Alzheimer's disease - input of vitamin D with mEmantine assay (AD-IDEA trial): study protocol for a randomized controlled trial

BACKGROUND: Current treatments for Alzheimer\u27s disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine. METHODS: The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20), hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] < 30 ng/mL), normocalcemia (i.e., serum calcium < 2.65 mmol/L) and receiving no antidementia treatment at time of inclusion are being recruited. All participants receive memantine 20 mg once daily -titrated in 5 mg increments over 4 weeks- and each one is randomized to one of the two treatment options: either cholecalciferol (one 100,000 IU drinking vial every 4 weeks) or placebo (administered at the same pace). One hundred and twenty participants are being recruited and treatment continues for 24 weeks. Primary outcome measure is change in cognitive performance using Alzheimer\u27s Disease Assessment Scale-cognition score. Secondary outcomes are changes in other cognitive scores (MMSE, Frontal Assessment Battery, Trail Making Test parts A and B), change in functional performance (Activities of Daily Living scale, and 4-item Instrumental Activities of Daily Living scale), posture and gait (Timed Up & Go, Five Time Sit-to-Stand, spatio-temporal analysis of walking), as well as the between-groups comparison of compliance to treatment and tolerance. These outcomes are assessed at baseline, 12 and 24 weeks, together with the serum concentrations of 25OHD, calcium and parathyroid hormone. DISCUSSION: The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01409694

Sleep-related breathing disorders and gait variability: a cross-sectional preliminary study

BACKGROUND: Sleep-related breathing disorders (SRBDs) provoke cognitive and structural brain disorders. Because these disorders have been associated with unsafe gait characterized by an increase in stride-to-stride variability of stride time (STV), we hypothesised that SRBDs could be associated with an increased STV. The aim of this study was to examine the association between SRBDs and STV in French healthy older community-dwellers. METHODS: A total of 49 participants (mean age 69.6 ± 0.8years; 65.2% female) were included in this cross-sectional study. All participants, who were free of clinically diagnosed SRBDs before their inclusion, had a nocturnal unattended home-sleep assessment. There were separated in three group based on apnea + hypopnea index (AHI): AHI <15 defining the absence of SRBD, AHI between 15–30 defining mild SRBD, and AHI >30 defining moderate-to-severe SRBD. Coefficient of variation of stride time, which is a measure of STV, was recorded while usual walking using SMTEC® footswitches system. Digit span score was used as a measure of executive performance. Age, gender, body mass index (BMI), number of drugs daily taken, vision, proprioception, history of falls, depression symptoms, global cognitive functioning were also recorded. RESULTS: STV and BMI were higher in participants with mild SRBDs (P = 0.031 and P = 0.020) and moderate-to-severe SRBDs (P = 0.004 and P = 0.002) compared to non-SRBDs. STV positively correlated with AHI (P = 0.036). Lower (i.e., better) STV was associated with the absence of SRBDs (P = 0.021), while greater (i.e., worse) STV was associated with moderate-to-severe SRBD (P < 0.045) but not with mild SRBD (P > 0.06). CONCLUSION: Our results show a positive association between STV and SRBDs, with moderate-to-severe SRBD being associated with greater gait variability. This association opens new perspectives for understanding gait disorders in older adults with SRBDs and opens the door to treatments options since SRBDs are potential treatable factors

Instrumented gait analysis: a measure of gait improvement by a wheeled walker in hospitalized geriatric patients

Background In an increasing aging society, reduced mobility is one of the most important factors limiting activities of daily living and overall quality of life. The ability to walk independently contributes to the mobility, but is increasingly restricted by numerous diseases that impair gait and balance. The aim of this cross-sectional observation study was to examine whether spatio-temporal gait parameters derived from mobile instrumented gait analysis can be used to measure the gait stabilizing effects of a wheeled walker (WW) and whether these gait parameters may serve as surrogate marker in hospitalized patients with multifactorial gait and balance impairment. Methods One hundred six patients (ages 68–95) wearing inertial sensor equipped shoes passed an instrumented walkway with and without gait support from a WW. The walkway assessed the risk of falling associated gait parameters velocity, swing time, stride length, stride time- and double support time variability. Inertial sensor-equipped shoes measured heel strike and toe off angles, and foot clearance. Results The use of a WW improved the risk of spatio-temporal parameters velocity, swing time, stride length and the sagittal plane associated parameters heel strike and toe off angles in all patients. First-time users (FTUs) showed similar gait parameter improvement patterns as frequent WW users (FUs). However, FUs with higher levels of gait impairment improved more in velocity, stride length and toe off angle compared to the FTUs. Conclusion The impact of a WW can be quantified objectively by instrumented gait assessment. Thus, objective gait parameters may serve as surrogate markers for the use of walking aids in patients with gait and balance impairments

Measures of frailty in population-based studies: An overview

Although research productivity in the field of frailty has risen exponentially in recent years, there remains a lack of consensus regarding the measurement of this syndrome. This overview offers three services: first, we provide a comprehensive catalogue of current frailty measures; second, we evaluate their reliability and validity; third, we report on their popularity of use