Perspectives of general practitioners and memory clinic patients on ageing and cognitive decline to inform the design of a decentralised antihypertensive dementia prevention trial.

BACKGROUND: The global burden dementia is growing each year. Clinical trials investigating approaches to preventing dementia have been occurring for decades, but they are particularly challenging including the requirement to include large numbers of healthy 'at-risk' people who need to be followed up for a long period of time. Community and consumer involvement in trial design helps to ensure that the methods are acceptable to the involved stakeholders, the design and operation of clinical trials are suitable and applicable to the target population, and that key areas of concern are identified and addressed at an early stage. OBJECTIVES: To gain insights from samples of memory clinic patients without dementia and general practitioners on the acceptability of, and attitudes towards, the proposed design of a decentralised antihypertensive dementia prevention trial. Topics addressed included the assessment of cognition, antihypertensive medication use, and motivation to participate in research. METHODS: Two focus groups (total n = 7) with memory clinic patients and individual interviews with GPs (n = 5) were conducted. Transcripts were analysed using qualitative thematic framework analysis. RESULTS: The proposed design was acceptable, with some possible barriers identified regarding computer use, GP time restraints, and concerns about medication interactions. Additional themes included the importance of communication and social connectedness in research participation and perceptions of ageing in medical settings. Future directions of research into larger studies and consumer-led research practices were discussed. CONCLUSION: The proposed trial design was agreed to be acceptable with some operational considerations, which were incorporated in the trial design.

REducing Sleep Apnoea for the PrEvention of Dementia (REShAPED): Protocol for a multi-site feasibility randomised controlled trial.

There is accumulating evidence that has linked OSA with increased risk of cognitive decline and dementia. Here we present the protocol for an Australian, multi-site randomised controlled, parallel open-label trial which will evaluate the feasibility for a full-scale trial investigating the effects of treating OSA on cognitive decline in older adults at risk of dementia within memory clinic settings. We will randomise 180 older adults to either the treatment intervention group or control group for 2 years. Inclusion criteria include: 50-85 years; mild-severe OSA (defined average ODI ≥ 10 with 3% oxygen desaturation determined by wrist oximetry over two nights); and subjective cognitive complaints or mild cognitive impairment. The treatment intervention arm aims to achieve an optimal treatment response based on reducing hypoxic burden with either CPAP, mandibular advancement splint, positional therapy, or oxygen therapy. Furthermore, participants will receive up to 8 sessions which involve motivational interviewing, collaborative goal setting, and behavioural sleep management. The control arm will not receive OSA treatment as part of this trial, however there will be no OSA treatment restrictions, and any treatment will be documented. Primary outcomes are 1) acceptability based upon willingness of participants to be randomised; 2) alleviating hypoxic burden by reducing OSA severity; 3) tolerability of the trial burden based upon collection of outcomes over the 2-year follow-up. Secondary outcomes include safety and cognitive function. Outcomes will be collected at 0, 6 and 24-months. This feasibility study aims to will provide the basis for a larger longer-term trial of dementia prevention.

Assessing sleep architecture and cognition in older adults with depressive symptoms attending a memory clinic.

BACKGROUND: While depression is intrinsically and bidirectionally linked with both sleep disturbance and cognition, the inter-relationships between sleep, cognition, and brain integrity in older people with depression, especially those with late-onset depression are undefined. METHODS: One hundred and seventy-two older adults (mean age 64.3 ± 6.9 years, Depression: n = 66, Control: n = 106) attending a memory clinic underwent a neuropsychological battery of declarative memory, executive function tasks, cerebral magnetic resonance imaging and overnight polysomnography with quantitative electroencephalography. RESULTS: The time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, slow-wave activity, sleep spindles, hippocampal volume and prefrontal cortex thickness did not differ between depression and control and depression onset groups. However, sleep onset latency (p = 0.005) and REM onset latency (p = 0.02) were later in the Depression group compared to controls. Less SWS was associated with poorer memory (r = 0.31, p = 0.023) in the depression group, and less SWS was related to better memory in the control group (r = -0.20, p = 0.043; Fishers r-to-z = -3.19). LIMITATIONS: Longitudinal studies are needed to determine if changes in sleep in those with depressive symptoms predict cognitive decline and illness trajectory. CONCLUSION: Older participants with depressive symptoms had delayed sleep initiation, suggestive of delayed sleep phase. The association between SWS and memory suggests SWS may be a useful target for cognitive intervention in older adults with depression symptoms. Reduced hippocampal volumes did not mediate this relationship, indicating a broader distributed neural network may underpin these associations.

Delivery of Neuropsychological Interventions for Adult and Older Adult Clinical Populations: An Australian Expert Working Group Clinical Guidance Paper.

Delivery of neuropsychological interventions addressing the cognitive, psychological, and behavioural consequences of brain conditions is increasingly recognised as an important, if not essential, skill set for clinical neuropsychologists. It has the potential to add substantial value and impact to our role across clinical settings. However, there are numerous approaches to neuropsychological intervention, requiring different sets of skills, and with varying levels of supporting evidence across different diagnostic groups. This clinical guidance paper provides an overview of considerations and recommendations to help guide selection, delivery, and implementation of neuropsychological interventions for adults and older adults. We aimed to provide a useful source of information and guidance for clinicians, health service managers, policy-makers, educators, and researchers regarding the value and impact of such interventions. Considerations and recommendations were developed by an expert working group of neuropsychologists in Australia, based on relevant evidence and consensus opinion in consultation with members of a national clinical neuropsychology body. While the considerations and recommendations sit within the Australian context, many have international relevance. We include (i) principles important for neuropsychological intervention delivery (e.g. being based on biopsychosocial case formulation and person-centred goals); (ii) a description of clinical competencies important for effective intervention delivery; (iii) a summary of relevant evidence in three key cohorts: acquired brain injury, psychiatric disorders, and older adults, focusing on interventions with sound evidence for improving activity and participation outcomes; (iv) an overview of considerations for sustainable implementation of neuropsychological interventions as 'core business'; and finally, (v) a call to action.

Heart rate variability during slow wave sleep is linked to functional connectivity in the central autonomic network.

Reduced heart rate variability can be an early sign of autonomic dysfunction in neurodegenerative diseases and may be related to brain dysfunction in the central autonomic network. As yet, such autonomic dysfunction has not been examined during sleep-which is an ideal physiological state to study brain-heart interaction as both the central and peripheral nervous systems behave differently compared to during wakefulness. Therefore, the primary aim of the current study was to examine whether heart rate variability during nocturnal sleep, specifically slow wave (deep) sleep, is associated with central autonomic network functional connectivity in older adults 'at-risk' of dementia. Older adults (n = 78; age range = 50-88 years; 64% female) attending a memory clinic for cognitive concerns underwent resting-state functional magnetic resonance imaging and an overnight polysomnography. From these, central autonomic network functional connectivity strength and heart rate variability data during sleep were derived, respectively. High-frequency heart rate variability was extracted to index parasympathetic activity during distinct periods of sleep, including slow wave sleep as well as secondary outcomes of non-rapid eye movement sleep, wake after sleep onset, and rapid eye movement sleep. General linear models were used to examine associations between central autonomic network functional connectivity and high-frequency heart rate variability. Analyses revealed that increased high-frequency heart rate variability during slow wave sleep was associated with stronger functional connectivity (F = 3.98, P = 0.022) in two core brain regions within the central autonomic network, the right anterior insular and posterior midcingulate cortex, as well as stronger functional connectivity (F = 6.21, P = 0.005) between broader central autonomic network brain regions-the right amygdala with three sub-nuclei of the thalamus. There were no significant associations between high-frequency heart rate variability and central autonomic network connectivity during wake after sleep onset or rapid eye movement sleep. These findings show that in older adults 'at-risk' of dementia, parasympathetic regulation during slow wave sleep is uniquely linked to differential functional connectivity within both core and broader central autonomic network brain regions. It is possible that dysfunctional brain-heart interactions manifest primarily during this specific period of sleep known for its role in memory and metabolic clearance. Further studies elucidating the pathophysiology and directionality of this relationship should be conducted to determine if heart rate variability drives neurodegeneration, or if brain degeneration within the central autonomic network promotes aberrant heart rate variability.

Identifying subtle functional change in individuals with mild cognitive impairment: development and validation of the Healthy Brain Ageing - Functional Assessment Questionnaire.

Accumulating research suggests that individuals with Mild Cognitive Impairment (MCI) experience subtle functional changes, but that available functional assessment tools are insensitive to this. To address this gap, we describe the development and validation of the self-report, "Healthy Brain Ageing Functional Assessment Questionnaire" (HBA-FAQ). We examined the factor structure and psychometric properties of the HBA-FAQ in 503 participants with normal cognition, subjective cognitive decline (SCD), MCI or dementia. Our results found the HBA-FAQ to have good reliability, validity and stronger discriminative ability between healthy control participants and those with SCD (0.734, p = .001), MCI (0.666, p = .012) and dementia (0.798, p < .001) compared to a widely-used instrumental activities of daily living screener. In conclusion, the HBA-FAQ is a valid, reliable self-report tool, providing an efficient and sensitive approach to identifying subtle changes in daily functioning in older people at risk of dementia.

Not all mentally stimulating activities are alike: insights from a 4-factor model and implications for late-life cognition.

It is not yet known which specific qualities of cognitively stimulating activities are most likely to enhance cognitive reserve in older adults. Taking an inductive approach to this problem, we asked 504 older adults with subjective and/or cognitive impairment to complete the Cognitively Stimulating Activities Questionnaire (CSA-Q). Exploratory factor analysis identified a 4-factor structure within a split-half sample, after which confirmatory factor analysis cross-validated the model. Retaining 12 CSA-Q items, the 4 factors were dubbed CSA-Processing, CSA-Challenging, CSA-Connecting and CSA-Socializing. Resulting factor weights were analyzed relative to cognitive reserve proxies and neuropsychological domains. All factors except CSA-Challenging were positively linked to cognitive reserve. Neuropsychologically, CSA-Challenging was modestly and positively correlated with processing speed and executive function, while CSA-Processing was positively correlated with executive function. CSA-Socializing had a small positive correlation with processing speed. Our findings offer new insights into late-life stimulating activities, laying the groundwork for longitudinal and intervention studies.

A Systematic Review of Quality Dementia Clinical Guidelines for the Development of WHO's Package of Interventions for Rehabilitation.

BACKGROUND AND OBJECTIVES: As part of the WHO Rehabilitation 2030 call for action, the WHO Rehabilitation Programme is developing its Package of Interventions for Rehabilitation (PIR) to support ministries of health around the globe in integrating rehabilitation services into health systems. As a vital step for this PIR development, we conducted a systematic review of clinical practice guidelines (CPGs) for dementia to identify interventions for rehabilitation and related evidence. RESEARCH DESIGN AND METHODS: Following WHO Rehabilitation Programme and Cochrane Rehabilitation's methodology, quality CPGs published in English between January 2010 and March 2020 were identified using PubMed, Embase, CINAHL, PEDro, Google Scholar, guideline databases, and professional society websites. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation (II). RESULTS: Of the 22 CPGs that met the selection criteria, 6 satisfied the quality evaluation. Three hundred and thirty rehabilitation-related recommendations were identified, mostly concentrated in the areas of cognition, emotion, and carer support. There were many strong interventions, with moderate- to high-quality evidence that could be easily introduced in routine practice. However, major limitations were found both in the quality of evidence and scope, especially in areas such as education and vocation, community and social life, and lifestyle modifications. DISCUSSION AND IMPLICATIONS: Further rigorous research is needed to build quality evidence in dementia rehabilitation in general, and especially in neglected areas for rehabilitation. Future work should also focus on the development of CPGs for dementia rehabilitation. A multipronged approach is needed to achieve Universal Health Coverage for dementia rehabilitation.

Hippocampal Neuronal Integrity and Functional Connectivity Within the Default Mode Network in Mild Cognitive Impairment: A Multimodal Investigation.

Background: In older people with mild cognitive impairment (MCI), the relationship between early changes in functional connectivity and in vivo changes in key neurometabolites is not known. Two established correlates of MCI diagnosis are decreased N-acetylaspartate (NAA) in the hippocampus, indicative of decreased neuronal integrity, and changes in the default mode network (DMN) functional network. If and how these measures interrelate is yet to be established, and such understanding may provide insight into the processes underpinning observed cognitive decline. Objectives: To determine the relationship between NAA levels in the left hippocampus and functional connectivity within the DMN in an aging cohort. Methods: In a sample of 51 participants with MCI and 30 controls, hippocampal NAA was determined using magnetic resonance spectroscopy, and DMN connectivity was quantified using resting-state functional MRI. The association between hippocampal NAA and the DMN functional connectivity was tested within the MCI group and separately within the control group. Results: In the DMN, we showed a significant inverse association between functional connectivity and hippocampal NAA in 20 specific brain connections for patients with MCI. This was despite no evidence of any associations in the healthy control group or group differences in either of these measures alone. Conclusions: This study suggests that decreased neuronal integrity in the hippocampus is associated with functional change within the DMN for those with MCI, in contrast to healthy older adults. These results highlight the potential of multimodal investigations to better understand the processes associated with cognitive decline. Impact statement This study measured activity within the default mode network (DMN) and quantified N-acetylaspartate (NAA), a measure of neuronal integrity, within the hippocampus in participants with mild cognitive impairment (MCI) and healthy controls. In participants with MCI, NAA levels were inversely associated with connectivity between specific regions of the DMN, a relationship not evident in healthy controls. This association was present even in the absence of group differences in DMN connectivity or NAA levels. This research illustrates the possibility of using multiple magnetic resonance modalities for more sensitive measures of early cognitive decline to identify and intervene earlier.

Engagement in cognitively stimulating activities in individuals with Mild Cognitive Impairment: relationships with neuropsychological domains and hippocampal volume.

Late-life participation in cognitively stimulating activities is thought to contribute to an individual's cognitive reserve and thus protect against cognitive decline, yet its association with clinical markers of neurodegeneration is not well established. To investigate, we developed a 13-item self-report "cognitively stimulating activities" questionnaire (CSA-Q), which was completed by a community sample of 269 older adults (>50 years) at risk of dementia. Participants met criteria for Mild Cognitive Impairment (MCI) and were classified as amnestic (aMCI; n = 93) or non-amnestic (naMCI; n = 176). Weighted CSA-Q dimensions were calculated for activity intensity, mental engagement and social engagement via a panel of 23 inter-raters. The CSA-Q mean and its dimensions were examined in relation to: (a) demographics (age, sex), (b) cognitive reserve proxies (years of education, premorbid IQ), (c) neuropsychological markers across cognitive domains of executive function, processing speed, learning, and memory storage, and (d) neuroimaging markers (left and right hippocampal volume). Analyses were conducted for all MCI, as well as for aMCI and naMCI sub-types. The CSA-Q was found to have concurrent validity with cognitive reserve proxies. Among all MCI, the CSA-Q dimensions of intensity and mental engagement had moderate associations with left hippocampal volume, but not with neuropsychological performance. For naMCI, the CSA-Q had moderate associations with left hippocampal volume, and small associations with aspects of executive functioning and processing speed. No equivalent associations emerged for the aMCI subtype. Our findings show that the CSA-Q may be particularly useful for older adults with non-amnestic cognitive deficits.

Thalamic abnormalities in older adults with remitted early-onset depression using structural magnetic resonance imaging.

BACKGROUND: The thalamus is a key diencephalic structure involved in major depressive disorder (MDD). Studies have consistently revealed abnormalities in thalamic volumes in older adults with late-onset depression (LOD), however abnormalities in older adults with early-onset depression (EOD) have not yet been well-studied. METHODS: Fifty-nine euthymic participants with a history of EOD and fifty-nine matched comparison participants without a lifetime history of depression underwent neuroimaging, medical and neuropsychological assessments. Thalamic volumes were compared between groups. To investigate the previously-proposed right hemispheric (RH) dominance theory of MDD, we explored the bilateral, right and left hemispheric (LH) thalamic volumes. Multiple regression analyses were used to evaluate between-group and within-group effects. Correlational analyses examined associations between group and cognitive performance. RESULTS: Relative to the comparison group, those with EOD had significantly larger bilateral, LH and RH thalamic volumes. Those with EOD, those who were younger, and those who had fewer years of education demonstrated larger bilateral and LH thalamic volumes. For RH thalamic volumes, those with EOD and those who were younger demonstrated larger RH thalamic volumes. EOD within-group models were also run to assess associations between relevant depression variables. The results showed that only age was significant for bilateral and RH thalamic volumes. For the LH thalamic volumes, the model was not significant. No significant correlations were found between cognitive performance and EOD groups. CONCLUSION: Older adults with a history of EOD showed significantly larger bilateral, RH and LH thalamic volumes. Further research is needed to delineate potential underlying mechanisms of this change.

Poorer Theory of Mind in Amnestic Mild Cognitive Impairment Is Associated with Decreased Functional Connectivity in the Default Mode Network.

BACKGROUND: Older adults living with amnestic mild cognitive impairment (aMCI) not only demonstrate impairments in Theory of Mind (ToM), relative to adults with non-amnestic MCI (naMCI), but are also at a higher risk of developing dementia. OBJECTIVE: Our primary objective was to ascertain whether default mode network (DMN) functional connectivity was differentially associated with ToM abilities between MCI subgroups. METHODS: Using functional magnetic resonance imaging, we investigated alterations in resting-state functional connectivity within the brain's DMN in a sample of 43 older adults with aMCI (n = 19) and naMCI (n = 24), previously reported to demonstrate poorer ToM abilities. RESULTS: Compared to naMCI, the aMCI subgroup revealed a significant association between poorer ToM performance and reduced functional connectivity between the bilateral temporal pole (TempP) and the left lateral temporal cortex (LTC) (LTC_L-TempP_L: b = -0.06, t(33) = -3.53, p = 0.02; LTC_L-TempP_R: b = -0.07,t(33) = -3.20, p = 0.03); between the right TempP and the dorsal medial prefrontal cortex (dMPFC) (b = -0.04, t(33) = -3.02, p = 0.03) and between the left and right TempP (b = -0.05, t(33) = -3.26, p = 0.03). In the naMCI subgroup, the opposite relationship was present between the bilateral TempP and the left LTC (Combined correlation: r = -0.47, p = 0.02), however, not between the right TempP and the dMPFC (r = -0.14, p = 0.51) or the left and right TempP (r = -0.31, p = 0.14). CONCLUSION: Our findings suggest that alterations in functional connectivity within the DMN involving temporal and frontal lobe regions are associated with ToM deficits in aMCI.

Using Staged Care to Provide "Right Care First Time" to People With Common Affective Disorders.

An ongoing need exists for innovation in service delivery to ensure that mental health services deliver high-quality treatment and prevention in the population. This Special Article proposes the adoption of "staged care" as a population health-oriented service delivery model for packages of specialized services delivered largely in ambulatory care settings for individuals with common affective disorders. Staged care integrates measures of clinical need alongside clinical stage and personal choice to select hierarchically arranged service packages for individuals. Packages then vary according to the intensity, duration, and mix of treatment options. This Special Article describes five levels of care in staged care: self- or family-directed monitoring and management, low-intensity services, moderate-intensity services, high-intensity services, and acute and specialist community mental health services. The care environment, treatment team, and length of treatment are also described, and provisional criteria are specified for assigning individuals to different care levels on the basis of current clinical need and clinical stage. Staged care is presented as a model that guides treatment selection and health service delivery to ensure that the high-quality care aims of "right care first time" and prevention are achieved and optimal use of available resources is considered.

Association between lifetime depression history, hippocampal volume and memory in non-amnestic mild cognitive impairment.

Hippocampal subfield volume loss in older adults with amnestic mild cognitive impairment (aMCI) and depression history are associated with amyloid beta and tau pathology, thereby increasing the risk for Alzheimer's disease (AD). However, no studies have exclusively examined distinct alterations in hippocampal subfields in non-amnestic MCI (naMCI) in relation to depression history. Here, we used both longitudinal and transverse hippocampal segmentation methods using the automated FreeSurfer software to examine whether a lifetime depression history is associated with differences in hippocampal head/body/tail (H/B/T) and key subfield volumes (CA1, subiculum, dentate gyrus) in older adults with naMCI. Further, we explored whether differences in hippocampal H/B/T and subfield volumes were associated with structured and unstructured verbal encoding and retention, comparing those with and without a depression history. The naMCI with a depression history group demonstrated larger or relatively preserved right CA1 volumes, which were associated with better unstructured verbal encoding and as well as structured verbal memory retention. This association between memory encoding and hippocampal CA1 and total head volume was significantly different to those with no depression history. The relationship between right CA1 volume and memory retention was also moderated by depression history status F (5,143) = 7.84, p < 0.001, R2  = 0.22. Those participants taking antidepressants had significantly larger hippocampal subiculum (p = 0.008), and right hippocampal body (p = 0.004) and better performance on structured encoding (p = 0.011) and unstructured memory retention (p = 0.009). These findings highlight the importance of lifetime depression history and antidepressant use on the hippocampus and encoding and memory retention in naMCI.

Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study.

INTRODUCTION: Melatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI). METHODS AND ANALYSIS: The study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia. ETHICS AND DISSEMINATION: This protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190). PROTOCOL VERSION: V.8 15 October 2020.

Obesity and Oxidative Stress in Older Adults At Risk for Dementia: A Magnetic Resonance Spectroscopy Study.

OBJECTIVE: This study aimed to investigate the relationship between obesity and oxidative stress in older adults at risk for dementia. It also aimed to explore the influence of physical activity on the relationship between obesity and oxidative stress in this at risk cohort. METHODS: Older adults at risk for dementia underwent comprehensive medical, neuropsychological, and psychiatric assessment. At risk was defined as participants with subjective or mild cognitive impairment. Glutathione was assessed by magnetic resonance spectroscopy in the left hippocampus and the anterior and posterior cingulate cortex. Body mass index (BMI) was calculated and classified as healthy (BMI <25 kg/m2) or overweight/obese (BMI ≥25 kg/m2). RESULTS: Sixty-five older adults (mean age=66.2 y) were included for analysis. The overweight/obese group had significantly greater glutathione in the hippocampus compared with the healthy weight group (t=-2.76, P=0.008). No significant difference in glutathione was observed between groups in the anterior or posterior cingulate. In the overweight/obese group, a higher BMI was associated with a diabetes diagnosis and lower total time engaging in physical activity (r=-0.36, P=0.025), however, glutathione did not correlate with activity levels across groups. CONCLUSION: This study demonstrates that changes in in vivo markers of oxidative stress are present in overweight/obese older adults at risk for dementia. Future research should explore the relationship with diabetes and the longitudinal relationship between BMI and oxidative stress, and response to therapeutic interventions.

Irregular sleep-wake patterns in older adults with current or remitted depression.

BACKGROUND: Disturbed sleep and irregular sleep-wake patterns have been associated with poor outcomes in older adults. Sleep regularity however has not been studied in a sample with current or remitted major depression. METHODS: 138 participants (63.8±8.6 years; n=27 current major depression, n=64 remitted, and n=47 healthy controls) were monitored using wrist-worn actigraphy. The Sleep Regularity Index (SRI), sleep-wake fragmentation and stability, sleep onset and offset timing, number of awakenings and measures from cosinor analysis were computed. RESULTS: Compared with controls, older adults with current depression had lower SRI (p < 0.01), lower relative amplitude (p < 0.05), and higher activity during sleeping and post-midnight hours (p < 0.05). Older adults with remitted depression displayed lower activity during the day (p < 0.05), showed reduced average activity and lower amplitude than controls. Total sleep time, sleep timing, and number of awakenings did not differ between groups. All groups differed significantly in self-reported sleep quality and depression severity. LIMITATIONS: Longitudinal studies which examine how sleep-wake patterns change based on depressive episode recency, severity and how medications may influence these patterns are needed. CONCLUSIONS: Older adults with current or remitted major depression do not differ from controls on traditional sleep metrics but do report poor quality sleep and show differences in sleep regularity and rest-activity patterns. Reducing the risk of poor outcomes in both groups may be aided by interventions that help promote sleep regularity and increased activity.

Altered heart rate variability during sleep in mild cognitive impairment.

STUDY OBJECTIVES: Cardiovascular autonomic dysfunction, as measured by short-term diurnal heart rate variability (HRV), has been reported in older adults with mild cognitive impairment (MCI). However, it is unclear whether this impairment also exists during sleep in this group. We, therefore, compared overnight HRV during sleep in older adults with MCI and those with subjective cognitive impairment (SCI). METHODS: Older adults (n = 210) underwent overnight polysomnography. Eligible participants were characterized as multi-domain MCI or SCI. The multi-domain MCI group was comprised of amnestic and non-amnestic subtypes. Power spectral analysis of HRV was conducted on the overnight electrocardiogram during non-rapid eye movement (NREM), rapid eye movement (REM), N1, N2, N3 sleep stages, and wake periods. High-frequency HRV (HF-HRV) was employed as the primary measure to estimate parasympathetic function. RESULTS: The MCI group showed reduced HF-HRV during NREM sleep (p = 0.018), but not during wake or REM sleep (p > 0.05) compared to the SCI group. Participants with aMCI compared to SCI had the most pronounced reduction in HF-HRV across all NREM sleep stages-N1, N2, and N3, but not during wake or REM sleep. The naMCI sub-group did not show any significant differences in HF-HRV during any sleep stage compared to SCI. CONCLUSIONS: Our study showed that amnestic MCI participants had greater reductions in HF-HRV during NREM sleep, relative to those with SCI, suggesting potential vulnerability to sleep-related parasympathetic dysfunction. HF-HRV, especially during NREM sleep, may be an early biomarker for dementia detection.

Actigraphy-recorded sleep efficiency and hippocampal volume are related to visual and verbal rate of forgetting in older adults.

This study aimed to determine if older adults "at-risk" for dementia (those with MCI or SMC) exhibit accelerated long-term forgetting (ALF) and whether rate of forgetting (RoF) is associated with sleep efficiency, hippocampal volume and demographic/clinical features. Forty-nine "at-risk" participants and eighteen controls underwent examination. Memory was assessed using the Scene Memory Task (SMT) and WMS-III Logical Memory (LM) subtest. Tests were administered at baseline, 24 hours and 2 weeks. While our study did not find ALF in those "at-risk" for dementia, on the SMT, RoF over 24 hours and 2 weeks was negatively correlated with sleep efficiency. For LM, RoF at 2 weeks was moderately associated with left hippocampal volume. Neither visual or verbal RoF was correlated with demographic or clinical variables (age, MMSE, IQ, GDS-15). While ALF was not observed in this sample, our results suggest that visual and verbal forgetting have differential predictors.

Objective measurement of sleep in mild cognitive impairment: A systematic review and meta-analysis.

Older adults with mild cognitive impairment (MCI) are at-risk of developing dementia, particularly Alzheimer's disease. While some research suggests that alterations in sleep architecture may mediate cognitive decline, the nature and magnitude of changes to sleep macro- (sleep stages) and micro-architecture (electroencephalography (EEG) oscillations) in MCI is not yet clear. This study aimed to systematically review and meta-analyse case-control studies objectively measuring sleep in MCI. A systematic search was conducted using PubMed, Scopus, Web of Science, Embase and Psycinfo databases and after review, a total of 10 studies met inclusion criteria. Of these, all reported sleep macro-architecture and four reported micro-architecture outcomes. A combined total of 430 participants (209 with and 221 without MCI) underwent objective sleep assessments in the included full text articles. Findings show that compared to healthy controls, those with MCI have pronounced changes in sleep macro-architecture with greater wake after sleep onset, reduced total sleep time, lower sleep efficiency, longer sleep onset latency, longer rapid eye movement sleep (REM) latency, reduced REM sleep, greater N1 sleep, and worse severity of hypoxemia. Pooling of sleep micro-architecture EEG measures was not possible due to limited studies, however reduced spindles in non-REM sleep and greater EEG slowing in REM sleep were reported.