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Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models. Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI. •Plasma and cerebrospinal fluid neurofilament light (NFL) were moderately correlated.•Cerebrospinal fluid NFL was related to language and memory functions.•Plasma NFL exhibited widespread cognitive associations.•Plasma NFL associations were particularly robust in mild cognitive impairment.

INTRODUCTION Plasma phosphorylated tau‐181 (p‐tau181) associations with global cognition and memory are clear, but the link between p‐tau181 with other cognitive domains and subjective cognitive decline (SCD) across the clinical spectrum of Alzheimer's disease (AD) and how this association changes based on genetic and demographic factors is poorly understood. METHODS Participants were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and included 1185 adults >55 years of age with plasma p‐tau181 and neuropsychological test data. Linear regression models related plasma p‐tau181 to neuropsychological composite and SCD scores with follow‐up models examining plasma p‐tau181 interactions with cognitive diagnosis, apolipoprotein E (APOE) ε4 carrier status, age, and sex on cognitive outcomes. RESULTS Higher plasma p‐tau181 level was associated with worse memory, executive functioning, and language abilities, and greater informant‐reported SCD. Visuospatial abilities and self‐report SCD were not associated with plasma p‐tau181. Associations were generally stronger in mild cognitive impairment (MCI) or dementia, APOE ε4 carriers, women, and younger participants. DISCUSSION Higher levels of plasma p‐tau181 are associated with worse neuropsychological test performance across multiple cognitive domains; however, these associations vary based on disease stage, genetic risk status, age, and sex. Highlights Greater plasma p‐tau181 was associated with lower cognition across most domains. Associations between p‐tau181 and cognition were modified by age and sex. Level of p‐tau181 was more strongly associated with cognition in people with mild cognitive impairment (MCI) and apolipoprotein E (APOE) ε4.

Objective This study examined the effect of cognitive status, education, and sex on the association between subjective cognitive decline (SCD) and Alzheimer's disease (AD) biomarkers in non‐demented older adults. Methods Vanderbilt Memory and Aging Project participants (n = 129), dementia or stroke free, completed fasting lumbar puncture, SCD assessment, and cognitive assessment. Cerebrospinal fluid (CSF) biomarkers for AD were analyzed. Linear regression models related SCD to CSF AD biomarkers and follow‐up models assessed interactions of SCD × cognitive status, sex, reading level, and education on AD biomarkers. Results In main effect models, higher SCD was associated with more amyloidosis (p‐values <0.004). SCD was not associated with tau, p‐tau, or neurofilament light (NFL) levels (p‐values >0.38). SCD score interacted with cognitive status (p < 0.02), sex (p = 0.03), and education (p‐values <0.005) on amyloidosis. In stratified models, higher SCD was associated with more amyloid in cognitively unimpaired (p‐values <0.003), men (p = 0.0003), and higher education. No SCD score × reading‐level interaction was found (p‐values >0.51) though SCD related to amyloid markers in the higher reading‐level group (p‐values <0.004). Interpretation Higher SCD was associated with greater cerebral amyloid accumulation, one of the earliest pathological AD changes. SCD appears most useful in detecting early AD‐related brain changes prior to objective cognitive impairment, in men, and those with higher quantity and quality of education and highlight the importance of considering these factors.

INTRODUCTION Sedentary behavior may be a modifiable risk factor for Alzheimer's disease (AD). We examined how sedentary behavior relates to longitudinal brain structure and cognitive changes in older adults. METHODS Vanderbilt Memory and Aging Project participants (n = 404) completed actigraphy (7 days), neuropsychological assessment, and 3T brain MRI over a 7‐year period. Cross‐sectional and longitudinal linear regressions examined sedentary time in relation to brain structure and cognition. Models were repeated testing for effect modification by apolipoprotein E (APOE) ε4 status. RESULTS In cross‐sectional models, greater sedentary time related to a smaller AD‐neuroimaging signature (β = ‐0.0001, p = 0.01) and worse episodic memory (β = ‐0.001, p = 0.003). Associations differed by APOE‐ε4 status. In longitudinal models, greater sedentary time related to faster hippocampal volume reductions (β = ‐0.1, p = 0.008) and declines in naming (β = ‐0.001, p = 0.03) and processing speed (β = ‐0.003, p = 0.02; β = 0.01, p = 0.01). DISCUSSION Results support the importance of reducing sedentary time, particularly among aging adults at genetic risk for AD. Highlights Greater sedentary behavior is related to neurodegeneration and worse cognition. Associations differed by APOE‐ε4 carrier status in cross‐sectional models. Sedentary behavior is an independent risk factor for Alzheimer's disease.

INTRODUCTION Plasma phosphorylated tau231 (p‐tau231) has shown great promise for early identification of amyloid pathology. We tested various plasma biomarker combinations with p‐tau231 in relation to cerebrospinal fluid (CSF) amyloid positivity. METHODS One hundred and fifty‐five dementia‐free older adults were included. Plasma p‐tau231, glial fibrillary acidic protein (GFAP), β‐amyloid42/40, and neurofilament light chain (NfL) were related to amyloid positivity via logistic regression. Subsequent models assessing various combinations of biomarkers were compared to a base model containing only p‐tau231. RESULTS In single predictor models, p‐tau231 (AUC = 0.87, p = 0.005) and GFAP (AUC = 0.87, p = 0.01) were associated with amyloid positivity, and p‐tau231 remained significant in all multi‐predictor models (p‐values < 0.02). In comparison to the base model with p‐tau231 only, models adding GFAP improved the prediction of amyloid positivity (p < 0.03). DISCUSSION Plasma p‐tau231 and GFAP were associated with amyloid positivity. Models including both p‐tau231 and GFAP performed best, while including β‐amyloid42/40 and NfL did not produce a better fitting model. Highlights Plasma p‐tau231 and glial fibrillary acidic protein (GFAP) are accurate predictors of amyloid positivity. Combining plasma p‐tau231 and GFAP improves accuracy. Adding other biomarkers beyond p‐tau231 and GFAP does not improve models.

INTRODUCTION We test the hypothesis that high levels of neuroplasticity in the context of Alzheimer's disease (AD) risk factors are involved in AD pathogenesis by investigating interactions between cerebrospinal fluid (CSF) levels of growth‐associated protein‐43 (GAP‐43) and AD risk factors (female sex, cerebrovascular risk, mild cognitive impairment, apolipoprotein E [APOE] ε4 genotype, amyloid positivity) on CSF biomarkers of AD pathology (amyloid beta 42/40[Aβ42/40], phosphorylated tau (p‐tau)) and neurodegeneration (tau). METHODS Baseline GAP‐43 levels in 161 non‐demented older adults were related to cross‐sectional and longitudinal (mean follow‐up = 4 years) CSF biomarkers of AD, adjusting for covariates, with GAP‐43 x AD risk factor interaction terms. RESULTS Higher GAP‐43 was cross‐sectionally related to all AD biomarkers (p‐values < 0.0001) and predicted longitudinal reductions in Aβ42 (p < 0.0001). Associations were stronger in AD risk groups. DISCUSSION We found strong support linking increased levels of neuroplasticity in the context of AD risk factors to the pathological cascade of AD over a 4‐year mean follow‐up period. Highlights Cerebrospinal fluid growth‐associated protein‐43 (GAP‐43) is associated with Alzheimer's disease (AD) biomarkers cross‐sectionally and longitudinally. GAP‐43 interacts with AD risk factors to predict AD biomarkers. Increased neuroplastic activity may play a role in AD pathogenesis.

Plasma phosphorylated tau (p-tau ) has shown great promise for early identification of amyloid pathology. We tested various plasma biomarker combinations with p-tau231 in relation to cerebrospinal fluid (CSF) amyloid positivity. One hundred and fifty-five dementia-free older adults were included. Plasma p-tau231, glial fibrillary acidic protein (GFAP), β-amyloid42/40, and neurofilament light chain (NfL) were related to amyloid positivity via logistic regression. Subsequent models assessing various combinations of biomarkers were compared to a base model containing only p-tau . In single predictor models, p-tau231 (AUC = 0.87, p = 0.005) and GFAP (AUC = 0.87, p = 0.01) were associated with amyloid positivity, and p-tau231 remained significant in all multi-predictor models (p-values < 0.02). In comparison to the base model with p-tau231 only, models adding GFAP improved the prediction of amyloid positivity (p < 0.03). Plasma p-tau231 and GFAP were associated with amyloid positivity. Models including both p-tau231 and GFAP performed best, while including β-amyloid42/40 and NfL did not produce a better fitting model. Plasma p-tau231 and glial fibrillary acidic protein (GFAP) are accurate predictors of amyloid positivity. Combining plasma p-tau231 and GFAP improves accuracy. Adding other biomarkers beyond p-tau231 and GFAP does not improve models.

Familial Mediterranean Fever (FMF) is an autoinflammatory genetic disorder causing recurrent fever episodes due to MEFV gene mutations, typically affecting small and medium-sized vessels. We present a 69-year-old male with FMF exhibiting features suggestive of large vessel vasculitis, challenging the conventional understanding of FMF. The patient had an extended fever episode, a self-resolving groin rash, intermittent diarrhea, and a decline in health over six months. A PET scan showed increased uptake in large vessels, especially in the bilateral lower extremities, indicating possible large vessel vasculitis. The patient's positive response to corticosteroid therapy supported an inflammatory etiology. This case underscores the need for a broader differential diagnosis in atypical FMF presentations and suggests further research into the relationship between FMF and large vessel vasculitis.

Clonorchis Sinensis, a common liver fluke, is known to cause biliary disease and can present with a wide array of symptoms. It’s mostly found in Asian countries due to consumption of undercooked or raw fish. Although Cholangiocarcinoma is a known serious complication of this disease, Pancreatic neoplasms are rare and have seldom been reported. Here, we report a case of an 80-year-old man who presents with pancreatic adenocarcinoma associated with Clonorchis Sinensis infection

Aim Mitral valve pathology in rheumatic heart disease patients is a common cause of secondary pulmonary hypertension (PH). Our aim was to evaluate pulmonary hypertension severity as a predictor of in-hospital mortality and early complications following mitral valve replacement. Methods A retrospective review of rheumatic heart disease patients who underwent mitral valve replacement between January 2017 and August 2020 was performed. Systolic pulmonary artery pressure (sPAP) was used to classify patients as no PH (<35 mmHg), mild PH (35-44 mmHg), moderate PH (45-59 mmHg) or severe PH (>60 mmHg). Patients subjected to additional cardiac procedures (such as aortic valve replacement and coronary artery bypass grafting) were excluded from the study sample. Results The study group was composed of 159 patients (mean age: 40; 73 male, 86 female) categorized as no PH (n = 32; 20.1%), mild PH (n = 14; 8.8%), moderate PH (n = 65, 40.9%) and severe PH (n = 48, 30.2%) groups. Patient demographic data and preoperative comorbidities were comparable among the four groups. Use of intraoperative and postoperative blood products was similar in all the groups. Severe PH patients had similar in-hospital mortality (4.2%; p = 0.74) as in groups with lesser degrees of pulmonary hypertension. Likewise, increasing severity of pulmonary hypertension did not confer any significant increase in early postoperative complications, namely prolonged ICU stay (10.4%; p = 0.41), prolonged ventilation (2.1%; p = 0.70), reintubation (4.2%; p = 0.90), reopening for bleeding tamponade (6.3%; p = 0.39), new-onset renal failure (6.3%; p = 0.91), postoperative stroke (4.2%; p = 0.52) or prolonged length of stay (mean: 5.6 + 2.8 days; p = 0.49). Conclusions Increasing severity of pulmonary hypertension does not appear to have a significant impact on in-hospital mortality or early postoperative outcomes of patients undergoing mitral valve replacement.