An online intervention for carers to manage behavioral symptoms in motor neuron disease (MiNDToolkit): a randomized parallel multi-center feasibility trial.

BACKGROUND: Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design: Randomized, parallel, multi-center, feasibility trial. SETTING: England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23. PARTICIPANTS: Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control. INTERVENTION: MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables. MAIN OUTCOMES: One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period. CONCLUSION: The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted.

Effects of electromagnetic fields emitted by GSM phones on working memory: a meta-analysis.

BACKGROUND AND OBJECTIVE: Current treatments for Alzheimer's Disease (AD) do not affect the course of the illness and brain stimulation techniques are increasingly promoted as potential therapeutic interventions for AD. This study reviews the effects of electromagnetic field (EMF) exposure versus sham exposure on working memory (WM) performance of healthy human participants. METHOD: Online literature databases and previous systematic reviews were searched for studies of EMF and WM in participants without reported memory problems. Two thousand eight hundred and fifty seven studies were identified, and 10 studies met the inclusion criteria. An assessment of study quality was completed, and separate, random effects meta-analyses were conducted for each of the three WM tasks included: n-back, substitution and digit span forward. RESULTS: No differences were found between participants exposed to active EMF versus sham conditions in any of the three working memory tasks examined. CONCLUSION: Results indicate that EMF does not affect WM during the n-back, substitution and digit-span tasks. Future studies should focus on the possible effects of chronic exposure to EMF in older adults with AD using a battery of comparable WM and attention tasks, before EMF can be seriously considered as a potential modulator of WM in AD. Copyright © 2016 John Wiley & Sons, Ltd.

Do cognitive interventions improve general cognition in dementia? A meta-analysis and meta-regression.

OBJECTIVES: To review the efficacy of cognitive interventions on improving general cognition in dementia. METHOD: Online literature databases and trial registers, previous systematic reviews and leading journals were searched for relevant randomised controlled trials. A systematic review, random-effects meta-analyses and meta-regression were conducted. Cognitive interventions were categorised as: cognitive stimulation (CS), involving a range of social and cognitive activities to stimulate multiple cognitive domains; cognitive training (CT), involving repeated practice of standardised tasks targeting a specific cognitive function; cognitive rehabilitation (CR), which takes a person-centred approach to target impaired function; or mixed  CT and stimulation (MCTS). Separate analyses were conducted for general cognitive outcome measures and for studies using 'active' (designed to control for non-specific therapeutic effects) and non-active (minimal or no intervention) control groups. RESULTS: 33 studies were included. Significant positive effect sizes (Hedges' g) were found for CS with the mini-mental state examination (MMSE) (g=0.51, 95% CI 0.35 to 0.66; p<0.001) compared to non-active controls and (g=0.35, 95% CI 0.06 to 0.64; p=0.019) compared to active controls. Significant benefit was also seen with the Alzheimer's disease Assessment Scale-Cognition (ADAS-Cog) (g=-0.26, 95% CI -0.445 to -0.08; p=0.005). There was no evidence that CT or MCTS produced significant improvements on general cognition outcomes and not enough CR studies for meta-analysis. The lowest accepted minimum clinically important difference was reached in 11/17 CS studies for the MMSE, but only 2/9 studies for the ADAS-Cog. Additionally, 95% prediction intervals suggested that although statistically significant, CS may not lead to benefits on the ADAS-Cog in all clinical settings. CONCLUSIONS: CS improves scores on MMSE and ADAS-Cog in dementia, but benefits on the ADAS-Cog are generally not clinically significant and difficulties with blinding of patients and use of adequate placebo controls make comparison with the results of dementia drug treatments problematic.

Brain mechanisms of successful compensation during learning in Alzheimer disease.

OBJECTIVE: To determine whether patients with Alzheimer disease (AD) compensate for neuropathologic changes when performing a mnemonic task by recruiting 1) the same brain regions as age-matched, healthy controls, but to a greater extent; 2) additional brain regions not activated by controls; or 3) both. METHODS: Twelve patients with mild probable AD and 12 healthy age- and education-matched controls participated in an fMRI study of successful encoding and retrieval of visuospatial paired associates. To ensure successful performance in both groups, participants were given multiple attempts to learn associations between two and three object locations. RESULTS: The pattern of brain activity in patients with AD performing an easy version of the task was indistinguishable from that of controls performing a harder version of the task. Increased activation in left medial and right lateral prefrontal cortices was found in patients with AD compared to controls during encoding of two object locations, but not when this level of encoding in patients was compared with encoding of three object locations in controls. CONCLUSIONS: There was no evidence of neural plasticity in the form of recruitment of novel brain regions in patients with Alzheimer disease. Data supported greater recruitment of the same brain regions as age-matched controls as a means of compensating for neuropathology and associated cognitive impairment in Alzheimer disease.

fMRI BOLD response to increasing task difficulty during successful paired associates learning.

We used functional magnetic resonance imaging (fMRI) to assess cortical activations associated with increasing task difficulty (TD) in a visuospatial paired associates learning task. Encoding and retrieval were examined when 100% successful retrieval of three, four, or six object-location pairs had been attained (thus ensuring that performance was matched across subjects). As memory load increased, in general, the number of attempts taken to achieve 100% successful retrieval increased, while the number of trials correctly completed on the first attempt decreased. By modelling parametric variations in working memory load with BOLD signal changes we were able to identify brain regions displaying linear and nonlinear responses to increasing load. During encoding, load-independent activations were found in occipitoparietal cortices (excluding the precuneus for which linear load dependency was demonstrated), anterior cingulate, and cerebellum, while linear load-dependent activations in these same regions were found during retrieval. Nonlinear load-dependent responses, as identified by categorical contrasts between levels of load, were found in the right DLPFC and left inferior frontal gyrus. The cortical response to increasing cognitive demands or TD appears to involve the same, rather than an additional, network of brain regions "working harder."

Measuring cognitive change in a cohort of patients with Alzheimer's disease.

Annualized rates of cognitive change in Alzheimer's disease (AD), an important index of disease progression, show marked variability. To determine factors leading to such variability, we computed rates of change in a cohort of patients with AD tested annually with the Mini Mental State Examination (MMSE) and the more detailed Dementia Rating Scale (DRS). Estimates of rates of change (slopes) and intercepts were calculated using least squares and best linear unbiased predictors (BLUPs). Potential predictors of rates of change were examined using multivariate linear regression analysis. We found that the MMSE had more noise than the DRS. For the MMSE, slopes showed a moderate floor effect and a slight ceiling, depending on initial MMSE scores. These effects were less prominent for the DRS, for which slopes increased as intercepts decreased. In analyses of predictors of change, the MMSE was less useful than the DRS. In multiple linear regression models using DRS data, predictors showed statistically stronger effects and explained a greater extent of variation of slopes than did similar models using MMSE data. For example, among patients who died and underwent brain examination at autopsy, neuropathology of Lewy bodies plus AD (Lewy Body variant; LBV) was associated with significantly faster rates of cognitive decline compared to pure AD in analyses that used the DRS, but only trends were identified with the MMSE. The metric properties and longitudinal characteristics of cognitive tests and the statistical methods used to calculate change are key factors in obtaining reliable estimates of change in studying cohorts of patients with AD.

Some pros and cons of computer-assisted psychotherapy.

We briefly describe a method of short-term computer-assisted psychotherapy for stress-related conditions and then reply to a number of objections to the method that have been voiced by professional colleagues.