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  1. Ng TP, Niti M, Chiam PC, Kua EH
    J Gerontol A Biol Sci Med Sci, 2006 Jul;61(7):726-35.
    PMID: 16870636
    BACKGROUND: We sought to assess the validity of the physical and cognitive domains of Lawton and Brody's Instrumental Activities of Daily Living (IADL) scale and its cross-cultural applicability across ethnic groups in an Asian population of community-living older adults.

    METHODS: Using data from a random population sample of noninstitutionalized Chinese, Malay, and Indian older adults 60 years old and older in Singapore (N = 1072), we modeled the dimensional structure of the 8-item IADL Scale using exploratory and confirmatory factor analyses, and assessed its convergent and divergent validity using known group differences and strengths of association.

    RESULTS: Factor analyses yielded two strong and reliable factors representing underlying physical and cognitive dimensions of IADL. The validity of the model was supported by the pattern of associations of the IADL with age, gender, education, self-reported health status, hospitalization, physical comorbidities, dementia and depression, and Mini-Mental State Examination (MMSE) scores. Notably, cognitive IADL showed a greater total effect on MMSE cognitive performance score than did physical IADL, with the effect of physical IADL on MMSE score mostly explained by cognitive IADL. Reasonably good cross-cultural validity was demonstrated among Chinese, Malays, and Indians, with strongest validity for Indians.

    CONCLUSION: The eight-item IADL Scale has physical and cognitive domains and is cross-culturally applicable. The cognitive IADL domain taps a set of activities directly related to cognitive functioning.

  2. Saedon NI, Pin Tan M, Frith J
    J Gerontol A Biol Sci Med Sci, 2020 01 01;75(1):117-122.
    PMID: 30169579 DOI: 10.1093/gerona/gly188
    BACKGROUND: Orthostatic hypotension (OH) is associated with increased risk of falls, cognitive impairment and death, as well as a reduced quality of life. Although it is presumed to be common in older people, estimates of its prevalence vary widely. This study aims to address this by pooling the results of epidemiological studies.

    METHODS: MEDLINE, EMBASE, PubMed, Web of Science, and ProQuest were searched. Studies were included if participants were more than 60 years, were set within the community or within long-term care and diagnosis was based on a postural drop in systolic blood pressure (BP) ≥20 mmHg or diastolic BP ≥10 mmHg. Data were extracted independently by two reviewers. Random and quality effects models were used for pooled analysis.

    RESULTS: Of 23,090 identified records, 20 studies were included for community-dwelling older people (n = 24,967) and six were included for older people in long-term settings (n = 2,694). There was substantial variation in methods used to identify OH with differing supine rest duration, frequency and timing of standing BP, measurement device, use of standing and tilt-tables and interpretation of the diagnostic drop in BP. The pooled prevalence of OH in community-dwelling older people was 22.2% (95% CI = 17, 28) and 23.9% (95% CI = 18.2, 30.1) in long-term settings. There was significant heterogeneity in both pooled results (I2 > 90%).

    CONCLUSIONS: OH is very common, affecting one in five community-dwelling older people and almost one in four older people in long-term care. There is great variability in methods used to identify OH.

  3. Makkar SR, Lipnicki DM, Crawford JD, Kochan NA, Castro-Costa E, Lima-Costa MF, et al.
    J Gerontol A Biol Sci Med Sci, 2020 09 25;75(10):1863-1873.
    PMID: 32396611 DOI: 10.1093/gerona/glaa116
    We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.
  4. Kua CH, Reeve E, Tan DSY, Koh T, Soong JL, Sim MJL, et al.
    J Gerontol A Biol Sci Med Sci, 2021 05 22;76(6):1053-1060.
    PMID: 31965159 DOI: 10.1093/gerona/glaa018
    BACKGROUND: Knowledge of decision-making preference of patients and caregivers is needed to facilitate deprescribing. This study aimed to assess the perspectives of caregivers and older adults towards deprescribing in an Asian population. Secondary objectives were to identify and compare characteristics associated with these attitudes and beliefs.

    METHOD: A cross-sectional survey of two groups of participants was conducted using the Revised Patients' Attitudes Towards Deprescribing questionnaire. Descriptive results were reported for participants' characteristics and questionnaire responses from four factors (belief in medication inappropriateness, medication burden, concerns about stopping, and involvement) and two global questions. Correlation between participant characteristics and their responses was analyzed.

    RESULTS: A total of 1,057 (615 older adults; 442 caregivers) participants were recruited from 10 institutions in Singapore. In which 511 (83.0%) older adults and 385 (87.1%) caregivers reported that they would be willing to stop one or more of their medications if their doctor said it was possible, especially among older adults recruited from acute-care hospitals (85.3%) compared with older adults in community pharmacies (73.6%). Individuals who take more than five medications and those with higher education were correlated with greater agreement in inappropriateness and involvement, respectively.

    CONCLUSIONS: Clinicians should consider discussing deprescribing with older adults and caregivers in their regular clinical practice, especially when polypharmacy is present. Further research is needed into how to engage older adults and caregivers in shared decision making based on their attitudes toward deprescribing.

  5. Deo P, Dhillon VS, Thomas P, Fenech M
    PMID: 34628492 DOI: 10.1093/gerona/glab307
    Red blood cell (RBC) fatty acids status is used as a biomarker of dietary intake of fats however, there is still a paucity of evidence regarding individual fatty acids and modulation of endogenous advanced glycation end-product (AGE) levels. Due to membrane PUFA being a well-known target for peroxidation, we hypothesized that cellular PUFAs are positively associated with circulatory N ε-carboxymethyllysine (CML) that is also influenced by glyoxal (GO) levels in healthy cohorts. To test this, we investigated the association between RBC fatty acids and circulatory AGEs biomarkers in healthy individuals. The results showed a negative association between saturated fatty acids (SFA) and CML and stepwise multivariate regression analysis indicated stearic acid was negatively associated with CML levels (β = -0.200, p=0.008) after adjusting for age, BMI, and gender. In addition, stearic acid: palmitic acid ratio was also negatively correlated with plasma concentrations of CML (rp= -0.191, p = 0.012) and glucose (rp= -0.288, p = 0.0001). Polyunsaturated fatty acids (PUFA) showed a positive association with CML levels particularly, docosapentaenoic acid, γ-Linolenic acid, arachidonic acid, and docosadienoic acid. However, these associations were not evident after the multiple regression analysis adjusted for age, BMI, and gender. A strong negative correlation (rp= -0.98, p< 0.0001) between total PUFA and total SFA was observed. Furthermore, the SFA:PUFA ratio was inversely correlated with CML (rp= -0.227, p< 0.003). Overall, this study indicates that different fats and their combinations may influence the formation of AGEs and that carefully controlled interventions are required to further test this hypothesis.
  6. Dhillon VS, Deo P, Chua A, Thomas P, Fenech M
    J Gerontol A Biol Sci Med Sci, 2022 Feb 03;77(2):243-249.
    PMID: 34508574 DOI: 10.1093/gerona/glab264
    Significant alterations in sleep duration and/or quality of sleep become more pronounced as people get older. Poor sleep in elderly people is associated with adverse health outcomes and cellular aging. We examined the relationship between telomere length (TL) and sleep duration, Health Promotion Index (HPI), and tested whether the presence of Apolipoprotein-E4 (ApoE-ε4) allele affects both sleep and TL. The present study was carried out in 174 healthy participants (21% male; mean age 53.79 years) from South Australia. Lymphocyte TL was measured by real-time quantitative PCR (qPCR) and ApoE genotype was determined by TaqMan assay. HPI was calculated from a questionnaire regarding 8 lifestyle habits, including sleeping hours. Multivariate regression analysis was used to establish these associations adjusted for specified confounders. TL was found to be inversely associated with age (r = -0.199; p = .008) and body mass index (r = -0.121; p = .11), and was significantly shorter in participants who slept for less than 7 hours (p = .001) relative to those sleeping ≥7 hours. TL was positively correlated with HPI (r = 0.195; p = .009). ApoE-ε4 allele carriers who slept for less than 7 hours had shortest TL (p = .01) compared to noncarriers. Plasma soluble receptor for advanced glycation end product (sRAGE) level was significantly (p = .001) lower in individuals who sleep less than 7 hours and ApoE-ε4 carriers. Our results suggest that inadequate sleep duration or poor HPI is associated with shorter TL in cognitively normal people and that carriage of APOE-ε4 genotype may influence the extent of these effects.
  7. Tan FHP, Ting ACJ, Najimudin N, Watanabe N, Shamsuddin S, Zainuddin A, et al.
    J Gerontol A Biol Sci Med Sci, 2023 Oct 28;78(11):1944-1952.
    PMID: 37453137 DOI: 10.1093/gerona/glad169
    Alzheimer's disease (AD) is the most prevalent type of dementia globally. The accumulation of amyloid-beta (Aβ) extracellular senile plaques in the brain is one of the hallmark mechanisms found in AD. Aβ42 is the most damaging and aggressively aggregating Aβ isomer produced in the brain. Although Aβ42 has been extensively researched as a crucial peptide connected to the development of the characteristic amyloid fibrils in AD, the specifics of its pathophysiology are still unknown. Therefore, the main objective was to identify novel compounds that could potentially mitigate the negative effects of Aβ42. 3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-carbonyl]amino]propanoic acid (THICAPA) was identified as a ligand for Aβ42 and for reducing fibrillary Aβ42 aggregation. THICAPA also improved cell viability when administered to PC12 neuronal cells that were exposed to Aβ42. Additionally, this compound diminished Aβ42 toxicity in the current AD Drosophila model by rescuing the rough eye phenotype, prolonging the life span, and enhancing motor functions. Through next-generation RNA-sequencing, immune response pathways were downregulated in response to THICAPA treatment. Thus, this study suggests THICAPA as a possible disease-modifying treatment for AD.
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