Serum Placental Growth Factor as a Marker of Cerebrovascular Disease Burden in Alzheimer's Disease.

BACKGROUND: Concomitant cerebrovascular diseases (CeVD) have been identified as an important determinant of Alzheimer's disease (AD) progression. Development of robust blood-based biomarkers will provide critical tools to evaluate prognosis and potential interventional strategies for AD with CeVD. OBJECTIVE: This study investigated circulating placental growth factor (PlGF), a potent pro-angiogenic factor related to endothelial dysfunction and vascular inflammation, in an Asian memory clinic cohort of non-demented individuals as well as AD, including its associations with neuroimaging markers of CeVD. METHODS: 109 patients with AD, 76 cognitively impaired with no dementia (CIND), and 56 non-cognitively impaired (NCI) were included in this cross-sectional study. All subjects underwent 3T brain magnetic resonance imaging to assess white matter hyperintensities (WMH), lacunes, cortical infarcts, and cerebral microbleeds (CMBs). Serum PlGF concentrations were measured by electrochemiluminescence immunoassays. RESULTS: Serum PlGF was elevated in AD, but not CIND, compared to the NCI controls. Adjusted concentrations of PlGF were associated with AD only in the presence of significant CeVD. Elevated PlGF was significantly associated with higher burden of WMH and with CMBs in AD patients. CONCLUSIONS: Serum PlGF has potential utility as a biomarker for the presence of CeVD, specifically WMH and CMBs, in AD. Further studies are needed to elucidate the underlying pathophysiological mechanisms linking PlGF to CeVD, as well as to further assess PlGF's clinical utility.

Detection of Bacterial Neutral Ceramidase in Diabetic Foot Ulcers with an Optimized Substrate and Chemoenzymatic Probes.

Ceramidases (CDases) are important in controlling skin barrier integrity by regulating ceramide composition and affording downstream signal molecules. While the functions of epidermal CDases are known, roles of neutral CDases secreted by skin-residing microbes are undefined. Here, we developed a one-step fluorogenic substrate, S-B, for specific detection of bacterial CDase activity and inhibitor screening. We identified a non-hydrolyzable substrate mimic, C6, as the best hit. Based on C6, we designed a photoaffinity probe, JX-1, which efficiently detects bacterial CDases. Using JX-1, we identified endogenous low-abundance PaCDase in a P. aeruginosa monoculture and in a mixed skin bacteria culture. Harnessing both S-B and JX-1, we found that CDase activity positively correlates with the relative abundance of P. aeruginosa and is negatively associated with wound area reduction in clinical diabetic foot ulcer patient samples. Overall, our study demonstrates that bacterial CDases are important regulators of skin ceramides and potentially play a role in wound healing.

Associations of Blood Cardiovascular Biomarkers With Brain Free Water and Its Relationship to Cognitive Decline: A Diffusion-MRI Study.

BACKGROUND AND OBJECTIVES: There is an increasing awareness of the "Heart-Brain Connection," whereby cardiovascular function is connected with cognition. Diffusion-MRI studies reported higher brain free water (FW) was associated with cerebrovascular disease (CeVD) and cognitive impairment. In this study, we investigated whether higher brain FW was related to blood cardiovascular biomarkers and whether FW mediated the associations between blood biomarkers and cognition. METHODS: Participants recruited from 2 Singapore memory clinics between 2010 and 2015 underwent collection of blood samples and neuroimaging at baseline and longitudinal neuropsychological assessments up to 5 years. We examined the associations of blood cardiovascular biomarkers (high-sensitivity cardiac troponin-T [hs-cTnT], N-terminal pro-hormone B-type natriuretic peptide [NT-proBNP], and growth/differentiation factor 15 [GDF-15]) with brain white matter (WM) and cortical gray matter (GM) FW derived from diffusion MRI using whole brain voxel-wise general linear regression. We then assessed the relationships among baseline blood biomarkers, brain FW, and cognitive decline using path models. RESULTS: A total of 308 older adults (76 with no cognitive impairment, 134 with cognitive impairment no dementia, and 98 with Alzheimer disease dementia and vascular dementia; mean [SD] age: 72.1 [8.3]) were included. We found that blood cardiovascular biomarkers were associated with higher FW in widespread WM regions and in specific GM networks including the default mode, executive control, and somatomotor networks at baseline (p < 0.01, family-wise error corrected). Baseline FW in widespread WM and network-specific GM fully mediated the associations of blood biomarkers with longitudinal cognitive decline over 5 years. Specifically, in GM, higher FW in the default mode network mediated the relationship with memory decline (hs-cTnT: ß = -0.115, SE = 0.034, p = 0.001; NT-proBNP: ß = -0.154, SE = 0.046, p = 0.001; GDF-15: ß = -0.073, SE = 0.027, p = 0.006); by contrast, higher FW in the executive control network was responsible for executive function decline (hs-cTnT: ß = -0.126, SE = 0.039, p = 0.001; NT-proBNP: ß = -0.110, SE = 0.038, p = 0.004; GDF-15: ß = -0.117, SE = 0.035, p = 0.001). Similar full mediation effects of brain FW were also identified for baseline cognition. DISCUSSION: Results suggested a role of brain FW in linking cardiovascular dysfunction to cognitive decline. These findings provide new evidence for brain-heart interactions, paving the way for prediction and monitoring of domain-specific cognitive trajectory.

Qualitative study exploring heterogeneity in caregiving experiences post-stroke in Singapore.

OBJECTIVE: Stroke, a common illness in older adults, accounts for up to 4% of direct medical costs in developed nations. Informal caregiving contributing a significant proportion of economic burden post-stroke warrants a deeper understanding of the caregiving context to sustain caregiving arrangement. While literature exists describing differences in motivation and preferences of caregivers, limited literature explores differences in caregiving experiences of different types of caregivers (ie, spouse, adult-child, sibling or others). Addressing this gap, our study aimed to explore the caregiving experience of stroke survivors and their family caregivers across different caregiver identities in an Asian setting. DESIGN: Qualitative descriptive study. SETTING: Community setting. PARTICIPANTS: We conducted semi-structured interviews with 26 stroke survivors and 35 caregivers purposively sampled from an outpatient rehabilitation setting, an outpatient clinic and a support organisation. Data were analysed using thematic analysis. OUTCOME MEASURES: Themes including caregiving experience of stroke survivors and their family caregivers across different caregiver identities. RESULTS: Following five themes were reported: caregiver reserve, coping strategies, caregiver burden, competing commitments and role of foreign domestic worker (FDW) in family caregiving. Spouse caregivers were less willing to ask for help, commonly adopted faith-based, and spacing or recharging types of coping, reported emotional strain and shared limited accounts of FDWs. Adult-child caregivers were more willing to ask for help, engaged in alternative care arrangements involving FDWs, commonly adopted action-focussed coping and reported multidimensional caregiver burden. CONCLUSION: Our findings illustrated the heterogeneity in factors affecting caregiving experience across spouse and adult-child caregivers. Practical implications include conducting a needs assessment for caregiver-stroke survivor dyads and providing tailored support, training and information to help caregivers cope better.

Serum Cathepsin D Is a Potential Biomarker for Alzheimer's Disease Dementia and Cognitive Decline.

BACKGROUND: The lysosomal protease cathepsin D (catD) has been reported to be upregulated in postmortem Alzheimer's disease (AD) cortex, where it colocalized with neurofibrillary tangles and correlated with levels of phosphorylated tau, suggesting pathophysiological links between catD and neurodegeneration. In contrast, studies of serum catD in AD have yielded conflicting results, and potential associations between baseline serum catD and functional outcomes of patients are at present unknown. OBJECTIVE: We aimed to examine the status of serum catD in a Singapore-based longitudinal study of dementia and investigate catD associations with functional and cognitive decline. METHODS: 35 subjects with no cognitive impairment, 40 patients with cognitive impairment no dementia and 34 with AD dementia underwent annual neuropsychological assessments (mean follow-up=4.3 years), as well as collection of baseline serum for catD measurements by ELISA. RESULTS: Higher serum catD at baseline was associated with AD clinical diagnosis (odds ratios [OR]: 10.0; 95% confidence interval [CI]: 1.02-97.95) as well as with cortical atrophy. Furthermore, higher catD was associated with global cognitive and functional decline (OR: 9.94; 95% CI: 1.02-97.34). CONCLUSION: The associations of serum catD with AD dementia as well as atrophy provide further support for the proposed links between catD and neurodegeneration, as well as for the assessment of serum catD as a prognostic biomarker predicting global cognitive and functional decline in larger studies.

Age-Related Eye Diseases in Individuals With Mild Cognitive Impairment and Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) and age-related eye diseases pose an increasing burden as the world's population ages. However, there is limited understanding on the association of AD/cognitive impairment, no dementia (CIND) with age-related eye diseases. Methods: In this cross-sectional, memory clinic-based study of multiethnic Asians aged 50 and above, participants were diagnosed as AD (n = 216), cognitive impairment, no dementia (CIND) (n = 252), and no cognitive impairment (NCI) (n = 124) according to internationally accepted criteria. Retinal photographs were graded for the presence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) using standard grading systems. Multivariable-adjusted logistic regression models were used to determine the associations between neurological diagnosis and odds of having eye diseases. Results: Over half of the adults had at least one eye disease, with AMD being the most common (60.1%; n = 356), followed by DR (8.4%; n = 50). After controlling for age, sex, race, educational level, and marital status, persons with AD were more likely to have moderate DR or worse (OR = 2.95, 95% CI = 1.15-7.60) compared with NCI. In the fully adjusted model, the neurological diagnosis was not associated with AMD (OR = 0.75, 95% CI = 0.45-1.24). Conclusion: Patients with AD have an increased odds of having moderate DR or worse, which suggests that these vulnerable individuals may benefit from specific social support and screening for eye diseases.

Deep-learning retinal vessel calibre measurements and risk of cognitive decline and dementia.

Previous studies have explored the associations of retinal vessel calibre, measured from retinal photographs or fundus images using semi-automated computer programs, with cognitive impairment and dementia, supporting the concept that retinal blood vessels reflect microvascular changes in the brain. Recently, artificial intelligence deep-learning algorithms have been developed for the fully automated assessment of retinal vessel calibres. Therefore, we aimed to determine whether deep-learning-based retinal vessel calibre measurements are predictive of risk of cognitive decline and dementia. We conducted a prospective study recruiting participants from memory clinics at the National University Hospital and St. Luke's Hospital in Singapore; all participants had comprehensive clinical and neuropsychological examinations at baseline and annually for up to 5 years. Fully automated measurements of retinal arteriolar and venular calibres from retinal fundus images were estimated using a deep-learning system. Cox regression models were then used to assess the relationship between baseline retinal vessel calibre and the risk of cognitive decline and developing dementia, adjusting for age, gender, ethnicity, education, cerebrovascular disease status, hypertension, hyperlipidemia, diabetes, and smoking. A total of 491 participants were included in this study, of whom 254 developed cognitive decline over 5 years. In multivariable models, narrower retinal arteriolar calibre (hazard ratio per standard deviation decrease = 1.258, P = 0.008) and wider retinal venular calibre (hazard ratio per standard deviation increase = 1.204, P = 0.037) were associated with increased risk of cognitive decline. Among participants with cognitive impairment but no dementia at baseline (n = 212), 44 progressed to have incident dementia; narrower retinal arteriolar calibre was also associated with incident dementia (hazard ratio per standard deviation decrease = 1.624, P = 0.021). In summary, deep-learning-based measurement of retinal vessel calibre was associated with risk of cognitive decline and dementia.

Alzheimer's Disease THErapy With NEuroaid (ATHENE): A Randomized Double-Blind Delayed-Start Trial.

OBJECTIVES: Preclinical and clinical studies indicate a role for MLC901 (NeuroAiD II) in Alzheimer's disease (AD). The primary aim was to investigate its safety as add-on therapy to standard treatment and the secondary aims its effect on cognition and slowing disease progression. DESIGN: Randomized double-blind placebo-controlled delayed-start study. SETTING AND PARTICIPANT: Patients with mild to moderate probable AD by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n = 125), were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months when all patients received MLC901, in a delayed-start design (clinical trial registration: ClinicalTrials.gov, NCT03038035). METHODS: The primary outcome measure was occurrence of serious adverse events (SAEs) at 6 months. Secondary outcomes included the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and other assessment scales. RESULTS: There was no significant difference in the risk of SAEs between early and delayed starters at month (M) 6 (22.6% vs 27.0%, risk difference -4.4%, 90% CI -16.9% to 8.3%). Similarly, there was no significant difference in the risk of adverse events and the occurrence of stroke or vascular events between early and delayed starters throughout the 12-month study period. Early starters did not differ significantly on ADAS-Cog from delayed starters at M6 [mean difference (MD) -1.0, 95% CI -3.3 to 1.3] and M12 (MD -2.35, 95% CI -5.45 to 0.74) on intention-to-treat analysis. Other cognitive assessment scales did not show significant differences. CONCLUSIONS AND IMPLICATIONS: This study of 125 persons with dementia found no evidence of a significant increase in adverse events between MLC901 and placebo, thus providing support for further studies on both efficacy and safety. Analyses suggest the potential of MLC901 in slowing down AD progression, but this requires further confirmation in larger and longer studies using biomarkers for AD.

Association Between Cerebral Cortical Microinfarcts and Perilesional Cortical Atrophy on 3T MRI.

BACKGROUND AND OBJECTIVES: Cerebral cortical microinfarcts (CMIs) are a novel MRI marker of cerebrovascular disease (CeVD) that predicts accelerated cognitive decline. Presence of CMIs is known to be associated with global cortical atrophy, although the mechanism linking the two is unclear. Our primary objective was to examine the relation between CMIs and cortical atrophy and to establish possible perilesional atrophy surrounding CMIs. Our secondary objective was to examine the role of cortical atrophy in CMI-associated cognitive impairment. METHODS: Patients were recruited from 2 Singapore memory clinics between December 2010 and September 2013 and included if they received the diagnosis no objective cognitive impairment, cognitive impairment (with or without a history of stroke), or Alzheimer or vascular dementia. Cortical thickness, chronic CMIs, and MRI markers of CeVD were assessed on 3T MRI. Patients underwent cognitive testing. Cortical thickness was compared globally between patients with and without CMIs, regionally within individual patients with CMIs comparing brain regions with CMIs to the corresponding contralateral region without CMIs, and locally within individuals patients in a 50-mm radius of CMIs. Global cortical thickness was analyzed as mediator in the relation between CMI and cognitive performance. RESULTS: Of the 238 patients (mean age 72.5 years, SD 9.1 years) enrolled, 75 had ≥1 CMIs. Patient with CMIs had a 2.1% lower global cortical thickness (B = -0.049 mm, 95% confidence interval [CI] 0.091 to -0.007, p = 0.022) compared to patients without CMIs, after correction for age, sex, education, and intracranial volume. In patients with CMIs, cortical thickness in brain regions with CMIs was 2.2% lower than in contralateral regions without CMIs (B = -0.048 mm [95% CI -0.071 to -0.026], p < 0.001). In a 20-mm radius area surrounding the CMI core, cortical thickness was lower than in the area 20 to 50 mm from the CMI core (mean difference -0.06 mm [-0.10 to -0.02], p = 0.002). Global cortical thickness was a significant mediator in the relationship between CMI presence and cognitive performance as measure with the Mini-Mental State Examination (B = -0.12 [-0.22 to -0.01], p = 0.025). DISCUSSION: We found cortical atrophy surrounding CMIs, suggesting a perilesional effect in a cortical area many times larger than the CMI core. Our findings support the notion that CMIs affect brain structure beyond the actual lesion site.

Seeking healthcare services post-stroke: a qualitative descriptive study exploring family caregiver and stroke survivor perspectives in an asian setting.

AIM: Exploration of the healthcare journey post-stroke is incomplete without acknowledging the crucial role of family caregivers. With limited literature documenting the role of caregivers in the healthcare journey post-stroke, we aimed to describe the healthcare experiences of family caregivers and stroke survivors across different caregiver identities in Singapore. METHODS: We conducted a qualitative descriptive study involving semi-structured interviews with transcripts analysed using thematic analysis. 26 stroke survivors and 35 family caregivers purposively sampled from multiple settings. RESULTS: Findings were summarized into seeking care and experience of healthcare encounters. Seeking care comprised of the following themes: factors influencing seeking care, decision to seek care and role of caregiver in seeking care. Experience of healthcare encounters comprised of the following themes: service around the patient, service with care and role of caregiver in healthcare encounters. CONCLUSION: Multi-dimensional role of caregivers in healthcare experience emerged as a major finding. Unique to our Asian context, as per the participants' accounts, family caregivers seemed to be central in healthcare decision-making for stroke survivors, with adult-child caregivers commonly reported being engaged in collaborative decision-making. While spousal caregivers preferred a relational healthcare experience, adult-child caregivers preferred a transactional one. Practical implications include equipping caregivers with skillset to make healthcare decisions, provision of supportive decision-making environment for caregivers and reinforcing communication aspects in the medical, nursing and allied healthcare curriculum to improve healthcare experience.

A wireless and battery-free wound infection sensor based on DNA hydrogel.

The confluence of wireless technology and biosensors offers the possibility to detect and manage medical conditions outside of clinical settings. Wound infections represent a major clinical challenge in which timely detection is critical for effective interventions, but this is currently hindered by the lack of a monitoring technology that can interface with wounds, detect pathogenic bacteria, and wirelessly transmit data. Here, we report a flexible, wireless, and battery-free sensor that provides smartphone-based detection of wound infection using a bacteria-responsive DNA hydrogel. The engineered DNA hydrogels respond selectively to deoxyribonucleases associated with pathogenic bacteria through tunable dielectric changes, which can be wirelessly detected using near-field communication. In a mouse acute wound model, we demonstrate that the wireless sensor can detect physiologically relevant amounts of Staphylococcus aureus even before visible manifestation of infection. These results demonstrate strategies for continuous infection monitoring, which may facilitate improved management of surgical or chronic wounds.

Support system diversity among family caregivers of stroke survivors: a qualitative study exploring Asian perspectives.

BACKGROUND: Caregiving is a global phenomenon which is bound to increase in tandem with the aging population worldwide. Stroke is a condition common in older people that requires complex caregiving necessitating provision of adequate support to the caregivers. Past literature consists of limited accounts of types and organization of support arrangements needed by different caregivers. We aimed to describe the support system of caregivers of stroke survivors in Singapore, highlighting differences across the different caregiver identities (i.e. spouse, adult-child, etc.). METHODS: We conducted a qualitative descriptive study in the community setting involving 61 purposively sampled and recruited stroke survivors and caregivers. Semi-structured interviews were conducted, and transcripts were analysed using thematic analysis. RESULTS: Our findings were summarized across the following 4 themes: 1) cultural influence and caregiving; 2) caregiver support system with the following sub-themes: 2.1) dyadic caregiver support type, 2.2) extended caregiver support type, 2.3.) distributed caregiver support type and 2.4) empowering caregiver support type; 3) breaks in care of stroke survivor and 4) complex relationship dynamics. We operationalized the caregiver support system as comprising of type, people and activities that enable the caregiver to participate in caregiving activities sustainably. While spouse caregivers preferred dyadic and extended support systems positioning themselves in a more central caregiving role, adult-child caregivers preferred distributed support system involving family members with paid caregivers playing a more central role. CONCLUSIONS: Our findings highlight caregiver identity as a surrogate for the differences in the caregiver support systems. Practical implications include imparting relationship-building skills to the stroke survivor-caregiver dyads to sustain dyadic support system and educating clinicians to include differences in caregiving arrangements of stroke survivors in practising family-centred care.

Burden of informal care in stroke survivors and its determinants: a prospective observational study in an Asian setting.

BACKGROUND: Informal caregiving is an integral part of post-stroke recovery with strenuous caregiving demands often resulting in caregiving burden, threatening sustainability of caregiving and potentially impacting stroke survivor's outcomes. Our study aimed to examine and quantify objective and subjective informal care burden after stroke; and to explore the factors associated with informal care burden in Singapore. METHODS: Stroke patients and their informal caregivers were recruited from all five tertiary hospitals in Singapore from December 2010 to September 2013. Informal care comprised of assistance provided by informal caregivers with any of the activities of daily living. Informal care burden was measured by patients' likelihood of requiring informal care, hours of informal care required, and informal caregivers' Zarit's Burden Score. We examined informal care burden at 3-months and 12-months post-stroke. Generalized linear regressions were applied with control variables including patients' and informal caregivers' demographic characteristics, arrangement of informal care, and patients' health status including stroke severity (measured using National Institute of Health Stroke Scale), functional status (measured using Modified Rankin Scale), self-reported depression, and common comorbidities. RESULTS: Three hundred and five patients and 263 patients were examined at 3-months and 12-months. Around 35% were female and 60% were Chinese. Sixty three percent and 49% of the patients required informal care at 3-months and 12-months point, respectively. Among those who required informal care, average hours required per week were 64.3 h at 3-months and 76.6 h at 12-months point. Patients with higher functional dependency were more likely to require informal care at both time points, and required more hours of informal care at 3-months point. Female informal caregivers and those caring for patients with higher functional dependency reported higher Zarit's Burden. While informal caregivers who worked full-time reported higher burden, those caring for married stroke patients reported lower burden at 3-months point. Informal caregivers who co-cared with foreign domestic workers, i.e.: stay-in migrant female waged domestic workers, reported lower burden. CONCLUSIONS: Informal care burden remains high up to 12-months post-stroke. Factors such as functional dependency, stroke severity, informal caregiver gender and co-caring with foreign domestic workers were associated with informal care burden.

Role of caregiver factors in outpatient medical follow-up post-stroke: observational study in Singapore.

BACKGROUND: Outpatient medical follow-up post-stroke is not only crucial for secondary prevention but is also associated with a reduced risk of rehospitalization. However, being voluntary and non-urgent, it is potentially determined by both healthcare needs and the socio-demographic context of stroke survivor-caregiver dyads. Therefore, we aimed to examine the role of caregiver factors in outpatient medical follow-up (primary care (PC) and specialist outpatient care (SOC)) post-stroke. METHOD: Stroke survivors and caregivers from the Singapore Stroke Study, a prospective, yearlong, observational study, contributed to the study sample. Participants were interviewed 3-monthly for data collection. Counts of PC and SOC visits were extracted from the National Claims Database. Poisson modelling was used to explore the association of caregiver (and patient) factors with PC/SOC visits over 0-3 months (early) and 4-12 months (late) post-stroke. RESULTS: For the current analysis, 256 stroke survivors and caregivers were included. While caregiver-reported memory problems of a stroke survivor (IRR: 0.954; 95% CI: 0.919, 0.990) and caregiver burden (IRR: 0.976; 95% CI: 0.959, 0.993) were significantly associated with lower early post-stroke PC visits, co-residing caregiver (IRR: 1.576; 95% CI: 1.040, 2.389) and negative care management strategies (IRR: 1.033; 95% CI: 1.005, 1.061) were significantly associated with higher late post-stroke SOC visits. CONCLUSION: We demonstrated that the association of caregiver factors with outpatient medical follow-up varied by the type of service (i.e., PC versus SOC) and temporally. Our results support family-centred care provision by family physicians viewing caregivers not only as facilitators of care in the community but also as active members of the care team and as clients requiring care and regular assessments.

Stroke Rehabilitation Use and Caregiver Psychosocial Health Profiles in Singapore: A Latent Profile Transition Analysis.

OBJECTIVES: To identify and describe caregiver profiles based on their psychosocial health characteristics over a 12-month period and transitions among these profiles, to determine if stroke rehabilitation use at 12 months post-stroke differed by caregiver profile transition patterns, and to investigate if caregiver profiles at 3 months post-stroke moderate the association of stroke rehabilitation use at 3 months and 12 months post-stroke after accounting for covariates. DESIGN: Latent profile transition analysis of caregiver psychosocial health with stroke rehabilitation use at 12 month post-stroke as outcome. SETTING AND PARTICIPANTS: A total of 149 stroke patient-caregiver dyads from the Singapore Stroke Study. METHODS: Cross-sectional latent profile analyses were conducted on caregiver psychosocial health indicators of burden, depression, health status, quality of relationship with patient, and social support. Changes in latent profile classification over 3 time points (baseline, 3 months, and 12 months post-stroke) were analyzed using latent transition analysis. A transition model with stroke rehabilitation use at 12 months post-stroke as the outcome was tested after accounting for covariates. RESULTS: Two distinct caregiver psychosocial health latent profiles were found across time: nondistressed and distressed. Most caregivers were classified as nondistressed and remained nondistressed over time. Distressed caregivers at baseline were 76% likely to become nondistressed at 12 month post-stroke. Regardless of profile transition patterns, nondistressed caregivers at 12 months post-stroke tended to have cared for stroke rehabilitation nonusers at 12 months post-stroke. Patient depression explained profile classification at 3 months and 12 months post-stroke. After accounting for covariates, rehabilitation users at 3 months post-stroke tended to continue using rehabilitation at 12 months post-stroke only when they had nondistressed caregivers at 3 months post-stroke. CONCLUSIONS AND IMPLICATIONS: Whether caregiver adaptation explains the associations between the latent profile transition patterns and rehabilitation use at 12 months post-stroke should be examined. Early psychosocial health assessment and sustained support should be made available to stroke caregivers to enhance their well-being and subsequent patient rehabilitation participation.

Effects of multi-domain lifestyle interventions on sarcopenia measures and blood biomarkers: secondary analysis of a randomized controlled trial of community-dwelling pre-frail and frail older adults.

Few studies have comprehensively described changes in blood biomarkers of the physiological responses underlying sarcopenia reduction associated with lifestyle interventions. In this study, we performed secondary analyses of data in a randomized controlled trial of multi-domain lifestyle interventions (6-month duration physical exercise, nutritional enrichment, cognitive training, combination and standard care control) among 246 community-dwelling pre-frail and frail elderly, aged ≥65 years, with and without sarcopenia. Appendicular lean mass (ALM), lower limb strength, gait speed, and blood levels of markers of muscle metabolism, inflammation, anti-oxidation, anabolic hormone regulation, insulin signaling, tissue oxygenation were measured at baseline, 3-month and 6-month post-intervention. Multi-domain interventions were associated with significant (p < 0.001) reduction of sarcopenia at 3-month and 6-month post-intervention, improved gait speed, enhanced lower limb strength, and were equally evident among sarcopenic participants who were slower at baseline than non-sarcopenic participants. Active intervention was associated with significantly reduced inflammation levels. Sarcopenia status and reduction were associated with blood biomarkers related to muscle metabolism, steroid hormone regulation, insulin-leptin signaling, and tissue oxygenation. Physical, nutritional and cognitive intervention was associated with measures of sarcopenia reduction, together with changes in circulating biomarkers of anabolic and catabolic metabolism underlying sarcopenia.

Plasma osteopontin as a biomarker of Alzheimer's disease and vascular cognitive impairment.

Cerebrovascular disease (CeVD) and neurodegenerative dementia such as Alzheimer's disease (AD) are frequently associated comorbidities in the elderly, sharing common risk factors and pathophysiological mechanisms including neuroinflammation. Osteopontin (OPN) is an inflammatory marker found upregulated in vascular diseases as well as in AD. However, its involvement in vascular dementia (VaD) and pre-dementia stages, namely cognitive impairment no dementia (CIND), both of which fall under the spectrum of vascular cognitive impairment (VCI), has yet to be examined. Its correlations with inflammatory cytokines in cognitive impairment also await investigation. 80 subjects with no cognitive impairment (NCI), 160 with CIND and 144 with dementia were included in a cross-sectional study on a Singapore-based memory clinic cohort. All subjects underwent comprehensive clinical, neuropsychological and brain neuroimaging assessments, together with clinical diagnoses based on established criteria. Blood samples were collected and OPN as well as inflammatory cytokines interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF) were measured using immunoassays. Multivariate regression analyses showed significant associations between increased OPN and VCI groups, namely CIND with CeVD, AD with CeVD and VaD. Interestingly, higher OPN was also significantly associated with AD even in the absence of CeVD. We further showed that increased OPN significantly associated with neuroimaging markers of CeVD and neurodegeneration, including cortical infarcts, lacunes, white matter hyperintensities and brain atrophy. OPN also correlated with elevated levels of IL-6, IL-8 and TNF. Our findings suggest that OPN may play a role in both VCI and neurodegenerative dementias. Further longitudinal analyses are needed to assess the prognostic utility of OPN in disease prediction and monitoring.

Primary Care Prognostic (PCP) Index of 11-Year Mortality Risk: Development and Validation of a Brief Prognostic Tool.

BACKGROUND: Healthcare providers use a life expectancy of at least 5 to 10 years in shared clinical decision-making with older adults about cancer screening, major surgeries, and disease prevention interventions. At present, few prognostic indexes predict long-term mortality beyond 10 years or are suited for use in primary care settings. OBJECTIVE: We developed and validated an 8-item multidimensional index predicting 11-year mortality for use in primary care. DESIGN, SETTING, AND PARTICIPANTS: Using data from the Singapore Longitudinal Ageing Studies (SLAS), we developed a Primary Care Prognostic (PCP) Index for predicting 11-year mortality risk in a development cohort (n = 1550) and validated it in a geographically different cohort (n = 928). MAIN MEASURES: The PCP Index was derived from eight indicators (body mass loss, weakness, slow gait, comorbidity, polypharmacy, IADL/BADL dependency, low albumin, low total cholesterol, out of 25 candidate indicators) using stepwise Cox proportional hazard models. KEY RESULTS: In the developmental cohort, the mortality hazard ratio increased by 53% per PCP point score increase, independent of age and sex. Across risk categories, absolute risks of mortality increased from 5% (score 0) to 67.9% (scores 7-9), with area under curve (AUC = 0.77 (95% CI 0.73-0.80)). The PCP Index also predicted mortality in the validation cohort, with AUC = 0.70 (95% CI 0.64-0.75). CONCLUSIONS: The PCP Index using simple clinical assessments and point scoring is a potentially useful prognostic tool for predicting long-term mortality and is well suited for risk stratification and shared clinical decision-making with older adults in primary care.