The effectiveness of brief non-pharmacological interventions in emergency departments and psychiatric inpatient units for people in crisis: A systematic review and narrative synthesis.

OBJECTIVE: Heterogeneous brief non-pharmacological interventions and guidelines exist to treat the burgeoning presentations to both emergency department and inpatient settings, for those in a crisis of mental ill-health. We systematically reviewed the literature to create a taxonomy of these brief non-pharmacological interventions, and review their evaluation methods and effectiveness. METHOD: We conducted a systematic review across Cochrane, CINAHL, DARE, Embase, MEDLINE, PsycINFO databases. Studies meeting quality criteria, using Joanna Briggs Institute tools, were eligible. Interventions were categorised, and outcomes synthesised. RESULTS: Thirty-nine studies were included: 8 randomised controlled trials, 17 quasi-experimental, 11 qualitative studies, and 3 file audits. Taxonomy produced six coherent intervention types: Skills-focussed, Environment-focussed, Special Observation, Psychoeducation, Multicomponent Group and Multicomponent Individual. Despite this, a broad and inconsistent range of outcome measures reflected different outcome priorities and prevented systematic comparison of different types of intervention or meta-analysis. Few brief non-pharmacological interventions had consistent evidential support: sensory modulation rooms consistently improved distress in inpatient settings. Short admissions may reduce suicide attempts and readmission, if accompanied by psychotherapy. Suicide-specific interventions in emergency departments may improve depressive symptoms, but not suicide attempt rates. There was evidence that brief non-pharmacological interventions did not reduce incidence of self-harm on inpatient wards. We found no evidence for frequently used interventions such as no-suicide contracting, special observation or inpatient self-harm interventions. CONCLUSION: Categorising brief non-pharmacological interventions is feasible, but an evidence base for many is severely limited if not missing. Even when there is evidence, the inconsistency in outcomes often precludes clinicians from making inferences, although some interventions show promise.

Circadian rhythm and sleep alterations in older people with lifetime depression: a case-control study.

BACKGROUND: Depression is common in older people and is associated with underlying brain change increasing the risk of dementia. Sleep disturbance is frequently reported by those with lifetime depression, however whether circadian misalignment also exists is unclear. We aimed to examine circadian rhythms and sleep associations in older patients with and without lifetime depression. METHODS: Thirty-four older people meeting DSM-IV criteria for lifetime major depression (mean age = 63.9 years), and 30 healthy controls (mean age = 65.7 years) were recruited. Participants underwent 2-weeks of actigraphy followed by a 3-night protocol including dim light melatonin onset (DLMO) assessment and overnight polysomnography (PSG) for sleep architecture. DLMO and phase angle of entrainment were computed. RESULTS: Compared to controls, participants with depression had a significantly longer phase angle of entrainment (6.82 h ± 1.45 vs. 5.87 h ± 1.60, p = 0.02, Cohens-d = 0.62). A small to moderate yet non-significant difference in DLMO times, with earlier DLMO (34 ± 27 min) observed in depression (20:36 ± 1:48 vs. 21:10 ± 1:48, p = 0.22, Cohens-d = 0.32). Individuals with depression had longer sleep latency and latency to rapid eye movement sleep than controls (all p < 0.05). CONCLUSION: Circadian advancement and alterations to the timing of sleep and REM onset are evident in older people with lifetime major depression, despite having only mild residual symptoms. Further research examining the prognostic significance of these changes is warranted as well as chronotherapeutic treatment studies.

Current sleep disturbance in older people with a lifetime history of depression is associated with increased connectivity in the Default Mode Network.

BACKGROUND: The present study investigated Default Mode Network (DMN) functional connectivity in subjects with a lifetime history of major depression, comparing those with and without current sleep disturbance. Controls were included to assess DMN abnormalities specific to depression. METHODS: A total of 93 adults aged 50 years and over were recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney, Australia. The sample comprised two groups, including 22 controls and 71 participants with a lifetime history of DSM-IV major depression (with depressive episode current or remitted). 52 of those with a lifetime history of depression also met criteria for Mild Cognitive Impairment (MCI). Participants underwent resting-state fMRI along with comprehensive psychiatric, neuropsychological, and medical assessment. Subjective sleep quality was assessed via the Pittsburgh Sleep Quality Index (PSQI). Sleep disturbance was defined as a PSQI score > 5. A total of 68% (n = 48) of cases with a lifetime history of depression met criteria for sleep-disturbance. DMN functional connectivity was assessed via ROI-to-ROI analyses. RESULTS: Relative to controls, those with lifetime major depression demonstrated significantly increased functional connectivity between the ventromedial prefrontal cortex and the temporal pole. Within the depression group (n = 48), those with current sleep disturbance had significantly increased connectivity between the anterior medial prefrontal cortex and both the parahippocampal cortex and the hippocampal formation, relative to those without sleep disturbance (n = 23). These results were present after controlling for MCI diagnosis. CONCLUSIONS: Current sleep disturbance together with depression is associated with distinct abnormalities in DMN functioning incorporating regions responsible for self-reflection and declarative memory processes. Impaired sleep is associated with increased connectivity between these regions. Future studies may augment these findings with complementary imaging techniques including cortical thickness and diffusion tensor imaging, as well as high density electroencephalogram recording.

Spectroscopic markers of memory impairment, symptom severity and age of onset in older people with lifetime depression: Discrete roles of N-acetyl aspartate and glutamate.

BACKGROUND: Glutamate (Glu) and N-acetyl aspartate (NAA) are markers of excitatory processes and neuronal compromise respectively. Increased Glu and decreased NAA concentrations have been implicated in the pathophysiology of depression and cognitive impairment respectively. OBJECTIVE: To determine the relationship between NAA, Glu, memory and key clinical features in older people with lifetime depression compared to comparison subjects. METHOD: Thirty-five health-seeking older adults (mean age=63.57 years), with a lifetime depression diagnosis, and 21 age-matched healthy comparison subjects (mean age=65.48 years) underwent neuropsychological testing, psychiatric assessment and proton magnetic resonance spectroscopy from which Glu and NAA were measured (reported as a ratio to creatine). RESULTS: Compared to comparison subjects, the depressed subjects showed poorer verbal learning and memory retention. Hippocampal NAA and Glu did not differ significantly between groups. However, in comparison subjects, lower levels of hippocampal Glu were associated with poorer memory retention (r=0.55, p=0.018). In the depressed subjects, lower levels of hippocampal NAA were related to poorer verbal learning (r=0.44, p=0.008) and memory retention (r=0.41, p=0.018). Greater hippocampal Glu was associated with more severe depressive symptoms (r=0.35, p=0.039) and an earlier age of illness onset (r=-0.37, p=0.031). LIMITATIONS: This is a cross sectional study with a heterogeneous group of depressed subjects. CONCLUSION: Our findings highlight that hippocampal neurometabolites are entwined with both clinical and cognitive features associated with depression in older adults and further suggest that differential mechanisms may underpin these features.

Randomized controlled trial of a healthy brain ageing cognitive training program: effects on memory, mood, and sleep.

BACKGROUND: With the rise in the ageing population and absence of a cure for dementia, cost-effective prevention strategies for those 'at risk' of dementia including those with depression and/or mild cognitive impairment are urgently required. OBJECTIVE: This study evaluated the efficacy of a multifaceted Healthy Brain Ageing Cognitive Training (HBA-CT) program for older adults 'at risk' of dementia. METHODS: Using a single-blinded design, 64 participants (mean age = 66.5 years, SD = 8.6) were randomized to an immediate treatment (HBA-CT) or treatment-as-usual control arm. The HBA-CT intervention was conducted twice-weekly for seven weeks and comprised group-based psychoeducation about cognitive strategies and modifiable lifestyle factors pertaining to healthy brain ageing, and computerized cognitive training. RESULTS: In comparison to the treatment-as-usual control arm, the HBA-CT program was associated with improvements in verbal memory (p = 0.03), self-reported memory (p = 0.03), mood (p = 0.01), and sleep (p = 0.01). While the improvements in memory (p = 0.03) and sleep (p = 0.02) remained after controlling for improvements in mood, only a trend in verbal memory improvement was apparent after controlling for sleep. CONCLUSION: The HBA-CT program improves cognitive, mood, and sleep functions in older adults 'at risk' of dementia, and therefore offers promise as a secondary prevention strategy.

Hippocampal volume in older adults at risk of cognitive decline: the role of sleep, vascular risk, and depression.

BACKGROUND AND OBJECTIVES: Decreased hippocampal volume in older adults is associated with neurodegenerative and psychiatric diseases. Several modifiable risk factors have been associated with the size of this structure, however the relative contribution of these factors to hippocampal atrophy is unclear. This study aimed to examine the relationship between modifiable risk factors and hippocampal volume in older adults at risk of cognitive decline. METHODS: Two hundred and eighteen participants (mean age = 67.3 years, MMSE = 28.6) with mood and/or memory complaints underwent clinical and neuropsychological assessment, and magnetic resonance imaging. Measures of depression, global cognitive functioning, exercise, vascular health, cognitive reserve, sleep, and memory were collected. Hippocampal volumes were derived using image segmentation as implemented by FMRIB Software Library. RESULTS: Smaller hippocampal volumes were strongly associated with poorer verbal learning and memory as well as diagnoses of either multiple or amnestic mild cognitive impairment. Based on univariate correlations, multivariable regressions were performed (controlling for age and total intracranial volume) to determine which modifiable risk factors were associated with hippocampal volume. For the left hippocampus, poor sleep efficiency and greater than five years untreated depressive illness remained significant predictors. For the right hippocampus, diabetes and low diastolic blood pressure significant predictors. CONCLUSIONS: Although their contribution is small, lower sleep efficiency, low blood pressure, diabetes, and untreated depression are associated with reduced hippocampal volumes. Studies exploring the impact of early intervention for these risk factors on hippocampal integrity are warranted.

Cognitive training enhances pre-attentive neurophysiological responses in older adults 'at risk' of dementia.

BACKGROUND: With predicted increases in dementia incidence, interventions targeting neuroplasticity and neuroprotection are required. Cognitive Training (CT) is an intervention which has been shown to improve aspects of cognition, but the pathophysiological mechanisms contributing to its efficacy are unknown. OBJECTIVE: We aimed to explore the neurobiological correlates of CT using Mismatch Negativity (MMN), a neurophysiological marker of pre-attentive information processing, which in turn, is postulated to underpin higher-order cognitive processes. METHODS: As part of a larger randomized controlled trial, forty 'at risk' (i.e., mild cognitive impairment or late-life depression) participants aged 51-79 years underwent neurophysiological, neuropsychological, and psychiatric assessments before and after a multi-faceted seven-week CT program or a 'treatment-as-usual' seven-week waitlist period. RESULTS: The treatment group demonstrated significantly increased fronto-central MMN responses (p < 0.05), as well as improved phonemic verbal fluency (p < 0.05) and decreased self-rated memory difficulties (p < 0.05) following CT, in comparison to the waitlist control group. However, there were no significant correlations between enhanced MMN and cognitive/psychosocial outcomes. CONCLUSIONS: Results from this preliminary investigation indicate that CT is associated with enhanced neurophysiological mechanisms suggestive of improved pre-attentive processing, which may reflect alterations in underlying neurobiology. Further research is warranted to confirm these findings, to explicate whether CT is associated with restorative or compensatory neuroplastic processes and to determine whether MMN is a useful biomarker for treatment response.

Screening for sleep apnoea in mild cognitive impairment: the utility of the multivariable apnoea prediction index.

Purpose. Mild cognitive impairment (MCI) is considered an "at risk" state for dementia and efforts are needed to target modifiable risk factors, of which Obstructive sleep apnoea (OSA) is one. This study aims to evaluate the predictive utility of the multivariate apnoea prediction index (MAPI), a patient self-report survey, to assess OSA in MCI. Methods. Thirty-seven participants with MCI and 37 age-matched controls completed the MAPI and underwent polysomnography (PSG). Correlations were used to compare the MAPI and PSG measures including oxygen desaturation index and apnoea-hypopnoea index (AHI). Receiver-operating characteristics (ROC) curve analyses were performed using various cut-off scores for apnoea severity. Results. In controls, there was a significant moderate correlation between higher MAPI scores and more severe apnoea (AHI: r = 0.47, P = 0.017). However, this relationship was not significant in the MCI sample. ROC curve analysis indicated much lower area under the curve (AUC) in the MCI sample compared to the controls across all AHI severity cut-off scores. Conclusions. In older people, the MAPI moderately correlates with AHI severity but only in those who are cognitively intact. Development of further screening tools is required in order to accurately screen for OSA in MCI.

The role of glia in late-life depression.

Late-life depression (LLD) has a complex and multifactoral etiology. There is growing interest in elucidating how glia, acting alone or as part of a glial-neuronal network, may contribute to the pathophysiology of depression. In this paper, we explore results from neuroimaging studies showing gray-matter volume loss in key frontal and subcortical structures implicated in LLD, and present the few histological studies that have examined neuronal and glial densities in these regions. Compared to results in younger people with depression, there appear to be age-dependent differences in neuronal pathology but the changes in glial pathology may be more subtle, perhaps reflecting a longer-term compensatory gliosis to earlier damage. We then consider the mechanisms by which both astrocytes and microglia may mediate and modulate neuronal dysfunction and possible degeneration in depression. These include a critical role in the response to peripheral inflammation and central microglial activation, as well as a key role in glutamate metabolism. Advances in our understanding of glia are highlighted, including the role of microglia as "electricians" of the brain and astrocytes as key communicating cells, an integral part of the tripartite synapse. Finally, implications for clinicians are discussed, including the consideration of glia as biomarkers for LLD and incorporation of glia into future therapeutic strategies.

The neurobiology of depression in later-life: clinical, neuropsychological, neuroimaging and pathophysiological features.

As the population ages, the economic and societal impacts of neurodegenerative and neuropsychiatric disorders are expected to rise sharply. Like dementia, late-life depressive disorders are common and are linked to increased disability, high healthcare utilisation, cognitive decline and premature mortality. Considerable heterogeneity in the clinical presentation of major depression across the life cycle may reflect unique pathophysiological pathways to illness; differentiating those with earlier onset who have grown older (early-onset depression), from those with illness onset after the age of 50 or 60 years (late-onset depression). The last two decades have witnessed significant advances in our understanding of the neurobiology of early- and late-onset depression, and has shown that disturbances of fronto-subcortical functioning are implicated. New biomedical models extend well beyond perturbations of traditional monoamine systems to include altered neurotrophins, endocrinologic and immunologic system dysfunction, inflammatory processes and gene expression alterations. This more recent research has highlighted that a range of illness-specific, neurodegenerative and vascular factors appear to contribute to the various phenotypic presentations. This review highlights the major features of late-life depression, with specific reference to its associated aetiological, clinical, cognitive, neuroimaging, neuropathological, inflammatory and genetic correlates. Data examining the efficacy of pharmacological, non-pharmacological and novel treatments for depression are discussed. Ultimately, future research must aim to evaluate whether basic biomedical knowledge can be successfully translated into enhanced health outcomes via the implementation of early intervention paradigms.

Reduced mismatch negativity in mild cognitive impairment: associations with neuropsychological performance.

Mild cognitive impairment (MCI) refers to a transitory state between healthy aging and dementia. Biomarkers are needed to facilitate early identification of MCI and predict progression to dementia. One potential neurophysiological biomarker, mismatch negativity (MMN), is an event-related potential reflecting fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging and dementia and in neuropsychiatric samples and is associated with verbal memory deficits and poor executive functioning. This study aimed to investigate auditory MMN and its relationship to neuropsychological performance in MCI. Twenty-eight MCI participants and fourteen controls, aged ≥50 years, underwent neurophysiological and neuropsychological assessment, and completed questionnaires pertaining to disability. Relative to controls, the MCI group demonstrated reduced temporal MMN amplitude (p < 0.01). Reduced right temporal MMN was significantly associated with poorer verbal learning (r = 0.496; p < 0.01) and reduced left temporal MMN was significantly associated with increased self-reported disability (r = -0.419; p < 0.05). These results indicate that patients with MCI exhibit altered pre-attentive information processing, which in turn is associated with memory and psychosocial deficits. These findings overall suggest that MMN may be a viable neurophysiological biomarker of underlying disease in this 'at risk' group.

Sleep disturbance relates to neuropsychological functioning in late-life depression.

BACKGROUND: Sleep-wake disturbance in older people is a risk factor for depression onset and recurrence. The aim of this study was to determine if objective sleep-wake disturbance in late-life depression relates to neuropsychological functioning. METHODS: Forty-four older patients with a lifetime history of major depression and 22 control participants underwent psychiatric, medical and neuropsychological assessments. Participants completed self-report sleep measures, sleep diaries and wore wrist actigraphy for two weeks. Outcome measures included sleep latency, the number and duration of nocturnal awakenings and the overall sleep efficiency. RESULTS: Patients with depression had a greater duration of nocturnal awakenings and poorer sleep efficiency, in comparison to control participants. Sleep disturbance in patients was associated with greater depression severity and later ages of depression onset. It also related to poorer psychomotor speed, poorer verbal and visual learning, poorer semantic fluency as well as poorer performance on tests of executive functioning. These relationships largely remained significant after controlling for depression and estimated apnoea severity. LIMITATIONS: This sample had only mild levels of depression severity and results require replication in patients with moderate to severe depression. The inclusion of polysomnography and circadian markers would be useful to delineate the specific features of sleep-wake disturbance that are critical to cognitive performance. CONCLUSIONS: Sleep-wake disturbance in older patients with depression is related to neuropsychological functioning and to later ages of illness onset. This study suggests that common neurobiological changes may underpin these disease features, which may, in turn, warrant early identification and management.

Enhancing memory in late-life depression: the effects of a combined psychoeducation and cognitive training program.

OBJECTIVE: To evaluate the efficacy of a multifactorial cognitive training (CT) program for older people with a lifetime history of depressive disorder. METHODS: This was a single-blinded waitlist control design. The study was conducted in the Healthy Brain Ageing Clinic, a specialist outpatient clinic at the Brain & Mind Research Institute, Sydney, Australia. Forty-one participants (mean age = 64.8 years, sd = 8.5) with a lifetime history of major depression were included. They were stabilized on medication and had depressive symptoms in the normal to mild range. The intervention encompassed both psychoeducation and CT. Each component was 1-hour in duration and was delivered in a group format over a 10-week period. Psychoeducation was multifactorial, was delivered by health professionals and targeted cognitive strategies, as well depression, anxiety, sleep, vascular risk factors, diet and exercise. CT was computer-based and was conducted by Clinical Neuropsychologists. Baseline and follow-up neuropsychological assessments were conducted by Psychologists who were blinded to group allocation. The primary outcome was memory whilst secondary outcomes included other aspects of cognition and disability. RESULTS: CT was associated with significant improvements in visual and verbal memory corresponding to medium to large effect sizes. CONCLUSION: CT may be a viable secondary prevention technique for late-life depression, a group who are at risk of further cognitive decline and progression to dementia.

Can older "at risk" adults benefit from psychoeducation targeting healthy brain aging?

BACKGROUND: Multifactorial strategies that prevent or delay the onset or progress of cognitive decline and dementia are needed, and should include education regarding recognized risk factors. The current study sought to investigate whether older adults "at risk" of cognitive decline benefit from psychoeducation targeting healthy brain aging. METHODS: 65 participants (mean age 64.8 years, SD 9.6) with a lifetime history of major depression; vascular risk as evidenced by at least one vascular risk factor; and/or subjective or objective memory impairment were allocated to weekly psychoeducation sessions or a waitlist control group. The small group sessions were conducted over ten weeks by a team of medical and allied health professionals with expertise in late-life depression and cognition. Sessions focused on modifiable risk factors for cognitive decline including vascular risk, diet, exercise, depression, anxiety and sleep disturbance, as well as providing practical strategies for memory and cognition. Both the psychoeducation and waitlist group completed a 20-item knowledge test at baseline and follow-up. Participants in the psychoeducation group were asked to complete follow-up self-report satisfaction questionnaires. RESULTS: Repeated measures ANOVA showed a significant interaction effect depicting improvements in knowledge associated with psychoeducation, corresponding to an improvement of 15% from baseline. Satisfaction data additionally showed that 92.3% of participants rated the program as "good" to "excellent", and over 90% suggested they would recommend it to others. CONCLUSIONS: A group-based psychoeducation program targeting healthy brain aging is effective in improving knowledge. Additionally, it is acceptable and rated highly by participants.

Sleep well, think well: sleep-wake disturbance in mild cognitive impairment.

While literature suggests that sleep is important for cognition and mood, and that sleep disturbance is a prominent feature of neurodegenerative and neuropsychiatric disorders, these relationships have not yet been examined in older people ''at risk" of dementia. In this study, 15 older people with the nonamnestic subtype of mild cognitive impairment ([MCI] mean age = 66.7 years, SD = 8.7) underwent psychiatric and neuropsychological assessment. Participants completed sleep diaries, questionnaires, and 2 weeks of actigraphy. Key outcome data during the rest interval were time spent ''awake" or wake after sleep onset (WASO) and the number of arousals/wake bouts. Results showed that even after controlling for age, greater WASO was associated with reduced attention and executive functioning and increased arousals were related to poorer nonverbal learning and problem solving. This preliminary data suggests that sleep-wake disturbance in nonamnestic forms of MCI is related to cognitive functioning and may be indicative of shared neurobiological underpinnings.

Does sleep disturbance mediate neuropsychological functioning in older people with depression?

BACKGROUND: Depression in older adults is associated with neuropsychological dysfunction, fronto-subcortical brain changes and sleep disturbance. Research suggests that adequate sleep is critical for many aspects of cognition including processing speed, verbal skills and memory. However, the association between sleep disturbance and neuropsychological functioning in depression has not been well evaluated. The current study therefore aimed to investigate these relationships. METHODS: Forty-eight people (mean age=59.6, sd=8.2) meeting DSM-IV criteria for unipolar major depression were included for analysis. Neuropsychological assessment included assessment of processing speed, learning and memory, verbal fluency and executive functions. Early and late insomnia were defined by scores on the Hamilton Depression Rating Scale. RESULTS: While early insomnia was related to depression severity and poorer global cognition, late insomnia was associated with later age of depression onset, depression severity, and poorer scores on tests of verbal fluency and memory. The associations between cognition and late insomnia were not accounted for by depression severity or age of onset of disorder. LIMITATIONS: This study was retrospective in nature, and did not include objective measures of sleep. CONCLUSIONS: This is the first known study to indicate that late insomnia in older people with major depression may be independently and aetiologically linked to neuropsychological performance, particularly verbal fluency and memory. It may also indicate underlying structural and neurochemical changes. Sleep and circadian disturbance may serve as a biomarker for ongoing cognitive decline and may be a potentially modifiable risk factor.