Lin, Michelle

Background Studies suggest that hypoperfusion from heart failure (HF) may contribute to cognitive decline. However, the relationship between the HF subtypes and cognition remains poorly described in real‐world populations. Methods We conducted a cross‐sectional study of patients aged ≥18 years seen at the Mayo Clinic in 2022 who underwent echocardiogram and cognitive assessment within 1 year. HF was classified per the 2022 American Heart Association as no HF, HF with preserved ejection fraction (EF), HF with mildly reduced EF, and HF with reduced EF. Cognitive impairment was categorized using the Montreal Cognitive Assessment score as normal (≥26), mild (18–25), and moderate to severe (<18). Linear regression assessed EF–Montreal Cognitive Assessment correlation and logistic regression the association between HF subtypes and cognitive dysfunction, adjusting for age, sex, race, and vascular risk factors. Results A total of 1592 patients met inclusion criteria (mean age, 75.7±13.8 years; 48.5% women). Lower EF was associated with worse cognitive performance (postadjustment β=0.033, P =0.013). Patients with HF with reduced EF and patients with HF with preserved EF had significantly lower Montreal Cognitive Assessment scores than those without HF (17.6±6.2 and 18.9±5.8 versus 19.9±6.0, P <0.001). The prevalence of moderate to severe cognitive impairment was highest in HF with reduced EF (43.3%), followed by HF with preserved EF (34.4%), no heart failure (28.6%), and HF with mildly reduced EF (23.4%) (adjusted trend P =0.032). Conclusions HF, independent of ejection fraction alone, is associated with cognitive impairment. Further studies should confirm these findings and evaluate the impact of interventions targeting EF and HF subtypes on cognitive outcomes.

The effect of induced hypertension (iHTN) on functional outcomes in noncardioembolic acute ischemic stroke (AIS) with early neurological deterioration remains unclear. We performed a systematic review and meta-analysis evaluating the safety and efficacy of iHTN vs medical management. A literature search of PubMed/MEDLINE, Web of Science, Ovid Embase, and Scopus from inception through November 6th, 2025. The protocol was registered in PROSPERO (CRD420261282211). Studies evaluating iHTN within 72 h of AIS onset and reporting 90-day functional independence (modified Rankin Scale [mRS] 0-2) were included. Safety outcome was hemorrhagic transformation. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects model based on Restricted Maximum-Likelihood (REML) methods. Three studies were included, comprising 366 patients (iHTN, n = 180; control, n = 186). Mean age was 65.8 ± 11.8 years, 60.9% were men, and the mean initial NIHSS was 5.4 ± 3.5. Target systolic blood pressure (SBP) was a 15-25% increase from baseline SBP using phenylephrine. Functional independence at 90-days occurred more often in the iHTN group than in controls (68.8% vs 50.5%; RR = 1.37; 95% CI, 1.09-1.73; P = 0.007). Hemorrhagic transformation was uncommon and did not differ significantly between groups (3.3% vs 0.5%; RR = 2.08; 95% CI, 0.05-88.07; P = 0.70). In our study, phenylephrine-induced hypertension was associated with greater 90-day functional independence in selected AIS subtypes,without a significant increase in hemorrhagic transformation. However, the limited studies, predominance of retrospective designs, exclusively Asian cohorts, and heterogeneity in treatment protocols and populations warrant cautious interpretation and underscore the need for larger multicenter RCTs.

Objectives: This study aims to identify retinal biomarkers of NOTCH3 mutation carriers using optical coherence tomography (OCT) data from the UK Biobank. Methods: We conducted a cross-sectional, matched case-control study of individuals with or without NOTCH3 mutation from the UK Biobank between 2006 and 2010. All participants had macular OCT scan and cognitive assessment. Cases were identified based on pathogenic/likely pathogenic NOTCH3 mutations and 1:1 matched with controls based on age, sex, hypertension, diabetes mellitus, and cigarette smoking status. Baseline characteristics and cognitive test scores were compared using χ 2 or Mann-Whitney U test appropriately. Macular thickness at central, inner, and outer subfields and at each retinal layer was compared using Wilcoxon signed-rank test. Results: Our analysis included 134 participants (67 cases, 67 controls) with a mean age of 54 ± 9 years. NOCTH3 mutation carriers performed worse in prospective memory ( P =0.043), verbal and numerical reasoning ( P =0.178), visual memory ( P =0.227), and processing speed ( P =0.101) than matched controls. There were no differences in visual acuity between the 2 groups. NOTCH3 mutation carriers had significantly thinner macular inner subfield at the superior ( P =0.006), temporal ( P =0.008), and nasal ( P =0.034) quadrants, and significantly thinner macular RNFL ( P =0.008) compared with age-, sex-, and vascular risk factor-matched controls. Conclusion: The presence of NOTCH3 mutation is associated with reduced thickness in the inner macular subfield and macular RFNL. These retinal changes may reflect early pericyte dysfunction and microvascular ischemia. Longitudinal studies are needed to assess the temporal relationship between these retinal changes, cerebrovascular disease progression, and clinical severity of disease.

Background: The management of asymptomatic high-grade carotid stenosis remains challenging, particularly in identifying individuals at highest risk for hypoperfusion-related stroke. Impaired cerebrovascular reactivity (CVR) has emerged as a potential predictor of future cerebrovascular events. Objective: To perform a systematic review and meta-analysis to quantify the association between impaired CVR and the risk of ipsilateral ischemic stroke or TIA in patients with asymptomatic high-grade carotid stenosis/occlusion. Methods: A systematic literature search of PubMed, Embase and Scopus was conducted from inception till July 2025. Eligible studies included asymptomatic patients with ≥70% carotid stenosis or occlusion who underwent CVR assessment and reported ipsilateral ischemic stroke or TIA outcomes. Pooled relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Forest plots were generated, and heterogeneity was assessed using the chi-square test and the I 2 statistic. Results: Six prospective observational studies including a total of 361 patients with asymptomatic high-grade carotid stenosis/occlusion (mean age 70.4 years; 73.6% male; 71.2% with hypertension; 28.6% with diabetes; 29.6% current or former smokers) were included in the analysis. Of these, 120 patients had impaired CVR and 241 had preserved CVR. Transcranial Doppler (TCD) was the most frequently used modality to assess CVR, with acetazolamide or CO 2 as the vasodilatory stimulus. Following CVR assessment, patients were monitored for a weighted mean follow-up of 26.2 months (range: 21.5 to 42.5 months). The incidence of ipsilateral ischemic stroke or TIA was 14.2% in patients with impaired CVR versus 2.1% in those with preserved CVR (RR 3.98; 95% CI 1.62–9.76; P = 0.003; Figure 1). When limited to ipsilateral ischemic stroke alone, the incidence was 21.4% in the impaired CVR group compared to 4.3% in the preserved CVR group (RR 3.35; 95% CI 1.54–7.25; P = 0.002; Figure 2). Conclusions: Impaired CVR is associated with a 3- to 4-fold increased risk of ipsilateral ischemic stroke or TIA in patients with high-grade carotid stenosis/occlusion. CVR assessment may help stratify risk and guide individualized management in this population.

Background: Previous studies have reported the mean difference in homocysteine level in patients with and without silent brain infarction. However, evidence regarding the rate of silent brain infarcts in the presence versus absence of hyperhomocysteinemia remains limited. Objective: We aim to perform a systematic review and meta-analysis to compare the rate of silent brain infarcts in patients with hyperhomocysteinemia compared with patients with normal or low homocysteine levels. Methods: A systematic search of PubMed, Embase, Web of Science, Scopus were searched from inception to June 18, 2025. Eligible studies compared the rate of image-confirmed silent brain infarcts in patients with hyperhomocysteinemia versus those with normal homocysteine levels. The primary outcome was the rate of silent brain infarcts; the secondary outcome was cognition assessed by the Mini-Mental State Examination (MMSE). Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model, and heterogeneity was assessed using I 2 statistics. Subgroup analyses were performed according to increasing hyperhomocysteinemia cutoffs (>12 μmol/L and 9–12 μmol/L) as defined in the included the studies. Results: Four observational studies involving 2331 patients were included (mean age was 58.0±6.4 years, 45.8% women). Of these, 1087 had hyperhomocysteinemia and 1244 had normal levels. The rate of silent brain infarcts was 23.3% (253/1087) in patients with hyperhomocysteinemia versus 22.8% (284/1244) in controls (OR 1.82; 95% CI 1.11-3.00; P = 0.02, Figure 1A). The association was higher in studies using a > 12 µmol/L cutoff (OR 3.08; 95% CI 1.85-5.11; P < 0.0001, Figure 1B). Patients with hyperhomocystinemia had lower MMSE score compared with controls (mean difference of -1.55; 95% CI -3.60-0.50; P = 0.14, Figure 2). Conclusions: Hyperhomocysteinemia is associated with increased risk of silent brain infarcts and numerically lower cognitive performance. Findings suggest a possible dose-dependent relationship between homocysteine level and silent stroke risk. Prospective studies are needed to determine whether homocysteine is a modifable therapeutic tharget for reducing silent infarcts and cognitive decline.

Introduction: Studies suggest that stroke and hypoperfusion from heart failure (HF) may contribute to cognitive decline. However, the relationship between the HF subtypes and cognition remains poorly described in real-world populations. Hypothesis: We hypothesized that HF subtypes are differentially associated with cognitive impairment and that lower left ventricular ejection fraction (LVEF) correlates with poorer cognitive performance. Methods: We conducted a cross-sectional study of patients aged ≥18 years seen at a Heath System in 2022 who underwent both echocardiogram and cognitive assessment within one year. HF was classified into four groups based on 2022 American Heart Association HF guideline: No heart failure, HFpEF (HF with preserved LVEF), HFmrEF (HF with mid-range LVEF), and HFrEF (HF with reduced LVEF). Cognitive impairment was categorized using the Montreal Cognitive Assessment (MOCA) as normal (≥26), mild (18–25), moderate (10–17), and severe (<10). Multivariable linear regression assessed the correlation between EF and MoCA, and logistic regression evaluated the association between HF subtypes and severity of cognitive loss, adjusting for age, sex, race, hypertension, diabetes, dyslipidemia, chronic kidney disease, stroke. Results: A total of 1,695 patients were included in the study (mean age, 75.3±14 years; 48.3% female). 82.0% had HFpEF; 7.1%, HFmrEF; 7.9%, HFrEF, and 3.0% no HF. LVEF was positively associated with MoCA score (β=0.028, p=0.032). Patients with LVEF ≤40% had lower MoCA scores (17.7 ± 6.2 vs. 19.1 ± 5.9, p=0.008) and higher adjusted odds of moderate/severe cognitive impairment (aOR 2.49, 95%CI 1.20-5.15, p=0.014), compared to those with LVEF >40%. Adjusted odds of moderate to severe cognitive impairment were 1.14 for HFpEF, 0.99 for HFmrEF, and 2.81 for HFrEF compared to patients with no heart failure (trend-P=0.031, Table). Conclusions: Lower LVEF was independently associated with worse cognitive performance. Patients with HFrEF had a 2.5-fold higher risk of moderate to severe cognitive impairment. This association was not observed in patients with HFpEF or HFmrEF, suggesting differential cognitive effects across HF subtypes. Further studies are warranted to confirm these findings and evaluate the impact of interventions targeting EF and HF subtypes on cognitive outcomes.

Introduction: Cerebral amyloid angiopathy (CAA) is a progressive cerebrovascular disease caused by amyloid-beta (Aβ) deposition in cerebral vasculature. While CAA is a recognized cause of intracerebral hemorrhage (ICH) and cognitive decline, emerging evidence suggests that seizures are among a broader array of CAA clinical manifestations. However, the risk of seizures and status epilepticus in CAA remains poorly characterized. This study aimed to estimate incidence of seizures and status epilepticus in CAA using real-world data. Methods: A retrospective, longitudinal study was conducted using a nationally representative sample of administrative claims from US Medicare and commercial insurance beneficiaries (2017–2024). Patients with CAA (aged > 50 years with > 1 physician encounter with a validated ICD-10 code (I68.0)) were matched 1:4 to age- and sex-matched controls. The primary outcome was occurrence of seizure, ascertained using validated ICD-10 codes during acute care; the secondary outcome was hospitalization for status epilepticus. Follow-up continued until the end of enrollment or death. Descriptive statistics summarized patient characteristics and Poisson regression estimated incidence rates with 95% CIs. Cox proportional hazards regression assessed associations between CAA and outcomes of interest vs controls, adjusted for chronic kidney disease, liver disease, prior ICH, and seizure history. Results: We included 7294 patients with CAA and 29176 controls (median age: 77 years; 53.7% women; median follow-up: 29.4 months). Patients with CAA had higher rates of prior ICH (32.4% vs 0.5%) and prior seizure (18.7% vs 1.8%) than controls. The incidence rate of seizures was higher in patients with CAA than controls: 8.1 per 100 person-years (PY; 95% CI: 7.6–8.6) vs 0.4 per 100 PY (95% CI: 0.4–0.5). In the CAA cohort, seizure incidence rate was higher for those with prior ICH than those with no ICH history: 13.6 per 100 PY (95% CI: 12.5–14.8) vs 5.7 per 100 PY (95% CI: 5.2–6.3). Status epilepticus rates were higher in patients with CAA than controls: 0.7 per 100 PY (95% CI: 0.6–0.9) vs 0.03 per 100 PY (95% CI: 0.02–0.04). Adjusted models showed that CAA was associated with higher risk of seizures (HR: 6.7, 95% CI: 5.8–7.7) and status epilepticus (HR: 8.1, 95% CI: 4.8–13.7) than controls (Table 1). Conclusions: Patients with CAA have an increased risk of seizures and status epilepticus. These findings broaden the possible clinical spectrum of CAA.