Predictors of primary care psychological therapy outcomes for depression and anxiety in people living with dementia: evidence from national healthcare records in England.

BACKGROUND: Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown. AIMS: To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD. METHOD: National linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored. RESULTS: People with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08-8.22; P = 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15-7.55; P = 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92-0.98, P < 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04-2.90, P = 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96-0.99, P = 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51-0.90, P = 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10-3.73, P = 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09-1.16, P < 0.001) were associated with worse therapy outcomes in PLWD. CONCLUSIONS: Dementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.

Psychological therapies for depression and cardiovascular risk: evidence from national healthcare records in England.

AIMS: People with depression are up to 72% more at risk to develop cardiovascular disease (CVD) in their lifetime. Evidence-based psychotherapies are first-line interventions for the treatment of depression and are delivered nationally in England through the National Health Service via the Improving Access to Psychological Therapy (IAPT) primary care programme. It is currently unknown whether positive therapy outcomes may be associated with cardiovascular risk reduction. This study aimed to examine the association between psychotherapy outcomes for depression and incident CVD. METHODS AND RESULTS: A cohort of 636 955 individuals who have completed a course of psychotherapy was built from linked electronic healthcare record databases of national coverage in England: the national IAPT database, the Hospital Episode Statistics (HES) database, and the HES-ONS (Office of National Statistics) mortality database. Multivariable Cox models adjusting for clinical and demographic covariates were run to estimate the association between reliable improvement from depression and the risk of subsequent incidence of cardiovascular events. After a median follow-up of 3.1 years, reliable improvement from depression symptoms was associated with a lower risk of new onset of any CVD [hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.86, 0.89], coronary heart disease (HR: 0.89, 95% CI: 0.86, 0.92), stroke (HR: 0.88, 95% CI: 0.83, 0.94), and all-cause mortality (HR: 0.81, 95% CI: 0.78, 0.84). This association was stronger in the under 60 compared with the over 60 for all outcomes. Results were confirmed in sensitivity analyses. CONCLUSION: Management of depression through psychological interventions may be associated with reduced risk of CVD. More research is needed to understand the causality of these associations.

Associations between psychological therapy outcomes for depression and incidence of dementia.

BACKGROUND: Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia. METHODS: National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later. RESULTS: Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83-0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77-0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83-1.00). CONCLUSIONS: Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research.

Depressive symptoms in cognitively unimpaired older adults are associated with lower structural and functional integrity in a frontolimbic network.

Subclinical depressive symptoms are associated with increased risk of Alzheimer's disease (AD), but the brain mechanisms underlying this relationship are still unclear. We aimed to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroimaging data. We included cognitively unimpaired older adults from the baseline data of the primary cohort Age-Well (n = 135), and from the replication cohort ADNI (n = 252). In both cohorts, subclinical depressive symptoms were assessed using the 15-item version of the Geriatric Depression Scale; based on this scale, participants were classified as having depressive symptoms (>0) or not (0). Voxel-wise between-group comparisons were performed to highlight differences in gray matter volume, glucose metabolism and amyloid deposition; as well as white matter integrity (only available in Age-Well). Age-Well participants with subclinical depressive symptoms had lower gray matter volume in the hippocampus and lower white matter integrity in the fornix and the posterior parts of the cingulum and corpus callosum, compared to participants without symptoms. Hippocampal atrophy was recovered in ADNI, where participants with subclinical depressive symptoms also showed glucose hypometabolism in the hippocampus, amygdala, precuneus/posterior cingulate cortex, medial and dorsolateral prefrontal cortex, insula, and temporoparietal cortex. Subclinical depressive symptoms were not associated with brain amyloid deposition in either cohort. Subclinical depressive symptoms in ageing are linked with neurodegeneration biomarkers in the frontolimbic network including brain areas particularly sensitive to AD. The relationship between depressive symptoms and AD may be partly underpinned by neurodegeneration in common brain regions.

Traumatic life events and risk for dementia: a systematic review and meta-analysis.

OBJECTIVES: To systematically review the association between traumatic life events (TLE) and dementia risk. DESIGN: Systematic review and meta-analysis. DATA SOURCES: APA, PsychINFO, Embase and MEDLINE from their inception to 29.05.21 and updated on 20.04.22. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Original research articles published in peer reviewed journals examining the association between TLE and all cause dementia in individuals aged 60 and over. Two researchers independently assessed the risk of bias using the Newcastle-Ottawa Scale. We conducted a generic inverse variance random effects meta-analysis to provide an overall estimate of TLE impact on dementia risk. MAIN OUTCOME MEASURES: Risk, odds and hazards ratios relating to dementia risk. RESULTS: Initially, 3,487 studies were retrieved in the search and seven studies were included in the meta-analysis with data being used from 276,570 participants. TLE were associated with increased dementia risk. Trauma in general had a pooled HR of 1.21, (95% CI 1.03, 1.43, P = 0.0001). War/ Holocaust trauma and childhood trauma were also associated with increased dementia risk (HR = 1.28 (95% CI 1.01-1.63, P = 0.02) and HR = 1.76 (95% CI 1.17-2.64, P = 0.007) respectively). CONCLUSIONS: We have found an association between TLE and dementia risk. Future research exploring the dimensions of TLE and individual level factors are needed to better understand the relationship between TLE and dementia. TRIAL REGISTRATION: PROSPERO CRD42021253090.

The Effect of Mindfulness-based Programs on Cognitive Function in Adults: A Systematic Review and Meta-analysis.

Mindfulness-based programs (MBPs) are increasingly utilized to improve mental health. Interest in the putative effects of MBPs on cognitive function is also growing. This is the first meta-analysis of objective cognitive outcomes across multiple domains from randomized MBP studies of adults. Seven databases were systematically searched to January 2020. Fifty-six unique studies (n = 2,931) were included, of which 45 (n = 2,238) were synthesized using robust variance estimation meta-analysis. Meta-regression and subgroup analyses evaluated moderators. Pooling data across cognitive domains, the summary effect size for all studies favored MBPs over comparators and was small in magnitude (g = 0.15; [0.05, 0.24]). Across subgroup analyses of individual cognitive domains/subdomains, MBPs outperformed comparators for executive function (g = 0.15; [0.02, 0.27]) and working memory outcomes (g = 0.23; [0.11, 0.36]) only. Subgroup analyses identified significant effects for studies of non-clinical samples, as well as for adults aged over 60. Across all studies, MBPs outperformed inactive, but not active comparators. Limitations include the primarily unclear within-study risk of bias (only a minority of studies were considered low risk), and that statistical constraints rendered some p-values unreliable. Together, results partially corroborate the hypothesized link between mindfulness practices and cognitive performance. This review was registered with PROSPERO [CRD42018100904].

Association of quality of life with structural, functional and molecular brain imaging in community-dwelling older adults.

BACKGROUND: As the population ages, maintaining mental health and well-being of older adults is a public health priority. Beyond objective measures of health, self-perceived quality of life (QoL) is a good indicator of successful aging. In older adults, it has been shown that QoL is related to structural brain changes. However, QoL is a multi-faceted concept and little is known about the specific relationship of each QoL domain to brain structure, nor about the links with other aspects of brain integrity, including white matter microstructure, brain perfusion and amyloid deposition, which are particularly relevant in aging. Therefore, we aimed to better characterize the brain biomarkers associated with each QoL domain using a comprehensive multimodal neuroimaging approach in older adults. METHODS: One hundred and thirty-five cognitively unimpaired older adults (mean age ± SD: 69.4 ± 3.8 y) underwent structural and diffusion magnetic resonance imaging, together with early and late florbetapir positron emission tomography scans. QoL was assessed using the brief version of the World Health Organization's QoL instrument, which allows measuring four distinct domains of QoL: self-perceived physical health, psychological health, social relationships and environment. Multiple regression analyses were carried out to identify the independent global neuroimaging predictor(s) of each QoL domain, and voxel-wise analyses were then conducted with the significant predictor(s) to highlight the brain regions involved. Age, sex, education and the other QoL domains were entered as covariates in these analyses. Finally, forward stepwise multiple regressions were conducted to determine the specific items of the relevant QoL domain(s) that contributed the most to these brain associations. RESULTS: Only physical health QoL was associated with global neuroimaging values, specifically gray matter volume and white matter mean kurtosis, with higher physical health QoL being associated with greater brain integrity. These relationships were still significant after correction for objective physical health and physical activity measures. No association was found with global brain perfusion or global amyloid deposition. Voxel-wise analyses revealed that the relationships with physical health QoL concerned the anterior insula and ventrolateral prefrontal cortex, and the corpus callosum, corona radiata, inferior frontal white matter and cingulum. Self-perceived daily living activities and self-perceived pain and discomfort were the items that contributed the most to these associations with gray matter volume and white matter mean kurtosis, respectively. CONCLUSIONS: Better self-perceived physical health, encompassing daily living activities and pain and discomfort, was the only QoL domain related to brain structural integrity including higher global gray matter volume and global white matter microstructural integrity in cognitively unimpaired older adults. The relationships involved brain structures belonging to the salience network, the pain pathway and the empathy network. While previous studies showed a link between objective measures of physical health, our findings specifically highlight the relevance of monitoring and promoting self-perceived physical health in the older population. Longitudinal studies are needed to assess the direction and causality of the relationships between QoL and brain integrity.

Effects of a Mindfulness-Based Intervention versus Health Self-Management on Subclinical Anxiety in Older Adults with Subjective Cognitive Decline: The SCD-Well Randomized Superiority Trial.

INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a heightened risk of developing dementia and frequently experience subclinical anxiety, which is itself associated with dementia risk. OBJECTIVE: To understand whether subclinical anxiety symptoms in SCD can be reduced through behavioral interventions. METHODS: SCD-Well is a randomized controlled trial designed to determine whether an 8-week mindfulness-based intervention (caring mindfulness-based approach for seniors; CMBAS) is superior to a structurally matched health self-management program (HSMP) in reducing subclinical anxiety. Participants were recruited from memory clinics at 4 European sites. The primary outcome was change in anxiety symptoms (trait subscale of the State-Trait Anxiety Inventory; trait-STAI) from pre- to postintervention. Secondary outcomes included a change in state anxiety and depression symptoms postintervention and 6 months postrandomization (follow-up). RESULTS: One hundred forty-seven participants (mean [SD] age: 72.7 [6.9] years; 64.6% women; CMBAS, n = 73; HSMP, n = 74) were included in the intention-to-treat analysis. There was no difference in trait-STAI between groups postintervention (adjusted change difference: -1.25 points; 95% CI -4.76 to 2.25) or at follow-up (adjusted change difference: -0.43 points; 95% CI -2.92 to 2.07). Trait-STAI decreased postintervention in both groups (CMBAS: -3.43 points; 95% CI -5.27 to -1.59; HSMP: -2.29 points; 95% CI -4.14 to -0.44) and reductions were maintained at follow-up. No between-group differences were observed for change in state anxiety or depression symptoms. CONCLUSIONS: A time-limited mindfulness intervention is not superior to health self-management in reducing subclinical anxiety symptoms in SCD. The sustained reduction observed across both groups suggests that subclinical anxiety symptoms in SCD are modifiable. ClinicalTrials.gov identifier: NCT03005652.

Post-traumatic stress disorder as a risk factor for dementia: systematic review and meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been identified as a potential risk factor for developing dementia. There are currently, however, no meta-analyses quantifying this risk. AIMS: To systematically review and quantify the risk of future dementia associated with PTSD across populations. PROSPERO registration number CRD42019130392. METHOD: We searched nine electronic databases up to 25 October 2019 for longitudinal studies assessing PTSD and risk of dementia. We used random- and fixed-effects meta-analyses to pool estimates across studies. RESULTS: PTSD was associated with a significant risk for all-cause dementia: pooled hazard ratio HR = 1.61 (95% CI 1.43-1.81, I2= 85.8%, P < 0.001; n = 1 693 678; 8 studies). Pooled HR was 1.61 (95% CI 1.46-1.78; I2= 80.9%, P < 0.001; n = 905 896; 5 studies) in veterans, and 2.11 (95% CI 1.03-4.33, I2= 91.2%, P < 0.001; n = 787 782; 3 studies) in the general population. The association between PTSD and dementia remained significant after excluding studies with high risk of bias (HR = 1.55, 95% CI 1.39-1.73, I2= 83.9%, P < 0.001; n = 1 684 928; 7 studies). Most studies included were retrospective and there was evidence of high heterogeneity. CONCLUSIONS: This is the first meta-analysis quantifying the association of PTSD and risk of dementia showing that PTSD is a strong and potentially modifiable risk factor for all-cause dementia. Future studies investigating potential causal mechanisms, and the protective value of treating PTSD are needed.

APPLE-Tree (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline) programme: Protocol.

BACKGROUND: Observational studies indicate that approximately a third of dementia cases are attributable to modifiable cardiometabolic, physical and mental health, and social and lifestyle risk factors. There is evidence that intensive behaviour change interventions targeting these factors can reduce cognitive decline. [Figure: see text] METHODS AND ANALYSIS: We will design and test a low intensity, secondary dementia-prevention programme (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline, "APPLE-Tree") to slow cognitive decline in people with subjective cognitive decline with or without objective cognitive impairment. We will embed our work within social science research to understand how dementia prevention is currently delivered and structured. We will carry out systematic reviews and around 50 qualitative interviews with stakeholders, using findings to coproduce the APPLE-Tree intervention. We plan a 10-session group intervention, involving personalised goal-setting, with individual sessions for those unable or unwilling to attend groups, delivered by psychology assistants who will be trained and supervised by clinical psychologists. The coproduction group (including public and patient involvement [PPI], academic and clinical/third-sector professional representatives) will use the Behaviour Change Wheel theoretical framework to develop it. We will recruit and randomly allocate 704 participants, 1:1 to the intervention: informational control group. This sample size is sufficient to detect a between-group difference at 2 years of 0.15 on the primary outcome (cognition: modified neuropsychological test battery; 90% power, 5% significance, effect size 0.25, SD 0.6). DISSEMINATION: We will work with Public Health England and third-sector partners to produce an effective national implementation approach, so that if our intervention works, it is used in practice.

Repetitive negative thinking is associated with subjective cognitive decline in older adults: a cross-sectional study.

BACKGROUND: In the absence of a cure or effective treatment for dementia, attention has shifted towards identifying risk factors for prevention. Subjective Cognitive Decline (SCD) describes self-perceived worsening of cognition despite unimpaired performance on neuropsychological tests. SCD has been associated with an increased dementia risk and steeper memory decline. Repetitive negative thinking (RNT) is a transdiagnostic process that manifests across several mental health disorders associated with increased vulnerability to dementia. RNT has thus been proposed as a candidate marker of risk for dementia and, relatedly, could contribute to the manifestation of SCD. We aimed to investigate the relationship between SCD and RNT alongside other proposed psychological risk/protective factors for dementia and cognitive decline. METHODS: In a cross-sectional online survey, 491 older adults (mean = 64.9 years, SD = 4.2; 63.1% female) completed measures of RNT, personality traits, purpose in life, worry, rumination, and meditation practice. SCD was assessed continuously via self-perceived cognitive function (Neuro-QoL) and categorically via endorsement (yes/no) of memory complaints. Regression models, using a stepwise backwards elimination, were built to assess associations between SCD, demographics, and all risk/protective factors. RESULTS: A total of 24.2% of participants reported memory complaints. In the final prediction models, RNT was the only psychological variable associated with lower self-perceived cognitive function and with a higher likelihood of memory complaints. CONCLUSIONS: This study empirically corroborates the theoretical relationship between SCD and RNT. Longitudinal studies are needed to establish whether RNT is a prodromal symptom or an independent risk factor, and whether RNT can be a promising construct for future research on SCD and dementia risk.

Repetitive negative thinking is associated with amyloid, tau, and cognitive decline.

INTRODUCTION: The Cognitive Debt hypothesis proposes that repetitive negative thinking (RNT), a modifiable process common to many psychological risk factors for Alzheimer's disease (AD) may itself increase risk. We sought to empirically examine relationships between RNT and markers of AD, compared with anxiety and depression symptoms. METHODS: Two hundred and ninety-two older adults with longitudinal cognitive assessments, including 113 with amyloid-positron emission tomography (PET) and tau-PET scans, from the PREVENT-AD cohort and 68 adults with amyloid-PET scans from the IMAP+ cohort were included. All participants completed RNT, anxiety, and depression questionnaires. RESULTS: RNT was associated with decline in global cognition (P = .02); immediate (P = .03) and delayed memory (P = .04); and global amyloid (PREVENT-AD: P = .01; IMAP+: P = .03) and entorhinal tau (P = .02) deposition. Relationships remained after adjusting for potential confounders. DISCUSSION: RNT was associated with decline in cognitive domains affected early in AD and with neuroimaging AD biomarkers. Future research could investigate whether modifying RNT reduces AD risk.

Non-Pharmacologic Interventions for Older Adults with Subjective Cognitive Decline: Systematic Review, Meta-Analysis, and Preliminary Recommendations.

In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

The criteria used to rule out mild cognitive impairment impact dementia incidence rates in subjective cognitive decline.

BACKGROUND: The research criteria for subjective cognitive decline (SCD) exclude mild cognitive impairment (MCI), but do not stipulate the use of specific MCI criteria. This study compared different approaches to defining (i.e., excluding) MCI during the ascertainment of SCD, focusing on the impact on dementia incidence rates in SCD. METHODS: This cohort study utilized routine healthcare data collected in the Essex Memory Clinic from 1999 to 2023. Two different operationalizations of the SCD criteria were used to categorize the cohort into two SCD patient samples. One sample was based on local clinical practice - MCI was excluded according to the Winblad criteria (this sample was termed SCDWinblad). The other sample was created via the retrospective application of the Jak/Bondi criteria for the exclusion of MCI (termed SCDJak/Bondi). Only patients aged ≥ 55 years at baseline with ≥ 12 months follow-up were considered for inclusion. The initial clinical/demographic characteristics of the samples were compared. Rates of incident dementia were calculated for each sample, and unadjusted and Mantel-Haenszel-adjusted incidence rate ratios were calculated to compare dementia incidence between the SCD samples. RESULTS: The Essex Memory Clinic database included 2,233 patients in total. The SCD and study eligibility criteria were used to select SCDWinblad (n = 86) and SCDJak/Bondi (n = 185) samples from the database. Median follow-up (3 years) did not differ between the two samples. The SCDJak/Bondi sample was significantly older than the SCDWinblad at first assessment (median age: 74 versus 70 years) and had poorer scores on tests of global cognition, immediate and delayed verbal recall, and category fluency. Following adjustment for age, the dementia incidence rate ratio [95% confidence interval] was 3.7 [1.5 to 9.3], indicating a significantly greater rate of progression to dementia in SCDJak/Bondi. CONCLUSIONS: This study highlights that the approach used to ascertain SCD has important implications for both SCD phenotypes and prognosis. This underscores the importance of how MCI is operationalized within SCD studies. More broadly, the findings add to a growing body of work indicating that objective cognition should not be overlooked in SCD, and offer a potential explanation for the heterogeneity across the SCD prognostic literature.

Associations Between Repetitive Negative Thinking and Objective and Subjective Sleep Health in Cognitively Healthy Older Adults.

Objective: Poor sleep and high levels of repetitive negative thinking (RNT), including future-directed (ie, worry) and past-directed (ie, brooding) negative thoughts, have been associated with markers of dementia risk. The relationship between RNT and sleep health in older adults is unknown. This study aimed to investigate this association and its specificities including multiple dimensions of objective and subjective sleep. Methods: This study used a cross sectional quantitative design with baseline data from 127 cognitively healthy older adults (mean age 69.4 ± 3.8 years; 63% female) who took part in the Age-Well clinical trial, France. RNT (ie, worry and brooding) levels were measured using the Penn State Worry Questionnaire and the Rumination Response Scale (brooding subscale). Polysomnography was used to assess sleep objectively, and the Pittsburgh Sleep Quality Index and the St. Mary's Hospital Sleep Questionnaire were used to measure sleep subjectively. In primary analyses the associations between RNT and sleep (ie, objective sleep duration, fragmentation and efficiency and subjective sleep disturbance) were assessed via adjusted regressions. Results: Higher levels of RNT were associated with poorer objective sleep efficiency (worry: ß=-0.32, p<0.001; brooding: ß=-0.26, p=0.002), but not objective sleep duration, fragmentation, or subjective sleep disturbance. Additional analyses, however, revealed differences in levels of worry between those with short, compared with typical and long objective sleep durations (p < 0.05). Conclusion: In cognitively healthy older adults, RNT was associated with sleep characteristics that have been implicated in increased dementia risk. It will take additional research to ascertain the causal link between RNT and sleep characteristics and how they ultimately relate to the risk of developing dementia.

Impact of mindfulness-based and health self-management interventions on mindfulness, self-compassion, and physical activity in older adults with subjective cognitive decline: A secondary analysis of the SCD-Well randomized controlled trial.

INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a higher risk of dementia. Reducing this risk through behavioral interventions, which can increase emotional well-being (mindfulness and compassion) and physical activity, is crucial in SCD. METHODS: SCD-Well is a multicenter, observer-blind, randomized, controlled, superiority trial. Three hundred forty-seven participants (mean [standard deviation] age: 72.7 [6.9] years; 64.6% women) were recruited from memory clinics in four European sites to assess the impact of an 8-week caring mindfulness-based approach for seniors (CMBAS) and a health self-management program (HSMP) on mindfulness, self-compassion, and physical activity. RESULTS: CMBAS showed a significant within-group increase in self-compassion from baseline to post-intervention and both a within- and between-group increase to follow-up visit (24 weeks). HSMP showed a significant within- and between-group increase in physical activity from baseline to post-intervention and to follow-up visit. DISCUSSION: Non-pharmacological interventions can differentially promote modifiable factors linked to healthy aging in older adults with SCD.

The Effect of Meditation-Based Interventions on Patients with Fatigue Symptoms: A Systematic Review and Meta-Analysis.

Persistent fatigue constitutes a prevalent and debilitating symptom in several diseases. The symptom is not effectively alleviated by pharmaceutical treatments, and meditation has been proposed as a non-pharmacological intervention. Indeed, meditation has been shown to reduce inflammatory/immune problems, pain, stress, anxiety and depression which are associated with pathological fatigue. This review synthesizes data from randomized control trials (RCTs) that explored the effect of meditation-based interventions (MeBIs) on fatigue in pathological conditions. Eight databases were searched from inception to April 2020. Thirty-four RCTs met eligibility criteria and covered six conditions (68% cancer), 32 of which were included in the meta-analysis. The main analysis showed an effect in favor of MeBIs compared to control groups (g = 0.62). Separate moderator analyses assessing control group, pathological condition, and MeBI type, highlighted a significantly moderating role of the control group. Indeed, compared to actively controlled studies, studies using a passive control group were associated with a statistically significantly more beneficial impact of the MeBIs (g = 0.83). These results indicate that MeBIs alleviate pathological fatigue and it seems that the studies with a passive control group showed a greater effect of MeBI on the reduction of fatigue compared to studies using active control groups. However, the specific effect of meditation type and pathological condition should be analyzed with more studies, and there remains a need to assess meditation effects on different types of fatigue (i.e., physical and mental) and in additional conditions (e.g., post-COVID-19).

Association between anxiety symptoms and Alzheimer's disease biomarkers in cognitively healthy adults: A systematic review and meta-analysis.

OBJECTIVE: Anxiety has been identified as both a risk factor and prodromal symptom for Alzheimer's disease (AD) and related dementias, however, the underlying neurobiological correlates remain unknown. The aim of this systematic review and meta-analysis was to examine the association between anxiety symptoms and two defining markers of AD neuropathology: amyloid-beta (Aß) and tau. METHODS: Systematic literature searches were conducted across 5 databases. Studies investigating the relationship between anxiety and AD neuropathology (i.e., Aß and/or tau) in cognitively healthy adults were eligible. Where possible, effect sizes were combined across studies, for Aß and tau separately, using random-effects meta-analyses. Sensitivity analyses were performed to assess whether results differed according to anxiety type (i.e., state and trait) and biomarker assessment modality (i.e., positron emission tomography and cerebrospinal fluid). RESULTS: Twenty-seven studies reporting data from 14 unique cohorts met eligibility criteria. Random-effects meta-analyses revealed no associations between self-reported anxiety symptoms and either Aß (13 studies, Fisher's z = 0.02, 95% confidence interval [CI] -0.01-0.05, p = 0.194) or tau (4 studies, Fisher's z = 0.04, 95% CI -0.02-0.09, p = 0.235). Results remained unchanged across sensitivity analyses. CONCLUSIONS: In cognitively healthy adults, meta-analytic syntheses revealed no associations between anxiety symptoms and either Aß or tau. There is a critical need, however, for larger studies with follow-up periods to examine the effect of anxiety symptom onset, severity, and chronicity on AD neuropathology. Additionally, further research investigating other potential neurobiological correlates is crucial to advance scientific understanding of the relationship between anxiety and dementia.

Trait Mindfulness Is Associated With Less Amyloid, Tau, and Cognitive Decline in Individuals at Risk for Alzheimer's Disease.

Background: Mindfulness, defined as nonjudgmental awareness of the present moment, has been associated with an array of mental and physical health benefits. Mindfulness may also represent a protective factor for Alzheimer's disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in older adults at risk for AD dementia. Methods: Measures of trait mindfulness, longitudinal cognitive assessments, and amyloid-ß (Aß) and tau positron emission tomography scans were collected in 261 nondemented older adults with a family history of AD dementia from the PREVENT-AD (Pre-symptomatic Evaluation of Experimental or Novel Treatments for AD) observational cohort study. Multivariate partial least squares analyses were used to examine relationships between combinations of different facets of trait mindfulness and 1) cognitive decline, 2) Aß, and 3) tau. Results: Higher levels of mindful nonjudgment, describing, and nonreactivity were associated with less cognitive decline in attention, global cognition, and immediate and delayed memory. Higher levels of mindful nonjudgment and nonreactivity were related to less Aß positron emission tomography signal in bilateral medial and lateral temporoparietal and frontal regions. Higher levels of mindful acting with awareness, describing, nonjudgment, and nonreactivity were associated with less tau positron emission tomography signal in bilateral medial and lateral temporal regions. Conclusions: Trait mindfulness was associated with less cognitive decline and less Aß and tau in the brain in older adults at risk for AD dementia. Longitudinal studies examining the temporal relationship between trait mindfulness and AD markers, along with mindfulness intervention studies, will be important for further clarifying the potential protective benefits of mindfulness on AD risk.