Citations

AbstractBackgroundThe DEMQOL (Dementia Quality of Life) scale is a patient reported questionnaire and proxy form that captures subjective life quality. Participants in ALLFTD and their Study Partners (SP) complete these questionnaires at each study visit.MethodWe analyzed the DEMQOL in participants and their SPs when the SP was reported to be a spouse or equivalent. Analyses focused on the final overall quality of life (QoL) rating for the participant (poor, fair, good, or very good).ResultDEMQOL responses from 907 dyads (participant: mean age 58.3±13.4 years, 44% female, and mean education 15.9±2.5 years) were analyzed. Participants rated their overall QoL as very good (45.8%), good (36.5%), fair (14%), and poor (3.5%). SPs rated their participant’s overall QoL as very good (33.6%), good (41%), fair (19.4%), and poor (6%). There was a discordance in ratings between participants and SPs (p<0.0001); in almost 50% of cases, participants rated their QoL better (33.2%) or worse (15.2%) than their SP rated their QoL. When considering disease severity (CDR®+NACC‐FTLD global score), participants rated their QoL better than their SP rated their QoL (CDR®+NACC‐FTLD = 0: 19.4%, CDR®+NACC‐FTLD = 0.5: 42%, and CDR®+NACC‐FTLD = 1+: 33.2%), worse than (CDR®+NACC‐FTLD = 0: 15.1%, CDR®+NACC‐FTLD = 0.5: 13.3%, and CDR®+NACC‐FTLD = 1+: 15.2%), or the same (CDR®+NACC‐FTLD = 0: 65.6%, CDR®+NACC‐FTLD = 0.5: 44.8%, and CDR®+NACC‐FTLD = 1+: 51.6%).ConclusionAmong participants and SPs, similarities and differences in QoL ratings are fairly consistent regardless of global CDR®+NACC‐FTLD rating. Generally, participants are equally or more optimistic about QoL than their SPs. Longitudinal analyses are forthcoming.

AbstractBackgroundFor blood‐based biomarkers to fulfill their potential to revolutionize diagnosis and management of Alzheimer’s disease (AD), additional research in diverse populations remains critical. Here, we analyzed a biracial sample to assess the profiles of blood‐based AD biomarkers and their relationships to cognition and medical comorbidities.MethodsSelf‐reported African‐American (AA; n = 267) and non‐Hispanic White (NHW; n = 268) participants evaluated through the Mayo Jacksonville Alzheimer’s Disease Research Center were matched on age, sex, and clinical diagnosis. Plasma AD biomarkers (Aβ42/40, p‐tau181, GFAP, NfL) were measured using the Quanterix SiMoA HD‐X analyzer. Cognition was assessed with the Mini Mental State Examination. Wilcoxon rank sum tests were used to assess for differences in plasma biomarker levels by sex. Linear models tested for associations of race, chronic kidney disease (CKD), and vascular risk factors with plasma AD biomarker levels, covarying for age and sex. Additional models assessed for interactions between race and plasma biomarkers in predicting cognition, further covarying for education.ResultsThe sample included adults aged 43‐100 years, with 69% women. Education was higher in NHW participants (median 16 vs. 12 years, p<0.001). APOE (apolipoprotein E) ε4 positivity was higher in AA participants (43% vs. 34%; p = 0.04). There were no differences in plasma AD biomarker levels between AA and NHW participants. These findings were unchanged after stratifying by cognitive status (unimpaired versus impaired). Although the association between p‐tau181 and cognition appeared stronger in NHW participants while the association between Aβ42/40 and cognition appeared stronger in AA participants, these findings did not survive after excluding individuals with CKD. Women displayed higher GFAP (p = 0.002) and lower p‐tau181 (p = 0.001) levels than men. Diabetes was inversely associated with GFAP levels (p<0.001).ConclusionsIn a biracial, community‐based sample, we observed that sex differences, CKD, and vascular risk factors contributed to variation in plasma AD biomarkers, while self‐reported race did not. Our results reinforce the critical need to account for sex and systemic medical comorbidities in equitably deploying blood‐based AD biomarkers in the general population.

AbstractBackgroundPlasma biomarkers for Alzheimer’s disease (AD) such as phosphorylated tau protein 181 (p‐tau 181), neurofilament light chain (NfL), amyloid‐β 42/40 ratio (Aβ42/40), and glial fibrillary acidic protein (GFAP) have shown high performance in the discrimination of those with clinical mild cognitive impairment (MCI) or dementia from cognitively unimpaired individuals, but few population‐based autopsy studies have evaluated the neuropathological correlates of plasma biomarkers.MethodWe utilized a population‐based prospective study of 350 participants with autopsy and antemortem plasma biomarker data. Plasma biomarkers Aβ42/40 ratio, p‐tau181, GFAP, and NfL were measured using Quanterix Simoa assays. We predicted AD neuropathological change (ADNC), Braak staging, and neuritic plaque score using these plasma biomarkers and investigated the added utility of cognitive and demographic information. We utilized a variable selection procedure in cross‐validated (CV) logistic regression models by minimizing the Bayesian Information Criterion to identify the best set of predictors for a given outcome among plasma biomarkers, demographic variables, and neuropsychological tests included in the Mayo Clinic Preclinical Alzheimer Cognitive Composite (Mayo‐PACC).ResultADNC was best predicted with plasma GFAP, NfL, p‐tau181 biomarkers along with APOE ε4 carrier status and Mayo‐PACC cognitive score (CV AUC = 0.821). Braak staging was best predicted using plasma GFAP, p‐tau181, and cognitive scores (CV AUC = 0.788). Neuritic plaque score was best predicted using plasma Aβ42/40 ratio, p‐tau181, GFAP, and NfL biomarkers (CV AUC = 0.778). Inclusion of plasma biomarkers demonstrated significantly better prediction of Braak staging (p<0.01) and neuritic plaque score (p<0.01), but not ADNC (p = 0.13), when compared to models that included only cognitive and demographic information. Univariate models consistently underperformed in comparison to multivariate models.ConclusionPlasma biomarkers can provide valuable predictive information about the presence of AD pathology, which can facilitate earlier recognition and diagnosis of AD. Incorporation of demographic and cognitive variables along with plasma variables in multivariable models will improve prediction accuracy of AD pathology, specifically Braak staging and ADNC.

Abstract The Heidenhain variant of Creutzfeld-Jakob disease (CJD) is a rare form that initially presents with visual disturbances. In early stages, the presentation can mimic neuromyelitis optica spectrum disorders (NMOSD) and lead to unnecessary treatment modalities. Herein, we describe a case of a 66-year-old man who presented with bilateral vision loss and retro-orbital discomfort. In addition to immunosuppressive therapy, he received 4 rounds of therapeutic plasma exchange after his preliminary diagnosis of NMOSD. We were surprised to note that his condition did not show improvement but deteriorated, with severe neurocognitive symptoms. Eventually, CJD was suspected, and real-time quaking-induced conversion (RT-QuIC) was performed. By the time the diagnosis of Heidenhain variant of CJD was confirmed, the patient was discharged to hospice care and died shortly after.

Study Design Retrospective comparative study. Objective To compare patient-reported physical activity between anterior thoracic vertebral body tethering and posterior lumbar spine tethering (ATVBT/PLST) and posterior spinal instrumentation and fusion (PSIF) with minimum 2 year follow-up. Methods Consecutive skeletally immature patients with idiopathic scoliosis and a thoracic and lumbar curve magnitude ≥40° who underwent either ATVBT/PLST or PSIF from 2015-2019 were included. The primary outcome was rate of returning to sport. Secondary outcomes included ability to bend and satisfaction with sport performance as well as weeks until return to sport, school, physical education (PE) classes, and running. Results Ten patients underwent ATVBT/PLST and 12 underwent PSIF. ATVBT/PLST patients reported significantly faster return to sport (13.5 weeks vs 27.9 weeks, P = .04), running (13.3 weeks vs 28.8 weeks, P = .02), and PE class (12.6 weeks vs 26.2 weeks, P = .04) compared to PSIF patients. ATVBT/PLST patients reported that they had to give up activities due to their ability to bend at lower rates than PSIF patients while reporting “no changes” in their ability to bend after surgery at higher rates than PSIF patients (0% vs 4% giving up activities and 70% vs 0% reporting no changes in bending ability for ATVBT/PLST and PSIF, respectively, P = .01). Compared to PSIF patients, ATVBT/PLST patients experienced less main thoracic and thoracolumbar/lumbar curve correction at most recent follow-up (thoracic: 41 ± 19% vs 69 ± 18%, P = .001; thoracolumbar/lumbar: 59 ± 25% vs 78 ± 15%, P = .02). No significant differences in the number of revision surgeries were observed between ATVBT/PLST and PSIF patients (4 (40%) and 1 (8%) for ATVBT/PLST and PSIF, respectively, P = .221). Conclusions ATVBT/PLST patients reported significantly faster rates of returning to sport, running, and PE. In addition, ATVBT/PLST patients were less likely to have to give up activities due to bending ability after surgery and reported no changes in their ability to bend after surgery more frequently than PSIF patients. However, the overall rate of return to the same or higher level of sport participation was high amongst both groups, with no significant difference observed between ATVBT/PLST and PSIF patients.