Patrick Manckoundia

Five times sit to stand test is a predictor of recurrent falls in healthy community-living subjects aged 65 and older.

in nonrenal anemia. A study of 1,005 subjects aged 65 and older demonstrated that the endogenous erythropoietin response is sluggish with age and decline in renal function, contributing to anemia. The findings in Table 1 lend some credibility to the fact that chronic anemia in the Agnihotri et al. study may have been, at least in part, secondary to CKD, in which the endogenous erythropoietin response to declining hemoglobin is known to be blunted, but the response to recombinant epoetin alfa therapy is favorable. In summary, many patients in the study, with a mean age in the 70s, may conceivably have had CKD of varying severity (with or without additional comorbid conditions that cause chronic anemia), and their favorable response to epoetin alfa was to be expected. However, the relatively larger doses of epoetin used (20–40,000 U weekly) bring into consideration the presence of factors that cause resistance to epoetin. Once hemoglobin increases in response to epoetin alfa, better QOL (and less fatigue) likely follows. Analyzing the data in Table 1 further, one would like to know which category of patients (based on GFR, normal versus CKD Stages 1 to 4, ferrokinetics, and non-renal anemias) had a better or poorer response to epoetin and accordingly an effect on QOL. Is it ‘‘chronic anemia’’ (of any etiology, based on the higher doses of epoetin used), or is it ‘‘anemia of CKD,’’ one cause of anemia of chronic disease, that responded favorably to epoetin therapy and improved QOL? These specific conclusions from the present study may have important implications for management of chronic anemia; the cause of anemia does matter!

Treatment With Multiple Blood Pressure Medications, Achieved Blood Pressure, and Mortality in Older Nursing Home Residents The PARTAGE Study

IMPORTANCE Clinical evidence supports the beneficial effects of lowering blood pressure (BP) levels in community-living, robust, hypertensive individuals older than 80 years. However, observational studies in frail elderly patients have shown no or even an inverse relationship between BP and morbidity and mortality. OBJECTIVE To assess all-cause mortality in institutionalized individuals older than 80 years according to systolic BP (SBP) levels and number of antihypertensive drugs. DESIGN, SETTING, AND PARTICIPANTS This longitudinal study included elderly residents of nursing homes. The interaction between low (<130 mm Hg) SBP and the presence of combination antihypertensive treatment on 2-year all-cause mortality was analyzed. A total of 1127 women and men older than 80 years (mean, 87.6 years; 78.1% women) living in nursing homes in France and Italy were recruited, examined, and monitored for 2 years. Blood pressure was measured with assisted self-measurements in the nursing home during 3 consecutive days (mean, 18 measurements). Patients with an SBP less than 130 mm Hg who were receiving combination antihypertensive treatment were compared with all other participants. MAIN OUTCOMES AND MEASURES All-cause mortality over a 2-year follow-up period. RESULTS A significant interaction was found between low SBP and treatment with 2 or more BP-lowering agents, resulting in a higher risk of mortality (unadjusted hazard ratio [HR], 1.81; 95% CI, 1.36-2.41); adjusted HR, 1.78; 95% CI, 1.34-2.37; both P < .001) in patients with low SBP who were receiving multiple BP medicines compared with the other participants. Three sensitivity analyses confirmed the significant excess of risk: propensity score-matched subsets (unadjusted HR, 1.97; 95% CI, 1.32-2.93; P < .001; adjusted HR, 2.05; 95% CI, 1.37-3.06; P < .001), adjustment for cardiovascular comorbidities (HR, 1.73; 95% CI, 1.29-2.32; P < .001), and exclusion of patients without a history of hypertension who were receiving BP-lowering agents (unadjusted HR, 1.82; 95% CI, 1.33-2.48; P < .001; adjusted HR, 1.76; 95% CI, 1.28-2.41; P < .001). CONCLUSIONS AND RELEVANCE The findings of this study raise a cautionary note regarding the safety of using combination antihypertensive therapy in frail elderly patients with low SBP (<130 mm Hg). Dedicated, controlled interventional studies are warranted to assess the corresponding benefit to risk ratio in this growing population.

Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis

OBJECTIVE Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1. CONCLUSION This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.

Comparison of motor strategies in sit-to-stand and back-to-sit motions between healthy and Alzheimer’s disease elderly subjects

We studied the kinematics of shoulder displacement during sit-to-stand and back-to-sit in 6 healthy elderly subjects and six elderly subjects with mild to moderate Alzheimers disease in order to elucidate the impact of Alzheimers disease on motor planning and control processes. During sit-to-stand, Alzheimers disease subjects reduced their forward displacement and started their upward displacement earlier than healthy elderly subjects. Furthermore, shoulder path curvatures were more pronounced for upward compared with downward displacement in healthy elderly group, in contrast with Alzheimers disease group. Temporal analysis found that: 1) for both groups, profiles of velocity of sit-to-stand and back-to-sit showed two peaks corresponding respectively to forward/upward and to downward/backward displacements, 2) peaks of velocity were almost comparable between the two groups, 3) duration of sit-to-stand was shorter than duration of back-to-sit in the two groups and 4) duration of sit-to-stand and back-to-sit was shorter in Alzheimers disease group than in healthy elderly group. However, dissimilarities were observed for transition and deceleration phases during sit-to-stand, and for acceleration and transition phases during back-to-sit, between the two groups. Interestingly, while sit-to-stand and back-to-sit differed in healthy elderly subjects during transition and deceleration phases, such a difference was not observed for Alzheimers disease subjects. So, our study showed that invariant spatio-temporal movement parameters in the two groups differed, while non-invariant parameters did not, and suggests that higher level motor process of whole body motions are affected by Alzheimers disease, while lower level motor features remain intact.

Stroke in the Very Old: Incidence, Risk Factors, Clinical Features, Outcomes and Access to Resources – A 22-Year Population-Based Study

Background: For several years, the burden of stroke in very old patients has been increasing in western countries. Nevertheless, we have little information about this new challenge in individuals ≧80. Methods: We ascertained all first-ever strokes in the population of Dijon, France (150,000 inhabitants), from 1985 to 2006. The incidence of stroke, risk factors, clinical presentation, resource mobilization and 1-month outcome were evaluated in individuals ≧80 and compared to the data obtained in younger patients. Results: We collected 1,410 first-ever strokes in people ≧80 years (39%) versus 2,130 in those <80 years. The incidence was 997/100,000, and 68/100,000, respectively. Over the 22 years, the incidence of stroke in individuals ≧80 years rose significantly. A lower prevalence of diabetes, hypercholesterolemia and alcohol intake, as well as a higher prevalence of hypertension, atrial fibrillation, previous myocardial infarction and use of prestroke antiplatelet agents were noted in patients ≧80 years. The clinical presentation was severer and the 1-month outcome in terms of case fatality and handicap was worse, despite improvements observed over time. Finally, in patients ≧80 years, the use of CT scan, MRI, cervical Doppler, angiography and carotid surgery were significantly lower than for younger patients. Length of stay >30 days was more frequent, and discharge to prestroke residence was less common. However, all these improved between the first and the last study periods. Conclusions: Our findings have important implications not only for clinical management but also for initiating preventive strategies and health policy.

Impact of cognitive task on the posture of elderly subjects with Alzheimer's disease compared to healthy elderly subjects

The aims of this study were to analyze the effects of cognitive task on static posture in Alzheimers disease (AD) and in healthy elderly (HE) subjects and to evaluate whether those effects were greater in AD subjects than in HE subjects. We performed a posturographic analysis on 13 subjects with mild AD (mean age, 79.7 ± 5.1 years, Mini‐Mental State Examination scores between 18 and 23) and on 17 HE subjects (mean age, 78.5 ± 4.4 years). After watching a video sequence, the subjects were asked to maintain a stable upright posture while standing on a force platform. Then, the postural sway was measured during the following two conditions: (1) quiet standing and (2) both standing and answering questions about the video sequence. We were interested in the center of pressure (CoP) area and path. For each group, the single task was compared to the dual task for the CoP area and path. We also compared the variability of both CoP area (variation of the CoP area between the single and the dual task) and path (variation of the CoP path between the single and the dual task) between the two groups. We showed that there was no significant difference between the single and the dual task in HE subjects concerning the CoP area and path, in contrast to the AD group, and that variability of both the CoP area and path were significantly greater in the AD subjects than in the HE subjects. This finding may contribute to the risk of falls in AD patients.

Falls and Depression in Older People

Background: Depression is one of the most common risk factors for falls, but links between falls and depression are still unclear. Few studies have examined the relationship between depression and gait alteration, which may increase the risk of fall. Objective: This study aims to assess a possible relationship between depression, postural and gait abnormalities, and falls. Methods: We conducted a 1-year prospective study on patients ≧70 years who were admitted to a geriatric unit for ‘spontaneous’ unexplained falls. Patients were tested for depression using the 30-item Geriatric Depression Scale (GDS). Their motor performances were assessed using the Mini Motor Test (MMT), which is an easy direct-observation test, validated in France, for assessment of frail old people who present with severe postural and gait impairment. This scale is composed of 4 categories of items: (1) abilities in bed; (2) quality of the sitting position; (3) abilities in the standing position, and (4) quality of gait. Results: Sixty-nine patients were included. Depression was found in 46 patients (66.7%). The MMT score was higher in the non-depressed fallers (NDF) group (GDS ≤10) compared to the depressed fallers (DF) group (GDS>10; p < 0.05). The 2 groups were compared for each of the 4 items of the MMT: the difference between the DF and NDF groups was mainly explained by the impairment of postural abilities in the standing position. Conclusions: Our results support the idea that depression is associated with postural abnormalities in the standing position, which may predispose to falls. In clinical practice, more attention should be given to old fallers concerning diagnosis and treatment of associated depression.

Blood pressure and pulse wave velocity values in the institutionalized elderly aged 80 and over: baseline of the PARTAGE study.

Objective The aim of the longitudinal study PARTAGE (predictive values of blood pressure and arterial stiffness in institutionalized very aged population) was to determine the predictive value of blood pressure (BP) and arterial stiffness for overall mortality, major cardiovascular events and cognitive decline in a large population of institutionalized patients aged 80 and over. In the study herein, we present the baseline data values of this study. Methods A total of 1130 patients were recruited (878 women), living in French and Italian nursing homes. Clinical and 3-day self-measurements of BP were conducted. Aortic and upper limb pulse wave velocity were obtained using a PulsePen tonometer. Results Of this population, 76% of women and 60% of men had a known hypertension and over 91% of the patients were under antihypertensive treatment; 51% of the treated hypertensive patients were well controlled (systolic BP <140 mmHg). No significant differences were found between clinical and self-measured BP. With age, there was an increase in pulse pressure (P < 0.001) due to a decrease in diastolic BP (P < 0.001), without any increase in systolic BP. Aortic but not peripheral pulse wave velocity significantly increased with age (P < 0.005). Conclusion Baseline values obtained herein demonstrate that elderly patients living in nursing homes present hemodynamic characteristics which are different to those described in community-living elderly populations, and indicate the interest of assessing, in longitudinal studies, the role of BP and arterial stiffness in morbidity and mortality in this population.

Backward disequilibrium in elderly subjects.

Backward disequilibrium is observed frequently in daily clinical practice. However, there are no epidemiological data concerning this postural disorder. Defined by a posterior position of the centre of mass with respect to the base of support, backward disequilibrium is abnormal postural behavior, usually characterized by a posterior trunk tilt in standing and sitting positions, which predisposes subjects to backward falls. Many afflictions whether they are somatic (degenerative, ischemic and traumatic brain lesions), psychosomatic (psychomotor disadaptation syndrome, confinement to bed, nonuse situations) or psychological (depression) can cause backward disequilibrium. A vicious circle of falls, and loss of autonomy can arise and this is the main consequence of backward disequilibrium. Thus, in this paper, we review backward disequilibrium in elderly subjects with regard to the causes, consequences, assessment, and management.

Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands.