BACKGROUND:

Experiencing anxiety and depression is very common in people with dementia and mild cognitive impairment (MCI). Psychological interventions have been suggested as a potential treatment for these populations. Current research suggests that people with dementia and MCI have limited opportunities for psychological treatments aimed at improving their well-being. A systematic review of the evidence on their effectiveness is likely to be useful in terms of improving outcomes for patients and for future recommendations for practice.
OBJECTIVES:

The main objective of this review was to assess the effectiveness of psychological interventions in reducing anxiety and depression in people with dementia or mild cognitive impairment (MCI).
SEARCH METHODS:

We searched the Cochrane Dementia and Cognitive Improvement Group Specialized Register and additional sources for both published and unpublished data.
Selection criteria

We included randomised controlled trials (RCTs) comparing a psychological intervention with usual care or a placebo intervention (social contact control) in people with dementia or MCI.
DATA COLLECTION AND ANALYSIS:

Two review authors worked independently to select trials, extract data and assess studies for risk of bias, using a data extraction form. We contacted authors when further information was not available from the published articles.
MAIN RESULTS:

Six RCTs involving 439 participants with dementia were included in the review, but no studies of participants with MCI were identified. The studies included people with dementia living in the community or in nursing home care and were carried out in several countries. Only one of the studies was classified as low risk of bias. Five studies were at unclear or high risk of bias due to uncertainties around randomisation, blinding and selective reporting of results. The studies used the different psychological approaches of cognitive behavioural therapy (CBT), interpersonal therapy and counselling. Two studies were of multimodal interventions including a specific psychological therapy. The comparison groups received either usual care, attention-control educational programs, diagnostic feedback or services slightly above usual care.

Meta-analysis showed a positive effect of psychological treatments on depression (6 trials, 439 participants, standardised mean difference (SMD) -0.22; 95% confidence interval (CI) -0.41 to -0.03, moderate quality evidence) and on clinician-rated anxiety (2 trials, 65 participants, mean difference (MD) -4.57; 95% CI -7.81 to -1.32, low quality evidence), but not on self-rated anxiety (2 trials, SMD 0.05; 95% CI -0.44 to 0.54) or carer-rated anxiety (1 trial, MD -2.40; 95% CI -4.96 to 0.16). Results were compatible with both benefit and harm on the secondary outcomes of patient quality of life, activities of daily living (ADLs), neuropsychiatric symptoms and cognition, or on carers' self-rated depressive symptoms, but most of the studies did not measure these outcomes. There were no reports of adverse events.
AUTHORS' CONCLUSIONS:

We found evidence that psychological interventions added to usual care can reduce symptoms of depression and clinician-rated anxiety for people with dementia. We conclude that psychological interventions have the potential to improve patient well-being. Further high quality studies are needed to investigate which treatments are most effective and to evaluate the effect of psychological interventions in people with MCI.

/pdf/psychological-treatments-for-depression-and-anxiety-in-x009e03htp.pdf

Psychological treatments for depression and anxiety in dementia and mild cognitive impairment.

Background
Functional analysis (FA) for the management of challenging behaviour is a promising behavioural intervention that involves exploring the meaning or purpose of an individual’s behaviour. It extends the ‘ABC’ approach of behavioural analysis, to overcome the restriction of having to derive a single explanatory hypothesis for the person’s behaviour. It is seen as a first line alternative to traditional pharmacological management for agitation and aggression. FA typically requires the therapist to develop and evaluate hypotheses-driven strategies that aid family and staff caregivers to reduce or resolve a person’s distress and its associated behavioural manifestations.

Objectives
To assess the effects of functional analysis-based interventions for people with dementia (and their caregivers) living in their own home or in other settings.

Search methods
We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 3 March 2011 using the terms: FA, behaviour (intervention, management, modification), BPSD, psychosocial and Dementia.

Selection criteria
Randomised controlled trials (RCTs) with reported behavioural outcomes that could be associated with functional analysis for the management of challenging behaviour in dementia.

Data collection and analysis
Four reviewers selected trials for inclusion. Two reviewers worked independently to extract data and assess trial quality, including bias. Meta-analyses for reported incidence, frequency, severity of care recipient challenging behaviour and mood (primary outcomes) and caregiver reaction, burden and mood were performed. Details of adverse effects were noted.

Main results
Eighteen trials are included in the review. The majority were in family care settings. For fourteen studies, FA was just one aspect of a broad multi-component programme of care. Assessing the effect of FA was compromised by ill-defined protocols for the duration of component parts of these programmes (i.e. frequency of the intervention or actual time spent). Therefore, establishing the real effect of the FA component was not possible.

Overall, positive effects were noted at post-intervention for the frequency of reported challenging behaviour (but not for incidence or severity) and for caregiver reaction (but not burden or depression). These effects were not seen at follow-up.

Authors' conclusions
The delivery of FA has been incorporated within wide ranging multi-component programmes and study designs have varied according to setting - i.e. family care, care homes and hospital, with surprisingly few studies located in care homes. Our findings suggest potential beneficial effects of multi-component interventions, which utilise FA. Whilst functional analysis for challenging behaviour in dementia care shows promise, it is too early to draw conclusions about its efficacy.

Functional analysis‐based interventions for challenging behaviour in dementia

Previous findings indicate that the acquisition and consolidation of recognition memory involves dopaminergic activity. Although dopamine deregulation has been observed in Alzheimer's disease (AD) patients, the dysfunction of this neurotransmitter has not been investigated in animal models of AD. The aim of this study was to assess, by in vivo microdialysis, cortical and hippocampal dopamine, norepinephrine, and glutamate release during the acquisition of object recognition memory (ORM) in 5- and 10-mo-old triple-transgenic Alzheimer's disease mice (3xTg-AD) and to relate the extracellular changes to 24-h memory performance. Five- and 10-mo-old wild-type mice and 5-mo-old 3xTg-AD showed significant cortical but not hippocampal dopamine increase during object exploration. On a 24-h ORM test, these three groups displayed significant ORM. In contrast, 10-mo-old 3xTg-AD mice showed impaired dopamine release in the insular cortex during ORM acquisition, as well as significant impairment in ORM. In addition, cortical administration of a dopamine reuptake blocker produced an increase of dopamine levels in the 10-mo-old 3xTg-AD mice and attenuated the memory impairment. These data suggest that activation of the dopaminergic system in the insular cortex is involved in object recognition memory, and that dysfunction of this system contributes to the age-related decline in cognitive functioning of the 3xTg-AD mice.

http://learnmem.cshlp.org/content/19/10/453.full.pdf

Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer's disease

Object recognition memory and BDNF expression are reduced in young TgCRND8 mice

Currently prescribed medications for the treatment of Alzheimer’s disease (AD) that are based on acetylcholinesterase inhibition only offer symptomatic relief but do not provide protection against neurodegeneration. There appear to be an intense need for the development of therapeutic strategies that not only improve brain functions but also prevent neurodegeneration. The oxidative stress is one of the main causative factors of AD. Various antioxidants are being investigated to prevent neurodegeneration in AD. The objective of this study was to investigate the neuroprotective effects of naringenin (NAR) against AlCl3+D-gal induced AD-like symptoms in an animal model. Rats were orally pre-treated with NAR (50 mg/kg) for two weeks and then exposed to AlCl3+D-gal (150 mg/kg + 300 mg/kg) intraperitoneally for one week to develop AD-like symptoms. The standard drug, donepezil (DPZ) was used as a stimulator of cholinergic activity. Our results showed that NAR pre-treatment significantly protected AD-like behavioral disturbances in rats. In DPZ group, rats showed improved cognitive and cholinergic functions but the neuropsychiatric functions were not completely improved and showed marked histopathological alterations. However, NAR not only prevented AlCl3+D-gal induced AD-like symptoms but also significantly prevented neuropsychiatric dysfunctions in rats. Results of present study suggest that NAR may play a role in enhancing neuroprotective and cognition functions and it can potentially be considered as a neuroprotective compound for therapeutic management of AD in the future.

/pdf/naringenin-protects-alcl3-d-galactose-induced-neurotoxicity-51xxrff8kc.pdf

Naringenin protects AlCl3/D-galactose induced neurotoxicity in rat model of AD via attenuation of acetylcholinesterase levels and inhibition of oxidative stress.

There is considerable evidence that visual recognition memory is largely affected by Alzheimer's disease (AD). Deficits might concern the forming, maintaining, and matching of the memory representation of the visual stimulus, especially when long interitem lags occur. The aim of the present study was to assess the effect of repetition lag on picture identification in mild- and moderate-AD patients, as well as in elderly controls. Participants underwent an old/new paradigm. To manipulate the temporal gradient, short and long lags were introduced between the first and second presentations. Pictures were presented at different levels of spatial filtering, following a coarse-to-fine order. This allowed for the measurement of the amount of physical information required for the identification of stimuli as a function of prior exposure and repetition lag. In the elderly, the magnitude of repetition priming did not differ as a function of interitem lag. Instead, repetition-lag effects interacted with dementia severity, and the capacity to retain memory traces for longer intervals worsened as the disease progresses. Current findings suggest that severe cortical degeneration may render AD patients unable to maintain their perceptual memories, and that dementia severity is a critical variable in the visual recognition memory assessment.

Visual recognition memory in Alzheimer's disease: repetition-lag effects

The selection of meaningful activities as a treatment for day-care in dementia.

Category-specific visual identification of filtered objects in Alzheimer's disease.

Evaluation of non-pharmacological intervention on antisocial behavior in patients suffering from Alzheimer's disease in a day care center.

Validation of the Cohen-Mansfield agitation inventory (CMAI-long form) on a sample of Italian demented patients

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