Functional mobility decline and incident mild cognitive impairment and early dementia in community-dwelling older adults: the Singapore Longitudinal Ageing Study.

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).

Cardiometabolic and Vascular Disease Factors and Mild Cognitive Impairment and Dementia.

INTRODUCTION: There is empirical evidence that cardiovascular risk factors and vascular pathology contribute to cognitive impairment and dementia. METHODS: We profiled cardiometabolic and vascular disease (CMVD) and CMVD burden in community-living older adults in the Singapore Longitudinal Ageing Study cohort and examined the association of CMVD risk markers with the prevalence and incidence of mild cognitive impairment (MCI) and dementia from a median 3.8 years of follow-up. RESULTS: Prevalent MCI and dementia, compared with normal cognition, was associated with higher proportions of persons with any CMVD, hypertension, diabetes, coronary heart disease, atrial fibrillation, or stroke. Diabetes, stroke, and the number of CMVD risk markers remained significantly associated with dementia or MCI after adjusting for age, sex, formal education level, APOE-ε4 genotype, and level of physical, social, or productive activities, with odds ratios ranging from 1.3 to 5.7. Among cognitively normal participants who were followed up, any CMVD risk factor, dyslipidemia, diabetes, or heart failure at baseline predicted incident MCI or its progression to dementia after adjusting for potential confounders. CONCLUSION: Older adults with higher burden of CMVD, driven especially by diabetes, are likely to increase the risk of prevalent and incident MCI and dementia.

The development and validation of a prototype mobility tracker for assessing the life space mobility and activity participation of older adults.

BACKGROUND: There is increasing interest in examining the life space mobility and activity participation of older adults in the community using sensor technology. Objective data from these technologies may overcome the limitations of self-reported surveys especially in older adults with age-associated cognitive impairment. This paper describes the development and validation of a prototype hybrid mobility tracker for assessing life space mobility and out-of-home activities amongst 33 community-ambulant older adults in Singapore. METHODS: A hybrid mobility tracker was developed by combining a passive Global Positioning System logger, tri-axial accelerometer and radio-frequency identification. Objective measures of life space, derived from 1 week of tracking data using Geographic Information Systems, were the maximum Euclidean distance from home (Max Euclid) and the area of the minimum convex polygon surrounding all GPS waypoints (MCP area). Out-of-home activities were quantified by visually identifying the total number of activity nodes, or places where participants spent ≥5 min, from mobility tracks. Self-reported measure of life space in 4 weeks was obtained using the University of Alabama at Birmingham Study of Life Space Assessment (UAB-LSA) questionnaire. Self-reported out-of-home activities were recorded daily in a travel diary for 1 week. Bivariate correlations were used to examine convergent validity between objective and subjective measures of life space and out-of-home activities. RESULTS: The mean age of participants was 69.2 ± 7.1 years. The mean UAB-LSA total score was 79.1 ± 17.4. The median (range) Max Euclid was 2.44 km (0.26-7.50) per day, and the median (range) MCP area was 3.31 km2 (0.03-34.23) per day. The UAB-LSA total score had good correlation with Max Euclid (r = 0.51, p = 0.002), and moderate correlation with MCP area (r = 0.46, p = 0.007). The median (range) total number of activity nodes measured by tracker of 20 (8-47) per week had a good correlation with the total activity count recorded in the travel diaries of 15 (6-40) per week (r = 0.52, p = 0.002). CONCLUSIONS: The tracking system developed to understand out-of-home travel was feasible and reliable. Comparisons with the UAB-LSA and travel diaries showed that it provided reliable and valid spatiotemporal data to assess the life space mobility and activity participation of older adults.

RNA Secondary Structure-Based Design of Antisense Peptide Nucleic Acids for Modulating Disease-Associated Aberrant Tau Pre-mRNA Alternative Splicing.

Alternative splicing of tau pre-mRNA is regulated by a 5' splice site (5'ss) hairpin present at the exon 10-intron 10 junction. Single mutations within the hairpin sequence alter hairpin structural stability and/or the binding of splicing factors, resulting in disease-causing aberrant splicing of exon 10. The hairpin structure contains about seven stably formed base pairs and thus may be suitable for targeting through antisense strands. Here, we used antisense peptide nucleic acids (asPNAs) to probe and target the tau pre-mRNA exon 10 5'ss hairpin structure through strand invasion. We characterized by electrophoretic mobility shift assay the binding of the designed asPNAs to model tau splice site hairpins. The relatively short (10-15 mer) asPNAs showed nanomolar binding to wild-type hairpins as well as a disease-causing mutant hairpin C+19G, albeit with reduced binding strength. Thus, the structural stabilizing effect of C+19G mutation could be revealed by asPNA binding. In addition, our cell culture minigene splicing assay data revealed that application of an asPNA targeting the 3' arm of the hairpin resulted in an increased exon 10 inclusion level for the disease-associated mutant C+19G, probably by exposing the 5'ss as well as inhibiting the binding of protein factors to the intronic spicing silencer. On the contrary, the application of asPNAs targeting the 5' arm of the hairpin caused an increased exon 10 exclusion for a disease-associated mutant C+14U, mainly by blocking the 5'ss. PNAs could enter cells through conjugation with amino sugar neamine or by cotransfection with minigene plasmids using a commercially available transfection reagent.

Caregiving burden in foreign domestic workers caring for frail older adults in Singapore.

ABSTRACTBackground:Although foreign domestic workers (FDWs) play a significant role in caring for frail seniors in Singapore and are vulnerable to caregiving burden, there has been little research conducted hitherto. We explored caregiver burden and its determinants in this study. METHODS: FDWs (N = 221, Mage = 32.3, SD = 6.23) recruited from a hospital geriatric unit completed the Zarit Burden Interview (ZBI) administered in English, Bahasa Melayu, or Burmese. Univariate and multivariate regression were employed to investigate factors influencing caregiving burden in FDWs. RESULTS: Majority were Indonesians (60.0%), married (57.5%) with children (62.4%), with secondary-level education (59.7%), and providing care for >1 year (79.9%). Importantly, 25.1% reported physical health problems and 23.1% encountered language difficulties with employers. Univariate analysis revealed three significant factors associated with caregiving burden: nationality (p < 0.001), lack of privacy (p = 0.029), and caring for persons with dementia (PWD) (p = 0.001). On multivariate regression, FDWs who cared for PWD were 5.47 times (p = 0.013) more likely to experience burden, while FDWs who encountered language difficulties were 5.46 times (p = 0.030) more likely to experience burden. Filipinos FDWs were 9.73 times more likely to express burden (p < 0.001) compared to their Indonesian and Burmese counterparts. CONCLUSION: The study highlights caregiver burden in FDWs and potential ways to alleviate it by empowering FDWs with dementia-specific caregiving skills, providing language training opportunities, and supporting particular FDW ethnic groups with more emotional and practical help.

Hearing Loss and Risk of Mild Cognitive Impairment and Dementia: Findings from the Singapore Longitudinal Ageing Study.

AIM: To investigate the associations between hearing loss and prevalent and incident mild cognitive impairment (MCI), dementia and MCI or dementia (all cases). METHODS: Cross-sectional and longitudinal analyses of baseline and follow-up data were performed in a population-based cohort. The baseline sample of 2,599 adults aged ≥55 included 1,515 cognitively normal subjects who were followed up to 8 years. Hearing loss at baseline was determined by the whispered voice test, and MCI and dementia by Mini-Mental State Examination screening, Clinical Dementia Rating scale, neurocognitive tests, MRI, and panel consensus diagnosis. RESULTS: Hearing impairment was associated with increased prevalence of dementia (odds ratio = 3.63, 95% confidence interval [CI] 1.16-11.4, p = 0.027) but not MCI alone or all cases of MCI or dementia, adjusted for sex, age, ethnicity, education, central obesity, hypertension, diabetes, dyslipidemia, smoking, alcohol, leisure time activity, cardiac diseases, and depressive symptoms. Among participants who were cognitively normal at baseline, those with hearing impairment were more likely to develop MCI or dementia (hazard ratio [HR] = 2.30, 95% CI 1.08-4.92, p = 0.032). Hearing loss was associated with elevated but statistically nonsignificant estimates of adjusted HR (1.85, 95% CI 0.78-4.40) for incident MCI alone. CONCLUSIONS: Hearing loss is independently associated with prevalent dementia and incident MCI or dementia.

Delirium superimposed on dementia: phenomenological differences between patients with and without behavioral and psychological symptoms of dementia in a specialized delirium unit.

BACKGROUND: Overlap between neuropsychiatric symptoms of dementia and delirium complicates diagnosis of delirium superimposed on dementia (DSD). This study sought to examine differences in delirium presentation and outcomes between DSD patients with and without pre-existing behavioral and psychological symptoms of dementia (BPSD). METHODS: This was a prospective cohort study of older adults with DSD admitted to a specialized delirium unit (December 2010-August 2012). We collected data on demographics, comorbidities, illness severity, delirium precipitants, and cognitive and functional scores. Delirium severity was assessed using Delirium Rating Scale Revised-98 (DRS-R-98) and Cognitive Assessment Method severity score (CAM-sev). Patients were categorized as DSD-BPSD+ and DSD-BPSD- based on elicited behavioral and psychological disturbances. RESULTS: We recruited 174 patients with DSD (84.4 +/-7.4 years) with 37 (21.3%) having BPSD. At presentation, delirium severity and symptom frequency on DRS-R98 were similar, but DSD-BPSD+ more often required only a single precipitant (40.5% vs. 21.9%, p = 0.07), and had significantly longer delirium duration (median days: 7 vs. 5, p < 0.01). At delirium resolution, DSD-BPSD+ exhibited significant improvement in sleep-wake disturbances (89.2% vs. 54.1%, p < 0.01), affect lability (81.1% vs. 56.8%, p = 0.05), and motor agitation (73% vs. 40.5%, p < 0.01), while all non-cognitive symptoms except motor retardation were improved in DSD-BPSD-. Pharmacological restraint was more prevalent (62.2% vs. 40.1%, p = 0.03), and at higher doses (chlorpromazine equivalents 0.95 +/-1.8 vs. 0.40 +/-1.2, p < 0.01) in DSD-BPSD+. CONCLUSIONS: BPSD may increase vulnerability of dementia patients to delirium, with subsequent slower delirium recovery. Aggravation of sleep disturbance, labile affect, and motor agitation should raise suspicion for delirium among these patients.

A Risk Score for the Prediction of Neurocognitive Disorders among Community-Dwelling Chinese Older Adults.

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.

A Combined Cognitive Stimulation and Physical Exercise Programme (MINDVital) in Early Dementia: Differential Effects on Single- and Dual-Task Gait Performance.

BACKGROUND: Gait disorders are common in early dementia, with particularly pronounced dual-task deficits, contributing to the increased fall risk and mobility decline associated with cognitive impairment. OBJECTIVE: This study examines the effects of a combined cognitive stimulation and physical exercise programme (MINDVital) on gait performance under single- and dual-task conditions in older adults with mild dementia. METHODS: Thirty-nine patients with early dementia participated in a multi-disciplinary rehabilitation programme comprising both physical exercise and cognitive stimulation. The programme was conducted in 8-week cycles with participants attending once weekly, and all participants completed 2 successive cycles. Cognitive, functional performance and behavioural symptoms were assessed at baseline and at the end of each 8-week cycle. Gait speed was examined under both single- (Timed Up and Go and 6-metre walk tests) and dual-task (animal category and serial counting) conditions. A random effects model was performed for the independent effect of MINDVital on the primary outcome variable of gait speed under dual-task conditions. RESULTS: The mean age of patients enroled in the rehabilitation programme was 79 ± 6.2 years; 25 (64.1%) had a diagnosis of Alzheimer's dementia, and 26 (66.7%) were receiving a cognitive enhancer therapy. There was a significant improvement in cognitive performance [random effects coefficient (standard error) = 0.90 (0.31), p = 0.003] and gait speed under both dual-task situations [animal category: random effects coefficient = 0.04 (0.02), p = 0.039; serial counting: random effects coefficient = 0.05 (0.02), p = 0.013], with reduced dual-task cost for gait speed [serial counting: random effects coefficient = -4.05 (2.35), p = 0.086] following successive MINDVital cycles. No significant improvement in single-task gait speed was observed. Improved cognitive performance over time was a significant determinant of changes in dual-task gait speed [random effects coefficients = 0.01 (0.005), p = 0.048, and 0.02 (0.005), p = 0.003 for category fluency and counting backwards, respectively]. CONCLUSION: A combined physical and cognitive rehabilitation programme leads to significant improvements in dual-task walking in early dementia, which may be contributed by improvement in cognitive performance, as single-task gait performance remained stable.

Automated assessment of thigh composition using machine learning for Dixon magnetic resonance images.

OBJECTIVES: To develop and validate a machine learning based automated segmentation method that jointly analyzes the four contrasts provided by Dixon MRI technique for improved thigh composition segmentation accuracy. MATERIALS AND METHODS: The automatic detection of body composition is formulized as a three-class classification issue. Each image voxel in the training dataset is assigned with a correct label. A voxel classifier is trained and subsequently used to predict unseen data. Morphological operations are finally applied to generate volumetric segmented images for different structures. We applied this algorithm on datasets of (1) four contrast images, (2) water and fat images, and (3) unsuppressed images acquired from 190 subjects. RESULTS: The proposed method using four contrasts achieved most accurate and robust segmentation compared to the use of combined fat and water images and the use of unsuppressed image, average Dice coefficients of 0.94 ± 0.03, 0.96 ± 0.03, 0.80 ± 0.03, and 0.97 ± 0.01 has been achieved to bone region, subcutaneous adipose tissue (SAT), inter-muscular adipose tissue (IMAT), and muscle respectively. CONCLUSION: Our proposed method based on machine learning produces accurate tissue quantification and showed an effective use of large information provided by the four contrast images from Dixon MRI.

Which frailty measure is a good predictor of early post-operative complications in elderly hip fracture patients?

INTRODUCTION: Current pre-operative assessment using, e.g., American Society of Anaesthesiologists score does not accurately predict post-operative outcomes following hip fracture. The multidimensional aspect of frailty syndrome makes it a better predictor of post-operative outcomes in hip fracture patients. We aim to discover which frailty measure is more suitable for prediction of early post-operative outcomes in hip fracture patients. METHODS: Hundred consecutive hip fracture patients seen by the orthogeriatric service were included. We collected baseline demographic, functional and comorbidity data. In addition to ASA, a single blinded rater measured frailty using two scales (i) modified fried criteria (MFC) and (ii) reported edmonton frail scale (REFS). The MFC adopted a surrogate gait speed measure with two questions: (i) Climbing one flight of stairs and (ii) Ability to walk 1 km in the last 2 weeks. Immediate post-operative complications during the inpatient stay were taken as the primary outcome measure. RESULTS: Subjects had mean age of 79.1 ± 9.6 years. Sixty six percent were female and 87 % of Chinese ethnicity. Eighty two percent had surgery, of which 37.8 % (n = 31) had post-operative complications. Frailty, measured by MFC (OR 4.46, p = 0.04) and REFS (OR 6.76, p = 0.01) were the only significant predictors of post-operative complications on univariate analyses. In the hierarchical logistic regression model, only REFS (OR 3.42, p = 0.04) predicted early post-operative complications. At 6 months follow-up, REFS significantly predicted [basic activities of daily living (BADL)] function on the multivariable logistic regression models. (BADL, OR 6.19, p = 0.01). CONCLUSIONS: Frailty, measured by the REFS is a good predictor of early post-operative outcomes in our pilot study of older adults undergoing hip surgery. It is also able to predict 6 months BADL function. We intend to review its role in longer-term post-operative outcomes and validate its potential role in pre-operative assessment of older adults undergoing hip surgery.

New DSM-V neurocognitive disorders criteria and their impact on diagnostic classifications of mild cognitive impairment and dementia in a memory clinic setting.

OBJECTIVE: To examine diagnostic agreement between Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) Neurocognitive Disorders (NCDs) criteria and DSM, Fourth Edition (DSM-IV) criteria for dementia and International Working Group (IWG) criteria for mild cognitive impairment (MCI) and DSM-V's impact on diagnostic classifications of NCDs. The authors further examined clinical factors for discrepancy in diagnostic classifications between the different operational definitions. METHODS: Using a cross-sectional study in tertiary memory clinic, the authors studied consecutive new patients aged 55 years or older who presented with cognitive symptoms. Dementia severity was scored based on the Clinical Dementia Rating scale (CDR). All patients completed neuropsychological evaluation. Agreement in diagnostic classifications between DSM-IV/IWG and DSM-V was examined using the kappa test and AC1 statistic, with multinomial logistic regression for factors contributing to MCI reclassification as major NCDs as opposed to diagnostically concordant MCI and dementia groups. RESULTS: Of 234 patients studied, 166 patients achieved concordant diagnostic classifications, with overall kappa of 0.41. Eighty-six patients (36.7%) were diagnosed with MCI and 131 (56.0%) with DSM-IV-defined dementia. With DSM-V, 40 patients (17.1%) were classified as mild NCDs and 183 (78.2%) as major NCDs, representing a 39.7% increase in frequency of dementia diagnoses. CDR sum-of-boxes score contributed independently to differentiation of MCI patients reclassified as mild versus major NCDs (OR: 0.01; 95% CI: 0-0.09). CDR sum-of-boxes score (OR: 5.18; 95% CI: 2.04-13.15), performance in amnestic (OR: 0.14; 95% CI: 0.06-0.34) and language (Boston naming: OR: 0.52; 95% CI: 0.29-0.94) tests, were independent determinants of diagnostically concordant dementia diagnosis. CONCLUSION: The authors observed moderate agreement between the different operational definitions and a 40% increase in dementia diagnoses with operationalization of the DSM-V criteria.

Unconditional and Conditional Standards Using Cognitive Function Curves for the Modified Mini-Mental State Exam: Cross-Sectional and Longitudinal Analyses in Older Chinese Adults in Singapore.

OBJECTIVE: The conventional practice of assessing cognitive status and monitoring change over time in older adults using normative values of the Mini-Mental State Exam (MMSE) based on age bands is imprecise. Moreover, population-based normative data on changes in MMSE score over time are scarce and crude because they do not include age- and education-specific norms. This study aims to develop unconditional standards for assessing current cognitive status and conditional standards that take prior MMSE score into account for assessing longitudinal change, with percentile curves as smooth functions of age. METHODS: Cross-sectional and longitudinal data of a modified version of the MMSE for 2,026 older Chinese adults from the Singapore Longitudinal Aging Study, aged 55-84, in Singapore were used to estimate quantile regression coefficients and create unconditional standards and conditional standards. RESULTS: We presented MMSE percentile curves as a smooth function of age in education strata, for unconditional and conditional standards, based on quantile regression coefficient estimates. We found the 5th and 10th percentiles were more strongly associated with age and education than were higher percentiles. Model diagnostics demonstrated the accuracy of the standards. CONCLUSION: The development and use of unconditional and conditional standards should facilitate cognitive assessment in clinical practice and deserve further studies.

Montreal Cognitive Assessment for screening mild cognitive impairment: variations in test performance and scores by education in Singapore.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) was developed as a screening instrument for mild cognitive impairment (MCI). We evaluated the MoCA's test performance by educational groups among older Singaporean Chinese adults. METHOD: The MoCA and Mini-Mental State Examination (MMSE) were evaluated in two independent studies (clinic-based sample and community-based sample) of MCI and normal cognition (NC) controls, using receiver operating characteristic curve analyses: area under the curve (AUC), sensitivity (Sn), and specificity (Sp). RESULTS: The MoCA modestly discriminated MCI from NC in both study samples (AUC = 0.63 and 0.65): Sn = 0.64 and Sp = 0.36 at a cut-off of 28/29 in the clinic-based sample, and Sn = 0.65 and Sp = 0.55 at a cut-off of 22/23 in the community-based sample. The MoCA's test performance was least satisfactory in the highest (>6 years) education group: AUC = 0.50 (p = 0.98), Sn = 0.54, and Sp = 0.51 at a cut-off of 27/28. Overall, the MoCA's test performance was not better than that of the MMSE. In multivariate analyses controlling for age and gender, MCI diagnosis was associated with a <1-point decrement in MoCA score (η(2) = 0.010), but lower (1-6 years) and no education was associated with a 3- to 5-point decrement (η(2) = 0.115 and η(2) = 0.162, respectively). CONCLUSION: The MoCA's ability to discriminate MCI from NC was modest in this Chinese population, because it was far more sensitive to the effect of education than MCI diagnosis.

Caregiver Burden: Looking Beyond the Unidimensional Total Score.

The Zarit Burden Interview allows caregiver burden to be interpreted from a total score. However, recent studies propose a multidimensional Zarit Burden Interview model. This study aims to determine the agreement between unidimensional (UD) and multidimensional (MD) classification of burden, and differences in predictors among identified groups. We studied 165 dyads of dementia patients and primary caregivers. Caregivers were dichotomized into low-burden and high-burden groups based upon: (1) UD score using quartile cutoffs; and (2) MD model via exploratory cluster analysis. We compared UD versus MD 2×2 classification of burden using κ statistics. Caregivers not showing agreement by either definition were classified as "intermediate" burden. We performed binary logistic regression to ascertain differences in predictive factors. The 2 models showed moderate agreement (κ=0.72, P<0.01), yielding 104 low, 20 intermediate (UD "low burden"/MD "high burden"), and 41 high-burden caregivers. Neuropsychiatric symptoms [odds ratio (OR)=1.27, P=0.003], coresidence (OR=6.32, P=0.040), and decreased caregiving hours (OR=0.99, P=0.018) were associated with intermediate burden, whereas neuropsychiatric symptoms (OR=1.21, P=0.001) and adult children caregivers (OR=2.80, P=0.055) were associated with high burden. Our results highlight the differences between UD and MD classification of caregiver burden. Future studies should explore the significance of the noncongruent intermediate group and its predictors.

Identifying phenomenological differences and recovery of cognitive and non-cognitive symptomatology among delirium superimposed upon dementia patients (DsD) versus those without dementia (DaD) in an acute geriatric care setting.

BACKGROUND: Phenomenological differences between delirium superimposed on dementia (DsD) versus delirium in the absence of dementia (DaD) remain poorly understood. We aimed to identify phenomenological differences in delirium symptoms (cognitive and non-cognitive) and compare delirium recovery trajectories between DsD and DaD. METHODS: We conducted a prospective observational study on individuals admitted to the Geriatric Monitoring Unit (GMU), a five-bed unit specializing in managing older adults with delirium, between December 2010 and August 2012 (n = 234; mean age 84.1 ± 7.4). We collected data on demographics, comorbidities, severity of illness, cognitive and functional scores, and number of precipitants. Cognitive status was assessed using locally validated Chinese Mini-Mental State Examination (CMMSE) and delirium severity assessed using Delirium Rating Scale-Revised-98 (DRS-R98). Delirium disease trajectory was plotted over five days. RESULTS: DsD patients had a longer duration of delirium with slower recovery in terms of cognition and delirium severity scores compared with DaD patients (0.33 (0.0-1.00) vs. 1.0 (0.36-2.00) increase in CMMSE per day, p < 0.001, and 1.49 ± 1.62 vs. 2.63 ± 2.28 decrease in DRS-R98 severity per day, p < 0.001). When cognitive and non-cognitive sub-scores of DRS-R98 were examined separately, we observed steeper recovery in both sub-scores in DaD patients. These findings remained significant after adjusting for significant baseline differences. CONCLUSIONS: Our findings of slower cognitive symptom recovery in DsD patients suggest cognitive reserve play a role in delirium syndrome development and recovery. This merits further studies to potentially aid in appropriate discharge planning and to identify potential pharmacological and non-pharmacological cognitive interventions for hospitalized older persons with delirium.

Prospective longitudinal study of frailty transitions in a community-dwelling cohort of older adults with cognitive impairment.

BACKGROUND: Frailty and cognitive impairment are seemingly distinct syndromes, but have a shared vulnerability to stress in older adults, resulting in poorer outcomes. Although there has been recent interest in cognitive frailty, frailty transitions in relation to cognitive deterioration in older adults with cognitive impairment have not yet been well studied. We thus aim to study frailty transitions and change in cognitive status over 1-year follow-up among subjects with cognitive impairment attending a tertiary Memory Clinic. METHODS: This is a prospective cohort study of mild cognitive impairment (MCI) and mild-moderate Alzheimer's disease (AD) community-dwelling subjects. We obtained data on clinical measures, muscle mass and physical performance measures. Cognitive status was measured using Chinese Mini-Mental State Examination (CMMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. We measured gait speed, hand grip strength, exhaustion and weight loss at baseline, 6 and 12 months to classify subjects according to the modified Fried criteria (involving strength, gait speed, body composition and fatigue) into non-frail (<2 frail categories) and frail categories (≥2 frail categories). Frailty transitions between baseline and 12-months were assessed. We performed random effects statistical modelling to ascertain baseline predictors of longitudinal frailty scores for all subjects and within MCI subgroup. RESULTS: Among 122 subjects comprising 41 MCI, 67 mild and 14 moderate AD, 43.9, 35.8 and 57.1% were frail at baseline respectively. Frailty status regressed in 32.0%, remained unchanged in 36.0%, and progressed in 32.0 % at 12 months. Random effects modelling on whole group showed longitudinal CDR-SB scores (coeff 0.09, 95% confidence interval (CI) 0.03-0.15) and age (coeff 0.04, 95 % CI 0.02-0.07) to be significantly associated with longitudinal frailty score. Among MCI subjects, only female gender (coeff 1.28, 95 % CI 0.21-2.36) was associated with longitudinal frailty score, while mild-moderate AD subjects showed similar results as those of the whole group. CONCLUSIONS: This is the first study to show longitudinal frailty state transitions in cognitively-impaired older adults. Frailty transitions appear to be independent of progression in cognitive status in earliest stages of cognitive impairment, while mild-moderate AD subjects showed associations with age and cognitive deterioration. The potential for cognitive frailty as a separate therapeutic entity for future physical frailty prevention requires further research with a suitably powered study over a longer follow-up period.

Differential perceptions of quality of life (QoL) in community-dwelling persons with mild-to-moderate dementia.

BACKGROUND: Discordance between patient- and caregiver-reported quality of life (QoL) is well recognized. This study sought to (i) identify predictors of discrepancy between patient- and caregiver-rated QoL amongst community-dwelling persons with mild-to-moderate dementia, and (ii) differentiate between patients who systematically rate their QoL lower versus those who rate their QoL higher relative to their caregiver ratings. METHODS: We recruited 165 patient-caregiver dyads with mild-to-moderate dementia. Quality of life in Alzheimer's disease (QoL-AD) scale was administered separately to patients and caregivers. Data on socio-demographics, interpersonal relationship, and disease-related characteristics (cognitive performance, mood, neuropsychiatric symptoms, functional ability, and caregiver burden) were collected. Patient-caregiver dyads were categorized based on whether patient-rated QoL was lower or higher than their respective caregiver ratings. Univariate analyses and multiple regression models were performed to identify predictors of dyadic rating discrepancy. RESULTS: Mean patient-rated QoL was significantly higher than caregiver rating (mean difference: 3.8 ± 7.1, p < 0.001). Majority (111 (67.2%)) of patients had more positive self-perceived QoL (QoL-ADp (QoL-AD self rated by the patient) > QoL-ADc (QoL-AD proxy-rated by a caregiver)), compared with those (44 (26.7%)) with poorer self-perceived QoL (QoL-ADp < QoL-ADc). Patient's education level, depressive symptoms, and severity of neuropsychiatric symptoms predicted magnitude of discrepancy. Depression (OR = 1.17, 95% CI = 1.02-1.35) and being cared for by other relative (non-spouse/adult child; OR = 7.54, 95% CI = 1.07-53.03) predicted poorer self-perceived QoL. CONCLUSIONS: Dyadic rating discrepancy in QoL should draw the clinician's attention to patient depression and neuropsychiatric symptoms. Consideration should also be given to nature of patient-caregiver relationship when discordance between patient and caregiver assessments of QoL is observed.

Worry about performance: a unique dimension of caregiver burden.

BACKGROUND: Recent studies that describe the multidimensionality of the Zarit Burden Interview (ZBI) challenge the traditional dual-factor paradigm of personal and role strains (Whitlatch et al., 1991). These studies consistently reported a distinct dimension of worry about caregiver performance (WaP) comprising items 20 and 21.The present study aims to compare WaP against conventional ZBI domains in a predominantly Chinese multi-ethnic Asian population. METHODS: We studied 130 consecutive dyads of family caregivers and patients. Factor analysis of the 22-item ZBI revealed four factors of burden. We compared WaP (factor 4) with the other three factors, personal strain, and role strain via: internal consistency; inter-factor correlation; item-to-total ratio across Clinical Dementia Rating (CDR) stages; predictors of burden; and interaction effect on total ZBI score using two-way analysis of variance. RESULTS: WaP correlated poorly with the other factors (r = 0.05-0.21). It had the highest internal consistency (Cronbach's α = 0.92) among the factors. Unlike other factors, WaP was highly endorsed in mild cognitive impairment and did not increase linearly with disease severity, peaking at CDR 1. Multiple regression revealed younger caregiver age as the major predictor of WaP, compared with behavioral and functional problems for other factors. There was a significant interaction between WaP and psychological strain (p = 0.025). CONCLUSION: Our results corroborate earlier studies that WaP is a distinct burden dimension not correspondent with traditional ZBI domains. WaP is germane to many Asian societies where obligation values to care for family members are strongly influential. Further studies are needed to better delineate the construct of WaP.

Cost of informal care for community-dwelling mild-moderate dementia patients in a developed Southeast Asian country.

BACKGROUND: Cost of informal care constitutes an important component of total dementia care cost. It also reflects resource utilization by patients and caregivers. We aim to quantify the informal cost of care for mild to moderate dementia patients. METHODS: We recruited 165 patient-caregiver dyads with mild to moderate dementia. Informal care burden was assessed using the Resource Utilization in Dementia (RUD)-Lite instrument. A generalized linear model was fitted for association between cost of informal care and cognitive impairment, taking into account patient demographics, disease factors, and use of paid domestic help. Marginal estimates were obtained from the model for the purpose of illustration and discussion. RESULTS: Total hours of informal care by primary caregiver doubled in moderate dementia patients, with 57.9% having paid domestic help to assist in care. Functional factors and use of paid domestic help were significantly associated with informal care costs. Costs were consistently higher for patients without paid domestic help for mild- and moderate dementia. CONCLUSION: This study demonstrates the informal care costs of caring for mild-moderate dementia patients in Singapore, with the unique cost savings provided by live-in paid domestic help, and potentially may aid policy-makers in allocation of resources and support to caregivers.