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Competing Interests: We declare no competing interests.

Background: Cognitive frailty, defined as having both physical frailty and cognitive impairment that does not satisfy the criteria for Major Neurocognitive Disorder, represents an elevated risk for morbidity. Hence, it is crucial to mitigate such risks. Physical activity interventions have been found effective in protecting against physical frailty and cognitive deterioration. This pilot RCT examines if smartwatches and mobile phone applications can help to increase physical activity, thereby improving physical and cognitive outcomes., Methods: Older individuals (n = 60) aged 60 to 85 years old will have their physical activity tracked using a smartwatch. The subjects will be randomized into two arms: one group will receive daily notification prompts if they did not reach the recommended levels of PA; the control group will not receive prompts. Outcome variables of physical activity level, neurocognitive scores, and physical frailty scores will be measured at baseline, T1 (3 months), and T2 (6 months). Sleep quality, levels of motivation, anxiety, and depression will be controlled for in our analyses. We hypothesize that the intervention group will have higher levels of physical activity resulting in improved cognitive and physical outcomes at follow-up. This study was approved by the National University of Singapore's Institutional Review Board on 17 August 2020 (NUS-IRB Ref. No.: H-20-038)., Discussion: Wearable sensors technology could prove useful by facilitating self-management in physical activity interventions. The findings of this study can justify the use of technology in physical activity as a preventive measure against cognitive frailty in older adults. This intervention also complements the rapidly rising use of technology, such as smartphones and wearable health devices, in our lives today., Registration Details: This study has been retrospectively registered on clinicaltrials.gov on 5th January 2021 (NCT Identifier: NCT04692974), after the first participant was recruited., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kiah Hui Siew et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This systematic review assessed the quality of clinical practice guidelines (CPGs) on the treatment of insomnia disorder and their reporting of recommendations, while summarizing the evidence and providing guidance on an algorithmic approach to appropriate pharmacological treatment., Methods: The PubMed and EMBASE databases, guideline repositories, and specialist association websites were searched. The quality of the CPGs was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, complemented by the AGREE-REX (Appraisal of Guidelines REsearch and Evaluation-Recommendations EXcellence). A multidisciplinary team identified the key clinical questions that a clinician would consider when taking an algorithmic approach to the use of medication for patients with insomnia disorder. By using a meta-synthesis approach, recommendations from the CPGs were characterized and summarized via a recommendation matrix., Results: A total of 10 records that met the inclusion criteria were included and appraised. Four CPGs were rated as high and 3 CPGs were rated as moderate in overall quality. Most of the CPGs recommended pharmacotherapy only if cognitive behavioral therapy for insomnia or other nonpharmacological interventions were unavailable, unsuccessful, or declined by patients. Recommendations on types of medicines and dose and duration of treatment varied and were nonspecific. Few of the CPGs provided recommendations on pharmacotherapy in special populations., Conclusions: Indications for starting medications are the only common thread in all of the reviewed CPGs. The CPGs diverged in the choice of first-line pharmacotherapy, and most of the CPGs did not provide recommendations on all subsequent clinical considerations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Motor and gait disturbances are evident in early Alzheimer and non-Alzheimer dementias and may predict the likelihood of mild cognitive impairment (MCI) or progression to dementia., Objective: We investigated the Timed-Up-and-Go (TUG) measure of functional mobility in predicting cognitive decline and incident MCI or early dementia (MCI-dementia)., Design: Prospective cohort study with 4.5 years follow-up., Setting: Population based., Participants: 2,544 community-dwelling older adults aged 55+ years., Methods: Participants with baseline data on TUG, fast gait speed (GS), knee extension strength (KES) and performance-oriented mobility assessment (POMA) gait and balance were followed up for cognitive decline (Mini-Mental State Exam; MMSE drop of ≥2, among 1,336 dementia-free participants) and incident MCI-dementia (among 1,208 cognitively normal participants). Odds ratio (OR) and 95% confidence intervals (95% CI) were adjusted for age, sex, education, smoking, physical, social and productive activity, multi-morbidity, metabolic syndrome and MMSE., Results: Per standard deviation increase in TUG, POMA, GS and KES were significantly associated with incident MCI-dementia: TUG (OR = 2.84, 95% CI = 2.02-3.99), GS (OR = 2.17, 95% CI = 1.62-2.91), POMA (OR = 1.88, 95% CI = 1.22-2.92) and KES (OR = 1.52, 95% CI = 1.15-2.02). Adjusted OR remained significant only for TUG (OR = 1.52, 95% CI = 1.01-2.31) and GS (OR = 1.53, 95% CI = 1.08-2.16). Areas under the curve (AUC) for TUG (AUC = 0.729, 95% CI = 0.671-0.787) were significantly greater than GS (AUC = 0.683, 95% CI = 0.619-0.746), KES (AUC = 0.624, 95% CI = 0.558-0.689) and POMA (AUC = 0.561, 95% CI = 0.485-0.637). Similar associations with cognitive decline were significant though less pronounced, and adjusted ORs remained significant for TUG, GS and POMA., Conclusion: Functional mobility decline precedes incident MCI and early dementia. The TUG appears to be especially accurate in predicting the future risks of adverse cognitive outcomes., Trial Registration: ClinicalTrials.gov NCT03405675. Registered 23 January 2018 (retrospectively registered)., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

There is a lack of evidence supporting an association between folate and vitamin B12 exposure with cognitive outcomes. We examined serum folate and vitamin B12 and plasma homocysteine in 690 cognitively-normal adults (aged ≥ 55) from the Singapore Longitudinal Aging Study (SLAS-2) followed-up over 4.5 years on incident neurocognitive disorder (NCD): mild cognitive impairment (MCI) and dementia. At follow-up, 5.7% (39) of participants developed NCD (34 MCI and 5 dementia). Comparing with those who remained cognitively-normal, participants progressed to NCD had significantly lower mean baseline vitamin B12 (420 [SD ± 221] vs. 510 [SD ± 290] pmol/L, p = 0.026), higher homocysteine (14.6 [SD ± 4.2] vs. 12.9 [SD ± 4.3], p = 0.018) and lower one-carbon index (Z-scores: -0.444 [SD ± 0.819] vs. -0.001 [SD ± 0.990], p = 0.006). Adjusted for confounders, significant associations with incident NCD were found for lower vitamin B12 (per-SD OR = 2.10, 95%CI = 1.26-3.52), higher homocysteine (per-SD OR = 1.96, 95%CI = 1.18-3.24) and lower one-carbon index (per-SD OR = 1.67, 95%CI = 1.06-2.64). Folate was not significantly associated with progression to NCD. Notably, low B12 in the presence of high folate was significantly associated with incident NCD (adjusted OR = 3.81, 95%CI = 1.04-13.9). Low B12, high homocysteine, low B12 in the presence of high folate, and a one-carbon index of hypo-methylation were independently associated with progression to NCD among cognitively normal.

Digital biomarker technologies coupled with predictive models are increasingly applied for early detection of age-related potentially reversible conditions including mild cognitive impairment (MCI) and pre-frailty (PF). We aimed to determine the predictive accuracy of digital biomarker technologies to detect MCI and PF with systematic review and meta-analysis. A computer-assisted search on major academic research databases including IEEE-Xplore was conducted. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines were adopted for reporting in this study. Summary receiver operating characteristic curve based on random-effect bivariate model was used to evaluate overall sensitivity and specificity for detection of the respective age-related conditions. A total of 43 studies were selected for final systematic review and meta-analysis. 26 studies reported on detection of MCI with sensitivity and specificity of 0.48-1.00 and 0.55-1.00, respectively. On the other hand, there were 17 studies that reported on the detection of PF with reported sensitivity of 0.53-1.00 and specificity of 0.61-1.00. Meta-analysis further revealed pooled sensitivities of 0.84 (95% CI: 0.79-0.88) and 0.82 (95% CI: 0.74-0.88) for in-home detection of MCI and PF, respectively, while pooled specificities were 0.85 (95% CI: 0.80-0.89) and 0.82 (95% CI: 0.75-0.88), respectively. Besides MCI, and PF, in this work during systematic review, we also found one study which reported a sensitivity of 0.93 and a specificity of 0.57 for detection of cognitive frailty (CF). The meta-analytic result, for the first time, quantifies the predictive efficacy of digital biomarker technologies for detection of MCI and PF. Additionally, we found the number of studies for detection of CF to be notably lower, indicating possible research gaps to explore predictive models on digital biomarker technology for detection of CF.

Telomere shortening is theorized to accelerate biological aging, however, this has not been tested in the brain and cognitive contexts. We used machine learning age-prediction models to determine brain/cognitive age and quantified the degree of accelerated aging as the discrepancy between brain and/or cognitive and chronological ages (i.e., age gap). We hypothesized these age gaps are associated with telomere length (TL). Using healthy participants from the ADNI-3 cohort (N = 196, Age mean =70.7), we trained age-prediction models using 4 modalities of brain features and cognitive scores, as well as a 'stacked' model combining all brain modalities. Then, these 6 age-prediction models were applied to an independent sample diagnosed with mild cognitive impairment (N = 91, Age mean =71.3) to determine, for each subject, the model-specific predicted age and age gap. TL was most strongly associated with age gaps from the resting-state functional connectivity model after controlling for confounding variables. Overall, telomere shortening was significantly related to older brain but not cognitive age gaps. In particular, functional relative to structural brain-age gaps, were more strongly implicated in telomere shortening., (Copyright © 2022. Published by Elsevier Inc.)

Background: With an aging population, developing non-pharmacological interventions (NPIs) to delay dementia has become critical. Apart from cognitive decline, dementia is associated with multiple pathophysiology, including increased oxidative stress, dysregulated gene expressions, cytokine, neurotrophin, and stress markers, telomere shortening, and deteriorations in brain connectivity. Although mindfulness practices have been proposed to ameliorate these biological changes, no empirical studies were conducted. We thus aimed to investigate the effects of mindfulness awareness practice (MAP) to prevent cognitive decline and improve peripheral biomarkers in community-dwelling older adults diagnosed with mild cognitive impairment (MCI)., Methods/design: This was a single-blinded and parallel-group randomized controlled trial with two arms (intervention and active control arms), conducted over nine months. A total of 60 consenting community-dwelling older adults diagnosed with MCI were planned to be randomized in a 1:1 ratio to either the MAP or the Health Education Program (HEP). Interventions were performed weekly for the initial 12 weeks, and monthly for the subsequent six months. Outcome measures were assessed at baseline, 3-month, and 9-month post-intervention by blinded assessors. Primary outcomes were neurocognitive tests, comprehensive peripheral biomarkers, and brain imaging scans. Secondary outcomes included basic health screening measures, affective symptoms, and measures of physical functions. Linear-mixed models were used to examine the effects of MAP on these outcome measures., Significance: This is the first randomized controlled trial to systematically investigate the effects of a mindfulness intervention in improving cognitive functions and various biomarkers in community-dwelling older adults diagnosed with MCI. Our findings have the potential to inform mindfulness intervention as a novel approach to delay dementia.

Geriatric depression and anxiety disorders often manifest as neuropsychiatric symptoms among those with mild cognitive impairment. Both tend to co-occur, and overlap in symptomology and etiology. Such commonalities are likely to be reflected in the brain as common neural correlates. Using connectome-based predictive modeling (CPM), we examined the functional and structural connectomes predicting depression and anxiety symptoms, and subsequently the overlap and cross-syndrome generalization of the connectomes associated with either disorder. Ninety-one older adults completed self-reported measures of depression and anxiety, and underwent diffusion tensor imaging and resting-state functional magnetic resonance imaging. Functional connectivity (FC) and structural connectivity (SC) matrices were derived from these scans and, in various combinations, entered into CPM models to predict either type of symptoms. Leave-one-out cross-validation was performed. Predictive accuracy was assessed via the correlation between predicted and observed scores (ρ predicted-observed ). While FC or SC features alone significantly predicted either type of symptoms, these symptoms were best predicted by models that consisted of both FC and SC features (depression: ρ predicted-observed  = 0.497; anxiety: ρ predicted-observed  = 0.455). The features common to depression and anxiety were identified and entered into another model which was similarly accurate in predicting either type of symptoms. Moreover, cross-syndrome generalization was observed- the depression-associated features significantly predicted anxiety symptoms (ρ predicted-observed  = 0.403) and vice-versa (ρ predicted-observed  = 0.378). These FC and SC features are complementary biomarkers of geriatric depression and anxiety symptoms. Both types of symptoms are largely underpinned by common patterns of altered FC and SC, alluding to the transdiagnostic neurobiological susceptibility in both disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Mild cognitive impairment (MCI) is characterized by subtle deficits that functional assessment via informant-report measures may not detect. Sensors can potentially detect deficits in everyday functioning in MCI. This study aims to establish feasibility and acceptability of using sensors in a smart home for performance-based assessments of two instrumental activities of daily living (IADLs)., Methods: Thirty-five older adults (>65 years) performed two IADL tasks in a smart home laboratory equipped with sensors and a web camera. Participants' cognitive states were determined using published criteria including measures of global cognition and comprehensive neuropsychological test batteries. Selected subtasks of the IADL assessment were autonomously captured by the sensors. Total time taken for each task and subtask were computed. A point scoring system captured accuracy and number of attempts. Acceptability of the smart home setup was assessed., Results: Participants with MCI (n = 21) took longer to complete both tasks than participants with healthy cognition (HC; n = 14), with significant time differences observed only in "Cost calculation." Completion time for IADL tasks and scores correlated in the expected direction with global cognition. Over 95% of the participants found the smart home assessment acceptable and a positive experience., Discussion: We demonstrated the feasibility and acceptability of the use of unobtrusive commercially available sensors in a smart home for facilitating parts of the objective assessment of IADL in older adults. Future studies need to identify more IADLs that are suitable for semi-automated or automated assessments through the use of simple, low-cost sensors., Competing Interests: None declared., (© 2021 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Mindfulness-based interventions can enhance cognitive abilities among older adults, thereby effectively delaying cognitive decline. These cognitive enhancements are theorized to accompany neuroplastic changes in the brain. However, this mindfulness-associated neuroplasticity has yet to be documented adequately. A randomized controlled trial was carried out among participants with mild cognitive impairment (MCI) to examine the effects of a mindfulness-based intervention on various cognitive outcomes and cortical thickness (CT) in the context of age-related cognitive impairment. Participants were assigned to a mindfulness awareness program (MAP)(n = 27) and an active control condition - health education program (n = 27). In both, they attended weekly sessions for three months and subsequently, monthly sessions for six months. Cognitive assessments and structural scans were carried out across three time-points. Whole brain analyses on CT were carried out and were supplemented with region of interest-based analyses. ROI values and cognitive outcomes were analyzed with mixed MANOVAs and followed up with univariate ANOVAs. Nine-month MAP-associated gains in working memory span and divided attention, along with an increased CT in the right frontal pole and decreased CT in the left anterior cingulate were observed. Three-month MAP-associated CT increase was observed in the left inferior temporal gyrus but did not sustain thereafter. MAP led to significant cognitive gains and various CT changes. Most of these neurobehavioral changes, may require sustained effort across nine months, albeit at a reduced intensity. MAP can remediate certain cognitive impairments and engender neuroplastic effects even among those with MCI., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Previous research on art therapy (AT) in cognitive aging has been lacking. AT can potentially engender significant cognitive gains, due to its rigorous cognitive involvement, making it useful to tackle age-related cognitive decline. Along with these cognitive gains, associated neuroplastic changes are hypothesized to arise from AT as well. The current intervention examined the effects of an AT intervention on cognitive outcomes and cortical thickness (CT) among participants with mild cognitive impairment., Method: Participants were assigned to AT (n = 22) and an active control group (n = 27). In both, weekly 45-min sessions were carried out across 3 months. Cognitive assessments and structural magnetic resonance imaging scans were carried out at baseline and 3-month follow-up. Whole brain analyses on CT were carried out. Cognitive outcomes were analyzed using hierarchical linear models., Results: Significant gains in immediate memory and working memory span were observed in the AT group, relative to the control group. Significantly increased CT in the AT group, relative to controls, was observed in a right middle frontal gyrus (MFG) cluster. Furthermore, CT changes in this cluster were significantly and positively correlated with changes in immediate memory., Conclusion: These findings highlighted the role of MFG neuroplasticity in enhancing certain cognitive functions in AT. AT is a neuroplastic intervention capable of engendering significant cognitive gains and associated cortical changes in the context of age-related cognitive decline, even when executed as a low-intensity intervention across 3 months. Given the preliminary nature of these findings, future larger sampled studies are needed.

Neuropsychological assessments are essential in diagnosing age-related neurocognitive disorders. However, they are lengthy in duration and can be unreliable at times. To this end, we explored a modified connectome-based predictive modeling approach to estimating individualized scores from multiple cognitive domains using structural connectivity (SC) and functional connectivity (FC) features. Multi-shell HARDI and resting-state functional magnetic resonance imaging scans, and scores from 10 cognitive measures were acquired from 91 older adults with mild cognitive impairment. SC and FC matrices were derived from these scans and, in various combinations, entered into models along with demographic covariates to predict cognitive scores. Leave-one-out cross-validation was performed. Predictive accuracy was assessed via the correlation between predicted and observed scores (r predicted-observed ). Across all cognitive measures, significant r predicted-observed (0.402 to 0.654) were observed from the best-predicting models. Six of these models consisted of multimodal features. For three cognitive measures, their best-predicting models' r predicted-observed were similar to that of a model that included only demographic covariates- suggesting that SC and/or FC features did not contribute significantly on top of demographics. Cross-prediction models revealed that the best-predicting models were similarly accurate in predicting scores of related cognitive measures- suggesting their limited specificity in predicting cognitive scores. Generally, multimodal connectomes together with demographics, can be exploited as sensitive markers, though with limited specificity, to predict cognitive performance across a spectrum in multiple cognitive domains. In certain situations, it may not be worthwhile to acquire neuroimaging data, considering that demographics alone can be similarly accurate in predicting cognitive scores., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Previous findings on the relationship between telomere length and cognition have inconclusive, despite the relatively consistent telomere-shortening associated atrophy in the subcortical regions. Perhaps, there could be other more important telomere-associated factors in the brain, such as functional connectivity (FC) and structural connectivity (SC) that modulate cognition. The current study examined the relationship between telomere length, connectivity, and cognition. Telomere length measurements, neurocognitive scores, diffusion tensor and resting-state functional magnetic resonance imaging scans were collected from 82 older adults with mild cognitive impairment. SC and FC matrices were derived from these scans and, in various combinations, entered into connectome-based predictive models to predict telomere length. The telomere-associated features were then used to predict memory and executive functions. Leave-one-out cross-validation was performed. Predictive accuracy was assessed via the correlation between predicted and observed scores (r predicted-observed ). Correlation analyses were carried out between cognition and telomere length. Telomere length was significantly and negatively correlated with executive functions (EF), after controlling for demographical confounds. Telomere length was best predicted by negative SC and positive FC features (r predicted-observed  = .57; p < .001). The telomere-associated negative SC features significantly predicted EF scores (r predicted-observed  = -.26; p = .015). Telomere-shortening was associated with better EF and alterations in both FC and SC. This enhanced EF can be partly attributed to the telomere-associated changes in SC. Given that telomere is known to be a nonspecific marker of health, our findings illustrated a potential clinical use of telomere length to predict individualized health-related information from FC and SC features., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Dementia is a global epidemic and incurs substantial burden on the affected families and the health care system. A window of opportunity for intervention is the predementia stage known as mild cognitive impairment (MCI). Individuals often present to services late in the course of their disease and more needs to be done for early detection; sensor technology is a potential method for detection., Objective: The aim of this cross-sectional study was to establish the feasibility and acceptability of utilizing sensors in the homes of senior citizens to detect changes in behaviors unobtrusively., Methods: We recruited 59 community-dwelling seniors (aged >65 years who live alone) with and without MCI and observed them over the course of 2 months. The frequency of forgetfulness was monitored by tagging personal items and tracking missed doses of medication. Activities such as step count, time spent away from home, television use, sleep duration, and quality were tracked with passive infrared motion sensors, smart plugs, bed sensors, and a wearable activity band. Measures of cognition, depression, sleep, and social connectedness were also administered., Results: Of the 49 participants who completed the study, 28 had MCI and 21 had healthy cognition (HC). Frequencies of various sensor-derived behavior metrics were computed and compared between MCI and HC groups. MCI participants were less active than their HC counterparts and had more sleep interruptions per night. MCI participants had forgotten their medications more times per month compared with HC participants. The sensor system was acceptable to over 80% (40/49) of study participants, with many requesting for permanent installation of the system., Conclusions: We demonstrated that it was both feasible and acceptable to set up these sensors in the community and unobtrusively collect data. Further studies evaluating such digital biomarkers in the homes in the community are needed to improve the ecological validity of sensor technology. We need to refine the system to yield more clinically impactful information., (©Iris Rawtaer, Rathi Mahendran, Ee Heok Kua, Hwee Pink Tan, Hwee Xian Tan, Tih-Shih Lee, Tze Pin Ng. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.05.2020.)

Introduction: Ageing is associated with a multitude of healthcare issues including dementia, depression, frailty, morbidity associated with chronic disease and high healthcare utilisation. With Singapore's population projected to age significantly over the next two decades, it has become increasingly important to understand the disease burden and etiological process among older adults. The Community Health and Intergenerational study aims to holistically examine ageing in place by investigating the resilience and vulnerability factors of the ageing process in the biological, psychological and social domains within the environment., Methods and Analysis: Using a cohort multiple randomised controlled trial design, comprehensive health profiles of community-dwelling older adults will be collected. The objective is to recruit 1000 participants (aged 60-99 years) living in the western region of Singapore within a period of 3 years (2018-2020). Assessments include basic sociodemographic, physical health and function (cardiac, oral and blood profiles and visual function), cognitive functioning, daily functioning, physical fitness, emotional state, free-flowing speech, sleep quality, social connectedness, caregiver burden, intergenerational communication, quality of life, life satisfaction, attitudes to ageing and gratitude and compassion. Results from the cohort will enable future studies to identify at-risk groups and develop interventions to improve the physical and mental health and quality of life of older adults., Ethics and Dissemination: Approval of the cohort study by the National University of Singapore Institutional Review Board (NUS-IRB Reference code: H-17-047) was obtained on 12 October 2017. Written consent will be obtained from all participants. Findings from the cohort study will be disseminated by publication of peer-reviewed manuscripts, presentations at scientific meetings and conferences with local stakeholders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data., Methods: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data., Results: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age., Conclusion: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals., Clinical Trials Registration: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454., (© 2019 American Academy of Neurology.)

This study aimed to determine the efficacy of mindfulness practice on emotional state and cognitive function of community-living elderly with mild cognitive impairment. A randomized controlled trial was conducted with the experimental group undergoing a Mindfulness Awareness Program (MAP) and an active control group undergoing a Health Education Program (HEP) over a nine month period. Sessions were conducted weekly for the first three months and monthly for the remaining six months. Self-reported questionnaires in English and Chinese were administered through face-to-face interviews to collect data at baseline, three months and nine months. Descriptive statistics and analysis of covariance (ANCOVA) were used to analyse data. Fifty-five elderly participants aged sixty and above, were randomized to MAP (N = 28) and HEP (N = 27) programs. Participants in both intervention arms experienced decreases in depressive and anxiety symptoms over the nine-month period. A significant improvement occurred in the HEP group in depression scores at three months and anxiety scores at both three and nine months. There were no statistically significant changes on cognitive function in both groups over the nine-month period. Both the MAP and HEP can benefit the emotional states of community-living elderly with mild cognitive impairment. Our study supports the usefulness of group-based HEP as a low cost intervention for promoting active aging and psychological health in a community setting., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: We investigated white matter differences associated with distinct neurocognitive profiles derived from a large cohort of marginally housed persons with comorbid physical and mental illnesses. Our prior work identified three profile cluster groups: a high functioning group (Cluster 1), a low functioning group with relative strength in decision-making (Cluster 3), and an intermediary group with a relative decision-making weakness (Cluster 2). This study extends previous findings of cortical gray matter differences between these groups with evidence for putative neurodevelopmental abnormalities in the low cognitive functioning group (i.e., Cluster 3). We hypothesized that altered white matter diffusion would be associated with the lowest functioning neurocognitive profile and would be associated with previously observed gray matter differences., Method: Participants from a socially impoverished neighborhood in Vancouver, Canada underwent neurocognitive evaluation and neuroimaging. We performed Tract-Based Spatial Statistics using diffusion tensor imaging data from 184 participants to examine whole-brain differences in white matter microstructure between cluster analytically derived neurocognitive profiles, as well as unitary neurocognitive measures. Correlations between frontal gray and white matter were also examined., Results: Cluster 3 showed increased diffusion in predominately bilateral frontal and interhemisphere tracts (vs. Clusters 1 and 2), with relatively greater diffusion in the left hemisphere (vs. Cluster 1). Differences in radial diffusivity were more prominent compared with axial diffusivity. A weak association between regional frontal fractional anisotropy and previously defined abnormalities in gyrification was observed., Conclusions: In a socially marginalized sample, we established several patterns in the covariation of white matter diffusion and neurocognitive functioning. These patterns elucidate the neurobiological substrates and vulnerabilities that are apt to underlie functional impairments inherent to this complex and heterogeneous population., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: Mild cognitive impairment (MCI) is a phase in cognitive decline when it is still possible to intervene to reverse the decline. Cognitive stimulation delivered through psychosocial interventions provides both psychological intervention and social stimulation to improve cognition. A pilot open-label parallel-arms randomized controlled trial was undertaken to examine the effects of art therapy (AT) and music reminiscence activity (MRA) compared to the control, on the primary outcome of neurocognitive domain assessments in elderly people with MCI., Methods: Community-living elderly people with MCI (Petersen's criteria), assessed for study eligibility, were randomized using a web-based system with equal allocation to two intervention arms: AT (guided viewing of art pieces and production of visual arts) and MRA (listening, and recalling memories related to music) and a control arm (standard care without any intervention). Interventions were led by trained therapists weekly for 3 months, then fortnightly for 6 months. Neurocognitive domains (mean of memory, attention, and visuo-spatial abilities standardized scores), psychological wellbeing (subsyndromal depression and anxiety) and telomere length as a biological marker of cellular ageing, were assessed by intervention-blinded assessors at baseline, 3 months and 9 months., Results: In total, 250 people were screened and 68 were randomized and included in the analysis. In the AT arm, neurocognitive domains improved compared to the control arm at 3 months (mean difference (d) = 0.40; 90% CI 0.126, 0.679) and were sustained at 9 months (d = 0.31; 90% CI 0.068, 0.548). There was some improvement in depression and anxiety at 3 and 9 months and in telomere length at 9 months, but this was not significant. Similar improvements were observed in the MRA arm over the control arm, but they were not significant. There were no intervention-related adverse effects., Conclusions: Art therapy delivered by trained staff as "art as therapy" and "art psychotherapy" may have been the significant contributor to cognitive improvements. The findings support cognitive stimulation for elderly people with cognitive decline and signal the need for larger studies and further investigation of carefully designed psycho-social interventions for this group., Trial Registration: Clinical Trials.gov, NCT02854085 . Registered on 7 July 2016.

The effect of horticultural therapy (HT) on immune and endocrine biomarkers remains largely unknown. We designed a waitlist-control randomized controlled trial to investigate the effectiveness of HT in improving mental well-being and modulating biomarker levels. A total of 59 older adults was recruited, with 29 randomly assigned to the HT intervention and 30 to the waitlist control group. The participants attended weekly intervention sessions for the first 3 months and monthly sessions for the subsequent 3 months. Biological and psychosocial data were collected. Biomarkers included IL-1β, IL-6, sgp-130, CXCL12/SDF-1α, CCL-5/RANTES, BDNF (brain-derived neurotrophic factor), hs-CRP, cortisol and DHEA (dehydroepiandrosterone). Psychosocial measures examined cognitive functions, depression, anxiety, psychological well-being, social connectedness and satisfaction with life. A significant reduction in plasma IL-6 level ( p = 0.02) was observed in the HT intervention group. For the waitlist control group, significant reductions in plasma CXCL12 (SDF-1α) ( p = 0.003), CXCL5 (RANTES) ( p = 0.05) and BDNF ( p = 0.003) were observed. A significant improvement in social connectedness was also observed in the HT group ( p = 0.01)., Conclusion: HT, in reducing plasma IL-6, may prevent inflammatory disorders and through maintaining plasma CXCL12 (SDF-1α), may maintain hematopoietic support to the brain. HT may be applied in communal gardening to enhance the well-being of older adults.

Objectives: Poor sleep quality is highly prevalent among older adults and is associated with poor quality of life, cognitive and physical decline, depression, and increased mortality. Medication options commonly used are not ideal, and alternative treatment strategies are needed. We evaluate a community-based psychosocial intervention program and its effect on sleep quality in older adults., Method: Elderly participants aged 60 and above were included. Those with Geriatric Depression Scale and Geriatric Anxiety Inventory scores above 5 and 10, respectively, were excluded. The community program included tai chi exercise, art therapy, mindfulness awareness practice, and music reminiscence therapy. Pittsburgh Sleep Quality Index, Geriatric Depression Scale, and Geriatric Anxiety Inventory were administered at baseline and at 1 year., Results: A hundred and eighty-nine subjects (44 men, 145 women; mean age = 69 years, SD = 5.7, range = 60-89) participated. The proportion of participants with good sleep quality had increased from 58.2% to 64.6%. Sleep disturbance was significantly reduced (baseline, 1.04; postintervention, 0.76; mean difference 0.28; P < .01); men experienced greater improvement (P < .001). Improvements were independent of changes in depressive and anxiety symptoms., Conclusion: Participation in this community program led to positive effects on sleep disturbances after a year. Psychosocial interventions have potential as a nondrug intervention approach for sleep problems, and further research is needed to understand its mediating mechanisms., (© 2017 John Wiley & Sons Australia, Ltd.)

It has been reported that relaxation techniques can improve physical health and cognitive function. A number of studies involving different types of relaxation practices showed changes in expression of genes. We investigated the gene expression pattern of a cohort of elderly subjects of Asian descent after weekly (for the first three months) and monthly (for the subsequent six months) intervention. Sixty consenting elderly subjects (aged 60-90 years) with mild cognitive impairment were assigned to either the Mindfulness Awareness Practice (MAP) or Health Education Program (HEP) group in a randomized controlled trial to assess the effectiveness of the programs in preventing further cognitive decline and evaluate the influence on neurological, cellular and biochemical factors. Blood samples were collected before the start of intervention and after nine months for gene expression profiling using Affymetrix Human Genome U133 Plus 2.0 arrays. The dataset is publicly available for further analyses.

We characterized traumatic brain injury (TBI) and studied its associations with mental and physical health in a community cohort of homeless and vulnerably housed individuals. Detailed mental and physical health structured interviews, neuropsychological testing, and multimodal magnetic resonance imaging (MRI) were performed on 283 participants. Two TBI participant groups were defined for primary analyses: those with a self-reported history of TBI and those with MRI confirmation of TBI. By self-report, 174 participants (61.5%) reported a previous serious head or face injury (symptomatic or asymptomatic), with 100 (35.3%) experiencing symptoms consistent with TBI (any post-injury loss of consciousness, confusion, or memory loss). Persons self-reporting TBI had poorer current mental and physical health, more ongoing neurological symptoms, and a higher rate of mood disorders, compared to those with no TBI. The presence of a mood disorder, a TBI history, and an interaction between these factors contributed to lower mental health. There was evidence of TBI in 20 participants (6.9%) on clinical MRI sequences. These participants had globally lower cortical gray matter volumes and lower white matter fractional anisotropy (FA) values. Neurocognitive test scores positively correlated with both FA and cortical gray matter volumes in participants with MRI evidence of trauma. Previous TBI is associated with poorer mental and physical health in homeless and vulnerably housed individuals and interacts with mood disorders to exacerbate poor mental health. Focal traumatic lesions evident on MRI are associated with diffusely lower gray matter volumes and white matter integrity, which predict cognitive functioning.

Background: Due to a rapidly ageing population in the world, it is increasingly pertinent to promote successful ageing strategies which are cost-effective, easily accessible, and more likely to be acceptable to the elderly. Past research associates exposure to natural environments and horticultural therapy (HT) with positive psychological, social and physical health benefits. This Randomized Controlled Trial (RCT) is designed to evaluate the efficacy of HT in promoting Asian elderly' mental health, cognitive functioning and physical health., Methods/design: 70 elderly participants aged 60 to 85 years old will be randomized to participate in either the active horticultural therapy group or be in the waitlist control. Sessions will be weekly for 12 weeks, and monthly for 3 months. Mental health will be assessed through self-reports of depressive and anxiety symptomatology, life satisfaction, social connectedness and psychological well-being, collaborated with immunological markers. Outcome measures of cognitive functioning and physical health include neuropsychological tests of cognitive function and basic health screening. Outcomes will be assessed at baseline, 3 months and 6 months post-intervention., Discussion: This RCT comprehensively investigates the efficacy of a non-invasive intervention, HT, in enhancing mental health, cognitive functioning and physical health. The results have tremendous potential for supporting future successful ageing programs and applicability to larger populations., Trial Registration: ClinicalTrials.gov NCT02495194 . Trial registration date: July 13, 2015. Retrospectively registered.

Background: Individuals with mild cognitive impairment (MCI) commonly experience a number of sleep quality related issues. However, it remains unclear if these issues are specific to MCI or are simply attributed to the elevated levels depression and anxiety symptoms frequently observed among those with MCI. The present study sought to examine group differences between participants with MCI and matched controls on self-reported measures of sleep quality while controlling for depression and anxiety levels., Methods: Participants with MCI (N = 48) and demographically matched controls (N = 48) were administered with self-reported measures of anxiety, depression and sleep quality. Sleep quality between both groups were first analyzed using a Multivariate Analysis of Variance, and then subsequently a Multivariate Analysis of Covariance incorporating depression and anxiety scores as covariates., Results: The MCI group had significantly higher levels of depression and anxiety than the controls. On the sleep-related measures, the MCI group had significantly worse outcomes in sleep duration, disturbances, latency, efficiency, quality and daytime dysfunction. After controlling for depression and anxiety levels, with the exception of daytime dysfunction, all other differences remain significant, and are also associated with moderate to large effect sizes., Conclusion: The results suggest that sleep quality issues are present in MCI and are largely independent of depression and anxiety.

Background: Attention has shifted to the use of non-pharmacological interventions to prevent cognitive decline as a preventive strategy, as well as for those at risk and those with mild cognitive impairment. Early introduction of psycho-social interventions can address cognitive decline and significantly impact quality of life and the wellbeing of elderly individuals. This pilot study explores the feasibility of using art therapy and music reminiscence activity to improve the cognition of community living elderly with mild cognitive impairment., Methods/design: This open-label, interventional study involves a parallel randomized controlled trial design with three arms (two intervention arms and a control group) over a nine-month period. Participants will be community-living elderly individuals aged 60-85 years, both genders, who meet predefined inclusion and exclusion criteria. In the initial three months, interventions will be provided weekly and for the remaining six months fortnightly. A sample size of 90 participants is targeted based on expected neuropsychological test performance, a primary outcome measure, and drop-out rates. The randomization procedure will be carried out via a web-based randomization system. Interventions will be provided by trained staff with a control group not receiving any intervention but continuing life as usual. Assessments will be done at baseline, three months, and nine months, and include neuroimaging to measure cerebral changes and neuropsychological tests to measure for changes in cognition. Secondary outcome measures will include mood changes in anxiety and depression and telomere lengths. Statistical analysis will be undertaken by statisticians; all efficacy analysis will be carried out on an intention-to-treat basis. Primary and secondary outcomes will be modeled using the linear mixed model for repeated measurements and further analysis may be undertaken to adjust for potential confounders., Discussion: This will be the first study to compare the effectiveness of art therapy and music reminiscence activity in a randomized controlled trial. We expect that the trial will provide useful evidence for developing psychosocial interventions for the elderly with mild cognitive impairment., Trial Registration: The study was registered on 7 July 2016 at Clinical Trials.gov, a service of the US National Institute of Health ( NCT02854085 ), retrospectively.

Despite the abundance of studies on asymmetries in manual laterality, a marker for atypical brain lateralization in depression and anxiety, findings in this area are mixed. Traditionally, research have looked at individual differences in depression and anxiety as a function of the direction of asymmetry. However, recent research has emphasized on studying the degree of asymmetry in addition to its direction. To these ends, the present study aims to unravel the associations between the degree and direction of manual lateralization, and depression/anxiety. Cognitively healthy elderlies (N = 326, 91 males, M age  = 68) were administered grip strength assessments on both hands and self-report measures of depression and anxiety. Partial correlation analyses controlling for age, education and sex revealed significant positive associations between degree of lateralization and anxiety in the overall sample and among right-dominant participants, as well as a significant positive relationship between degree of lateralization and depression among right-dominant participants. None of the correlations involving the direction of lateralization yielded significance, neither was there significant differences between left- and right-dominant participants on depression and anxiety scores. These findings suggest that the degree of manual lateralization, but not direction, is related to depression and anxiety at least among right-dominant individuals.

Background: Indicators of social isolation or support such as living alone, loneliness, being married, and life satisfaction are possible psychosocial risk and protective factors for dementia., Objective: We investigate the associations of these overlapping psychosocial factors with incident MCI-dementia (neurocognitive disorder) in a population cohort., Methods: Using data from 1601 participants of the Singapore Longitudinal Ageing Study (SLAS) who were free of MCI or dementia at baseline and followed up to 8 years, we estimated hazards ratio (HR) of association of living alone, loneliness, being married, and high life satisfaction with incident MCI-dementia., Results: In univariate analyses, individual HRs of association with incident MCI-dementia for living alone was 1.86 [1.18 - 2.95], (p = 0.008), loneliness was 1.26 [0.86 - 1.84], (p = 0.23), being married was 0.54 [0.39 - 0.75] (p < 0.0001), and being very satisfied with life was 0.59 [0.38-0.91]), (p = 0.017). Adjusted mutually for other psychosocial variables, and for age, sex, education, ethnicity, smoking, alcohol, dyslipidemia, hypertension, diabetes, central obesity, history of stroke or heart disease, APOE-ɛ4, depression, physical, social, and productive activities, only being married (0.68 [0.47-0.99], p = 0.044), and being very satisfied with life (0.61 [0.39 - 0.96], p = 0.034) remained significant variables associated with lower risks of developing MCI-dementia., Conclusion: Individuals who were married and those who were very satisfied with life are protected against the risk of developing MCI and dementia. Controlling for the adverse effects of being without spousal support and low life satisfaction, living alone or a feeling of loneliness were not associated with increased risk of MCI-dementia.

Objective: The co-occurrence of sleep problems, cognitive impairment, and depression among the elderly suggests that these three conditions are likely to be interrelated. Recent findings suggest that depressive symptoms moderate the relationship between sleep problems and cognitive impairment in elderly people but methodological problems have led to inconsistent conclusions. The present study aims to better understand the relationship between sleep quality, depressive symptoms, and cognitive function., Method: We administered the Repeatable Battery for the Assessment of Neuropsychological Status and self-report measures of sleep quality and depression to 380 elderly participants (Mage = 68 years, SD= 5.7). Bootstrapped moderation analyses were conducted to examine the role of depressive symptoms in the relationship between sleep and various aspects of cognitive function., Results: This moderation effect was significant in the domains of delayed memory (ΔR(2) = .01, F = 4.5, p = .04), language (ΔR(2) = .01, F = 4.6, p = .035), and general cognitive status (ΔR(2) = .01, F = 5.3, p = .02). However, unlike previous studies, higher sleep quality corresponded to better outcomes in delayed memory, language abilities, and general cognitive status in participants with low levels of depressive symptoms. No significant relationship between sleep quality and any cognitive function was observed among participants with high levels of depressive symptoms., Conclusions: Among individuals who reported low levels of depressive symptoms, sleep quality was positively related to cognitive performance in the domains of delayed recall, language, and general cognitive status. However, sleep quality was not significantly associated with cognitive abilities in these domains among participants with elevated levels of depressive symptoms; participants had relatively poor outcomes in these cognitive domains regardless of their sleep quality.

Background: Research looking at the association between sleep and psychiatric symptoms in elderly Asian populations is lacking. The present study examines the sleep correlates of depression and anxiety in a sample of cognitively healthy older adults., Methods: The Geriatric Depression Scale, Geriatric Anxiety Inventory, and the Pittsburgh Sleep Quality Index were administered to a community sample of elderly participants (n = 107; 81 women; Mage = 71.3 years, SD = 5.7) RESULTS: Geriatric Depression Scale and Geriatric Anxiety Inventory scores are both significantly correlated with sleep disturbance. Geriatric Depression Scale scores are uniquely associated with daytime dysfunction, and Geriatric Anxiety Inventory scores are uniquely associated with perceived sleep quality, sleep latency, and global Pittsburgh Sleep Quality Index scores., Conclusions: Depression and anxiety in a cohort of elderly Asian subjects are associated with a number of sleep-related issues; both are related to a somewhat different profile of sleep problems., (© 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.)

Background: Several risk scores have been developed for predicting cognitive impairment and dementia, but none have been validated in Asian samples. We aimed to produce a risk score that best predicts incident neurocognitive disorder (NCD) among Chinese elderly and to validate this score against the modified risk score derived from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study., Methods: Data from participants enrolled in the Singapore Longitudinal Ageing Study (SLAS) 1 were analyzed. A total of 957 participants >55 years of age with normal cognition at baseline were included. Incident cases of NCD were measured using the global Clinical Dementia Rating (CDR) and determined by a consensus panel., Results: The best prediction model from SLAS included age, gender, education, depression, heart disease, social and productive activities and Mini-Mental State Examination score. This model predicted the short-term risk of incident NCD in elderly participants moderately well, with a C statistic (area under the curve) of 0.72. Modified CAIDE models applied to our sample had a C statistic of 0.71., Conclusion: Our risk score performs as well as other available risk scores. It is the only risk score formulated for ethnic Chinese, rendering it valuable for clinical use in Asia; at-risk individuals can be identified for early intervention., (© 2016 S. Karger AG, Basel.)

Objectives: Subsyndromal depression (SSD) and subsyndromal anxiety (SSA) are common in the elderly and if left untreated, contributes to a lower quality of life, increased suicide risk, disability and inappropriate use of medical services. Innovative approaches are necessary to address this public health concern. We evaluate a community-based psychosocial intervention program and its effect on mental health outcomes in Singaporean older adults., Method: Elderly participants with SSD and SSA, as assessed on the Geriatric Depression Scale and Geriatric Anxiety Inventory, were included. Intervention groups include Tai Chi exercise, Art Therapy, Mindfulness Awareness Practice and Music Reminiscence Therapy. The program was divided into a single intervention phase and a combination intervention phase. Outcomes were measured with the Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS) at baseline, 4 weeks, 10 weeks, 24 weeks and 52 weeks. The program had ethics board approval., Results: A hundred and one subjects (25 males, 76 females; mean age = 71 years, SD = 5.95) participated. There were significant reductions in SDS and SAS scores in the single intervention phase (P < 0.05), and these reductions remained significant at week 52, after completion of the combination intervention phase, relative to baseline (P < 0.001)., Conclusion: Participating in these psychosocial interventions led to a positive improvement in SSD and SSA symptoms in these elderly subjects over a year. This simple, inexpensive and culturally acceptable approach should be adequately studied and replicated in other communities., (© 2015 Wiley Publishing Asia Pty Ltd.)