL-6 (aOR = 1.19) and TNF-α (aOR = 1.14) were independent predictors of insulin resistance. Mediation analysis indicated that HOMA-IR, IL-6 and TNF-α jointly mediated ∼ 71% of the PCOS-p-tau181 association, suggesting a metabolic-inflammatory pathway linking PCOS to AD-related tau pathology.

Conclusions: PCOS is linked to peripheral markers of early Alzheimer's pathology, largely mediated by insulin resistance and inflammation. PCOS may provide a clinical context to explore metabolic-inflammatory contributors to early neurodegenerative changes.

Background: Timely access to endovascular treatment (EVT) for ischaemic stroke patients is critical for optimal outcomes, but Canada's size and population distribution create barriers to access. EVT is mostly available in tertiary centres located in large urban cities, and patients that arrive at intravenous thrombolysis (IVT)-only stroke centres need to be transferred for EVT.

Methods: Geographic modelling of access to an IVT-only centre and an EVT-capable centre was conducted for Canada. Canada was divided into small grid sections. Drive times from the centre of each grid section to the closest stroke centres and the population of each grid section were obtained. The onset to paramedic arrival time and on-scene time were assumed to be 30 and 30 minutes, respectively. In the suboptimal and optimal scenarios, the door-in-door-out (DIDO) times were 150 minutes and 45 minutes, respectively. The poor access regions and population were calculated for onset to thrombolysis at 4.5 hours and to EVT-capable centre arrival for EVT within 6 and 3 hours.

Results: The results show 99.37% of the population having access to thrombolysis within 4.5 hours. However, with a suboptimal DIDO time, 13.6% (5.2 million people) and 42.7% (16.2 million people) do not have access to EVT within 6 and 3 hours, respectively. With an efficient DIDO time, an additional 5.6% (2.1 million people) and 15.7% (6.0 million people) have access to EVT within 6 and 3 hours, respectively.

Conclusion: There is an imperative to reduce DIDO times to an ambitious median of 45 minutes to ensure optimal access to EVT across Canada.