Perivascular space burden interacts with APOE-ε4 status on cognition in older adults.

Enlarged perivascular spaces (ePVS) may adversely affect cognition. Little is known about how basal ganglia ePVS interact with apolipoprotein (APOE)-ε4 status. Vanderbilt Memory and Aging Project participants (n = 326, 73 ± 7, 59% male) underwent 3 T brain MRI at baseline to assess ePVS and longitudinal neuropsychological assessments. The interaction between ePVS volume and APOE-ε4 carrier status was related to baseline outcomes using ordinary least squares regressions and longitudinal cognition using linear mixed-effects regressions. ePVS volume interacted with APOE-ε4 status on cross-sectional naming performance (ß = -0.002, p = 0.002), and executive function excluding outliers (ß = 0.001, p = 0.009). There were no significant longitudinal interactions (p-values>0.10) except for Coding excluding outliers (ß = 0.002, p = 0.05). While cross-sectional models stratified by APOE-ε4 status indicated greater ePVS related to worse cognition mostly in APOE-ε4 carriers, longitudinal models stratified by APOE-ε4 status showed greater ePVS volume related to worse cognition among APOE-ε4 non-carriers only. Results indicated that greater ePVS volume interacts with APOE-ε4 status on cognition cross-sectionally. Longitudinally, the association of greater ePVS volume and worse cognition appears stronger in APOE-ε4 non-carriers, possibly due to the deleterious effects of APOE-ε4 on cognition across the lifespan.

Sex and Education Modify the Association Between Subjective Cognitive Decline and Amyloid Pathology.

Background: Subjective cognitive decline (SCD) may be an early risk factor for dementia, particularly in highly educated individuals and women. This study examined the effect of education and sex on the association between SCD and Alzheimer's disease (AD) biomarkers in non-demented older adults. Method: Vanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=156, 72±6 years, 37% mild cognitive impairment, 33% female) completed fasting lumbar puncture, SCD assessment, and Wide Range Achievement Test-III Reading subtest to assess reading level at baseline as a a proxy for educational quality. Cerebrospinal fluid (CSF) biomarkers for AD (ß-amyloid 42 (Aß42), Aß42/40 ratio, phosphorylated tau (p-tau), tau, and neurofilament light (NfL)) were analyzed in batch. Linear mixed effects models related SCD to CSF AD biomarkers and follow-up models assessed SCD x sex, SCD x reading level , and SCD x education interactions on AD biomarkers. Result: In main effect models, higher SCD was associated with lower Aß42 and Aß42/40 ratio (p-values<0.004). SCD was not associated with tau, p-tau, or NfL levels ( p- values>0.38). SCD score interacted with sex on Aß42/40 ratio ( p =0.03) but no other biomarkers ( p -values>0.10). In stratified models, higher SCD was associated with lower Aß42/40 ratio in men ( p =0.0003) but not in women ( p =0.48). SCD score interacted with education on Aß42 ( p =0.005) and Aß42/40 ratio ( p =0.001) such that higher education was associated with a stronger negative association between SCD and amyloid levels. No SCD score x reading level interaction was found (p-values> 0.51) though significant associations between SCD and amyloid markers were seen in the higher reading level group (p-values<0.004) but not the lower reading level group (p-values>0.12) when stratified by a median split in reading level. Conclusion: Among community-dwelling older adults free of clinical dementia, 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 in men and individuals with higher quantity and quality of education. SCD was not associated with CSF markers of tau pathology or neurodegeneration. These findings suggest that considering sex and education is important when assessing SCD in older adults.

Clinical and demographic factors modify the association between plasma phosphorylated tau-181 and cognition.

INTRODUCTION: Plasma phosphorylated tau181 (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 and included 1185 adults aged >55 years 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, APOE ε4 carrier status, age, and sex on cognitive outcomes. RESULTS: Higher plasma p-tau181 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 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.

Evidence of Cardiac Involvement in a Patient With Necrotizing Autoimmune Myopathy (NAM).

Necrotizing autoimmune myopathy (NAM) is a rare inflammatory myopathy primarily affecting skeletal muscles. Cardiac involvement has been reported in immune-mediated necrotizing myopathy (IMNM), but its extent remains poorly understood. We present a unique case of a 68-year-old male with anti-signal recognition particle (SRP) antibody-positive NAM initially presenting with elevated troponin levels. Our case demonstrates cardiac involvement as the presenting feature of NAM, which is a unique feature of inflammatory myopathy.

Baseline grey matter volumes and white matter hyperintensities predict decline in functional activities in older adults over a 5-year follow-up period.

INTRODUCTION: Functional independence is an essential predictor of quality of life in aging, yet few accessible predictors of functional decline have been identified. This study examined associations between baseline structural neuroimaging markers and longitudinal functional status. METHODS: Linear mixed effects models with follow-up time interaction terms related baseline grey matter volume and white matter hyperintensities (WMHs) to functional trajectory, adjusting for demographic and medical covariates. Subsequent models assessed interactions with cognitive status and apolipoprotein E (APOE) ε4 status. RESULTS: Smaller baseline grey matter volumes, particularly in regions commonly affected by Alzheimer's disease (AD), and greater baseline WMHs were associated with faster functional decline over a mean 5-year follow-up. Effects were stronger in APOE-ε4 carriers on grey matter variables. Cognitive status interacted with most MRI variables. DISCUSSION: Greater atrophy in AD-related regions and higher WMH burden at study entry were associated with faster functional decline, particularly among participants at increased risk of AD.

A Case of Concurrence of Clonorchis Sinensis and Pancreatic Adenocarcinoma-A Diagnostic Dilemma.

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.

Whole blood transcript and protein abundance of the vascular endothelial growth factor family relate to cognitive performance.

The vascular endothelial growth factor (VEGF) family of genes has been implicated in the clinical development of Alzheimer's Disease (AD). A previous study identified associations between gene expression of VEGF family members in the prefrontal cortex and cognitive performance and AD pathology. This study explored if those associations were also observed in the blood. Consistent with previous observations in brain tissue, higher blood gene expression of placental growth factor (PGF) was associated with a faster rate of memory decline (p=0.04). Higher protein abundance of FMS-related receptor tyrosine kinase 4 (FLT4) in blood was associated with biomarker levels indicative of lower amyloid and tau pathology, opposite the direction observed in brain. Also, higher gene expression of VEGFB in blood was associated with better baseline memory (p=0.008). Notably, we observed that higher gene expression of VEGFB in blood was associated with lower expression of VEGFB in the brain (r=-0.19, p=0.02). Together, these results suggest that the VEGFB, FLT4, and PGF alterations in the AD brain may be detectable in the blood compartment.

Enlarged perivascular space burden associations with arterial stiffness and cognition.

Enlarged perivascular spaces (ePVS) are difficult to quantify, and their etiologies and consequences are poorly understood. Vanderbilt Memory and Aging Project participants (n = 327, 73 ± 7 years) completed 3T brain MRI to quantify ePVS volume and count, longitudinal neuropsychological assessment, and cardiac MRI to quantify aortic stiffness. Linear regressions related (1) PWV to ePVS burden and (2) ePVS burden to cross-sectional and longitudinal neuropsychological performance adjusting for key demographic and medical factors. Higher aortic stiffness related to greater basal ganglia ePVS volume (ß = 7.0×10-5, p = 0.04). Higher baseline ePVS volume was associated with worse baseline information processing (ß = -974, p = 0.003), executive function (ß = -81.9, p < 0.001), and visuospatial performances (ß = -192, p = 0.02) and worse longitudinal language (ß = -54.9, p = 0.05), information processing (ß = -147, p = 0.03), executive function (ß = -10.9, p = 0.03), and episodic memory performances (ß = -10.6, p = 0.02). Results were similar for ePVS count. Greater arterial stiffness relates to worse basal ganglia ePVS burden, suggesting cardiovascular aging as an etiology. ePVS burden is associated with adverse cognitive trajectory, emphasizing the clinical relevance of ePVS.

Polygenic resilience score may be sensitive to preclinical Alzheimer's disease changes.

Late-onset Alzheimer's disease (LOAD) is a polygenic disorder with a long prodromal phase, making early diagnosis challenging. Twin studies estimate LOAD as 60-80% heritable, and while common genetic variants can account for 30% of this heritability, nearly 70% remains "missing". Polygenic risk scores (PRS) leverage combined effects of many loci to predict LOAD risk, but often lack sensitivity to preclinical disease changes, limiting clinical utility. Our group has built and published on a resilience phenotype to model better-than-expected cognition give amyloid pathology burden and hypothesized it may assist in preclinical polygenic risk prediction. Thus, we built a LOAD PRS and a resilience PRS and evaluated both in predicting cognition in a dementia-free cohort (N=254). The LOAD PRS had a significant main effect on baseline memory (ß=-0.18, P=1.68E-03). Both the LOAD PRS (ß=-0.03, P=1.19E-03) and the resilience PRS (ß=0.02, P=0.03) had significant main effects on annual memory decline. The resilience PRS interacted with CSF Aß on baseline memory (ß=-6.04E-04, P=0.02), whereby it predicted baseline memory among Aß+ individuals (ß=0.44, P=0.01) but not among Aß- individuals (ß=0.06, P=0.46). Excluding APOE from PRS resulted in mainly LOAD PRS associations attenuating, but notably the resilience PRS interaction with CSF Aß and selective prediction among Aß+ individuals was consistent. Although the resilience PRS is currently somewhat limited in scope from the phenotype's cross-sectional nature, our results suggest that the resilience PRS may be a promising tool in assisting in preclinical disease risk prediction among dementia-free and Aß+ individuals, though replication and fine-tuning are needed.

RNASE6 is a novel modifier of APOE-ε4 effects on cognition.

Apolipoprotein E4 (APOE-ε4), the strongest common genetic risk factor for Alzheimer's disease (AD), contributes to worse cognition in older adults. However, many APOE-ε4 carriers remain cognitively normal throughout life, suggesting that neuroprotective factors may be present in these individuals. In this study, we leverage whole-blood RNA sequencing (RNAseq) from 324 older adults to identify genetic modifiers of APOE-ε4 effects on cognition. Expression of RNASE6 interacted with APOE-ε4 status (p = 4.35 × 10-8) whereby higher RNASE6 expression was associated with worse memory at baseline among APOE-ε4 carriers. This interaction was replicated using RNAseq data from the prefrontal cortex in an independent dataset (N = 535; p = 0.002), suggesting the peripheral effect of RNASE6 is also present in brain tissue. RNASE6 encodes an antimicrobial peptide involved in innate immune response and has been previously observed in a gene co-expression network module with other AD-related inflammatory genes, including TREM2 and MS4A. Together, these data implicate neuroinflammation in cognitive decline, and suggest that innate immune signaling may be detectable in blood and confer differential susceptibility to AD depending on APOE-ε4.

Axonal Injury Partially Mediates Associations Between Increased Left Ventricular Mass Index and White Matter Damage.

BACKGROUND AND PURPOSE: Left ventricular (LV) mass index is a marker of subclinical LV remodeling that relates to white matter damage in aging, but molecular pathways underlying this association are unknown. This study assessed if LV mass index related to cerebrospinal fluid (CSF) biomarkers of microglial activation (sTREM2 [soluble triggering receptor expressed on myeloid cells 2]), axonal injury (NFL [neurofilament light]), neurodegeneration (total-tau), and amyloid-ß, and whether these biomarkers partially accounted for associations between increased LV mass index and white matter damage. We hypothesized higher LV mass index would relate to greater CSF biomarker levels, and these pathologies would partially mediate associations with cerebral white matter microstructure. METHODS: Vanderbilt Memory and Aging Project participants who underwent cardiac magnetic resonance, lumbar puncture, and diffusion tensor imaging (n=142, 72±6 years, 37% mild cognitive impairment [MCI], 32% APOE-ε4 positive, LV mass index 51.4±8.1 g/m2, NFL 1070±588 pg/mL) were included. Linear regressions and voxel-wise analyses related LV mass index to each biomarker and diffusion tensor imaging metrics, respectively. Follow-up models assessed interactions with MCI and APOE-ε4. In models where LV mass index significantly related to a biomarker and white matter microstructure, we assessed if the biomarker mediated white matter associations. RESULTS: Among all participants, LV mass index was unrelated to CSF biomarkers (P>0.33). LV mass index interacted with MCI (P=0.01), such that higher LV mass index related to increased NFL among MCI participants. Associations were also present among APOE-ε4 carriers (P=0.02). NFL partially mediated up to 13% of the effect of increased LV mass index on white matter damage. CONCLUSIONS: Subclinical cardiovascular remodeling, measured as an increase in LV mass index, is associated with neuroaxonal degeneration among individuals with MCI and APOE-ε4. Neuroaxonal degeneration partially reflects associations between higher LV mass index and white matter damage. Findings highlight neuroaxonal degeneration, rather than amyloidosis or microglia, may be more relevant in pathways between structural cardiovascular remodeling and white matter damage.

Lower cerebral oxygen utilization is associated with Alzheimer's disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers.

Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are markers of cerebral oxygen homeostasis and metabolism that may offer insights into abnormal changes in brain aging. The present study cross-sectionally related OEF and CMRO2 to cognitive performance and structural neuroimaging variables among older adults (n = 246, 74 ± 7 years, 37% female) and tested whether apolipoprotein E (APOE)-ε4 status modified these associations. Main effects of OEF and CMRO2 were null (p-values >0.06), and OEF interactions with APOE-ε4 status on cognitive and structural imaging outcomes were null (p-values >0.06). However, CMRO2 interacted with APOE-ε4 status on language (p = 0.002), executive function (p = 0.03), visuospatial (p = 0.005), and episodic memory performances (p = 0.03), and on hippocampal (p = 0.006) and inferior lateral ventricle volumes (p = 0.02). In stratified analyses, lower oxygen metabolism related to worse language (p = 0.02) and episodic memory performance (p = 0.03) among APOE-ε4 carriers only. Associations between CMRO2 and cognitive performance were primarily driven by APOE-ε4 carriers with existing cognitive impairment. Congruence across language and episodic memory results as well as hippocampal and inferior lateral ventricle volume findings suggest that APOE-ε4 may interact with cerebral oxygen metabolism in the pathogenesis of Alzheimer's disease and related neurodegeneration.

Elevated Aortic Pulse Wave Velocity Relates to Longitudinal Gray and White Matter Changes.

OBJECTIVE: To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years. Approach and Results: Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included T1-weighted imaging for quantifying gray matter volumes and T2-weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, cognitive diagnosis, Framingham stroke risk profile, APOE (apolipoprotein E)-ε4 carrier status, and intracranial volume. Two hundred seventy-eight participants (73±7 years, 58% male, 87% self-identified as non-Hispanic White, 159 with normal cognition, and 119 with mild cognitive impairment) from the Vanderbilt Memory & Aging Project (n=335) were followed on average for 4.9±1.6 years with PWV measurements occurring from September 2012 to November 2014 and longitudinal brain magnetic resonance imaging measurements occurring from September 2012 to June 2021. Higher baseline aortic PWV was related to greater decrease in hippocampal (ß=-3.6 [mm3/y]/[m/s]; [95% CI, -7.2 to -0.02] P=0.049) and occipital lobe (ß=-34.2 [mm3/y]/[m/s]; [95% CI, -67.8 to -0.55] P=0.046) gray matter volume over time. Higher baseline aortic PWV was related to greater increase in WMH volume over time in the temporal lobe (ß=17.0 [mm3/y]/[m/s]; [95% CI, 7.2-26.9] P<0.001). All associations may be driven by outliers. CONCLUSIONS: In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.

Pulmonary Hypertension as a Predictor of Early Outcomes of Mitral Valve Replacement: A Study in Rheumatic Heart Disease Patients.

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.

Lower Cardiac Output Relates to Longitudinal Cognitive Decline in Aging Adults.

BACKGROUND: Subclinical reductions in cardiac output correspond to lower cerebral blood flow (CBF), placing the brain at risk for functional changes. OBJECTIVES: This study aims to establish the consequences of reduced cardiac output on longitudinal cognitive outcomes in aging adults. METHODS: Vanderbilt Memory and Aging Project participants free of clinical dementia and heart failure (n = 306, 73 ± 7, 58% male) underwent baseline echocardiography to assess cardiac output (L/min) and longitudinal neuropsychological assessment at baseline, 18 months, 3 and 5 years. Linear mixed-effects regressions related cardiac output to trajectory for each longitudinal neuropsychological outcome, adjusting for age, sex, race/ethnicity, education, body surface area, Framingham Stroke Risk Profile score, apolipoprotein E (APOE) ε4 status and follow-up time. Models were repeated, testing interactions with cognitive diagnosis and APOE-ε4 status. RESULTS: Lower baseline cardiac output related to faster declines in language (ß = 0.11, p = 0.01), information processing speed (ß = 0.31, p = 0.006), visuospatial skills (ß = 0.09, p = 0.03), and episodic memory (ß = 0.02, p = 0.001). No cardiac output x cognitive diagnosis interactions were observed (p > 0.26). APOE-ε4 status modified the association between cardiac output and longitudinal episodic memory (ß = 0.03, p = 0.047) and information processing speed outcomes (ß = 0.55, p = 0.02) with associations stronger in APOE-ε4 carriers. CONCLUSION: The present study provides evidence that even subtle reductions in cardiac output may be associated with more adverse longitudinal cognitive health, including worse language, information processing speed, visuospatial skills, and episodic memory performances. Preservation of healthy cardiac functioning is important for maintaining optimal brain aging among older adults.

Cerebrospinal fluid biomarkers of neurodegeneration, synaptic dysfunction, and axonal injury relate to atrophy in structural brain regions specific to Alzheimer's disease.

INTRODUCTION: Patterns of atrophy can distinguish normal cognition from Alzheimer's disease (AD), but neuropathological drivers of this pattern are unknown. This study examined associations between cerebrospinal fluid biomarkers of AD pathology, synaptic dysfunction, and neuroaxonal injury with two AD imaging signatures. METHODS: Signatures were calculated using published guidelines. Linear regressions related each biomarker to both signatures, adjusting for demographic factors. Bootstrapped analyses tested if associations were stronger with one signature versus the other. RESULTS: Increased phosphorylated tau (p-tau), total tau, and neurofilament light (P-values <.045) related to smaller signatures (indicating greater atrophy). Diagnosis and sex modified associations between p-tau and neurogranin (P-values<.05) and signatures, such that associations were stronger among participants with mild cognitive impairment and female participants. The strength of associations did not differ between signatures. DISCUSSION: Increased evidence of neurodegeneration, axonopathy, and tau phosphorylation relate to greater AD-related atrophy. Tau phosphorylation and synaptic dysfunction may be more prominent in AD-affected regions in females.

Increased Incidence of Resistant Hypertension in Patients With Systemic Lupus Erythematosus: A Retrospective Cohort Study.

OBJECTIVE: To compare the risk of resistant hypertension (RHTN) in patients with systemic lupus erythematosus (SLE) and in controls without SLE, and to define factors associated with RHTN in patients with SLE. METHODS: We studied 1,044 patients with SLE and 5,241 control subjects using de-identified electronic health records from a tertiary care center. SLE was defined as ≥4 International Classification of Diseases, Ninth Revision codes for SLE and antinuclear antibody titer ≥1:160. RHTN was defined as uncontrolled blood pressure on 3 antihypertensive medications or requiring 4 or more antihypertensives to attain control. First, we compared the risk of RHTN between groups. Second, we examined the association between RHTN and all-cause mortality in patients with SLE. RESULTS: RHTN was nearly twice as prevalent in patients with SLE compared to control subjects (10.2% and 5.3%, respectively), with an incidence rate of 10.2 versus 6.1 cases per 1,000 person-years of observation (hazard ratio [HR] 1.72 [95% confidence interval 1.28-2.30]; P < 0.001, adjusted for age, sex, race, baseline end-stage renal disease [ESRD], creatinine, and calendar year). In patients with SLE, we found associations between RHTN and black race, lower renal function, hypercholesterolemia, and increased inflammatory markers. RHTN was associated with a significantly higher mortality risk (HR 2.91, P = 0.0005) after adjustment for age, sex, race, calendar year, creatinine, baseline ESRD, and number of visits. CONCLUSION: Patients with SLE have a higher risk of RHTN compared to frequency-matched controls, independent of multiple covariates. RHTN is an important comorbidity for clinicians to recognize in SLE, because it is associated with a higher risk of mortality.

A Rare Case of Isolated Unilateral Atresia of Pulmonary Artery in an Elderly Female.

Isolated unilateral agenesis/atresia of pulmonary artery (IUAPA) is a rare congenital disorder, an uncommon variant of unilateral agenesis of pulmonary artery (UAPA). Patients with IUAPA may remain asymptomatic and undiagnosed till late adulthood as they present with vague symptoms which may be overlooked. We report a case of IUAPA of right pulmonary artery in an elderly female who presented with complaints of productive cough and exertional dyspnea. Due to the formation of extensive collaterals, her lung parenchyma was preserved.

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition.

INTRODUCTION: Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Impact of Premature Greying of Hair on Socio-cultural Adjustment and Self-esteem among Medical Undergraduates in Foundation University, Islamabad.

Introduction Greying of hair is an inevitable phenomenon that occurs commonly as a person ages. It usually occurs in the fourth decade regardless of gender but now a days, even people in their early twenties can experience premature greying. The objective of our study was to determine the frequency of premature greying of hair and its impact on the socio-cultural spheres of life and self-esteem of medical students. Methodology It is a descriptive cross-sectional study conducted at Foundation University Medical College (FUMC) from January to February 2017. All medical students of FUMC who gave their consent were included in the study sample. Students who were absent or unwilling to participate were excluded. Data was collected through a self-administered questionnaire, which was then analysed using SPSS version 17 (SPSS Inc., Chicago, IL). Results Out of 673 students, 210 (31.2%) suffered from premature greying of hair. The prevalence was higher among females (155/73.8%) as compared to males (55/26.2%). There was a statistical difference in perception of both the genders, regarding those with premature greying of hair trying to hide it (p-value = 0.000), premature greying of hair as contagious (p-value = .009) and the affected looking older than their actual age (p-value = 0.036). Conclusion The study showed that premature greying affected the socio-cultural spheres of students' lives. Females were more prone to developing premature greying of hair. Genetics also play a significant role in the phenomenon. No positive correlation was found by using Rosenberg Self-esteem scale.