Donepezil for gait and falls in mild cognitive impairment: a randomized controlled trial.

BACKGROUND AND PURPOSE: Cognitive enhancers are commonly prescribed to people with Alzheimer's disease and related dementias to improve cognition and function. However, their effectiveness for individuals in the pre-stages of dementia, particularly in functional motor outcomes, remains unknown. We aimed to determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic neurotransmission, on gait performance in mild cognitive impairment (MCI). METHODS: This was a double-blind, placebo-controlled trial including 60 older adults with MCI, randomized to receive donepezil (10 mg/daily, maximal dose) or placebo. Primary outcome was gait speed (cm/s) under single and three dual-task conditions (counting backwards by 1 or 7 and naming animals) measured using an electronic walkway. Dual-task gait cost (DTC), a valid measure of motor-cognitive interaction, was calculated as the percentage change between single (S) and dual-task (D) gait speeds: [(S - D)/S] × 100. Secondary outcomes included attention, executive function, balance and falls. RESULTS: After 6 months, the donepezil group experienced an improvement in dual-task gait speed (range 4-11 cm/s), although this was not statistically significant. The donepezil group showed a significant reduction in DTC (improvement) by counting backwards by 1 and 7 compared with placebo (10.25% vs. 1.75%, P = 0.048; 21.38% vs. 14.64%, P = 0.037, intention-to-treat analysis). Per-protocol analyses showed that all three DTCs improved in the donepezil group, along with a non-significant reduction of rate of falls. CONCLUSIONS: Donepezil treatment improved dual-task gait speed and DTC in elderly patients with MCI. Our results support the concept of reducing falls in MCI by targeting the motor-cognitive interface.

Association Between Balance Self-efficacy and Walking Ability in Those With New Lower Limb Amputations.

BACKGROUND: A relationship between walking ability and self-efficacy has been demonstrated in various rehabilitation patient populations. In experienced prosthetic ambulators, walking ability is related to self-efficacy of balance, however, this relationship has not been quantified for those with newly acquired lower limb amputations (LLA). OBJECTIVES: To investigate the association between walking performance (objective) and self-reported walking abilities (subjective) on balance self-efficacy in those with LLA. METHODOLOGY: Cross-sectional study of 27 people (17 men; mean age=63.57±9.33) at discharge from inpatient prosthetic rehabilitation for first major unilateral LLA. Individuals completed 6m straight path walking and the L-Test under single- and dual-task conditions. The Prosthesis Evaluation Questionnaire (PEQ) was administered, and the Ambulation subscale provided subjective measures of walking ability. A single PEQ question on satisfaction with walking (16B) was also used as a proxy for subjective walking ability. The Activities-specific Balance Confidence Scale measured balance self-efficacy. Multivariable linear regression was used to evaluate the strength of association between walking ability (objective and subjective) and balance self-efficacy (dependent variable). FINDINGS: Walking velocity on the 6m straight path under single-task (p=0.011) and dual-task conditions (p=0.039), the single-task L-Test (p=0.035) and self-reported satisfaction with walking (p=0.019) were associated with self-efficacy of balance. CONCLUSIONS: Objective measures of walking ability that were independently associated with balance self-efficacy included straight path walking velocity under single and dual-task conditions and the single-task L-Test. Satisfaction with walking was also associated with balance self-efficacy. This highlights the interplay between physical and psychological factors during rehabilitation. More research in the area of self-efficacy and walking ability is needed to establish self-efficacy as a target during prosthetic rehabilitation for those with LLA.

A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein.

Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10-kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae-specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection.

The attentional demands of ambulating with an assistive device in older adults with Alzheimer's disease.

Ambulation with a mobility aid is a unique real-life situation of multi-tasking. These simultaneous motor tasks place increased demands on executive function in healthy young and older adults, but the demands have not been evaluated in people with Alzheimer's disease (AD). Mobility problems are common among adults with AD, leading to provision of a mobility aid to optimize independent activity. The study objectives were: (i) to determine the dual-task cost (DTC) associated with the use of a mobility aid in straight and complex path walking, and (ii) to evaluate the association between executive function and ambulation with a mobility aid in older adults with AD and age-sex matched cognitively normal controls. Fourteen people (mean age±SD, 72.6±9.9years) with a diagnosis of probable AD (MMSE range 12-25) and controls (mean age±SD, 72.9±9.5) walked at a self-selected pace and using a 4-wheeled walker in a 6m straight path and a Figure of 8 Test. Ambulation with the walker in a straight path produced a low DTC that was not different between the groups. Ambulation with the 4-wheeled walker in the complex path produced a significantly different DTC in the group with AD at -38.1±23.5% compared to -19.7±21.4% (p=0.041). Lower scores on executive function were associated with longer times across test conditions. Ambulation with a 4-wheeled walker, in particular maneuvering around obstacles, requires greater attentional costs in dementia. Future research should explore the timing for safely introducing mobility aids in AD and the role of improving executive function.

Dual-task testing to predict falls in community-dwelling older adults: a systematic review.

BACKGROUND: Cognitive impairment increases fall risk in older adults. Dual-task testing is an accepted way to assess the interaction between cognition and mobility; however, there is a lack of evidence-based recommendations for dual-task testing to evaluate fall risk in clinical practice. OBJECTIVES: To evaluate the association between dual-task testing protocols and future fall risk, and to identify the specific dual-task test protocols associated with elevated risk. DATA SOURCES: MEDLINE, Pubmed and EMBASE electronic databases were searched from January 1988 to September 2013. STUDY SELECTION: Two independent raters identified prospective cohort studies (duration of at least 1 year) of dual-task assessment in community-dwelling participants aged ≥60 years, with 'falls' as the primary outcome. STUDY APPRAISAL AND SYNTHESIS METHODS: Methodological quality was scored independently by two raters using a published checklist of criteria for evaluating threats to the validity of observational studies. RESULTS: Deterioration in gait during dual-task testing compared with single-task performance was associated with increased fall risk. Shortcomings within the literature significantly limit knowledge translation of dual-task gait protocols into clinical practice. LIMITATIONS: There is a paucity of prospective studies on the association of dual-task gait assessment with fall risk. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: Changes in gait under dual-task testing are associated with future fall risk, and this association is stronger than that for single-task conditions. Limitations in the available literature preclude development of detailed recommendations for dual-task gait testing procedures in clinical practice to identify and stratify fall risk in older adults.

Defining Rehabilitation Success in Older Adults with Dementia--Results from an Inpatient Geriatric Rehabilitation Unit.

OBJECTIVE: To quantify the magnitude of functional recovery in older adults with and without dementia admitted to an inpatient geriatric rehabilitation program by measuring change in measures of global physical function and physical therapy treatment outcomes. DESIGN: Retrospective cohort study. SETTING: Rehabilitation academic hospital. PARTICIPANTS: Consecutive subjects, with (N=65, age 81.9±6.0 y) and without (N=157, age 82.8±7.2 y) a dementia diagnosis, had assessment data at admission and discharge from inpatient geriatric rehabilitation unit. INTERVENTIONS: Not applicable. MEASUREMENTS: The Functional Independence Measure (FIM) was used to estimate level of independence on activities of daily living. The Berg Balance Scale (BBS), Timed Up and Go Test (TUG) and 2 Minute Walk Test (2MWT) were used to estimate functional mobility and endurance. The FIM (total, motor subscale, cognitive subscale scores) were used to calculate rehabilitation efficacy and efficiency scores. RESULTS: After controlling for confounding, there was no group difference for gains on the BBS, TUG, 2MWT; there was no group difference on rehabilitation efficacy and efficiency values based on the FIM motor subscale. The magnitude of the rehabilitation gain using the total FIM score was statistically different between groups, people with dementia having smaller gains. CONCLUSION: Older adults with a diagnosis of dementia are capable of making motor function recovery during inpatient sub-acute rehabilitation comparable to their peers without a dementia diagnosis. The metric used to evaluate functional recovery influences the determination of rehabilitation success between groups. Rehabilitation success should be defined among people with a dementia diagnosis by a change in the motor subscale of the FIM, rather than the total FIM score or the gain relative to the maximal FIM score.

Chemical synthesis of disaccharides of the specific phenolic glycolipid antigens from Mycobacterium leprae and of related sugars.

O-(3,6-Di-O-methyl-beta-D-glucopyranosyl)-(1----4)-2,3,-di-O-methyl-L -rhamnopyranose, which is the nonreducing disaccharide of the haptenic trisaccharide of the Mycobacterium leprae-specific, phenolic glycolipid I, O-(6-O-methyl-beta-D-glucopyranosyl)-(1----4)-2,3-di-O-methyl-L-rhamn opyranose, the nonreducing end of the specific, phenolic glycolipid III, and the nonhaptenic O-beta-(D-glucopyranosyl)-(1----4)-2,3-di-O-methyl-L-rhamnopyranose++ +, were synthesized in relatively good yield from 3-O-methyl-D-glucose, or D-glucose, and L-rhamnose via Koenigs-Knorr reactions. These disaccharides can be used as precursors in the synthesis of the trisaccharide unit of phenolic glycolipid I and of neoglycoconjugates suitable for the serodiagnosis of leprosy.

Chemical synthesis of the trisaccharide unit of the species-specific phenolic glycolipid from Mycobacterium leprae.

O-(3,6-Di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(2,3-di-O-methyl- alpha-L-rhamnopyranosyl)-(1----2)-3-O-methyl-L-rhamnopyranose, the haptenic trisaccharide of the Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) antigen, and related trisaccharides, were synthesized by allylation of O-2 of benzyl 4-O-benzyl-alpha-L-rhamnopyranoside using phase-transfer catalysis, methylation of the product, deallylation, and coupling to O-(2,4-di-O-acetyl-3,6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-2,3- di-O-methyl-L-rhamnopyranosyl bromide or related disaccharides. Anomeric mixtures of the trisaccharide derivatives were separated by preparative t.l.c., deacetylated, and hydrogenolyzed, to give the pure trisaccharides. It had already been demonstrated that only those trisaccharides containing an intact, terminal 3,6-di-O-methyl-beta-D-glucopyranosyl unit are effective in inhibiting the specific binding between PGL-I and anti-PGL-I immunoglobulin M antibodies in human lepromatous leprosy sera.

Demonstration that the galactosyl and arabinosyl residues in the cell-wall arabinogalactan of Mycobacterium leprae and Mycobacterium tuberculosis are furanoid.

By a complex process involving methylation, partial hydrolysis with acid, reduction with sodium borodeuteride, ethylation, further hydrolysis and reduction, and subsequent capillary gas-liquid chromatography-mass spectrometry of the derived alditol acetates, it was established that the arabinogalactans of Mycobacterium leprae and Mycobacterium tuberculosis contain arabinofuranyosyl and galactofuranosyl residues exclusively. Thus, the covalently bound, highly immunogenic arabinogalactan of mycobacteria, and presumably of other actinomycetes, is highly unusual, in that all of the glycosyl residues are in the furanoid form. Furthermore, by establishing that the galactofuranosyl residues are either 5-, 6-, or 5,6-linked, their linkage pattern was established, and the literature is corrected on this point.

Effective vaccination of mice against Mycobacterium leprae with density-gradient subfractions of soluble M. leprae proteins: clues to effective protein epitopes.

It had previously been discovered that intradermal mouse vaccination with a protein fraction of Mycobacterium leprae (called soluble proteins) in Freund's incomplete adjuvant (FIA) resulted in consistent and long-lived protection against M. leprae multiplication from subsequent viable footpad challenges. In this study certain density-gradient subfractions of this soluble protein, but not others, in FIA afforded vaccine protection. The results of this study suggest which M. leprae proteins may be involved in protective immunity, particularly 1-3 kD, 10 kD, 65 kD, and those of higher molecular weight.

The ambulatory oncology nurse's role.

The increasing complexity of cancer care in the ambulatory setting results in the role of the ambulatory oncology nurse being pivotal to ensuring quality health care. Nurses have created a variety of multifaceted roles that include the staff nurse, advanced practice nurse, clinical trials nurse, office nurse, and the head nurse or nurse manager. Common issues encountered by the ambulatory oncology nurse are telephone triage, limitation of time, and transition of care.

Facilitating Frailty Identification: Comparison of Two Methods among Community-Dwelling Order Adults.

BACKGROUND: Frailty is characterized by increased vulnerability for adverse events such as falls, fractures, placement, and death. Several frailty models have been developed, including the widely accepted Frailty Phenotype. However, the Frailty Phenotype can be difficult to apply in clinical practice. Alternatively, the Clinical Frailty Scale has been proposed based on its simplicity. To date, the Clinical Frailty Scale has not been validated against the Frailty Phenotype. OBJECTIVE: We aimed to test the inter-rater reliability of the Clinical Frailty Scale and its agreement with the Frailty Phenotype in frailty identification. DESIGN: Cross-sectional study. SETTING: Retirement community in London, Ontario, Canada. PARTICIPANTS: One hundred and four community-dwelling older adults (age ≥75 years). MEASUREMENTS: Participants were first classified using the Frailty Phenotype criteria as not frail, pre-frail or frail. Subsequently, two clinicians blinded to the first assessment, determined frailty status using the Clinical Frailty Scale. Differences between assessments were resolved by consensus. Inter-rater reliability was assessed using kappa statistics. Spearman Rho correlation coefficients evaluated the concurrent validity of the Clinical Frailty Scale against Frailty Phenotype components. RESULTS: Analysis with kappa statistic showed substantial agreement between raters in applying the Clinical Frailty Scale to the sample (κw= 0.76, 95% CI 0.68, 0.84). The Clinical Frailty Scale scores also positively correlated with an increasing number of Frailty Phenotype components (ρ=0.69, p<0.01). CONCLUSION: The Clinical Frailty Scale is reliable and comparable to the Frailty Phenotype in identifying frailty in community-dwelling older adults with the advantage of being easy to administer in clinical settings. Reliable tools to identify frailty in community-dwelling older adults may help provide timely interventions to ameliorate risk of adverse events.

A novel phenolic glycolipid from Mycobacterium leprae possibly involved in immunogenicity and pathogenicity.

A phenolic glycolipid was obtained in high amounts (2% of dry weight) from Mycobacterium leprae isolated from infected armadillo liver. Infrared and nuclear magnetic resonance spectroscopy showed that it is closely related to "mycoside A" from Mycobacterium kansasii and is therefore a glycosylphenolic phthiocerol diester. The crucial difference between the two products is in the composition of the attached trisaccharide. Gas-liquid chromatography-mass spectroscopy showed that the product from M. kansasii is composed of 2,4-di-O-methylrhamnose, 2-O-methylrhamnose, and 2-O-methylfucose, whereas that from M. leprae contains 2,3-di-O-methylrhamnose, 3-O-methylrhamnose, and 3,6-di-O-methylglucose. The distinct composition of the oligosaccharide segment of the glycolipid from M. leprae may make it useful for the chemical and serological differentiation of this organism from other mycobacteria. Surprisingly large quantities (2.2 mg/g of dry liver) of the glycolipid were also found in infected liver residue freed of M. leprae, suggesting that it may be responsible for the electron-transparent "foam" surrounding the organism in infected lepromatous tissue.

Further specific extracellular phenolic glycolipid antigens and a related diacylphthiocerol from Mycobacterium leprae.

Mycobacterium leprae in infected armadillo tissue produces extracellular phthiocerol-containing lipids in amounts well in excess of the bacterial mass. The principal component (1.38 mg in 1 g of liver, wet weight, containing 3.7 X 10(10) M. leprae bacilli) consists of a mixture of two phthiocerol homologs, 3-methoxyl-4-methyl-9, 11-dihydroxyoctacosane and 3-methoxyl-4-methyl-9, 11-dihydroxytriacontane, (formula: see text); in which the hydroxyl functions are acylated by a mixture of three 'mycocerosic acids': 2,4,6,8-tetramethylhexacosanoate, 2,4,6,8-tetramethyloctacosanoate, and 2,4,6,8-tetramethyltriacontanoate. The structures were established by saponification of the native lipid, direct probe electron impact- or chemical ionization-mass spectrometry of the phthiocerol or its permethylated derivative, and gas-liquid chromatography-electron impact-mass spectrometry of the methyl esters of the fatty acids. In addition to the previously reported M. leprae-specific triglycosylphenolicdiacyl phthiocerol (Hunter, S. W., Fujiwara, T., and Brennan, P. J. (1982) J. Biol. Chem. 257, 15072-15078), the extracellular products contain small amounts (about 60 micrograms/g of infected liver, wet weight) of two other phenolic glycolipids, one of which (Phenolic Glycolipid III) has been structurally elucidated, (formula: see text); assuming certain enantiomeric configurations for the sugar substituents; the R-acyl functions are identical with those in the diacylphthiocerol. Phenolic Glycolipid-III reacts in enzyme-linked immunosorbent assays with sera from patients with leprosy and with rabbit antisera raised against whole M. leprae. The phthiocerol-containing lipids may be synonymous with the electron transparent capsules of M. leprae, and their unreactive state may confer on them the role of passive protectors of the bacillus.