Faculty Bibliography

INTRODUCTION/BACKGROUND:This study aimed to explore the experience of living with amyotrophic lateral sclerosis (ALS) and to develop a conceptual model for this rare disease. METHODS:Concept elicitation interviews were conducted (January-September 2024) with people living with ALS (PLwALS; n = 31), caregivers (n = 20), and clinicians (n = 10). Qualitative data were analyzed separately to develop a conceptualization of the experience of living with ALS. Concept saturation was assessed every 5-6 interviews, and a conceptual model was developed. RESULTS:The mean age of PLwALS was 42.4 years (standard deviation [SD] 11.5), 81% were female, 84% were white, and 23% had SOD1-ALS. The mean time since diagnosis was 4.6 years (SD 4.2); mean normed Rasch Overall ALS Disability Scale score was 76 (SD 17.16). Signs, symptoms, and functions reported during PLwALS interviews included neuromuscular, bulbar, speech, neurocognitive (e.g., memory issues), and a range of physical functioning issues (e.g., motor coordination). PLwALS also reported impacts on a range of activities and psychosocial interactions (e.g., eating, depressed mood, and relationships), alongside management strategies they employed. Interviews with caregivers and clinicians supported findings from the PLwALS interviews. Caregivers also identified signs such as drooling/excess salivation, and impacts related to ALS management (e.g., need for writing aids). Clinicians additionally considered loss of speech and neurocognitive signs (e.g., behavior/personality change) as ALS clinical manifestations. Concept saturation was reached, and a consolidated, comprehensive conceptual model was developed. CONCLUSION/CONCLUSIONS:This research provides a holistic understanding of the experience of living with ALS and is the first conceptual model based on in-depth concept elicitation interviews. The findings highlight the range of signs, symptoms, and impacts that PLwALS experience, emphasizing its serious humanistic impact and high unmet need, and will help to guide patient-centric evaluation of clinical outcome assessments in future ALS studies.

BACKGROUND:Spinocerebellar ataxia type 27 B (SCA27B) caused by GAA trinucleotide repeats in the fibroblast growth factor 14 gene is emerging as a common cause of late-onset ataxia. Oscillopsia due to downbeat nystagmus (DBN) and diplopia are common symptoms, yet the causes of diplopia and strabismus patterns are poorly defined. METHODS:Retrospective chart review of 18 patients diagnosed with SCA27B over the past year. RESULTS:Ten of 18 patients had episodic or persistent oscillopsia or diplopia at disease onset, neurologically isolated in 4. Seventeen had detectable DBN, although it was often delayed in onset and was clinically obvious in only 5. Diplopia was present in 14 patients: vertical due to skew deviation (static and or alternating on lateral gaze) (n = 8) and/or horizontal due to vergence dysfunction (n = 11). Symptomatic vergence dysfunction included convergence insufficiency (CI) (n = 4) and divergence insufficiency (n = 5). Thirteen of 16 patients experienced improvement in oscillopsia or imbalance on 4-aminopyridine (4-AP). CONCLUSIONS:Strabismus patterns causing diplopia in patients with SCA27B are, not unexpectedly, largely attributable to cerebellar dysfunction and are not unique to SCA27B. The exceptions to cerebellar localization were CI, sixth nerve palsy, and slow saccades. Careful assessment for DBN in patients presenting with episodic or persistent diplopia from skew deviation or vergence disorders is important, as this may be key to confirming a cerebellar localization, subtle on examination, and guide toward genetic testing and 4-AP treatment.

Positive airway pressure (PAP) adherence is lower in African Americans (AAs) and, possibly, Hispanics as compared to Whites. Access to other treatment modalities is also limited in these groups. In children, obstructive sleep apnea (OSA) prevalence is higher among AAs, Hispanics, and Asian Americans. AA children have lower rates of adenotonsillectomy. Interventions to dissipate misconceptions about sleep and OSA, better patient-provider communication, and standardized and targeted surveys and procedures are necessary to minimize this problem. This section will review disparities in PAP treatment and other options, as well as children's phenotypes, associated factors, and potential interventions.

INTRODUCTION/BACKGROUND:Though brain fog is common in Long-coronavirus disease 2019 (Long-COVID), the incidence of mild cognitive impairment (MCI) is unknown. METHODS:In an observational cohort study, recovered COVID-positive, Long-COVID, and COVID-negative subjects underwent blinded evaluation using National Alzheimer's Coordinating Center (NACC) and National Institute on Aging (NIA) -Alzheimer's Association diagnostic criteria for dementia and MCI. The cumulative incidence of MCI was calculated for each group, and the hazard of MCI was compared between groups. RESULTS:Among 260 subjects, the cumulative incidence of MCI over 4.4 years was higher with Long-COVID (27%) versus recovered-COVID (5%) or COVID-negative status (1%). There was a higher hazard of MCI for patients with Long-COVID compared to those without (hazard ratio [HR] 3.93, 95% confidence interval [CI] 1.86-8.31, p < 0.001), and specifically for the Alzheimer's disease (AD) -related MCI subtype (HR 3.20, 95% confidence interval [CI] 1.14-9.00, p = 0.027). DISCUSSION/CONCLUSIONS:The cumulative incidence and adjusted hazard of MCI (and specifically AD-related MCI) at 4.4 years was significantly higher among Long-COVID patients compared to recovered-COVID and COVID-negative controls.

INTRODUCTION/BACKGROUND:We examined obstructive sleep apnea (OSA) severity's association with Alzheimer's disease (AD) plasma biomarkers, independent or synergistic with cerebrospinal fluid (CSF) amyloid, and as a proof of concept, whether plasma amyloid beta (Aβ)42/Aβ40 with OSA severity improves detection of amyloidosis and tau pathology. METHODS:In 120 cognitively normal older adults (70 with CSF data) from New York University sleep and aging studies (2013-2021), OSA severity was measured using apnea/hypopnea index with 4% desaturation; plasma Aβ40, Aβ42, tau, and neurofilament light chain (NfL) via single molecule array; CSF amyloid and tau via enzyme-linked immunosorbent assay. Associations evaluated adjusted correlations and generalized models; receiver operating characteristic analyses evaluated diagnostic accuracy. RESULTS:OSA severity correlated with plasma Aβ40 (r = 0.21), Aβ42 (r = 0.26), and Aβ42/Aβ40 (r = 0.20). Plasma tau and NfL associations depended on CSF-Aβ42. OSA severity with Aβ42/Aβ40 improved CSF amyloidosis (area under the curve [AUC] = 0.78) and tau pathology (AUC = 0.71) detection. DISCUSSION/CONCLUSIONS:OSA severity relates to elevated plasma Aβ and, with CSF amyloid, to tau/NfL. Combined plasma and OSA measures aid non-invasive AD associations' detection.

Obstructive Sleep Apnea (OSA) is an extremely prevalent disorder and mostly underdiagnosed. Its prevalence is even higher among African Americans (AA), Hispanic, Asian Americans and Native Americans (NA) adults and children. AA present younger, with more severe and comorbid OSA, and are sleepier than their white counterparts. Evidence suggests this problem could be as severe in Hispanics, Asian Americans and NA. This first part of the review will focus on epidemiology and data in the adult population.