Systematic review of strengths and limitations of randomized controlled trials for non-pharmacological interventions in mild cognitive impairment: focus on Alzheimer's disease.

BACKGROUND: Non-pharmacological interventions may improve cognition and quality of life, reduce disruptive behaviors, slow progression from Mild Cognitive Impairment (MCI) to dementia, and delay institutionalization. It is important to look at their trial designs as well as outcomes to understand the state of the evidence supporting non-pharmacological interventions in Alzheimer's disease (AD). An analysis of trial design strengths and limitations may help researchers clarify treatment effect and design future studies of non-pharmacological interventions for MCI related to AD. METHODS: A systematic review of the methodology of Randomized Controlled Trials (RCTs) targeting physical activity, cognitive interventions, and socialization among subjects with MCI in AD reported until March 2014 was undertaken. The primary outcome was CONSORT 2010 reporting quality. Secondary outcomes were qualitative assessments of specific methodology problems. RESULTS: 23 RCT studies met criteria for this review. Eight focused on physical activity, fourteen on cognitive interventions, and one on the effects of socialization. Most studies found a benefit with the intervention compared to control. CONSORT reporting quality of physical activity interventions was higher than that of cognitive interventions. Reporting quality of recent studies was higher than older studies, particularly with respect to sample size, control characteristics, and methodology of intervention training and delivery. However, the heterogeneity of subjects identified as having MCI and variability in interventions and outcomes continued to limit generalizability. CONCLUSIONS: The role for non-pharmacological interventions targeting MCI is promising. Future studies of RCTs for non-pharmacological interventions targeting MCI related to AD may benefit by addressing design limitations.

Formation of surface membranes in developing mammalian hair fibres.

Mammalian hair fibres result from complex mechanisms involving synthesis, assembly and stabilisation of keratin proteins in the follicle. The developing hair shaft consists of outer cuticle cells surrounding cortical and medullary (optional) cell types. Presumptive fibre cuticle (FC) is contained by the inner root sheath (IRS) consisting of IRS cuticle, Huxley and Henle cells which are in turn enclosed in an outer root sheath (ORS) of epidermal-like cells. In the current structural studies we have used energy filtered transmission electron microscopy (Zeiss 902A) on Merino sheep skin biopsies to examine the fine sequence of morphological changes involved in forming the fibre surface membrane and the associated underlying structural bands comprising the a-layer and exocuticle. Prior to the development of the exocuticle, FC cells demonstrate a typical plasma-membrane apposed to IRS cuticle plasma-membranes separated by an intercellular space. The formation of exocuticular lamellae is followed by degradation of the residual FC surface membrane and the appearance of intercellular laminae demonstrating a stained central band. As maturation continues cleavage between IRS cuticle and FC occurs along this central band liberating hair into the pilary canal. The mature surface consists of keratinized cells containing a well developed exocuticle and a-layer coated with paired lamina (presumably two lipid containing bilayers) of material approximately 10-12 nm thick derived from the intercellular laminae. The current observations show FC surface formation is similar to processes occurring in epidermal stratum corneum and that the cuticle surface membrane of mammalian fibres is not derived from a modified plasma-membrane as previously documented.