Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent.

BACKGROUND: Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD) making diagnosis challenging. Serum neurofilament light (sNfL) is a candidate biomarker to distinguish bvFTD from PPD, but large-scale studies in PPD are lacking. OBJECTIVE: Determine factors that influence sNfL from a large database of PPD patients, and test its diagnostic accuracy. DESIGN, SETTINGS, SUBJECTS, MEASUREMENTS: Clinical data of people aged 40-81 were obtained from healthy subjects (n = 69), and patients with PPD (n = 848) or bvFTD (n = 82). sNfL was measured using Simoa technology on an HD-X instrument. Data were analyzed using general linear models, and Receiver Operating Characteristic (ROC) curve analyses to determine global and age-specific sNfL cutoffs to distinguish bvFTD from PPD, using the Youden Index. RESULTS: sNfL increased with age, while sex, BMI and diabetes status were modestly associated with sNfL. sNfL was slightly higher in PPD than healthy subjects (14.1 versus 11.7 pg/mL), when controlling for covariates. sNfL was markedly lower in PPD than bvFTD (14.1 versus 44.1 pg/mL). sNfL could differentiate PPD from bvFTD with an AUC = 0.868, but the effect was driven by the younger subjects between age 40-60 years at a cutoff of 16.0 pg/mL. No valid cutoff was detected over age 60, however, values of sNfL above 38.5 pg/mL, or below 13.9 pg/mL, provided 90% diagnostic certainty of bvFTD or PPD, respectively. CONCLUSION: PPD have mildly elevated sNfL compared to healthy subjects but much lower than bvFTD. Results support the use of sNfL as a biomarker to differentiate PPD from bvFTD at age 60 or below, but accuracy decreases in older ages.

Temporal-spatial gait analysis by use of a portable walkway system in healthy Labrador Retrievers at a walk.

OBJECTIVE: To establish a protocol to collect temporal-spatial gait analysis variables by use of a portable walkway system in Labrador Retrievers at a walk and to determine reference values. ANIMALS: 56 healthy Labrador Retrievers. PROCEDURES: 6 passes across the walkway (3 passes in each direction) were recorded. Inclusion criteria for a pass were that the dog was at a walk (velocity, 60.0 to 90.0 cm/s) and had minimal head turning. The first 3 passes that met the inclusion criteria were analyzed for each dog. RESULTS: Mean stride length was 88.4 cm. Mean stance time (ST) of forelimbs and hind limbs was 0.62 and 0.56 seconds, respectively. Mean stance time percentage (ST%; proportion of stance time to total gait cycle time) for forelimbs and hind limbs was 55.6% and 50.2%, respectively. Mean total pressure index (TPI) of forelimbs and hind limbs was 27.1 and 17.4, respectively. Mean number of sensors (NS) activated by each paw strike of forelimbs and hind limbs was 17 and 13, respectively. Mean forelimb-to-hind limb symmetry ratios were 1.11 (ST), 1.10 (ST%), 1.62 (TPI), and 1.37 (NS). Symmetry ratios for left limbs to right limbs, left forelimb to right forelimb, and left hind limb to right hind limb were 1.00. CONCLUSIONS AND CLINICAL RELEVANCE: A protocol for collection of temporal-spatial gait analysis variables with a portable walkway system in Labrador Retrievers at a walk was developed, and reference values for variables and symmetry ratios were reported. Further research will determine the extent to which symmetry ratios differ in dogs with orthopedic disorders.

Sex hormone regulation of collagen concentrations in cranial cruciate ligaments of sexually immature male rabbits.

OBJECTIVE: To investigate the effects of gonadectomy on collagen homeostasis in cranial cruciate ligaments of male rabbits. ANIMALS: 30 sexually immature (16-week-old) male New Zealand White rabbits. PROCEDURES: Rabbits were randomly assigned to 5 groups of 6 rabbits each: sexually intact, placebo (control group); castrated, placebo; castrated, testosterone; castrated, dihydrotestosterone; and castrated, 17ß-estradiol (E(2)). Control rabbits underwent a sham operation, and all other rabbits underwent gonadectomy. At the time of gonadectomy, the placebo and sex hormones were administered via slow-release pellets implanted subcutaneously as assigned. After 21 days of hormone supplementation, measurements were obtained of serum testosterone and E(2) concentrations, ligament collagen characteristics, and androgen receptor, estrogen receoptor α, and matrix metalloproteinase expression. RESULTS: Following gonadectomy and hormone supplementation, the treatment groups differed in serum testosterone and E(2) concentrations to various degrees. Collagen concentrations were lower and fiber diameters higher in the absence of sex hormones, in association with the degrees of estrogen receptor a and androgen receptor expression. Although differences were detected among the groups in matrix metalloproteinase expression, these differences were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Sex hormones appeared to play a role in cranial cruciate ligament homeostasis in male rabbits. Physiologic changes triggered by the lack of sex hormones following gonadectomy in sexually immature rabbits may potentially predispose those rabbits to orthopedic injuries.