Knee extensor strength cutpoints provide objective markers to identify initially well-functioning older adults at high and low risk of future mobility limitation.

Thyroid dysfunction is associated with cognitive impairment and dementia, including Alzheimer's disease (AD). It remains unclear whether thyroid dysfunction results from, or contributes to, Alzheimer pathology. We determined whether thyroid function is associated with dementia, specifically AD, and Alzheimer-type neuropathology in a prospective population-based cohort of Japanese-American men. Thyrotropin, total and free thyroxine were available in 665 men aged 71-93 years and dementia-free at baseline (1991), including 143 men who participated in an autopsy sub-study. During a mean follow-up of 4.7 (S.D.: 1.8) years, 106 men developed dementia of whom 74 had AD. Higher total and free thyroxine levels were associated with an increased risk of dementia and AD (age and sex adjusted hazard ratio (95% confidence interval) per S.D. increase in free thyroxine: 1.21 (1.04; 1.40) and 1.31 (1.14; 1.51), respectively). In the autopsied sub-sample, higher total thyroxine was associated with higher number of neocortical neuritic plaques and neurofibrillary tangles. No associations were found for thyrotropin. Our findings suggest that higher thyroxine levels are present with Alzheimer clinical disease and neuropathology.

Objective. The ability of nonfluoroscopically guided radiography of the knee to assess joint space loss is an important issue in studies of progression and treatment of knee osteoarthritis (OA), given the practical limitations of protocols involving fluoroscopically guided radiography of the knee. We evaluated the ability of the nonfluoroscopically guided fixed-flexion radiography protocol to detect knee joint space loss over 3 years.Methods. We assessed the same-day test-retest precision for measuring minimum joint space width (JSW), the sensitivity for detection of joint space loss using serial films obtained a median of 37 months (range 23-47 months) apart, and the relationship of joint space loss to radiographic and magnetic resonance imaging (MRI) measures of knee OA. Participants were men and women (ages 70-79 years) with knee pain who were participating in the Health, Aging, and Body Composition Study. We assessed baseline radiographic OA and measured JSW using a computerized algorithm. Serial knee MRIs obtained over the same interval were evaluated for cartilage lesions.Results. A total of 153 knees were studied, 35% of which had radiographic OA at baseline. The mean ؎ SD joint space loss for all knees over 3 years was 0.24 ؎ 0.59 mm (P < 0.001 for change). In knees with OA at baseline, the mean ؎ SD joint space loss over 3 years was 0.43 ؎ 0.66 mm (P < 0.001), and in knees with joint space narrowing at baseline, joint space loss was 0.50 ؎ 0.67 mm (P < 0.001). Joint space loss and its standardized response mean increased with the severity of baseline joint space narrowing and with the presence of cartilage lesions at baseline and worsening during followup.Conclusion. Radiography of the knee in the fixedflexion view provides a sensitive and valid measure of joint space loss in multiyear longitudinal studies of knee OA, without the use of fluoroscopy to aid knee positioning.Serial radiographs remain the gold standard (and regulatory agency-approved) method of assessing cartilage loss in osteoarthritis (OA) of the knee. Although radiography does not permit direct visualization of cartilage, the minimum medial tibiofemoral interbone distance, or joint space width (JSW), parallels articular cartilage thickness in knees radiographed in a moderately flexed, weight-bearing position (1). Weight-bearing is essential to displace intervening joint fluid and bring the opposing cartilage surfaces into contact. Flexion of

Objective To examine the relationships between knee osteoarthritis (OA) and muscle parameters in a biracial cohort of older adults. Methods 858 participants in the Health, Aging and Body Composition Study were included in this cross-sectional analysis. Computed tomography (CT) was used to measure muscle area and quadriceps strength was measured isokinetically. Muscle quality (specific torque) was defined as strength per unit of muscle area for both total thigh and quadriceps. Knee OA was assessed based on radiographic features and knee pain. We compared muscle parameters between those with and without radiographic knee OA (+RKOA, −RKOA) and among four groups defined by +/− RKOA with and without pain. Results The mean age was 73.5 (2.9) years and mean BMI was 27.9 (4.8) kg/m2. 58% of participants were women and 44% were Black. Compared to − RKOA, +RKOA participants had a higher BMI (30.2 vs. 26.8 kg/m2), larger thigh muscles (117.9 vs. 108.9 cm2), and a greater amount of intermuscular fat (12.5 vs. 9.9 cm2) (all p<0.0001). In adjusted models, +RKOA subjects had significantly lower specific torque (p<0.001), indicating poorer muscle quality, than −RKOA subjects, but there was no difference between groups in quadriceps specific torque. +RKOA/−pain (p<0.05) and +RKOA/+pain (p<0.001) subjects had lower specific torque compared to −RKOA/−pain group. There were no significant differences in quadriceps specific torque among RKOA/pain groups. Conclusions Muscle quality was significantly poorer in participants with RKOA regardless of pain status. Future studies should address how lifestyle interventions might affect muscle quality and progression of knee OA.

As part of the Stage III Pig-a multilaboratory validation trial, we examined the induction of CD59-negative reticulocytes and total red blood cells (RET(CD59-) and RBC(CD59-) , respectively) in male Sprague Dawley(®) rats treated with 4-nitroquinoline-1-oxide (4NQO), for 28 consecutive days by oral gavage, at doses of 1.25, 2.50, 3.75, 5.00, and 7.50 mg kg(-1) day(-1) (the high dose group was sacrificed on Day 15 due to excessive morbidity/mortality). Animals also were evaluated for: micronucleated reticulocytes (mnRET) by flow cytometry; DNA damage in peripheral blood, liver, and stomach using the Comet assay; and chromosome aberrations (CAb) in peripheral blood lymphocytes (PBL). All endpoints were analyzed at two or more timepoints where possible. Mortality, body and organ weights, food consumption, and clinical pathology also were evaluated, and demonstrated that the maximum tolerated dose was achieved at 5.00 mg kg(-1) day(-1) . The largest increases observed for the genetic toxicology endpoints (fold-increase compared to control, where significant; all at 5.00 mg kg(-1) day(-1) on Day 29) were: RET(CD59-) (21X), RBC(CD59-) (9.0X), and mnRET (2.0X). In contrast, no significant increases were observed for the CAb or Comet response, in any tissue analyzed, at any timepoint. Because 4NQO is a well known mutagen, clastogen, and carcinogen, the lack of response for these latter endpoints was unexpected. These results emphasize the extreme care that must betaken in dose and endpoint selection when incorporating genotoxicity endpoints into routine toxicity studies as has been recommended or is under consideration by various regulatory and industrial bodies.

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