Citations

Abstract Background Agitation is a clinically significant symptom contributing to behavioral and psychological symptoms of dementia (BPSD) but is poorly understood across the different syndromes related to Frontotemporal Lobar Degeneration (FTLD). This study investigates sex differences in agitation across FTLD‐related syndromes and its relationship to various neuropsychiatric symptoms (NPS). Method We analyzed data from 1,654 participants (916 males, 738 females; average ages 65.8 and 65.9, respectively) from the National Alzheimer's Coordinating Center (NACC) and ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study with a FTLD‐related syndrome: behavioral variant FTD (bvFTD), Primary Progressive Aphasia (non‐fluent variant (nfvPPA), semantic variant (svPPA)), Corticobasal syndrome (CBS) and Progressive Supranuclear Palsy (PSP). Participants’ symptoms were assessed using the Neuropsychiatric Inventory (NPI). Prevalence ratios and odds ratios were computed to assess the likelihood of NPS comorbidities when agitation was present in males and females. Principal Component Analysis (PCA) was performed to identify NPS associated with agitation and how they varied by sex. Result Males were more likely to experience anxiety (bvFTD: p <0.001, CBS: p <0.01, PSP: p <0.0001), apathy (nfvPPA: p <0.01, PSP: p <0.01), depression (bvFTD: p <0.0001, PSP<0.01), disinhibition (nfvPPA: p <0.0001), PSP: p <0.001), and motor symptoms (bvFTD: p <0.01, CBS: p <0.01) when agitation was present. In contrast, females had a higher likelihood of experiencing disinhibition in svPPA ( p <0.001). These findings suggest that agitation is associated with a wider range of NPS in males than in females. Agitation and NPS are especially prominent in males with PSP. Conclusion This study reveals significant sex differences in NPS in FTLD‐related syndromes when agitation is present. Males and especially PSP, are more likely to experience a broader range of NPS in association with agitation. These findings underscore the need for further investigation into the underlying mechanisms driving these sex differences, particularly focusing on the neurobiological impact of agitation, the recognition of symptoms in the presence of greater behavioral disturbances, and potential variations from informant reports. Understanding these factors will provide valuable insights into the role of agitation in the presentation of NPS across FTLD‐related syndromes. Ultimately, addressing these gaps will enhance our ability to effectively treat and manage agitation in both male and female patients with FTLD‐related syndromes.

Abstract Background Staging disease severity in dementia research requires input from an informant. The Clinical Dementia Rating Sum of Boxes (CDR) is the most used instrument for staging in Alzheimer's Disease (AD); but has been expanded to stage patients with frontotemporal lobar degeneration (FTLD) with the CDR PLUS NACC‐FTLD. An informant effect on the CDR has been reported in AD. The aim of this study is to evaluate whether informant characteristics influence the CDR PLUS NACC‐FTLD in a large cohort of participants with frontotemporal dementia (FTD). Method We included participants with a FTLD‐related syndrome from the ALLFTD study. We included participants with a CDR PLUS NACC‐FTLD higher than 0, information on the Montreal Cognitive Assessment (MoCA) scores, and the Neuropsychiatric Inventory Questionnaire (NPI‐Q). We performed a conditional growth model using multilevel linear regression analysis. We performed an exploratory stratified analysis by patient sex. Result We included 1411 participants, totalling 2063 visits. The patient's age at the initial visit was 64.7±9.4 years and 44.0% were females. Females were 69.2% of the informants, and the relationship was 79.1% spouse or partner, 10.6% children, 4.1% were siblings and 6.2% other. The CDR PLUS NACC‐FTLD scores were affected by informant characteristics. The CDR PLUS NACC‐FTLD scores were 0.41 (CI 95%:0.08 to 0.75) higher with female informants. The frequency of visits was associated with a CDR PLUS NACC‐FTLD score 0.86 higher (CI 95%:0.17 to 0.56) when visiting at least once a week, 1.46 higher (CI 95%:0.46 to 2.47) when visiting daily, and 0.83 higher (CI 95%:0.06 to 1.60) when living with the patient compared with visiting less than once a week. As expected, CDR‐FLTD scores increased with lower MoCA and higher NPI‐Q scores. In the stratified analysis by sex, we found that female informant was associated with higher CDR PLUS NACC‐FTLD scores only when patients were male. Conclusion We found that the CDR PLUS NACC‐FTLD is influenced by informant sex and frequency of visits in patients with FTLD‐related syndromes. These results are similar to those observed in AD patients and underscore the need to recognize that informant characteristics may impact dementia severity scales.

Abstract INTRODUCTION Psychotropic medication (PM) use in behavioral‐variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD. METHODS We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study. We estimated ordinal odds ratio (OOR) of having more PM comparing sporadic and genetic bvFTD. Finally, we explored the neuropsychiatric symptom (NPS) combinations using classification and regression trees (CART). RESULTS We included 263 with sporadic and 193 with genetic bvFTD. The OOR for sporadic bvFTD to be on PM was 1.75 (95% confidence interval: 1.21 to 2.53) for the fully adjusted model. CART revealed the most common NPS combination was apathy + personality changes in 18% of participants. DISCUSSION Participants with sporadic bvFTD were twice as likely to be on PM compared to genetic bvFTD. The reason for increased PM usage in sporadic bvFTD participants should be further investigated. Highlights We report on patients with behavioral variant frontotemporal dementia (bvFTD). We evaluated the psychotropic medication (PM) prescription at baseline in the cohort. Patients with sporadic bvFTD had more prescriptions for PM than genetic patients. The frequency of symptoms combination was different in sporadic and genetic bvFTD.

Background: Periacetabular osteotomy (PAO) remains the gold-standard treatment for acetabular dysplasia in skeletally mature patients with preserved cartilage. The purpose of this multicenter cohort study was to delineate the long-term radiographic natural history of the dysplastic hip following PAO based on the final position of the acetabular fragment. Methods: We evaluated patients who underwent PAO performed by 4 hip preservation surgeons to treat acetabular dysplasia with or without concomitant retroversion from 1996 to 2012 at 3 academic institutions. There were 288 patients with a mean clinical and radiographic follow-up of 9 years (range, 5 to 21 years). Postoperative radiographs made at the first clinical visit were used to determine if the acetabular fragment fell into a safe zone according to the absence of retroversion, a lateral center-edge angle (LCEA) of 25° to 40°, an anterior center-edge angle (ACEA) of 25° to 40°, and a Tönnis angle of 0° to 10°. Every available subsequent radiograph was assessed for degenerative changes by the Tönnis classification (grades 0 to 3). The time to progression was analyzed using Cox proportional hazards regression and multistate modeling. Results: Only the absence of retroversion was independently associated with a decreased risk of progressing at least 1 Tönnis grade during follow-up: hazard ratio (HR), 0.60 (95% confidence interval [CI], 0.38 to 0.94; p = 0.025). Achieving the ACEA safe zone yielded the greatest time increase for remaining in Tönnis grade 0 or 1 (43 years for having an ACEA in the safe zone compared with 28 years for not having an ACEA in the safe zone), followed by the absence of retroversion (34 years for the absence of retroversion compared with 24 years for the presence of retroversion). However, attaining the Tönnis angle or LCEA safe zones did not delay progression. The achievement of additional safe zones generally increased the length of time that patients spent in Tönnis grade 0 or 1: 25 years for 0 safe zones, 36 years for 1 safe zone, 29 years for 2 safe zones, 37 years for 3 safe zones, and 44 years for 4 safe zones. Conclusions: This study demonstrates the importance of achieving appropriate acetabular reorientation to enhance the longevity of the native hip following PAO. Although the LCEA and the Tönnis angle are the most common metrics used to assess appropriate acetabular correction, this study shows that adequately addressing retroversion and the ACEA has a greater impact on improving the natural history. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: Unicompartmental knee arthroplasty (UKA) is a viable option for patients with symptomatic knee arthritis isolated to 1 compartment. Previous articles have suggested that mobile-bearing UKA should not be performed in patients without bone-on-bone arthritis. The purpose of this study was to compare the clinical outcomes and survivorship of mobile-bearing UKA in patients with severe osteoarthritis with bone-on-bone contact and patients with severe osteoarthritis but without bone-on-bone contact. Methods: We retrospectively reviewed a single surgeon’s experience with medial compartment mobile-bearing UKA in 219 patients (271 knees) who underwent the procedure between 2007 and 2015. Anteroposterior and posteroanterior radiographs were reviewed, and arthritis was graded using the International Knee Documentation Committee (IKDC) grading system. Only patients with grade D (severe arthritis) were studied. Of the patients who had grade-D arthritis, there were 81 patients (94 knees) with bone-on-bone arthritis and 82 patients (91 knees) without bone-on-bone contact. Functional outcomes were assessed using the Knee Society pain and function scores. Survivorship free of revision in these 2 groups was determined using Kaplan-Meier curves at 8 years. Results: There were no significant differences between the 2 groups in terms of age (p = 0.91), sex (p = 0.21), or body mass index (p = 0.63). At the time of the final follow-up, there was no significant difference in Knee Society pain scores (p = 0.59) or Knee Society function scores (p = 0.9) between the 2 groups. There were 5 revisions in the group with bone-on-bone contact and 2 revisions in the group without bone-on-bone contact. The survivorship free of revision at 8 years was 95% for the group with bone-on-bone contact and 98% for the group without bone-on-bone contact (p = 0.45). Conclusions: Patients with severe knee arthritis (IKDC grade D) without bone-on-bone contact had similar outcomes of mobile-bearing UKA compared with patients with bone-on-bone contact. UKA is a safe and reliable option in patients with severe osteoarthritis who do not have bone-on-bone contact on preoperative radiographs and it should therefore not be considered a contraindication for mobile-bearing UKA as long as the patient’s symptoms are severe enough to warrant surgical intervention. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Background: Periacetabular osteotomy (PAO) is the most common treatment for symptomatic acetabular dysplasia, or developmental dysplasia of the hip (DDH), in skeletally mature patients. The purpose of this multicenter cohort study was to delineate the long-term radiographic natural history of the dysplastic hip following PAO. Methods: We evaluated all patients undergoing PAO from 1996 to 2012 at 3 academic institutions in the United States. Inclusion criteria were PAO for DDH with a minimum 5-year radiographic follow-up. Exclusion criteria were PAO for isolated acetabular retroversion, neurogenic dysplasia, Legg-Calvé-Perthes disease, and prior hip surgery including osteotomies and arthroscopy. There were 288 patients, 83% of whom were women; the mean age and body mass index (BMI) were 29 years and 25 kg/m 2 , respectively. The mean clinical and radiographic follow-up was 9.2 years (range, 5.0 to 21.1 years). Every preoperative and postoperative hip radiograph was assessed to determine the degree of osteoarthritis according to the Tönnis classification. Survivorship was analyzed by multistate modeling, enabling assessment of progression through the Tönnis grades rather than just individual transitions as with Kaplan-Meier techniques. Results: At the time of final follow-up, 144 patients (50%) had progressed at least 1 Tönnis grade, with 42 patients (14.6%) undergoing total hip arthroplasty. The mean number of years spent in each Tönnis grade following PAO was 19 for Tönnis grade 1, 8 for Tönnis grade 2, and 4 for Tönnis grade 3. The probability of progression to total hip arthroplasty increased significantly on the basis of a higher initial Tönnis grade (p < 0.001). The most marked difference occurred between Tönnis grade 0 or 1 and Tönnis grade 2; for Tönnis grade 1, the probability of progression to total hip arthroplasty at 5 and 10 years was 2% and 11%, respectively, compared with 23% and 53%, respectively, for Tönnis grade 2. Conclusions: PAO effectively alters the natural history of DDH. Precise radiographic progression based on the Tönnis grade can now be used to ascribe prognosis for the native hip. Importantly, this investigation demonstrates a stark increase in progression to total hip arthroplasty within 10 years of PAO for patients with preoperative Tönnis grade-2 osteoarthritis compared with those with Tönnis grade-0 or 1 osteoarthritis. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.