Citations

Objective Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large‐scale comparative studies. Methods Three hundred ninety‐nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition. Results The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74–82) than in ADNI (71%, 95% CI = 67–75, p = 0.02). Lower Mini‐Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid‐positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD. Interpretation Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236–248

Aim Cognitive and behavioral phenomena define behavioral variant frontotemporal dementia (bvFTD), but neuropsychiatric symptoms (NPS) outside the core criteria are common throughout the illness. Identifying how NPS cluster in bvFTD may guide development of future therapies. Methods Participants ( n = 354) with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration Consortium. Dementia stage was defined as early (CDR® plus NACC FTLD ≤1) or advanced (CDR® plus NACC FTLD ≥1). Baseline and annual follow‐up visit data were analyzed to compare NPS across stages of bvFTD. Psychiatric states were captured using the Neuropsychiatric Inventory‐Questionnaire and Clinician Judgment of Symptoms. Polychoric cluster analysis was used to describe NPS clusters. Results NPS were highly prevalent (≥90%) in early and late bvFTD. Four NPS clusters were identified based on magnitude of factor loadings: affective, disinhibited, compulsive, and psychosis. Neuropsychiatric symptoms fluctuated across visits. In the affective cluster, depression showed the least visit‐to‐visit stability. In the disinhibited cluster, elation showed the least stability. Symptoms in the psychosis and compulsive clusters (hallucinations, delusions, obsessions/compulsions, and hyperorality) were largely stable, persisting from visit‐to‐visit in more than 50% of cases. Symptoms in the affective and disinhibited cluster were associated with the highest caregiver burden, while symptoms in the obsessive cluster were associated with the most functional impairment. Conclusion NPS in bvFTD are frequent and cluster into four discrete groups. The fluctuating nature of some NPS in bvFTD suggests that they may not be reliable markers of disease progression or stage.

Abstract Background: Self-efficacy theory proposes that confidence to engage in a health behavior is associated with engaging in that specific behavior. Most research examining self-efficacy has been conducted with white young adult populations. This secondary analysis examined the association of self-efficacy (i.e., confidence) for healthy eating and physical activity in two immigrant communities. Methods: At enrollment into the Healthy Immigrant Community study, a clinical weight management and cardiovascular risk reduction intervention set in southeastern [state], 475 participants completed assessments about their confidence for healthy eating and physical activity. Measurements also included self-reports of dietary quality and intake, physical activity, quality of life, and biometric assessments. Study materials were available in English, Spanish, and Somali. Results In total, 450 adults (Hispanic/Latinx = 267; Somali = 183) completed measures at baseline and were included for analysis. Their average age was 45 years (range 18–87) and 59% were female. Confidence for healthy eating was significantly associated with self-report of eating healthy snacks ( p = < 0.0001) and less consumption of high-calorie drinks ( p = 0.02) and regular soda ( p = < 0.0001). Confidence to be physically active was significantly associated with more self-reported physical activity ( p = < 0.01). Conclusions Confidence to eat healthy and be physically active appears to be associated with having a healthier diet and higher levels of physical activity. Given the large sample size and strength of the associations, it also appears that the theoretical model of self-efficacy can be effectively measured and applied within these immigrant populations. Self-efficacy theory may be useful in understanding potential mediating mechanisms when designing future interventions with immigrant communities. ClinicalTrials.gov registration: NCT05136339; April 23, 2022

Abstract INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison of cortical atrophy in EOAD and LOAD, using two large and well‐characterized cohorts (LEADS and ADNI). METHODS We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early‐stage AD), along with cognitively unimpaired participants. RESULTS After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD. DISCUSSION Our findings point to the clinical utility of MRI‐based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment. Highlights Early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.

Background and Objectives: Hearing loss is relatively common in older individuals, and individuals with frontotemporal lobar degeneration (FTLD) are no exception; this can exacerbate communication difficulties stemming from speech-language impairments. The co-occurrence of these symptoms can contribute to increased frustration and isolation for patients and their communication partners. The objective of this study was to evaluate the feasibility of self-administered hearing testing. Ultimately, this could be administered remotely, which would increase access to assessment and inform management for this population. Method: Seventeen patients with underlying FTLD, clinically presenting with progressive apraxia of speech with and without agrammatic aphasia, independently completed the Home Hearing Test supervised while in office. Results: Three patients self-reported hearing loss, but results for 100% recommended formal evaluation. Eleven patients demonstrated good test accuracy. Six patients had “poor” or not computable accuracy; among them, five had evidence of cognitive impairment and/or behavioral changes, and one had known severe hearing loss, although differences between those with good and poor test accuracy were not significant. Patients with poor test accuracy had more difficulty with limb praxis. Conclusions: Most participants independently completed the test, though some had reduced test accuracy that may have been associated with cognitive impairment and/or limb apraxia. This study supports the need for hearing screenings in all patients with progressive apraxia of speech and aphasia and highlights both the feasibility and caution required in implementing self-administered testing protocols. Further work should evaluate the feasibility of in-home hearing screenings in a broader range of FTLD phenotypes and directly compare sensitivity and specificity of hearing loss detection with in-clinic administration. Supplemental Material: https://doi.org/10.23641/asha.28306613

Background: Anterior cruciate ligament reconstruction (ACLR) is one of the most common orthopaedic procedures and one of the most well studied. Despite extensive research dedicated to ACLR, there is limited understanding of how chronic inflammatory systemic diseases (CIDs) such as rheumatoid arthritis and systemic lupus erythematosus affect outcomes. Purpose: To compare the outcomes of ACLR in cohorts of patients with and without CID. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective query of a regional data set was conducted for all patients who underwent ACLR from 1990 to 2021 for traumatic ACL rupture. All patients with CID were identified and propensity matched to non-CID controls. Baseline characteristics and clinical outcomes were identified through retrospective chart review, and patients were contacted for subjective outcomes. Results: A total of 30 patients with ACLR and a diagnosis of CID were identified. These patients were propensity matched to 120 non-CID controls. Baseline demographic and surgical characteristics demonstrated no statistical differences. Follow-up duration was similar between the CID and non-CID groups (mean, 14.6 vs 14.2 years; P = .868). The CID cohort had a higher arthrofibrosis rate (16.7% vs 4.3%; P = .031), higher osteoarthritis rate (33.3% vs 16.7%; P = .041), higher total knee arthroplasty (TKA) rate (16.7% vs 3.3%; P = .016), and earlier time to TKA (14.7 vs 23.5 years; P = .032). Knee range of motion, infection rate, retear rate, time to retear, and time to osteoarthritis were not statistically different between the cohorts. The CID cohort had higher visual analog scale pain scores (mean, 2.00 vs 1.20; P = .043) but slightly higher satisfaction (mean, 3.92 vs 3.39; P = .043). There were no differences in preinjury Tegner, postoperative Tegner, change in Tegner, or IKDC score. In a univariate Cox regression model, the CID cohort had a retear hazard ratio of 1.43 (95% CI, 0.46-4.51; P = .537). Kaplan-Meier survival revealed no significant differences in retear-free survival between the CID and non-CID cohorts at 25 years (85.7% vs 87.3%; P = .53). The CID cohort had a TKA hazard ratio of 3.94 (95% CI, 1.05-14.8; P = .042). Kaplan-Meier survival demonstrated significantly decreased TKA-free survival at 25 years in the CID cohort (64.9% vs 91.2%; P = .029). Conclusion: CID increases the incidence of arthrofibrosis, osteoarthritis, and TKA in those undergoing ACLR. Patients with CID also undergo TKA significantly sooner than non-CID counterparts. Notably, the majority of patient-reported outcome measures are no worse in patients who have a CID diagnosis. Thus, ACLR constructs themselves may not necessarily fare worse in patients with CID. Nonetheless, these patients need to be cautiously counseled on the clinical outlook after their ACLR.

Abstract Limbic predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) is highly prevalent in late life and a common co‐pathology with Alzheimer's disease neuropathologic change (ADNC). LATE‐NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE‐NC is associated with a more rapid course. With the emergence of anti‐amyloid therapeutics, discrimination of LATE‐NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co‐pathology with LATE‐NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE‐NC. We propose criteria for clinical diagnosis of LATE as an initial framework for further validation. In the context of progressive memory loss and substantial hippocampal atrophy, criteria are laid out for probable (amyloid negative) or possible LATE (amyloid biomarkers are unavailable or when amyloid is present, but hippocampal neurodegeneration is out of proportion to expected pure ADNC). Highlights Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) is a highly prevalent driver of neuropathologic memory loss in late life. LATE neuropathologic change (LATE‐NC) is a common co‐pathology with Alzheimer's disease neuropathologic change (ADNC) and may influence outcomes with emerging disease‐modifying medicines. We provide initial clinical criteria for diagnosing LATE during life either when LATE‐NC is the likely primary driver of symptoms or when observed in conjunction with AD. Definitions of possible and probable LATE are provided.