Peripheral stimulation affects subthreshold Triple Stimulation Technique.

BACKGROUND: Compared to conventional transcranial magnetic stimulation (TMS), the triple stimulation technique (TST) strongly decrease the effects of desynchronization of descending discharges and accompanying phase cancellation that follow TMS and offers a more sensitive method to quantify motor evoked potentials (MEPs). NEW METHOD: Using the TST, we explored as to whether sub-threshold TMS evokes peripheral motor neuron discharges (MNs). We compared the number of MEPs elicited by TMS and by TST in fifteen healthy participants. We used the subthreshold intensity of 80 % resting motor threshold. To control the TST assessment of the corticospinal tract, we included a peripheral stimulation control condition, which consisted of peripheral stimulation alone, in a subgroup of five volunteers. RESULTS: Compared to TMS, TST at sub-threshold intensities did not detect significantly more responses unequivocally attributable to the cortical stimulation. In contrast, the peripheral supra-maximal stimuli produced confounding effects in the TST condition that were, in part, indistinguishable from cortical responses. COMPARISON WITH EXISTING METHODS: At subthreshold TMS intensities, the TST does not detect more discharges of spinal MNs than conventional TMS and, in addition, it is confounded by effects from peripheral stimulation. CONCLUSION: The TST can be useful in assessing the integrity of the MN pool and of the corticospinal tract. However, if used at near threshold intensity, the confounding effects of peripheral stimulation need to be considered; for instance, in paired-pulse stimulation paradigms assessing the cortical physiology.

Relation of Disease with Standardized Phase Angle among Older Patients.

BACKGROUND: A low phase angle (PA) has been associated with negative outcome in specific diseases. However, many patients suffer from several co-morbidities. This study aims at identifying the impact of the type and the severity of diseases on PA in a retrospective cohort study of older people. METHODS: We included all people ≥65 years who underwent a PA measurement (Nutriguard®) between 1990 and 2011 at the Geneva University Hospitals. PA was standardized for gender, age and body mass index according to German reference values. Co-morbidities were reported in form of the Cumulative Illness Rating Scale which considers 14 different organs/systems (disease categories), each rated from 0 (healthy) to 4 (severe illness) (severity grades). The association between the diseases categories and standardized PA was evaluated by a multivariate linear regression. For each significant disease category, we performed univariate regression models. The adjusted R2 was used to identify the best predictors of standardized PA. We considered that the severity grade affected standardized PA if there was a progressive decrease in the regression coefficients. RESULTS: We included 1181 people (37% women). The multivariate regression model showed that the disease categories explain 17% of the variance of standardized PA. Many disease categories affect standardized PA and the ones best associated with standardized PA were the hematopoietic and vascular (R2 7.4%), the musculo-skeletal (R2 5.5%) and the respiratory (R2 4.0%) diseases. The regression coefficients in the univariate linear regression model decreased progressively with higher severity grades in respiratory (-0.15, -0.27, -0.55, -0.67) and musculo-skeletal diseases (-0.09, -0.46, -0.85, -0.86). CONCLUSIONS: Many different diseases affect standardized PA. The higher the severity grade in musculo-skeletal and respiratory diseases, the lower is the standardized PA.

Pain and health-related quality of life (HRQoL): a national observational study in community-dwelling older adults.

PURPOSE: Regarding the epidemiology of pain in older adults, data are lacking about the association between pain severity and its impact on health-related quality of life (HRQoL). This study was aimed to investigate pain prevalence and sites, self-reported interferences with daily life activities, and the effect of pain severity on HRQoL in a Swiss community-dwelling population aged ≥ 65 years. METHODS: This is a cross-sectional survey conducted with a national sample of individuals randomly selected from population records, stratified by age and gender. Respondents answered a face-face interview addressing pain location, intensity and interferences, and quality-of-life variables. Logit regression models were applied for binary outcomes, linear regression for continuous outcomes, and Poisson regression for count outcomes. For each analysis, Wald Chi square and 95% confidence intervals were used. RESULTS: Among the 2995 individuals considered, 36.4% reported pain. The results indicate that pain prevalence and intensity increased from age 80 onwards. Pain intensity was strongly associated with functional health, i.e., all scales involving physical activities were affected in individuals reporting severe pain; it was also associated with the individuals' perception of their overall HRQoL. CONCLUSION: Our results point to the importance of devoting attention to pain intensity rather than to the number of pain sites. Because of the demographic transition, the management of pain problems should emphasize early referral and timely treatment to prevent the burden of disease and functional loss associated with pain intensity.

Interaction between LRP5 and periostin gene polymorphisms on serum periostin levels and cortical bone microstructure.

We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. PURPOSE: The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women. METHODS: In 648 postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5, LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16. Volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. RESULTS: Serum periostin levels were associated with radial cortical porosity, including after adjustment for age, BMI, and years since menopause (p = 0.036). Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11 genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26 SNPs in 9 genes were associated with cortical porosity at the radius and/or at the tibia. WNT 16 was the gene with the highest number of SNPs associated with both trabecular and cortical microstructure. The periostin SNP rs9547970 was also associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1 and near the TNFRSF11A gene were associated with both cortical porosity and serum periostin levels. Eventually, we identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p = 0.01) and on radial cortical porosity (interaction p = 0.005). CONCLUSION: These results suggest that periostin expression is genetically modulated, particularly by polymorphisms in the Wnt pathway, and is thereby implicated in the genetic variation of bone microstructure.

The impact of low back pain on health-related quality of life in old age: results from a survey of a large sample of Swiss elders living in the community.

PURPOSE: The present study aims at investigating the effects of low back pain (LBP), i.e., type of symptoms, activity limitations, frequency, duration, and severity on health-related quality of life (HRQoL) in a sample of 707 community-dwelling men and women aged ≥ 65 years living in Switzerland. METHODS: The study is part of a larger survey conducted in Switzerland on a sample of older adults selected randomly from population records, stratified by age and sex. The Standardized Back Pain Definition was used to investigate LBP, and HRQoL was assessed by means of the EQ-5D, including Health Utility Index (HUI) measures. RESULTS: For more than half of the sufferers, pain was chronic, occurred most days or every day and induced activity limitations. One-third of the sufferers reported sciatica symptoms. Individuals reporting every day pain, severe pain and more than 3 years since the last episode without pain lost nearly 10 points of HRQoL. Amongst the dimension of HRQoL, Mobility was the most affected by LBP. CONCLUSIONS: These results provide further insight into the impact of qualitative aspects of LBP and in particular the importance of radiating leg pain and pain frequency and duration. While LBP-related activity limitations had little impact on both self-rated overall health and HUI, radiating leg pain and pain frequency and duration were associated with significantly decreased scores on both dimensions.

Decreased NOX2 expression in the brain of patients with bipolar disorder: association with valproic acid prescription and substance abuse.

Neuroinflammation and increased oxidative stress are believed to contribute to the development of psychiatric diseases. Animal studies have implicated NADPH oxidases (NOX) as relevant sources of reactive oxygen species in the brain. We have analyzed the expression of NOX isoforms in post-mortem brain samples from patients with psychiatric disorders (schizophrenia, bipolar disorder) and non-psychiatric subjects. Two collections from the Stanley Medical Research Institute were studied: the Array Collection (RNA, 35 individuals per group), and a neuropathology consortium collection (paraffin-embedded sections, 15 individuals per group). Quantitative PCR analysis revealed expression of NOX2 and NOX4 in prefrontal cortex. No impact of psychiatric disease on NOX4 levels was detected. Remarkably, the expression of NOX2 was specifically decreased in prefrontal and cingulate cortices of bipolar patients, as compared with controls and schizophrenic patients. NOX2 expression was not statistically associated with demographic parameters and post-mortem interval, but correlated with brain pH. Immunostaining demonstrated that NOX2 was predominantly expressed in microglia, which was corroborated by a decrease in the microglial markers CD68 and CD11b in the cingulate cortex of bipolar disorder patients. The analysis of potentially confounding parameters showed association of valproic acid prescription and heavy substance abuse with lower levels of NOX2. Taken together, we did not observe changes of NOX2 in schizophrenic patients, but a marked decrease of microglial markers and NOX2 in the brain of bipolar patients. This might be an underlying feature of bipolar disorder and/or a consequence of valproic acid treatment and substance abuse.

APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline.

BACKGROUND AND PURPOSE: The presence of apolipoprotein E4 (APOE*E4) is the strongest currently known genetic risk factor for Alzheimer disease and is associated with brain gray matter loss, notably in areas involved in Alzheimer disease pathology. Our objective was to assess the effect of APOE*E4 on brain structures in healthy elderly controls who subsequently developed subtle cognitive decline. MATERIALS AND METHODS: This prospective study included 382 community-dwelling elderly controls. At baseline, participants underwent MR imaging at 3T, extensive neuropsychological testing, and genotyping. After neuropsychological follow-up at 18 months, participants were classified into cognitively stable controls and cognitively deteriorating controls. Data analysis included whole-brain voxel-based morphometry and ROI analysis of GM. RESULTS: APOE*E4-related GM loss at baseline was found only in the cognitively deteriorating controls in the posterior cingulate cortex. There was no APOE*E4-related effect in the hippocampus, mesial temporal lobe, or brain areas not involved in Alzheimer disease pathology. Controls in the cognitively deteriorating group had slightly lower GM concentration in the hippocampus at baseline. Higher GM densities in the hippocampus, middle temporal lobe, and amygdala were associated with a decreased risk for cognitively deteriorating group status at follow-up. CONCLUSIONS: APOE*E4-related GM loss in the posterior cingulate cortex (an area involved in Alzheimer disease pathology) was found only in those elderly controls who subsequently developed subtle cognitive decline but not in cognitively stable controls. This finding might explain the partially conflicting results of previous studies that typically did not include detailed neuropsychological assessment and follow-up. Most important, APOE*E4 status had no impact on GM density in areas affected early by neurofibrillary tangle formation such as the hippocampus and mesial temporal lobe.

Desynchronization does not contribute to intracortical inhibition and facilitation: a paired-pulse paradigm study combined with TST.

The paired-pulse (PP) transcranial magnetic stimulation (TMS) paradigms allow the exploration of the motor cortex physiology. The triple stimulation technique (TST) improves conventional TMS by reducing effects of desynchronization of motor neuron discharges allowing a precise evaluation of the corticospinal conduction. The objective of our study was to explore PP TMS paradigms combined with the TST to study whether the desynchronization contributes to these phenomena and whether the combined TMS-TST protocol could improve the consistency of responses. We investigated the PP paradigms of short intracortical inhibition (SICI) with 2 ms interstimulus interval (ISI) and of intracortical facilitation (ICF) with 10 ms ISI in 22 healthy subjects applying either conventional TMS alone or combined with the TST protocol. The results of the PP paradigms combined with the TST of SICI and ICF do not differ from those with conventional TMS. However, combining the PP paradigm with the TST reduces their variability. These results speak against a contribution of the desynchronization of motor neuron discharges to the PP paradigms of SICI and ICF. Combining the PP TMS paradigm with the TST may improve their consistency, but the interindividual variability remains such that it precludes their utility for clinical practice.NEW & NOTEWORTHY Combining the triple stimulation technique with the paired-pulse stimulation paradigm improves the consistency of short intracortical inhibition and facilitation and could be useful in research, but the interindividual variability precludes their utility for clinical practice. Our findings do not suggest that desynchronization of descending discharges following transcranial magnetic stimulation contributes to short intracortical inhibition or intracortical facilitation.

Association of cortical microinfarcts and cerebral small vessel pathology in the ageing brain.

AIMS: Cortical microinfarcts (CMI) are frequently observed in the ageing brain independent of cognitive decline, but their aetiology is not fully elucidated. To examine the potential role of different vessel pathologies, including cerebral amyloid angiopathy (CAA), arteriolosclerosis-hyalinosis and thromboembolism in the development of CMI, we examined 80 autopsy cases with more than one CMI on routine neuropathological examination. METHODS: Pial and intracortical vessels around CMI were assessed for their integrity with haematoxylin-eosin staining and antibodies against amyloid-ß protein and fibrinogen using a semiquantitative four-level rating scale (absent to severe) in the hippocampus, and the frontal, temporal and occipital cortex. Four histological categories of changes were defined: CAA, vessel pathology other than CAA, thromboembolism and absence of vessel pathology near CMI. RESULTS: A differential distribution of microvascular pathology was observed depending on brain regions. In the occipital cortex, CAA was commonly associated with CMI. In contrast, in the hippocampus and the frontal cortex, cases without any vascular pathology in pial and intracortical vessels were significantly more frequent. CONCLUSIONS: The aetiology of CMI differs depending on brain location. CAA may play a role principally in the occipital cortex. The large number of intact vessels around the CMI (mainly in the frontal cortex and hippocampus) raises the possibility that pathologies other than structural microangiopathy, including hypoperfusion/arterial hypotension or large vessel atherosclerosis, play a role in the development of microvascular lesions. These results are relevant in the context of aetiopathogenesis of vascular changes associated with conditions like vascular dementia.

Malnutrition in Very Old Hospitalized Patients: A New Etiologic Factor of Anemia?

BACKGROUND: Anemia and malnutrition are highly prevalent, frequently concomitant and associated with negative outcomes and mortality in the elderly. OBJECTIVES: To evaluate the association between these two entities, and test the hypothesis that protein-energy deficit could be etiology of anemia. DESIGN: Prospective case-control study. SETTING: Geriatric and Rehabilitation Hospital, Geneva University Hospitals, Switzerland. PARTICIPANTS: 392 patients (mean age 84.8 years old, 68.6% female). MAIN OUTCOME MEASURES: Hematological (hemoglobin (Hb)), chemical (iron work up, cyanocobalamin, folates, renal function, C-Reactive Protein (CRP)) and nutrition (albumin, prealbumin) parameters, and mini nutritional assessment short form (MNA-SF). RESULTS: The prevalence of anemia (defined as Hb<120 g/l) was 39.3%. Anemic patients were more frequently malnourished or at risk of malnutrition according to the MNA-SF (p=0.047), with lower serum albumin (p <0.001) and prealbumin (p <0.001) levels. Thirty-eight percent of these patients had multiple causes and 14.3% had no cause found for anemia. Among the latter 90.9% of patients with unexplained anemia had albumin levels lower than 35g/l. After exclusion of iron,vitamin B12 and folic acid deficits, anemic patients had lower albumin (p<0.001) and prealbumin (p 0.007) levels. Albumin level explained 84.5% of the variance in anemia. In multivariate analysis albumin levels remain associated with Hb only in anemic patients, explaining 6.4% of Hb variance (adj R2) and 14.7% (adj R2) after excluding inflammatory parameters (CRP>10). CONCLUSIONS: Albumin levels are strongly associated with anemia in the elderly. Screening for undernutrition should be included in anemia assessment in those patients. Further prospective studies are warranted in order to explore the effect of protein and energy supplementation on hemoglobin level.

Low back pain and health-related quality of life in community-dwelling older adults.

PURPOSE: Investigation of self-reported of low back pain (LBP) over the last month and associated health-related quality of life (HRQoL) in a sample of a community-dwelling population aged ≥65. METHODS: Cross-sectional study including older adults selected randomly from population records. Data were collected within a sample stratified by age and sex. Physical and psychological healths were investigated using a standardized definition of LBP and the EuroQoL-5D for HRQoL. Analyses were first conducted on the entire sample (N = 3042) and subsequently considering the subsample who reported LBP and a paired sample drawn from the pool of LBP-free respondents. RESULTS: 889 (29 %) respondents reported LBP within the past month, present 'most days' or 'every day' in 52 % and limiting activities in the same proportion. Average pain score was 4.6 (SD 2.2; 0-10 scale). Age was associated with pain frequency and duration, with younger groups more often reporting pain 'some days' and 'dating back <3 months'. Results of regression analyses showed that individuals suffering from LBP had significantly more problems than LBP non-sufferers on all EQ-5D subscales, except self-care: pain/discomfort (OR 5.33; 95 % CI [4.19-6.79]), mobility (OR 2.66; 95 % CI [2.04-3.46]), usual activities (OR 1.92; 95 % CI [1.42-2.60]), anxiety/depression (OR 1.59; 95 % CI [1.23-2.04]) and self-care (OR 1.29; 95 % CI [0.84-1.98]). CONCLUSION: LBP appears to be a more permanent condition in the older groups. LBP may be a part of the definition of a subgroup of elderly at risk of becoming frail in relation with higher levels of functional limitations, psychological difficulties and social restrictions, hence globally impaired HRQoL.

Clinical presentation and management of patients with primary hyperparathyroidism of the Swiss Primary Hyperparathyroidism Cohort: a focus on neuro-behavioral and cognitive symptoms.

PURPOSE: To describe the clinical and biochemical profile of patients with primary hyperparathyroidism (PHPT) of the Swiss Hyperparathyroidism Cohort, with a focus on neurobehavioral and cognitive symptoms and on their changes in response to parathyroidectomy. METHODS: From June 2007 to September 2012, 332 patients were enrolled in the Swiss PHPT Cohort Study, a nationwide prospective and non-interventional project collecting clinical, biochemical, and outcome data in newly diagnosed patients. Neuro-behavioral and cognitive status were evaluated annually using the Mini-Mental State Examination, the Hospital Anxiety and Depression Scale, and the Clock Drawing tests. Follow-up data were recorded every 6 months. Patients with parathyroidectomy had one follow-up visit 3-6 months' postoperatively. RESULTS: Symptomatic PHPT was present in 43 % of patients. Among asymptomatic patients, 69 % (131/189) had at least one of the US National Institutes for Health criteria for surgery, leaving thus a small number of patients with cognitive dysfunction or neuropsychological symptoms, but without any other indication for surgery. At baseline, a large proportion showed elevated depression and anxiety scores and cognitive dysfunction, but with no association between biochemical manifestations of the disease and test scores. In the 153 (46 %) patients who underwent parathyroidectomy, we observed an improvement in the Mini-Mental State Examination (P = 0.01), anxiety (P = 0.05) and depression (P = 0.05) scores. CONCLUSION: PHPT patients often present elevated depression and anxiety scores and cognitive dysfunction, but rarely as isolated manifestations. These alterations may be relieved upon treatment by parathyroidectomy.

Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life.

UNLABELLED: This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age. INTRODUCTION: The age-associated loss of skeletal muscle quantity and function are critical determinants of independent physical functioning in later life. Longitudinal studies investigating how decrements in muscle components of sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults are lacking. METHODS: Twenty-six healthy older subjects (age, 74.1 ± 3.7; Short Physical Performance Battery (SPPB) score ≥10) and 22 mobility-limited older subjects (age, 77.2 ± 4.4; SPPB score ≤9) underwent evaluations of lower extremity muscle size and composition by computed tomography, strength and power, and physical performance at baseline and after 3-year follow-up. The Falls Efficacy Scale (FES) and Short Form-36 questionnaire (SF-36) were also administered at both timepoints to assess FoF and QoL, respectively. RESULTS: At 3-year follow-up, muscle cross-sectional area (CSA) (p < 0.013) and power decreased (p < 0.001), while intermuscular fat infiltration increased (p < 0.001). These decrements were accompanied with a longer time to complete 400 m by 22 ± 46 s (p < 0.002). Using linear mixed-effects regression models, declines of muscle CSA, strength and power, and SPPB score were associated with increased FES score (p < 0.05 for each model). Reduced physical component summary score of SF-36 over follow-up was independently associated with decreased SPPB score (p < 0.020), muscle CSA (p < 0.046), and increased 400 m walk time (p < 0.003). CONCLUSIONS: In older adults with and without mobility limitations, declining muscle mass, strength, power, and physical performance contribute independently to increase FoF, while declines of muscle mass and physical performance contribute to deterioration of QoL. These findings provide further rationale for developing interventions to improve aging muscle health.

Improvement in executive subfunctions following cerebrospinal fluid tap test identifies idiopathic normal pressure hydrocephalus from its mimics.

BACKGROUND AND PURPOSE: Patients with idiopathic normal pressure hydrocephalus (iNPH) present cognitive deficits that overlap with other neurological conditions such as Parkinson's disease or vascular dementia, therefore mimicking iNPH. This prospective study aimed to compare cognitive performances between iNPH and iNPH mimics before and after cerebrospinal fluid (CSF) tapping. METHODS: A total of 57 patients with suspicion of iNPH (75.84 ± 6.42 years; 39% female) were included in this study (37 iNPH and 20 iNPH mimics). Neuropsychological assessments were performed before and 24 h after CSF tapping of 40 ml. Multivariate logistic regressions were used to examine the association between iNPH and cognitive functions, adjusted for age, education, baseline cognitive assessment and disease duration. RESULTS: Both groups presented the same baseline cognitive performances. After CSF tapping, iNPH patients improved their semantic (P = 0.001) and phonemic verbal fluencies (P = 0.001), whereas iNPH mimics presented similar performances to before CSF tapping. The phonemic verbal fluency (odds ratio 1.43, 95% confidence interval 1.05; 1.96) and the Color Trails Test (odds ratio 0.10, 95% confidence interval 0.01; 0.76) improvements were the two discriminative cognitive tests that identified iNPH from iNPH mimics. CONCLUSION: Improvement in executive subfunctions after CSF tapping identified iNPH patients from other neurological conditions that mimic iNPH. These findings respond to clinical issues encountered on a daily basis and would improve the diagnostic process of iNPH.

Prior ankle fractures in postmenopausal women are associated with low areal bone mineral density and bone microstructure alterations.

UNLABELLED: In a cross-sectional analysis in postmenopausal women, prior ankle fractures were associated with lower areal bone mineral density (BMD) and trabecular bone alterations compared to no fracture history. Compared to women with forearm fractures, microstructure alterations were of lower magnitude. These data suggest that ankle fractures are another manifestation of bone fragility. INTRODUCTION: Whether ankle fractures represent fragility fractures associated with low areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) and/or bone microstructure alterations remains unclear, in contrast to the well-recognised association between forearm fractures and osteoporosis. The objective of this study was to investigate aBMD, vBMD and bone microstructure in postmenopausal women with prior ankle fracture in adulthood, compared with women without prior fracture or with women with prior forearm fractures, considered as typically of osteoporotic origin. METHODS: In a cross-sectional analysis in the Geneva Retirees Cohort study, 63 women with ankle fracture and 59 with forearm fracture were compared to 433 women without fracture (mean age, 65 ± 1 years). aBMD was measured by dual-energy X-ray absorptiometry; distal radius and tibia vBMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography. RESULTS: Compared with women without fracture, those with ankle fractures had lower aBMD, radius vBMD (-7.9%), trabecular density (-10.7%), number (-7.3%) and thickness (-4.6%) and higher trabecular spacing (+14.5%) (P < 0.05 for all). Tibia trabecular variables were also altered. For 1 standard deviation decrease in total hip aBMD or radius trabecular density, odds ratios for ankle fractures were 2.2 and 1.6, respectively, vs 2.2 and 2.7 for forearm fracture, respectively (P ≤ 0.001 for all). Compared to women with forearm fractures, those with ankle fractures had similar spine and hip aBMD, but microstructure alterations of lower magnitude. CONCLUSION: Women with ankle fractures have lower aBMD and vBMD and trabecular bone alterations, suggesting that ankle fractures are another manifestation of bone fragility.

Nasal salmon calcitonin blunts bone microstructure alterations in healthy postmenopausal women.

UNLABELLED: In healthy postmenopausal women, nasal salmon calcitonin blunted distal radius and tibia bone microstructure degradation. INTRODUCTION: Nasal salmon calcitonin (NSC) has been reported to lower vertebral fracture risk by 33%, but to modestly increase spine areal bone mineral density (aBMD) by 1.5%. Thus, NSC may also influence bone microstructure, another known determinant of bone strength. METHODS: In a randomized, double-blind, placebo-controlled trial, we investigated the effects of 200 IU/day NSC on distal radius and tibia bone microstructure (by high-resolution 3-dimensional peripheral quantitative computerized tomography), aBMD (by dual-energy X-ray absorptiometry), and serum bone turnover markers in healthy postmenopausal women. RESULTS: Mean age was 57.6 ± 0.8 (±SEM) and 57.4 ± 0.7 in NSC (n = 45) and placebo groups (n = 45), respectively. Mean femoral neck T-score was in the osteopenic range; prevalent vertebral fracture was 4% in each group. There was no observed between-group difference in the primary outcome distal radius BV/TV (-2.8 ± 0.6% vs. -4.3 ± 1.0%, NS). By 2 years, the decrease in distal radius total density vs. baseline was 4.4 ± 0.7% in controls and 2.1 ± 0.6% in NSC-receiving patients (p < 0.05). Distal radius and tibia cortical thickness decreased by 3.7 ± 1.0 and 2.4 ± 0.5% in placebo (p < 0.05 vs. baseline for both), respectively, but not in the NSC group. Distal radius total density and cortical thickness changes were lower in NSC group than in placebo (p < 0.05 for both) in the subgroup with baseline C-terminal telopeptides (CTX) above the median. By 6 and 12 months, serum CTX decreased by 17.3 ± 6.2 and 19.1 ± 6.6% (both p < 0.05 vs. baseline), respectively, in NSC, but remained stable in controls (NS vs. baseline). There was no difference in aBMD. NSC was well tolerated, with less arthralgia than the placebo group (14 vs. 26, p < 0.05). CONCLUSION: Nasal salmon calcitonin blunted the degradation of distal radius and tibia bone microstructure in healthy postmenopausal women.

Vitamin D and white matter abnormalities in older adults: a cross-sectional neuroimaging study.

BACKGROUND AND PURPOSE: Morphological brain changes related to hypovitaminosis D have been poorly studied. In particular, the age-related decrease in vitamin D concentrations may explain the onset of white matter abnormalities (WMA) in older adults. Our objectives were (i) to investigate whether there was an association between serum 25-hydroxyvitamin D (25OHD) concentration and the grade of WMA in older adults and (ii) to determine whether the location of WMA was associated with 25OHD concentration. METHODS: One hundred and thirty-three Caucasian older community-dwellers with no clinical hydrocephalus (mean 71.6 ± 5.6 years; 43.6% female) received a blood test and a magnetic resonance imaging scan of the brain. The grades of total, periventricular and deep WMA were scored using semiquantitative visual rating scales from T2-weighted fluid-attenuated inversion recovery images. The association of WMA with as-measured and deseasonalized 25OHD concentrations was evaluated with the following covariates: age, gender, body mass index, use of anti-vascular drugs, number of comorbidities, impaired mobility, education level, Mini-Mental State Examination score, medial temporal lobe atrophy, serum concentrations of calcium, thyroid-stimulating hormone and vitamin B12, and estimated glomerular filtration rate. RESULTS: Both as-measured and deseasonalized serum 25OHD concentrations were found to be inversely associated with the grade of total WMA (adjusted ß = -0.32, P = 0.027), specifically with periventricular WMA (adjusted ß = -0.15, P = 0.009) but not with deep WMA (adjusted ß = -0.12, P = 0.090). Similarly, participants with 25OHD concentration <75 nM had on average a 33% higher grade of periventricular WMA than those with 25OHD ≥75 nM (P = 0.024). No difference in average grade was found for deep WMA (P = 0.949). CONCLUSIONS: Lower serum 25OHD concentration was associated with higher grade of WMA, particularly periventricular WMA. These findings provide a scientific basis for vitamin D replacement trials.

Gait abnormalities in obstructive sleep apnea and impact of continuous positive airway pressure.

We aimed to determine the effect of continuous positive airway pressure (CPAP) on gait in obstructive sleep apnea (OSA) patients. Gait during single and dual tasks was recorded in 15 OSA patients at baseline and after 8 weeks of CPAP therapy. Step and stance time improved after CPAP. We showed a specific dual-task effect in the condition of verbal fluency. Eight weeks of CPAP seems to improve gait of OSA patients that are specifically disturbed by the dual task of verbal fluency.

A critical pathway for the management of elderly inpatients with malnutrition: effects on serum insulin-like growth factor-I.

BACKGROUND: Several guidelines recommend systematic screening for malnutrition in elderly inpatients for early dietary intakes assessment and treatment, but data demonstrating the efficacy of such interventions are scarce. The aim of this study was to evaluate a critical medical pathway for the detection and management of malnutrition in elderly inpatients. METHODS: In a 3-month prospective controlled study, 694 recently admitted inpatients were assigned to an intervention group (critical medical pathway; n=465) or a standard care control group (n=229). Nutritional status was assessed at the time of admission with a Mini Nutritional Assessment. A renutrition program tailored to the initial dietary assessment results was applied in the intervention group. The efficacy of the program was verified by measuring the evolution of serum insulin-like growth factor 1 (IGF-I) between admission and 3 weeks later. RESULTS: In the intervention group at baseline, 23% were malnourished, 51% were at risk and 26% were eunourished. Serum IGF-I increased in the intervention group (from 84±45 µg/l to 95±50 µg/l, P<0.0001; mean±s.d., n=209), but remained stable in the controls (from 79±43 µg/l to 81±35 µg/l, P=0.4; n=99), with a statistically significant between group difference (P<0.01). CONCLUSION: Early malnutrition assessment and targeted renutrition program in elderly inpatients were associated with an increase in serum IGF-I. It remains to be determined whether such variations are clinically relevant.