Patterns and predictive factors of loss of the independence trajectory among community-dwelling older adults.

BACKGROUND: Independence is related to the aging process. Loss of independence is defined as the inability to make decisions and participate in activities of daily living (ADLs). Independence is related to physical, psychological, biological, and socioeconomic factors. An enhanced understanding of older people's independence trajectories and associated risk factors would enable the develop early intervention strategies. METHODS: Independence trajectory analysis was performed on patients identified in the Unité de Prévention de Suivi et d'Analyse du Vieillissement (UPSAV) database. UPSAV cohort is a prospective observational study. Participants were 221 community-dwelling persons aged ≥75 years followed for 24 months between July 2011-November 2013 and benefits from a prevention strategy. Data were collected prospectively using a questionnaire. Independence was assessed using the "Functional Autonomy Measurement System (Système de Mesure de l'Autonomie Fonctionnelle (SMAF))". Group-based trajectory modeling (GBTM) was performed to identify independence trajectories, and the results were compared with those of k-means and hierarchical ascending classifications. A multinomial logistic regression was performed to identify predictive factors of the independence trajectory. RESULTS: Three distinct trajectories of independence were identified including a "Stable functional autonomy (SFA) trajectory" (53% of patients), a "Stable then decline functional autonomy decline (SDFA) trajectory" (33% of patients) and a "Constantly functional autonomy decline (CFAD) trajectory" (14% of patients). Not being a member of an association, and previous fall were significantly associated of a SDFA trajectory (P < 0.01). Absence of financial and human assistance, no hobbies, and cognitive disorder were significantly associated with a CFAD trajectory (P < 0.01). Previous occupation and multiple pathologies were predictive factors of both declining trajectories SDFA and CFAD. CONCLUSIONS: Community-living older persons exhibit distinct independence trajectories and the predictive factors. The evidence from this study suggests that the prevention and screening for the loss of independence of the older adults should be anticipated to maintaining autonomy.

Protein intake, weight loss, dietary intervention, and worsening of quality of life in older patients during chemotherapy for cancer.

Decreased health-related quality of life (HRQoL) is common in patients with cancer. We investigated the effects of dietary intervention and baseline nutritional status on worsening of HRQoL in older patients during chemotherapy. In this randomized control trial assessing the effect on mortality of dietary advice to increase dietary intake during chemotherapy, this post hoc analysis included 155 patients with cancer at risk of malnutrition. The effects of dietary intervention, baseline Mini Nutritional Assessment item scores, weight loss, and protein and energy intake before treatment on the worsening of HRQoL (physical functioning, fatigue) and secondary outcomes (Timed Up and Go test, one-leg stance time, depressive symptoms, basic (ADL), or instrumental (IADL) activities of daily living) were analyzed by multinomial regressions. Dietary intervention increased total energy and protein intake but had no effect on any examined outcomes. Worsening of fatigue and ADL was predicted by very low protein intake (< 0.8 g kg-1 day-1) before chemotherapy (OR 3.02, 95% CI 1.22-7.46, p = 0.018 and OR 5.21, 95% CI 1.18-22.73, p = 0.029 respectively). Increase in depressive symptomatology was predicted by 5.0-9.9% weight loss before chemotherapy (OR 2.68, 95% CI 1.10-6.80, p = 0.038). Nutritional intervention to prevent HRQoL decline during chemotherapy should focus on patients with very low protein intake along with those with weight loss.

Prevalence of mild hyponatremia and its association with falls in older adults admitted to an emergency geriatric medicine unit (the MUPA unit).

BACKGROUND: Hyponatremia is the most common electrolyte disorder in older adults and it can increase morbidity and mortality. Approximately one in three older adults fall each year; mild chronic hyponatremia can predispose this group to injurious falls and fractures and serum levels of sodium can also influence bone health. Little is known regarding the association between mild chronic hyponatremia and injurious fall prevalence in elderly patients admitted to the Emergency Department (ED). Therefore, the present study investigated the link between mild hyponatremia and the risk of injurious falls in elderly patients admitted to the Emergency Geriatric Medicine Unit (The MUPA Unit). METHODS: This cross-sectional study was conducted over 4 months and included patients ≥75 years of age who were admitted to the MUPA Unit of University Hospital Center of Limoges (France). Sociodemographic factors, fall events, comorbidities, medications, and sodium levels were assessed (hyponatremia was considered as sodium level < 136 mEq/L). Additionally, the short Comprehensive Geriatric Assessment (short-CGA), the Frailty score on the Short Emergency Geriatric Assessment (SEGA), and the Katz Activity of Daily Living (ADL) scale were administered. RESULTS: Of the 696 cases included in the final analysis, the mean age was 86.1 ± 5.6 years and 63.1% were female. The prevalence of falls was 27.9% (95% confidence interval [CI]: 24.6-31.2%) and that of mild hyponatremia was 15.9% (95% CI: 13.2-18.6%). The prevalence rate of mild hyponatremia was 13.2% (95% CI: 10.1-16.3%) in patients without falls and 26.1% (95% CI: 19.8-32.4%) in patients admitted for falls. Mild hyponatremia was significantly associated with falls (P < 0.001) and the adjusted odds ratio (OR) was 3.02 (95% CI: 1.84-4.96). CONCLUSIONS: Because mild hyponatremia might be a risk factor for injurious falls and ED admission, determination of sodium levels during basic biomarker assessment on ED admission could be an important component of fall prevention strategies for the elderly.

The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) randomized controlled trial: Case finding, screening and characteristics of eligible participants.

BACKGROUND: The ongoing "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT)" randomized controlled trial (RCT) is testing the efficacy of a multicomponent intervention in the prevention of mobility disability in older adults with physical frailty & sarcopenia (PF&S). Here, we describe the procedures followed for PF&S case finding and screening of candidate participants for the SPRINTT RCT. We also illustrate the main demographic and clinical characteristics of eligible screenees. METHODS: The identification of PF&S was based on the co-occurrence of three defining elements: (1) reduced physical performance (defined as a score on the Short Physical Performance Battery between 3 and 9); (2) low muscle mass according to the criteria released by the Foundation for the National Institutes of Health; and (3) absence of mobility disability (defined as ability to complete the 400-m walk test in 15 min). SPRINTT was advertised through a variety of means. Site-specific case finding strategies were developed to accommodate the variability across centers in catchment area characteristics and access to the target population. A quick "participant profiling" questionnaire was devised to facilitate PF&S case finding. RESULTS: During approximately 22 months, 12,358 prescreening interviews were completed in 17 SPRINTT sites resulting in 6710 clinic screening visits. Eventually, 1566 candidates were found to be eligible for participating in the SPRINTT RCT. Eligible screenees showed substantial physical function impairment and comorbidity burden. In most centers, project advertisement through mass media was the most rewarding case finding strategy. CONCLUSION: PF&S case finding in the community is a challenging, but feasible task. Although largely autonomous in daily life activities, older adults with PF&S suffer from significant functional impairment and comorbidity. This subset of the older population is therefore at high risk for disability and other negative health-related events. Key strategies to consider for successfully intercepting at-risk older adults should focus on mass communication methods.

Blood Inflammatory Mediators and Cognitive Decline in Alzheimer's Disease: A Two Years Longitudinal Study.

Peripheral inflammatory processes are involved in Alzheimer's disease (AD). We aimed to determine whether plasma inflammatory mediator levels at diagnosis are associated with cognitive decline through a 2-year follow-up in AD patients. Patients (n = 109, mean age 79.44 (6.82) years) were included at diagnosis with MMSE scores between 16 and 25, with C-reactive protein <10 mg/L, and without any acute or chronic inflammation status. Plasma IL-1ß, IL-6, TNF-α, and CCL5 were measured using Luminex X-MAP technology at baseline, and after one year and two years of follow-up. The mean values of IL-1ß, IL-6, TNF-α, and CCL5 at diagnosis were 0.3, 1.94, 6.57, and 69,615.81 pg/mL, respectively. Mean cognitive decline in MMSE was 3.35 points. No correlation between plasmatic value of IL-1ß, IL-6, TNF-α, or CCL5 at diagnosis and cognitive decline during the two years of follow-up was found. Cognitive decline in AD does not appear to be predictable by the tested inflammatory mediators.

Predictors of Rapid Cognitive Decline in Patients with Mild-to-Moderate Alzheimer Disease: A Prospective Cohort Study with 12-Month Follow-Up Performed in Memory Clinics.

BACKGROUND/AIMS: Alzheimer disease (AD) is particularly devastating, with no cure, no means of prevention, and no proven way to slow progression. AD is associated with the worsening of cognitive function attributable to a variety of factors of which little is known. Our main objective was to determine factors associated with rapid cognitive decline (RCD) in older AD patients. METHODS: We conducted a 12-month, prospective, multi-centre cohort study. Community-living individuals aged ≥65 years with mild-to-moderate AD were included. RCD was defined as the loss of ≥3 points/year in the Mini-Mental State Examination (MMSE) score. Potential individual-level predictors were collected at baseline. RESULTS: A total of 521 individuals were included. The mean age was 80.8 ± 9.0 years and 66.0% were females. The average baseline MMSE score was 20.5 ± 4.5. The incidence of RCD was 40.9% (95% confidence interval [CI], 36.7-45.1). RCD was more common in patients with moderate (53.5%) than mild (22.3%) AD. The factors associated with RCD were: a parental history of dementia (odds ratio [OR], 2.32 [95% CI, 1.24-4.21], p = 0.011), psychotic symptoms (OR, 2.06 [95% CI, 1.22-3.48], p = 0.007), malnutrition (OR, 1.61 [95% CI, 1.06-2.63], p = 0.028), and the female gender (OR, 1.48 [95% CI, 1.03-2.15], p = 0.036). An MMSE score < 20 at treatment onset was also associated with RCD (p < 0.001). CONCLUSION: The factors associated with RCD were an MMSE score < 20 at treatment onset, female gender, psychotic symptoms, malnutrition, and a family history of dementia. These results may be directly relevant to patients, their families, and their physicians, enabling early anticipation of difficult clinical trajectories and poor functional outcomes.

Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers.

INTRODUCTION: Diagnostic relevance of plasma amyloid ß (Aß) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aß42 and Aß40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers. METHODS: One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included. RESULTS: Plasma Aß1-42 and Aß1-40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aß1-42 and P = .04 for Aß1-40). Globally, plasma Aß1-42 correlated with age, Mini-Mental State Examination, and APOE Îµ4 allele. Plasma Aß1-42 correlated with all CSF biomarkers in MCI but only with CSF Aß42 in AD. DISCUSSION: Plasma Aß was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose.

High levels of an endothelial dysfunction marker (sVCAM-1) are associated with injurious and recurrent falls and mortality over a 5-year interval in an older population.

We investigated the association between elevated plasma concentrations of circulating soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and injurious falls and mortality over a 5-year period. We studied the prospective relationship between levels of circulating adhesion molecules and falls in 680 community-dwelling participants in the MOBILIZE Boston Study. The mean sVCAM-1 (±SD) concentration was 1192 ±â€¯428 ng/mL. Over 5-years of follow-up, 10.2% of participants died. The baseline sVCAM-1 (±SD) concentration was 1434 ±â€¯511 ng/mL in those who died vs. 1162 ±â€¯402 ng/mL in those who survived (P < 0.0001). sVCAM-1 level was associated with recurrent falls (P < 0.01); compared to the lowest quintile, the highest quintile of sVCAM-1 was associated with increased risk of injurious falls [multivariable adjusted Incidence Rate Ratio = 1.9, 95% CI (1.2-2.9), P = 0.009]. On survival analysis, the highest sVCAM-1 quintile was associated with the greatest mortality over 5 years (log-rank test, P < 0.0001). The adjusted hazard ratio was 2.4 [95% CI (2.1-2.7), P = 0.002]. High sVCAM-1 blood concentration was strongly associated with recurrent falls, injurious falls, and mortality in older adults.

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

BACKGROUND: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. METHODS: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). FINDINGS: 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. INTERPRETATION: The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. FUNDING: French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.

Accuracy of Teledentistry for Diagnosing Dental Pathology Using Direct Examination as a Gold Standard: Results of the Tel-e-dent Study of Older Adults Living in Nursing Homes.

IMPORTANCE: Dental neglect and high levels of unmet dental needs are becoming increasingly prevalent among elderly residents of long-term care facilities, although frail, elderly, and dependent populations are the most in need of professional dental care. Little is known about the validity of teledentistry for diagnosing dental pathology in nursing home residents. OBJECTIVES: To evaluate the accuracy of teledentistry for diagnosing dental pathology, assessing the rehabilitation status of dental prostheses, and evaluating the chewing ability of older adults living in nursing homes (using direct examination as a gold standard). DESIGN: Multicenter diagnostic accuracy study performed in France and Germany. SETTING: Eight nursing homes in France and Germany. PARTICIPANTS: Nursing home residents with oral or dental complaints, self-reported or reported by caregivers, willing to receive oral or dental preventive care. In total, 235 patients were examined. The mean age was 84.4 ± 8.3 years, and 59.1% of the subjects were female. INTERVENTION: The patients were examined twice. Each patient was his or her own control. First, the dental surgeon established a diagnosis by reviewing a video recorded in the nursing home and accessed remotely. Second, within a maximum of 7 days, patients were examined conventionally (face-to-face) by the same surgeon who established the initial diagnosis. MEASUREMENTS: All residents received a comprehensive clinical examination in their home by a trained geriatrician and underwent a dental hygiene evaluation that used the Silness-Loe and Greene-Vermillion dental hygiene assessment indices. The diagnoses established via the video recording and in the face-to-face setting were compared. The main outcome measure was number of dental pathologies. RESULTS: In total, 128 (55.4%) patients had a dental pathology. The sensitivity of teledentistry for diagnosing dental pathology was 93.8% (95% confidence interval [CI] 90.7-96.9), and the specificity was 94.2% (95% CI 91.2-97.2). Among the 128 cases of dental pathology identified by teledentistry, 6 (4.8%) were false positives. The teledentistry assessments were quicker than the face-to-to-face examinations (12 and 20 minutes, respectively). CONCLUSIONS: Teledentistry showed excellent accuracy for diagnosing dental pathology in older adults living in nursing homes; its use may allow more regular checkups to be carried out by dental professionals.

Elevated Soluble Vascular Cell Adhesion Molecule-1 Is Associated With Cerebrovascular Resistance and Cognitive Function.

BACKGROUND: Elevated plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial dysfunction, both in the brain and systemic circulation. Impairments in memory and cognition have been associated with cardiovascular diseases, but little is known about their relationships to abnormal cerebral endothelial function. METHODS: We studied the cross-sectional association between sVCAM-1 and markers of cerebrovascular hemodynamics and cognitive function in 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. Cognitive function was assessed using the Hopkins Verbal Learning Memory Test and Trail Making Tests (TMTs) A and B. Global cognitive impairment was defined as Mini-Mental State Examination (MMSE) score less than 24. sVCAM-1 was measured by ELISA assay. Beat-to-beat blood flow velocity (BFV) and cerebrovascular resistance (CVR = mean arterial pressure / BFV) in the middle cerebral artery were assessed at rest by transcranial Doppler ultrasound. RESULTS: sVCAM-1 concentrations were higher among participants with an MMSE score <24 versus ≥24 (1,201±417 vs 1,122±494ng/mL). In regression models adjusted for sociodemographic characteristics and health conditions, increasing levels of sVCAM-1 were linearly associated with higher resting CVR (p = .006) and lower performance on the Hopkins Verbal Learning Memory (immediate recall and delayed recall) and adjusted TMT B tests (p < .05). Higher levels of sVCAM-1 were also associated with global cognitive impairment on the MMSE (odds ratio = 3.9; 95% confidence interval: 1.4-10.9; p = .011). CONCLUSIONS: In this cohort of elderly participants, we observed a cross-sectional association between elevated sVCAM-1 levels and both cognitive impairment and increased cerebrovascular resistance. Longitudinal studies are needed to determine whether elevated sVCAM-1 is a cause or consequence of cerebrovascular damage.

Effectiveness of light paths coupled with personal emergency response systems in preventing functional decline among the elderly.

INTRODUCTION: The elderly population is at high risk of functional decline, which will induce significant costs due to long-term care. Dependency could be delayed by preventing one of its major determinants: falls. Light paths coupled with personal emergency response systems could prevent the functional decline through fall prevention. METHODS: This study aimed to evaluate the effectiveness of light paths coupled with personal emergency response systems on the functional decline in an elderly population living at home. It is a secondary analysis on data from a previous cohort. In all, 190 older adults (aged 65 years or more) living at home participated. Participants in the exposed group were equipped with home-based technologies: light paths coupled with personal emergency response systems. The participants' functional status was assessed using the Functional Autonomy Measurement System scale at baseline (T0) and at the end of the study (T12-month). Baseline characteristics were evaluated by a comprehensive geriatric assessment. RESULTS: After 1 year, 43% of the unexposed group had functional decline versus 16% of the exposed group. Light paths coupled with personal emergency response systems were significantly associated with a decrease in the functional decline (Δ Functional Autonomy Measurement System ⩾ 5) at home (odds ratio = 0.24, 95% confidence interval (0.11-0.54), p = 0.002). DISCUSSION: This study suggests that light paths coupled with personal emergency response systems prevent the functional decline over 12 months. This result may encourage the prescription and use of home-based technologies to postpone dependency and institutionalization, but they need a larger cost-effectiveness study to demonstrate the efficiency of these technologies.

[Medicines and frailty in older people. Towards a new nosological entity: A pharmacological frailty?]. / Médicaments et fragilité chez les personnes âgées. Vers une nouvelle entité : la fragilité pharmacologique ?

Frailty is a complex geriatric syndrome linked to the overall decrease of physiological reserves. It could lead to disability and to an increase in mortality. Frailty could have an impact on the effect and on the use of medications. Drugs could also affect the frailty process. Currently, no specific guidelines exist for appropriately prescribing medications to frail older people. The aim of this paper is to explore the body of current knowledge about the relationship between drugs and frailty in older people and to introduce a new nosological entity: pharmacological frailty.

Elevated circulating vascular cell Adhesion Molecule-1 (sVCAM-1) is associated with concurrent depressive symptoms and cerebral white matter Hyperintensities in older adults.

BACKGROUND: Circulating vascular adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial activation and dysfunction, but little is known about its association with mood. We hypothesized that elevated plasma concentrations of sVCAM-1 may be a marker of depressive symptoms due to cerebral vascular disease. METHODS: We studied 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. sICAM-1 and sVCAM-1 were measured by ELISA assay and depressive symptoms were assessed during home interviews using the Revised Center for Epidemiological Studies Depression Scale (CESD-R). Cerebral White Matter Hyperintensities (WMHs) were quantified by MRI in a subgroup of 25 participants. RESULTS: One hundred seventy nine (27 %) subjects had a CESD-R Score ≥ 16, indicative of depressive symptoms. The mean sVCAM-1 concentration (±SD) was 1176 ± 417 ng/mL in a group with CESD-R Scores <16 and 1239 ± 451 ng/mL in those with CESD-R Scores ≥16 (p = 0.036). CESD-R Score was positively associated with sVCAM-1 (r = 0.11, p = 0.004). The highest quintile of sVCAM-1, which is indicative of endothelial dysfunction, was significantly associated with depressive symptoms compared to the lowest quintile (OR = 1.97 (1.14-3.57) p = 0.015). In a subset of subjects, sVCAM-1 concentration was positively correlated with cerebral WMHs volume (p = 0.018). CONCLUSIONS: The association between high levels of sVCAM-1 and depressive symptoms may be due to endothelial dysfunction from cerebral microvascular damage. Future longitudinal studies are needed to determine whether sVCAM-1 can serve as a biomarker for cerebrovascular causes of depression.

Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.

Soluble vascular cell adhesion molecule-1 (sVCAM-1) is associated with hypertension, vascular inflammation, and systemic endothelial dysfunction. We evaluated whether elevated plasma sVCAM-1 is associated with impaired cerebrovascular function and mobility impairments in elderly people. We studied the cross-sectional relationships between plasma sVCAM-1 level, gait speed, and cerebrovascular hemodynamics, and its longitudinal relationship with falls in 680 community-dwelling participants aged ≥65 years in the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study. Falls were recorded prospectively for 1 year on daily calendars. sVCAM-1 was measured by ELISA assay and beat-to-beat blood flow velocity in the middle cerebral artery during rest and in response to changes in end-tidal CO2 was measured by transcranial Doppler ultrasound. sVCAM-1 concentration was 1094±340 ng/mL in normotensives, 1195±438 ng/mL in controlled hypertensives, and 1250±445 ng/mL in uncontrolled hypertensives (P=0.008). The mean resting blood flow velocity and cerebral vasomotor range were, respectively, 41.0±10.3 cm/s and 1.3±0.4 cm/s per millimeter of mercury. Elevated sVCAM-1 levels indicative of endothelial dysfunction were associated with reduced resting blood flow velocity (P=0.017) and cerebral vasomotor range (P=0.0048). Elevated sVCAM-1 levels were associated with slower gait speed (<0.8 m/s; odds ratio, 3.01; 95% confidence interval, 1.56-5.83; P=0.0011) and an increased odds of injurious falls (odds ratio, 2.4; 95% confidence interval, 1.4-4.2; P=0.0028). An elevated sVCAM-1 level may be a marker of cerebral blood flow dysregulation because of endothelial damage from hypertension. It may also signal the presence of cerebral microvascular disease and its clinical consequences, including slow gait speed and falls.

Reexamining the Effect of Antihypertensive Medications on Falls in Old Age.

Conflicting data on the relationship between antihypertensive medications and falls in elderly people may lead to inappropriate undertreatment of hypertension in an effort to prevent falls. We aimed to clarify the relationships between the chronic use of different classes of antihypertensive medications and different types of falls, to determine the effect of medication dose, and to assess whether the risk of falls is associated with differences in cerebral blood flow. We assessed demographics, clinical characteristics, and chronic antihypertensive medication use in 598 community-dwelling people with hypertension, aged 70 to 97 years, then followed them prospectively for self-reported falls using monthly calendar postcards and telephone interviews. Antihypertensive medication use was not associated with an increased risk of falls. Participants reporting use of angiotensin-converting enzyme inhibitors had a significantly decreased 1-year risk of injurious falls (odds ratio, 0.62; 95% confidence interval, 0.39-0.96), whereas those using calcium channel blockers had a decreased risk of all falls (odds ratio, 0.62; 95% confidence interval, 0.42-0.91) and indoor falls (odds ratio, 0.57; 95% confidence interval, 0.36-0.91), compared with participants not taking these drugs. Larger doses of these classes were associated with a lower fall risk. Participants taking calcium channel blockers had higher cerebral blood flow than those not taking these medications. In relatively healthy community-dwelling elderly people, high doses of antihypertensive agents are not associated with an increased risk of falls.

There is no correlation between peripheral inflammation and cognitive status at diagnosis in Alzheimer's disease.

BACKGROUND: Besides the neurofibrillary tangles and amyloid plaques, an inflammatory process is involved at central and peripheral levels in Alzheimer's disease (AD). We aimed to determine whether peripheral inflammatory parameter levels, in plasma and in peripheral blood mononuclear cells (PBMCs), could be correlated with the cognitive status at the time of AD diagnosis. METHODS: Patients were included at diagnosis with MMSE score between 16 and 25 and were naive of symptomatic treatment for AD. C-reactive protein >10 mg/L and any acute or chronic inflammation were considered as exclusion criteria. Cognitive assessment also included the ADAScog scale. Plasma interleukins (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and the chemokine ligand 5 (CCL5) were measured using Luminex(®) X-MAP(®) technology. A subgroup of patients also underwent measures of these parameters in extracellular and intracellular compartments of PBMCs (ancillary study). RESULTS: One hundred and nine patients were included; mean age 79.4 ± 6.8 years with 37 patients in the ancillary study. The mean values of IL-1ß, TNF-α, IL-6 and CCL5 values were 1.49, 7.18, 3.09 and 69,615.81 pg/mL, respectively. No correlation between plasma cytokines or chemokine levels and cognitive scores was found. In PBMCs, the levels of cytokines were detectable but did not either show any correlation with cognitive scores. CONCLUSION: Our data indicate that at diagnosis, peripheral levels of cytokines and CCL5 display low values without any correlation with the cognitive status. Further results of our study will show if these circulating markers are related to the progression of AD.

Prevalence of peripheral artery disease in the elderly population in urban and rural areas of Central Africa: the EPIDEMCA study.

OBJECTIVE: Data on peripheral artery disease in Africa are sparse and limited to urban areas. Given the urban/rural socio-economical gradient in these countries, we sought to determine the prevalence and risk factors of peripheral artery disease in urban and rural areas of two countries in Central Africa. METHODS: Individuals ≥65 years old living in two urban and rural areas of the Republic of Central Africa (ROC) and the Central African Republic (CAR) were invited. Demographic, clinical and biological data were collected. Ankle-brachial index ≤0.90 defined peripheral artery disease. RESULTS: Among the 1871 participants (age 73 years, 62% female) the prevalence of peripheral artery disease was 14.8%, higher in ROC than in CAR (17.4% vs. 12.2%, p = 0.007) and higher in females than males (16.6% vs. 11.9%, p = 0.012). The prevalence of peripheral artery disease increased with age, respectively at 10.9%, 14.9%, 15.1% and 22.2% for age bands of 65-69, 70-74, 75-79 and 80+years (p < 0.001). Higher rates of peripheral artery disease were found in urban areas in ROC (20.7% vs. 14.4% in rural areas, p = 0.011), but not in CAR (11.5% vs. 12.9%, p = NS). In multivariate analysis, peripheral artery disease was significantly associated with age (odds ratio (OR): 1.03; p = 0.004), dyslipidaemia (OR: 1.88; p = 0.003), smoking (OR: 1.78; p = 0.003), obesity (OR: 1.98; p = 0.034) and underweight (OR: 1.49; p = 0.023). Regular alcohol drinking was associated with decreased risk of peripheral artery disease (OR: 0.73; p = 0.044). CONCLUSION: The prevalence of peripheral artery disease in the elderly is high in Africa, especially in females. In ROC, with a higher urban-rural socio-economic gradient, peripheral artery disease is more frequent in the urban areas.

Temperature dependence of binding and catalysis for human serum arylesterase/paraoxonase.

The influence of temperature upon the hydrolysis of phenyl acetate, catalysed by purified human serum arylesterase/paraoxonase (E. C. 3.1.8.1), was studied in the temperature range 10 °C-40 °C by spectrophotometry in TRIS buffer, pH 8.0, using both initial rate analysis and progress curve analysis. The kinetic parameters (catalytic constant k(cat); Michaelis constant K(m); product inhibition constant K(p)) were determined by nonlinear regression. All parameters increased with temperature, but the ratios k(cat)/K(m) and K(p)/K(m) remained practically constant. Binding of both substrate and reaction product (phenol) was exothermic. A negative entropic term accounted for about 50% of the enthalpy change for both the binding and catalytic steps. Thermodynamic analysis suggested that: (1) the rate-limiting step is the nucleophilic attack of the carbonyl group of the substrate by a water molecule, (2) the active site is preorganized with no induced fit, (3) the enzyme-bound calcium plays an important role in stabilizing both the substrate and the transition state. The practical implications of these results are discussed.

Preventing and managing indoor falls with home-based technologies in mild and moderate Alzheimer's disease patients: pilot study in a community dwelling.

BACKGROUND: Alzheimer's disease (AD) is known to increase the risk of falls. We aim to determine the effectiveness of home-based technologies coupled with teleassistance service (HBTec-TS) in older people with AD. METHODS: A study of falls and the HBTec-TS system (with a light path combined with a teleassistance service) was conducted in the community. The 96 subjects, drawn from a random population of frail elderly people registered as receiving an allocation for lost autonomy from the county, were aged 65 or more and had mild-to-moderate AD with 1 year of follow-up; 49 were in the intervention group and 47 in the control group. RESULTS: A total of 16 (32.7%) elderly people fell in the group with HBTec-TS versus 30 (63.8%) in the group without HBTec-TS. The use of HBTec-TS was significantly associated with a reduction in the number of indoor falls among elderly people with mild-to-moderate AD (OR = 0.37, 95% CI = 0.15-0.88, p = 0.0245). CONCLUSION: The use of the HBTec-TS significantly reduced the incidence of primary indoor falling needing GP intervention or attendance at an emergency room among elderly people with AD and mild-to-moderate dementia.