Alain Koyama

Reduction in proximal femoral strength due to long-duration spaceflight

Loss of bone mass is a well-known medical complication of long-duration spaceflight. However, we do not know how changes in bone density and geometry ultimately combine to affect the strength of the proximal femur as a whole. The goal of this study was to quantify the changes in proximal femoral strength that result from long-duration spaceflight. Pre-and post-flight CT scan-based patient-specific finite element models of the left proximal femur of 13 astronauts who spent 4.3 to 6.5 months on the International Space Station were generated. Loading conditions representing single-limb stance and a fall onto the posterolateral aspect of the greater trochanter were modeled, and proximal femoral strength (F(FE)) was computed. Mean F(FE) decreased from 18.2 times body weight (BW) pre-flight to 15.6 BW post-flight for stance loading and from 3.5 BW pre-flight to 3.1 BW post-flight for fall loading. When normalized for flight duration, F(FE) under stance and fall loading decreased at mean rates of 2.6% (0.6% to 5.0%) per month and 2.0% (0.6% to 3.9%) per month, respectively. These values are notably greater than previously reported reductions in DXA total femoral bone mineral density (0.4 to 1.8% per month). In some subjects, the magnitudes of the reductions in proximal femoral strength were comparable to estimated lifetime losses associated with aging. Although average post-flight proximal femoral strength is greater than forces expected to occur due to falls or normal activities, some subjects have small margins of safety. If proximal femoral strength is not recovered, some crew members may be at increased risk for age-related hip fractures decades after their missions.

The Role of Peripheral Inflammatory Markers in Dementia and Alzheimer’s Disease: A Meta-Analysis

BACKGROUND Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimers disease (AD). METHODS The researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I (2) statistic. RESULTS Seven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I (2) = 0%-40%, p ≥ .16). CONCLUSIONS An increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.

Pelvic body composition measurements by quantitative computed tomography: Association with recent hip fracture

INTRODUCTION Loss of subcutaneous fat, decreased muscle cross-sectional area (CSA) and increased muscle adiposity are related to declining physical function and disability in the elderly, but there is little information about the relationship of these tissue changes to hip fracture. Thus we have compared body composition measures in women with hip fractures to age-matched controls, using quantitative computed tomography (QCT) imaging of the hip to characterize total adiposity, muscle CSA and muscle attenuation coefficient, a measure of adiposity. MATERIALS AND METHODS 45 Chinese women (mean age 74.71+/-5.94) with hip fractures were compared to 66 healthy control subjects (mean age 70.70+/-4.66). Hip QCT scans were analyzed to compute total adipose CSA as well as CSA and attenuation values of muscle groups in the CT scan field of view, including hip extensors, abductors, adductors and flexors. The total femur areal BMD (aBMD) was estimated from the QCT images. Logistic regression was employed to compare body composition measures between fracture subjects and controls after adjustment for age, height, BMI and aBMD. Receiver-operator curve (ROC) analyses determined whether combinations of aBMD and body composition had higher area under curve (AUC) than aBMD alone. RESULTS AND CONCLUSIONS Fracture subjects had lower fat CSA (p<0.0001) than controls but had higher muscle adiposity as indicated by lower attenuation in the adductor, abductor and flexor groups (0.00001<p<0.02). Fracture subjects also had lower extensor and adductor CSA values (p<0.0001). After age and BMI adjustment, the total fat CSA, the extensor and adductor CSA values, and the adductor attenuation values remained significantly lower in the fracture subjects (0.001<p<0.05). In ROC analyses, models combining aBMD with soft tissue measures had higher AUC than models containing only BMD (0.001<p<0.05). Combining body composition with skeletal measures may improve fracture prediction compared to bone measures alone.

Long-term Cognitive and Functional Effects of Potentially Inappropriate Medications in Older Women

BACKGROUND The use of potentially inappropriate medications in older adults can lead to known adverse drug events, but long-term effects are less clear. We therefore conducted a prospective cohort study of older women to determine whether PIM use is associated with risk of functional impairment or low cognitive performance. METHODS We followed up 1,429 community-dwelling women (≥ 75 years) for a period of 5 years at four clinical sites in the United States. The primary predictor at baseline was PIM use based on 2003 Beers Criteria. We also assessed anticholinergic load using the Anticholinergic Cognitive Burden scale. Outcomes included scores on a battery of six cognitive tests at follow-up and having one or more incident impairments in instrumental activities of daily living. Regression models were adjusted for baseline age, race, education, smoking, physical activity, a modified Charlson Comorbidity Index, and cognitive score. RESULTS The mean ± SD age of women at baseline was 83.2 ± 3.3. In multivariate models, baseline PIM use and higher ACB scores were significantly associated with poorer performance in category fluency (PIM: p = .01; ACB: p = .02) and immediate (PIM: p = .04; ACB: p = .03) and delayed recall (PIM: p = .04). Both PIM use (odds ratio [OR]: 1.36 [1.05-1.75]) and higher ACB scores (OR: 1.11 [1.04-1.19]) were also strongly associated with incident functional impairment. CONCLUSIONS The results provide suggestive evidence that PIM use and increased anticholinergic load may be associated with risk of functional impairment and low cognitive performance. More cautious selection of medications in older adults may reduce these potential risks.

Development and validation of a brief dementia screening indicator for primary care.

Detection of “any cognitive impairment” is mandated as part of the Medicare annual wellness visit, but screening all patients may result in excessive false positives.

Ten-Year Trajectory of Potentially Inappropriate Medications in Very Old Women: Importance of Cognitive Status

To determine which older adults tend to receive potentially inappropriate medications (PIMs), how this may differ according to cognitive status, and how the trajectories of PIM use change over time.

Association Between the Mediterranean Diet and Cognitive Decline in a Biracial Population

BACKGROUND Results from numerous studies suggest protective effects of the Mediterranean diet for cardiovascular disease, cancer, and mortality. Evidence for an association with a decreased risk of cognitive decline is less consistent and studies are limited by a lack of diversity in their populations. METHODS We followed 2,326 older adults (38.2% black, 51.3% female, aged 70-79 at baseline) over 8 years in a prospective cohort study in the United States (Health, Aging and Body Composition study). To measure adherence to a Mediterranean diet, we calculated race-specific tertiles of the MedDiet score (range: 0-55) using baseline food frequency questionnaires. Cognitive decline was assessed using repeated Modified Mini Mental State Examination scores over the study. We used linear mixed models to assess the association between MedDiet score and trajectory of cognitive decline. RESULTS Among blacks, participants with high MedDiet scores had a significantly lower mean rate of decline on the Modified Mini Mental State Examination score compared with participants with lower MedDiet scores (middle and bottom tertiles). The mean difference in points per year was 0.22 (95% confidence interval: 0.05-0.39; p = .01) after adjustment for age, sex, education, body mass index, current smoking, physical activity, depression, diabetes, total energy intake, and socioeconomic status. No association between MedDiet scores and change in Modified Mini Mental State Examination score was seen among white participants (p = .14). CONCLUSIONS Stronger adherence to the Mediterranean diet may reduce the rate of cognitive decline among black, but not white older adults. Further studies in diverse populations are needed to confirm this association and pinpoint mechanisms that may explain these results.

Evaluation of a Self-Administered Computerized Cognitive Battery in an Older Population

Objective: The aim of this study is to assess the utility of the Cogstate self-administered computerized neuropsychological battery in a large population of older men. Methods: We invited 7,167 men (mean age of 75 years) from the Health Professionals Follow-up Study, a prospective cohort of male health professionals. We considered individual Cogstate scores and composite scores measuring psychomotor speed and attention, learning and working memory and overall cognition. Multivariate linear regression was used to assess the association between risk factors measured 4 and 28 years prior to cognitive testing and each outcome. Results: The 1,866 men who agreed to complete Cogstate testing were similar to the 5,301 non-responders. Many expected risk factors were associated with Cogstate scores in multivariate adjusted models. Increasing age was significantly associated with worse performance on all outcomes (p < 0.001). For risk factors measured 4 years prior to testing and overall cognition, a history of hypertension was significantly associated with worse performance (mean difference of -0.08 standard units (95% CI -0.16, 0.00)) and higher consumption of nuts was significantly associated with better performance (>2 servings/week vs. <1 serving/month: 0.15 (0.03, 0.27)). Conclusions: The self-administered Cogstate battery showed significant associations with several risk factors known to be associated with cognitive function. Future studies of cognitive aging may benefit from the numerous advantages of self-administered computerized testing.

Serum oxidized low-density lipoprotein level and risk of cognitive impairment in older women.

We investigated the association between serum level of oxidized low-density lipoprotein (oxLDL) and risk of cognitive impairment (dementia or mild cognitive impairment) among 572 nondemented community-dwelling women from a prospective cohort study of aging. After 5 years of follow-up, 228 (39.9%) developed cognitive impairment; and this did not differ by tertile of baseline oxLDL level (highest compared with lowest tertile 38.2% vs. 39.5%; odds ratio, 0.90; 95% confidence interval, 0.63-1.43). Multivariate adjustment produced similar results (odds ratio, 0.91; 95% confidence interval, 0.60-1.39). These findings suggest that increased levels of serum oxLDL are not associated with a greater risk of incident cognitive impairment in older women.

Endogenous sex hormones and cognitive function in older women

We examined the association between endogenous sex hormones and both objective and subjective measures of cognitive function.