Citations

AbstractInfection is a rare occurrence after revision anterior cruciate ligament reconstruction (rACLR). Because of the low rates of infection, it has been difficult to identify risk factors for infection in this patient population. The purpose of this study was to report the rate of infection following rACLR and assess whether infection is associated with patient‐ and surgeon‐dependent risk factors. We reviewed two large prospective cohorts to identify patients with postoperative infections following rACLR. Age, sex, body mass index (BMI), smoking status, history of diabetes, and graft choice were recorded for each patient. The association of these factors with postoperative infection following rACLR was assessed. There were 1423 rACLR cases in the combined cohort, with 9 (0.6%) reporting postoperative infections. Allografts had a higher risk of infection than autografts (odds ratio, 6.8; 95% CI, 0.9–54.5; p = .045). Diabetes (odds ratio, 28.6; 95% CI, 5.5–149.9; p = .004) was a risk factor for infection. Patient age, sex, BMI, and smoking status were not associated with risk of infection after rACLR.

AbstractObjectiveThe Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects evaluates familial frontotemporal lobar degeneration (FTLD) kindreds with MAPT, GRN, or C9orf72 mutations. Objectives were to examine whether health‐related quality of life (HRQoL) correlates with clinical symptoms and caregiver burden, and whether self‐rated and informant‐rated HRQoL would correlate with each other.MethodsIndividuals were classified using the Clinical Dementia Rating (CDR®) Scale plus National Alzheimer's Coordinating Center (NACC) FTLD. HRQoL was measured with DEMQOL and DEMQOL‐proxy; caregiver burden with the Zarit Burden Interview (ZBI). For analysis, Pearson correlations and weighted kappa statistics were calculated.ResultsThe cohort of 312 individuals included symptomatic and asymptomatic individuals. CDR® plus NACC FTLD was negatively correlated with DEMQOL (r = −0.20, P = .001), as were ZBI and DEMQOL (r = −0.22, P = .0009). There was fair agreement between subject and informant DEMQOL (κ = 0.36, P <.0001).ConclusionLower HRQoL was associated with higher cognitive/behavior impairment and higher caregiver burden. These findings demonstrate the negative impact of FTLD on individuals and caregivers.

AbstractIntroductionBehavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments.MethodsA total of 135 sporadic (s‐bvFTD; mean age 63.3 years; 34% female) and 99 familial (f‐bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f‐bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule‐associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation.ResultsParticipants with f‐bvFTD were younger and had earlier age at onset. s‐bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI‐Q) scores due to more frequent endorsement of depression and irritability.Discussionf‐bvFTD and s‐bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

AbstractIntroductionWe created global rating scoring rules for the CDR® plus NACC FTLD to detect and track early frontotemporal lobar degeneration (FTLD) and to conduct clinical trials in FTLD.MethodsThe CDR plus NACC FTLD rating was applied to 970 sporadic and familial participants from the baseline visit of Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS). Each of the eight domains of the CDR plus NACC FTLD was equally weighed in determining the global score. An interrater reliability study was completed for 40 participants.ResultsThe CDR plus NACC FTLD showed very good interrater reliability. It was especially useful in detecting clinical features of mild non‐fluent/agrammatic variant primary progressive aphasia participants.DiscussionThe global CDR plus NACC FTLD score could be an attractive outcome measure for clinical trials in symptomatic FTLD, and may be useful in natural history studies and clinical trials in FTLD spectrum disorders.

AbstractIntroductionThe Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes.MethodsWe screened the major dementia‐associated genes in 302 sporadic and 390 familial (symptomatic or at‐risk) participants enrolled in these studies.ResultsAmong the sporadic patients, 16 (5.3%) carried chromosome 9 open reading frame 72 (C9orf72), microtubule‐associated protein tau (MAPT), and progranulin (GRN) pathogenic variants, whereas in the familial series we identified 207 carriers from 146 families. Of interest, one patient was found to carry a homozygous C9orf72 expansion, while another carried both a C9orf72 expansion and a GRN pathogenic variant. We also identified likely pathogenic variants in the TAR DNA binding protein (TARDBP), presenilin 1 (PSEN1), and valosin containing protein (VCP) genes, and a subset of variants of unknown significance in other rare FTD genes.DiscussionOur study reports the genetic characterization of a large FTD series and supports an unbiased sequencing screen, irrespective of clinical presentation or family history.

AbstractIntroductionLeisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsA total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non‐carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans.ResultsGreater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High‐activity carriers with frontotemporal atrophy (−1 standard deviation/year) demonstrated >two‐fold better cognitive performances per year compared to their less active peers with comparable atrophy rates.DiscussionActive lifestyles were associated with less functional decline and moderated brain‐to‐behavior relationships longitudinally. More active carriers “outperformed” brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

AbstractIntroductionConventional Z‐scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these “adjusted” Z‐scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z‐scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.MethodsIn this article, we consider nonlinear shape constrained additive models accounting for age, sex, and education (correcting for nonlinearity). Additional shape constrained additive models account for varying standard deviation of the cognitive scores with age (correcting for heterogeneity of variance).ResultsCorrected Z‐scores based on nonlinear shape constrained additive models provide improved adjustment for age, sex, and education, as indicated by higher adjusted‐R2.DiscussionNonlinearly corrected Z‐scores with respect to age, sex, and education with age‐varying residual standard deviation allow for improved detection of non‐normative extreme cognitive scores.