Gait variability at fast-pace walking speed: A biomarker of mild cognitive impairment?

Background

The interpretation of the increase in stride-to-stride variability of stride time (STV) regarding the evolution of cognitive deficits across the dementia spectrum is matter of debate.

Objective

The aim of this study was to compare STV at usual and fast-pace walking speeds of MCI patients with that of cognitively healthy individuals (CHI) and Alzheimer’s disease (AD) patients with mild dementia, while considering the effects of potential confounders.

Methods

STV while walking at usual and fast-pace walking speeds was recorded with the GAITRite® system from 116 older adults (mean age 75.6±6.5 years; 55.2% female) divided into 3 groups according to their cognitive status (44 CHI, 39 MCI patients and 33 AD patients with mild dementia).

Results

The full adjusted multiple linear regression models showed that high STV was associated with slow gait speed at usual-pace walking speed (P=0.002) and with the MCI status at fast-pace walking speed (P=0.015).

Conclusions

High STV at fast-pace walking speed was a specific gait disturbance of MCI patients in the sample of studied participants, and thus could be used in the future as a specific biomarker of MCI patients.     

Different components of nutritional status in older inpatients with cognitive impairment

Objectives

To evaluate different components of nutritional status in older patients with cognitive deficit, particularly in those with mild cognitive impairment (MCI).

Design

Cross-sectional study.

Setting and participants

560 elderly subjects aged ?? 65 years consecutively admitted to an acute Geriatric Unit of Apulia region of southern Italy.

Measurements

A standardized comprehensive geriatric assessment was used to evaluate medical, cognitive, affective and social aspects. Nutritional status was assessed using the mini nutritional assessment (MNA). The cognitive function was categorized into three levels ?? MCI, dementia or normal cognition (NoCI) ?? according to the neuropsychological test score.

Results

Subjects with cognitive decline had significantly lower frequency of well-nourished (MCI=10%, dementia=8%, NoCI=22%, p<0.05) and higher frequency of malnourished (MCI=47%, dementia=62%, NoCI=19%, p<0.001) than patients with normal cognition. Similarly, MNA total score, MNA-3 and MNA-4 subscores were significantly lower in patients with MCI and dementia than patients with normal cognition (p<0.001).

Conclusions

These results suggest that cognitive decline may be associated with malnutrition in this sample of hospitalized older patients. Dietary habits (MNA-3) and subjective assessment of self-perceived quality of health and nutrition (MNA-4) are particularly poor also in patients with MCI and could be. very important variables to be considered in the multidimensional evaluation of subjects with cognitive impairment.     

The advanced activities of daily living: A tool allowing the evaluation of subtle functional decline in mild cognitive impairment

Objectives

Assessment of advanced activities of daily living (a-ADL) can be of interest in establishing the diagnosis of Alzheimer’s disease (AD) in an earlier stage, since these activities demand high cognitive functioning and are more responsive to subtle changes. In this study we tested a new a-ADL tool, developed according to the International Classification of Functioning, Disability and Health (ICF). The a-ADL tool is based on the total number of activities performed (TNA) by a person and takes each subject as his own reference. It distinguishes a total Disability Index (a-ADL-DI), a Cognitive Disability Index (a-ADL-CDI), and a Physical Disability Index (a-ADL-PDI), with lower score representing more independency. We explored whether these indices allow distinction between cognitively healthy persons, patients with Mild Cognitive Impairment (MCI) and patients with mild AD.

Methods

Participants were on average 80 years old (SD 4.6; 66–90), were community dwelling, and were diagnosed as (1) cognitively healthy subjects (n=26); (2) patients with MCI (n = 17), or (3) mild AD (n = 25), based upon extensive clinical evaluation and a set of global, cognitive, mood and functional assessments. The a-ADL-tool was not part of the clinical evaluation.

Results

The a-ADL-CDI was significantly different between the three groups (p<.01). The a-ADL-DI was significantly different between MCI and AD (p<.001). The tool had good psychometrical properties (inter-rater reliability; agreement between patient and proxy; correlations with cognitive tests). Although the sample size was relatively small, ROC curves were computed for the a-ADL-DI and a-ADL-CDI with satisfactory and promising results.

Conclusion

The a-ADLCDI and a-ADL-DI might offer a useful contribution to the identification and follow up of patients with mild cognitive disorders in an older population.     

Characterizing magnitude and selectivity of attrition in a study of mild cognitive impairment

Objectives

Attrition is one of the greatest difficulties in longitudinal studies on cognitive ageing because of the associated risk of underestimating declines. The aims of this paper were to characterize the magnitude and selectivity of attrition in a study of mild cognitive impairment.

Design

Forty two patients with multiple-domain amnestic MCI, 71 with single-domain amnestic MCI, 35 with non-amnestic MCI and 318 healthy controls were recruited from primary care centers and assessed at baseline.

Measurements

All participants underwent extensive neuropsychological evaluation, including the Mini-Mental State Examination, the Californian Verbal Learning Test, the CAMCOG-R battery, the Counting Span task and Listening Span task, and the Subjective Memory Complaints Questionnaire.

Results

21.5% of the participants at baseline did not participate in the follow-up assessment. Comparison between respondents and non-returners did not reveal differences in cognitive performance in the MCI group. Data obtained at the initial assessment regarding comorbidity, social activities and attention given to memory training enabled prediction of the status of the participants in the follow-up assessment.

Conclusion

Identification of potential non- returners is relevant, especially in MCI studies, in order to develop retention strategies to minimize attrition.

     

Capacity to consent to biomedical research’s evaluation among older cognitively impaired patients. A study to validate the University of California Brief Assessment of Capacity to Consent questionnaire in French among older cognitively impaired patients

Context

Some studies have highlighted the difficulty for physicians to evaluate patient’s ability to consent to bio-medical research in the elderly population. The University of California Brief Assessment of Capacity to Consent (UBACC) is a rapid questionnaire to assess the ability to consent, previously validated among schizophrenic patients.

Objective

To evaluate the accuracy of the UBACC scale, French version, to determine the capacity to consent to biomedical studies of older people with normal cognition, mild cognitive impairment (MCI) or Alzheimer Disease (AD).

Design

A prospective validation study between September 2008 to November 2011.

Setting

A Memory clinic.

Patients

We included 61 subjects in a memory clinic who had already consented to participate to a biomedical research and had signed a consent form. Those subjects, who had memory impairment, had a comprehensive neuro-psychological (including Mini Mental State Examination (MMSE)/30), clinical, biological assessment and brain imagery during day-care hospital. They were classified as MCI or AD patients. Control group included patients’ caregivers without memory complaints and a normal comprehensive neuro-psychological assessment.

Intervention and measurements

The consent form was once again explained to the subjects by a physician who subjectively evaluated if subjects had understood the study. Then, the 10 questions of the French version of the UBACC scale (max score 20) were asked to the participants. This scale evaluates the understanding of the study’s aim, risks and benefits. A comparison was made between subjective assessment and the UBACC score.

Results

The physician considered that 18/61 patients (2 MCI and 16 AD) had not understood. These ones had a lower UBACC score (Score/20 (SD) [range]: 7.56 (3.03) [0–12] versus 17.72 (2.68) [13–28], p<0.001), a lower MMSE (Score/30 (SD): 21.1 (5.9) versus 27.3 (2.9); p<0.001) and were older (age (years old) 80.8 versus 76.6. p<0.0001) compared to those who had understood. Moreover, all the patients who had not understood had an UBACC score ≤ 12. The administration time was accurate in this population (<10 minutes).

Conclusion

The UBACC scale, in its French version, was accurate to assess capacity to consent in an older, cognitively impaired population.     

Effect of long-term treatment with galantamine on weight of patients with Alzheimer’s dementia

Objectives

There is discussion about the effect of cholinesterase inhibitors (CERs) on weight of patients with Alzheimer’s disease (AD). Given the adverse outcomes of weight loss in AD patients, it is important to establish the effect of CERs on weight. This study aimed tot assess the long-term effect of galantamine on weight of AD patients.

Design, setting and participants

This longitudinal study was performed at a large memory clinic in the North of the Netherlands. During the period 2002 to 2010, 303 communitydwelling AD patients, aged 65 years or older who started using a cholinesterase inhibitor (CER), were included.

Measurements

Socio-demographic characteristics and data on comorbidity, number of medications, type and dosage of CER, use of care, cognitive function, behaviour and nutritional status (weight, Body Mass Index (BMI)) were recorded at the time the diagnosis AD was made and at subsequent outpatient clinic visits. The Generalized Estimating Equations (GEE) model was used to determine the effect of galantamine of 16 mg and 24 mg on weight. The effect of galantamine in a dose of 16 and 24 mg was investigated because the other groups (rivastigmine, galantamine 8 mg) were too small to determine the effect on weight by GEE analysis. Donepezil is not available in the Netherlands.

Results

The median follow-up time between the moment patients started using a CER (T0) and the 1st visit was 6 months (n=300); between T0 and the 2nd visit 13 months (n=212); between T0 and the 3rd visit 25 months (n=117) and between T0 and the 4th visit 37 months (n=58). Galantamine 16 mg and 24 mg, corrected for age, gender, social status, informal care, professional care, comorbidity, number of medications, cognition, behaviour and appetite, had no effect on weight (p > 0.05). Male patients had a higher average weight compared to female patients (p=0.000, B=8.333). Patients without an informal caregiver (p=0.01, B=?3.697) or partner (p=0.042, B=?3.197) had a lower average weight compared to patients with an informal caregiver or partner.

Conclusion

Weight loss in AD patients should not be attributed to long-term treatment with galantamine. This is in accordance with the French guideline. If AD patients are losing weight, other causes, including insufficient care, should be investigated.     

Do general practitioners recognize mild cognitive impairment in their patients?

Objectives

The need for recognition of mild cognitive impairment (MCI) in primary care is increasingly discussed because MCI is a risk factor for dementia. General Practitioners (GPs) could play an important role in the detection of MCI since they have regular and long-term contact with the majority of the elderly population. Thus the objective of this study is to find out how well GPs recognize persons with MCI in their practice population.

Design

Cross-sectional study.

Setting

Primary care chart registry sample.

Participants

3,242 non-demented GP patients aged 75–89 years.

Measurements

GPs assessed the cognitive status of their patients on the Global Deterioration Scale (GDS). Thereafter, trained interviewers collected psychometric data by interviewing the patients at home. The interview data constitute the basis for the definition of MCI cases (gold standard).

Results

The sensitivity of GPs to detect MCI was very low (11–12%) whereas their specificity amounts to 93–94%. Patients with MCI with a middle or high level of education more often got a false negative assignment than patients with a low educational level. The risk of a false positive assignment rose with the patients’ degree of comorbidity. GPs were better at detecting MCI when memory or two and more MCIdomains were impaired.

Conclusion

The results show that GPs recognise MCI in a very limited number of cases when based on clinical impression only. A further development of the MCI concept and its operationalisation is necessary. Emphasis should be placed on validated, reliable and standardised tests for routine use in primary care encompassing other than only cognitive domains and on case finding approaches rather than on screening. Then a better attention and qualification of GPs with regard to the recognition of MCI might be achievable.     

Spatial variability during gait initiation while dual tasking is increased in individuals with mild cognitive impairment

Background

Gait initiation (GI) is a complex transition phase of gait that can induce postural instability. Gait impairment has been well documented in people with Alzheimer’s disease, but it is still inconclusive in individuals with Mild Cognitive Impairment (MCI). Previous studies have usually investigated gait performance of cognitive impaired persons under steady state walking.

Objective

This study aimed to examine spatiotemporal variability during GI under single- and dual-task conditions in people with and without MCI.

Methods

Spatiotemporal stepping characteristics and variability under single- and dual-task conditions (counting backwards by 3s) were assessed in 30 older adults with MCI and 30 cognitively intact controls. Mean and coefficients of variation (COV) of swing time, step time, step length and step width were compared between the two groups.

Results

Mixed-model repeated measures ANOVA revealed a significant Group x Walking condition interaction for COV of step length and step width (P<0.05). Post-hoc analysis revealed that variability for these measures were significantly larger in the MCI group compared with the control group under the dual-task condition (P<0.05).

Conclusions

Step length and step width variability is increased in people with MCI during GI, particularly in a condition involving a secondary cognitive task. These findings suggest that individuals with MCI have reduced balance control when undertaking a challenging walking task such as gait initiation, and this is exacerbated with an added cognitive task. Future studies should prospectively investigate the relationship between GI variability and fall risk in this population.     

Anticholinergic burden and functional status in older people with cognitive impairment: Results from the ReGAl project

Objective

The use of drugs with intrinsic anticholinergic properties is widespread among old age persons. A growing body of evidences suggest that a high anticholinergic burden is associated with physical and cognitive impairment. However, the association between anticholinergic drug use and functional status is still poorly investigated, particularly among subjects with initial cognitive impairment.

Design

Cross-sectional study examining the association between drug-related anticholinergic burden and functional status in cognitively healthy (CH) (n=691), mild cognitive impairment (MCI) (n=541) or mild Alzheimer’s diseases (AD) (n=1127) subjects.

Setting

Data were gathered from the ReGAl project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer’s disease), a large longitudinal Italian multicentric clinical-based study, promoted by the Italian Society of Gerontology and Geriatrics (SIGG).

Participants

2359 outpatients, older than 65 years, admitted to memory clinics. The total sample size, estimated according to a global effect size of 25% with type I error of 0.05 and a power of 95% is 2010 subjects.

Measurement

Functional status was evaluated by the Katz Index of Independence in Activities of Daily Living (ADL) and the Lawton-Brody Instrumental Activities of Daily Living (IADL) scales. The drug-related anticholinergic burden was estimated by the Anticholinergic Risk Scale (ARS).

Results

The 15.9 % (n=375) of total population used at least one drug with anticholinergic properties. Such a drug use was associated with partially dependence in ADL (OR:1.42, CI95%: 1.10-1.83; p=0.006), independently of gender, number of drugs, comorbidity index, presence of clinically relevant neuropsychiatric symptoms and adjusted MMSE. Anticholinergic drug use was associated with un-ability at each IADL task only in male MCI subjects, with significant impairment in shopping (p=0.011), and drug management (p=0.05).

Conclusions

The use of medications with anticholinergic properties is common among older persons cognitively health as well as with cognitive impairment. Our results suggest that the use of anticholinergic drugs is associated with functional impairment, especially in old age subjects with initial cognitive impairment. Minimizing anticholinergic burden should result in maintaining daily functioning, especially in a vulnerable population, such as MCI and mild AD.

     

Evolution of Aβ42 and Aβ40 levels and Aβ42/Aβ40 ratio in plasma during progression of Alzheimer’s disease: A multicenter assessment

Objective

To better understand the seemingly contradictory plasma β-amyloid (Aβ) results in Alzheimer’s disease (AD) patients by using a newly developed plasma Aβ assay, the INNO-BIA plasma Aβ forms, in a multicenter study.

Methods

A combined retrospective analysis of plasma Aβ isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers.

Results

Detection modules based on two different amino (N)-terminal specific Aβ monoclonal antibodies demonstrated that Aβ in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low Aβ42 plasma concentrations. Aβ40 and Aβ42 concentrations varied consistently with the ApoE genotype, while the Aβ42/Aβ40 ratio did not. Irrespective of the decrease of the Aβ42/Aβ40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF).

Conclusion

A highly robust assay for repeatedly measuring Aβ forms in plasma such as INNO-BIA plasma Aβ forms might be a useful tool in a future risk assessment of AD.     

Conversion from mild cognitive impairment to dementia: Influence of folic acid and vitamin B12 use in the vita cohort

Objective

Increased serum homocysteine and low folate levels are associated with a higher rate of conversion to dementia. This study examined the influence of vitamin B12/folic acid intake on the conversion from mild cognitive impairment (MCI) to dementia.

Participants

A community dwelling cohort of older adults (N=81) from the Vienna Transdanube aging study with MCI.

Design

Prospective study with a retrospective evaluation of vitamin intake.

Measurements

Laboratory measurements, brain magnetic resonance imaging, and cognitive functioning were assessed at baseline and at five-year follow-up.

Results

The self-reported combined use of folic acid and vitamin B12 for more than one year was associated with a lower conversion rate to dementia. Serum levels of homocysteine and vitamin B12 as measured at baseline or at five years were not associated with conversion. Higher folate levels at baseline in females predicted a lower conversion rate to dementia. The assessment of brain morphological parameters by magnetic resonance imaging revealed higher serum folate at baseline, predicting lower medial temporal lobe atrophy and higher levels of homocysteine at baseline, predicting moderate/severe global brain atrophy at five years. Users of vitamin B12 or folate, independent of time and pattern of use, had lower grades of periventricular hyperintensities and lower grades of deep white matter lesions as compared to non-users.

Conclusions

These results from a middle european study support observations on the protective ability of folate in MCI patients with respect to conversion to dementia; they also point to a participation of homocysteine metabolism on processes associated with brain atrophy.     

Virgin olive oil supplementation and long-term cognition: the Predimed-Navarra randomized, trial

Objective

XXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet).

Design

XXXrandomized trial after 6.5 years of nutritional intervention.

Setting

Eight primary care centers affiliated to the University of Navarra.

Participants

A random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1± 5.7 years at cognitive evaluation).

Interventions

Nutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil [EVOO] or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter.

Measurements

XXXcognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment [MCI] or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention.

Results

Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. After adjustment for sex, age, education, apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, this group also showed lower MCI (OR=0.34 95% CI: 0.12–0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls.

Conclusion

A long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.     

Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial

Background

Alzheimer's disease (AD) is characterized by early and region-specific declines in cerebral glucose metabolism. Ketone bodies are produced by the body during glucose deprivation and are metabolized by the brain. An oral ketogenic compound, AC-1202, was tested in subjects with probable AD to examine if ketosis could improve cognitive performance.

Methods

Daily administration of AC-1202 was evaluated in 152 subjects diagnosed with mild to moderate AD in a US-based, 90-day, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were on a normal diet and continued taking approved AD medications. Primary cognitive end points were mean change from Baseline in the AD Assessment Scale-Cognitive subscale (ADAS-Cog), and global scores in the AD Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC). AC-1202 was compared to Placebo in several population groups, including: intention-to-treat (ITT), per protocol, and dosage compliant groups. Results were also stratified by APOE4 carriage status (a predefined analysis based on the epsilon 4 (E4) variant of the apolipoprotein E gene). This trial was registered with ClinicalTrials.gov, registry number NCT00142805, information available at http://clinicaltrials.gov/ct2/show/NCT00142805

Results

AC-1202 significantly elevated a serum ketone body (β-hydroxybutyrate) 2 hours after administration when compared to Placebo. In each of the population groups, a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45: 1.9 point difference, p = 0.0235 in ITT; 2.53 point difference, p = 0.0324 in per protocol; 2.6 point difference, p = 0.0215 in dosage compliant. Among participants who did not carry the APOE4 allele (E4(-)), a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45 and Day 90. In the ITT population, E4(-) participants (N = 55) administered AC-1202 had a significant 4.77 point difference in mean change from Baseline in ADAS-Cog scores at Day 45 (p = 0.0005) and a 3.36 point difference at Day 90 (p = 0.0148) compared to Placebo. In the per protocol population, E4(-) participants receiving AC-1202 (N = 37) differed from placebo by 5.73 points at Day 45 (p = 0.0027) and by 4.39 points at Day 90 (p = 0.0143). In the dosage compliant population, E4(-) participants receiving AC-1202 differed from placebo by 6.26 points at Day 45 (p = 0.0011, N = 38) and 5.33 points at Day 90 (p = 0.0063, N = 35). Furthermore, a significant pharmacologic response was observed between serum β-hydroxybutyrate levels and change in ADAS-Cog scores in E4(-) subjects at Day 90 (p = 0.008). Adverse events occurred more frequently in AC-1202 subjects, were primarily restricted to the gastrointestinal system, and were mainly mild to moderate in severity and transient in nature.

Conclusion

AC-1202 rapidly elevated serum ketone bodies in AD patients and resulted in significant differences in ADAS-Cog scores compared to the Placebo. Effects were most notable in APOE4(-) subjects who were dosage compliant.     

The impact of protein supplementation on cognitive performance in frail elderly

Purpose

Maintenance of cognitive abilities is important for elderly to stay independent. With the aging of the population, the call for modifiable factors is emerging. Dietary protein might improve cognitive performance; however, this has hardly been studied. Therefore, we studied the impact of 24-week dietary protein supplementation on cognitive performance in pre-frail and frail elderly people.

Methods

Pre-frail and frail elderly subjects, according to the Fried criteria, randomly received a protein drink containing 15 g protein or a placebo drink twice a day. Cognitive performance was measured at baseline and after 24 weeks by means of a sensitive neuropsychological test battery. In addition, reaction time was assessed after both 12 and 24 weeks of intervention. Domain scores were calculated for the domains episodic memory, attention and working memory, information processing speed, and executive functioning. Analyses of covariance were used to determine differences between groups. Linear mixed models were used to determine differences in reaction time over time and per treatment.

Results

In total, 65 subjects (79 ± 8 years) with a median Mini-Mental State Examination score of 28 (interquartile range 26–30) were included. Reaction time improved more in the protein group (68 ms) than in the placebo group (18 ms, P = 0.03). Dietary protein had no significant effect on any of the cognitive domain scores.

Conclusions

Protein supplementation might improve reaction time performance in pre-frail and frail elderly, but did not improve other cognitive functions.     

Falls,Cognitive Impairment,and Gait Performance: Results From the GOOD Initiative

Objectives

Falls are highly prevalent in individuals with cognitive decline. The complex relationship between falls and cognitive decline (including both subtype and severity of dementia) and the influence of gait disorders have not been studied. This study aimed to examine the association between the subtype (Alzheimer disease [AD] versus non-AD) and the severity (from preclinical to moderate dementia) of cognitive impairment and falls, and to establish an association between falls and gait parameters during the course of dementia.

A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia

Background

Sarcopenia, the age-related loss of muscle mass [defined as appendicular LBM/Height² (aLBM/ht²) below peak value by>1SD], strength and function, is a major contributing factor to frailty in the elderly. MK-0773 is a selective androgen receptor modulator designed to improve muscle function while minimizing effects on other tissues.

Objectives

The primary objective of this study was to demonstrate an improvement in muscle strength and lean body mass (LBM) in sarcopenic frail elderly women treated with MK-0773 relative to placebo.

Design

This was a randomized, double-blind, parallel-arm, placebo-controlled, multicenter, 6-month study. Participants were randomized in a 1:1 ratio to receive either MK-0773 50mg b.i.d. or placebo; all participants received Vitamin D and protein supplementation.

Setting

General community.

Participants

170 Women aged ≥65 with sarcopenia and moderate physical dysfunction.

Measurements

Dual energy X-ray absorptiometry, muscle strength and power, physical performance measures.

Results

Participants receiving MK-0773 showed a statistically significant increase in LBM from baseline at Month 6 vs. placebo (p<0.001). Participants receiving both MK-0773 and placebo showed a statistically significant increase in strength from baseline to Month 6, but the mean difference between the two groups was not significant (p=0.269). Both groups showed significant improvement from baseline at Month 6 in physical performance measures, but there were no statistically significant differences between participants receiving MK-0773 and placebo. A greater number of participants experienced elevated transaminases in the MK-0773 group vs. placebo, which resolved after discontinuation of study therapy. MK-0773 was generally well-tolerated with no evidence of androgenization.

Conclusions

The MK-0773-induced increase in LBM did not translate to improvement in strength or function vs. placebo. The improvement of strength and physical function in the placebo group could be at least partly attributed to protein and vitamin D supplementation.     

Improvement of accommodation with anti-oxidant supplementation in visual display terminal users

Objective

To determine the antioxidant supplementation effect on accommodation among VDT users.

Design

A double blind randomized placebo controlled study. Registered under Clinical Trials.gov Identifier No. NCT00877201.

Participants and Controls

Fourty right eyes of 40 healthy VDT users (30 females, 10 males, mean age: 43.8±2.8 years, range: 40?C49 years). 20 subjects (15 females, 5 males; mean age: 44.0±2.7 years, range: 40?C49 years).

Methods

Subjects were required to take an antioxidant supplement, 20 age and sex matched subjects (15 females, 5 males; mean age: 43.6±3.1 years, range: 40?C49 years) were required to take placebo medication for 4 weeks.

Results

The mean of the change in accommodation power was significantly higher in the group receiving antioxidant supplements (0.20±0.50 Diopter(D)) compared to the placebo group (?0.12±0.48(D)) (p<0.05).

Conclusions

Antioxidant supplementation was observed to improve accommodation in Japanese Visual Display Terminal (VDT) Users.     

Disease progression and costs of care in Alzheimer’s disease patients treated with donepezil: a longitudinal naturalistic cohort

Background/Aims

Improved data and methods are needed for modeling disease progression in Alzheimer’s disease (AD) for economic evaluation of treatments. The aim is to estimate prediction models for long-term AD progression and subsequently economic outcomes.

Methods

Three-year follow-up data on 435 patients treated with the cholinesterase inhibitor donepezil in clinical practise were analyzed. Regression models were estimated for long-term prediction of decline in cognitive function (ADAS-cog) and activities in daily living (ADL) ability, risk of institutionalization and costs of care.

Results

The cognitive deterioration was estimated at between 1.6 and 4 ADAS-cog points per every 6?months, increasing with disease severity. Cognitive function was an important predictor of ADL-ability, which itself was the most important predictor of the risk of institutionalization and costs of care. Combining all models in a cross-validation process generated accurate predictions of costs of care at each 6?months follow-up.

Conclusion

The proposed methods for representing AD progression and economic outcomes can be used in micro-simulation models for the economic evaluation of new treatments.     

Die Vermeidung von Pflegekosten bei der Alzheimer-Erkrankung durch Galantamin

Aim

The aim of this paper is to systematically review health-economic evidence for treating Alzheimer’s disease with galantamine.

Methods

First, a structured literature search of relevant databases was conducted. In a second step, all hits were screened for their content and were evaluated separately by two different researchers. Subsequently, a structured review of all relevant papers was prepared.

Results

Of the initial 197 search results, eight health-economic studies were found to methodologically and thematically match with the study question. The results of all evaluated studies suggest an economic efficiency for treating Alzheimer’s disease with galantamine, although all studies face certain limitations; most of the underlying models made specific assumptions, resulting in additional uncertainty around the respective results.

Conclusion

Despite ongoing medical research in this area, galantamine, as compared with no drug therapy, can be considered an economically reasonable treatment alternative within the German health care system. Additional studies evaluating some of the models’ assumptions must be conducted in the future to further support these findings.     

Association between illness progression measures and total cost in Alzheimer’s disease

Objective

To compare the associations between dependence and clinical measures of cognition, function and behaviour and total care cost using data from a longitudinal study in Alzheimer’s disease (AD).

Design

Longitudinal, observational study.

Setting

Community-dwelling subjects.

Participants

Male and female subjects between 50 and 85 years of age with mild to moderate AD.

Intervention

None.

Measurements

Subject dependence was assessed using the Dependence Scale (DS), cognition (ADAS-Cog, MMSE), function (DAD), behaviour (NPI) and resource utilization with the Resource Utilization in Dementia Questionnaire.

Results

The repeated measures models confirmed a significant association between the DS and total care cost indicating an increase in cost with increasing dependence. A 1-unit increase in DS score was associated with a 28.60% increase in total care cost. Model 2 indicated that a one point change in MMSE, DAD and NPI is associated with 5.29%, 2.32% and 1.71% increase in total cost, respectively. Model 3 indicated that a one point change in ADAS-Cog, DAD and NPI is associated with a 1.74%, 2.42%and 1.62% increase in total cost, respectively.

Conclusion

Strategies which prevent deterioration in clinical measures or delay dependence should result in total cost savings. The quantitative relationships observed should assist in the economic assessment of interventions which effect cognition, function, behaviour and dependence.