Coffee and tea consumption and dementia risk: The role of sex and vascular comorbidities.

BACKGROUND: Coffee and tea consumption has been linked to dementia. However, it remained unknown how sex and vascular risk factors modify the association. We aimed to investigate the association of coffee and tea consumption with dementia and whether sex and vascular comorbidities modified the association. METHODS: We included 278 elderly patients with Alzheimer's disease (AD) and 102 patients with vascular dementia (VaD) from three hospitals; controls (N = 468) were recruited during the same period. We collected the frequency and amount of coffee and tea consumption and the presence of vascular comorbidities. The multinomial logistic regression model was utilized to evaluate the association of coffee and tea consumption with dementia, stratified by sex and vascular comorbidities. RESULTS: Different combinations and quantities of coffee and tea consumption protected against AD and VaD. Consumption of ≥3 cups of coffee or tea per day was protective against AD [adjusted odds ratio (aOR) = 0.42; 95% confidence interval (CI) = 0.22-0.78)] and VaD (aOR = 0.42; 95% CI = 0.19-0.94). Stratified analyses showed that the protective effects of a higher quantity of coffee and tea against AD were more pronounced among females and individuals with hypertension. Consumption of either coffee or tea was associated with a decreased risk of VaD among diabetic participants (aOR = 0.23; 95% CI = 0.06-0.98). Hyperlipidemia modified the association of coffee or tea consumption on the risk of AD and VaD (both Pinteraction < 0.01). CONCLUSION: The risk of AD and VaD was lower with increased consumption of coffee and tea; the impact differed by sex and vascular comorbidities including hypertension, hyperlipidemia, and diabetes.

Effect of indoor air quality on the association of long-term exposure to low-level air pollutants with cognition in older adults.

BACKGROUND: How indoor air quality affects the temporal associations of long-term exposure to low-level air pollutants with cognition remains unclear. METHODS: This cohort study (2011-2019) included 517 non-demented older adults at baseline with four repeated cognitive assessments. The time-varying exposure to PM2.5, PM10, NO2, SO2, CO, and O3 was estimated for each participant from 1994 to 2019. Indoor air quality was determined by ventilation status and daily indoor time. Generalized linear mixed models were used to analyze the association of air pollutants, indoor air quality, and cognition adjusting for important covariates. RESULTS: Over time, per 2.97 µg/m3 (i.e., an interquartile range) increment of PM2.5 was associated with the poor performance of memory (Z score of a cognitive test, ߈:-0.14), attention (߈:-0.13), and executive function (߈:-0.20). Similarly, per 2.05 µg/m3 increase in PM2.5-10 was associated with poor global cognition [adjusted odds ratio (aOR): 1.48, ߈:-0.28], attention (߈:-0.07), and verbal fluency (߈:-0.09); per 4.94 µg/m3 increase in PM10 was associated with poor global cognition (aOR: 1.78; ߈:-0.37). In contrast, per 2.74 ppb increase in O3 was associated with better global cognition (߈:0.36 to 0.47). These associations became more evident in participants with poor ventilation or short daily indoor time (<12.5 h/day). For global cognition, the exposure to a 10-µg/m3 increment in PM2.5, PM2.5-10, and PM10 corresponded to 1.4, 5.8, and 2.8 years of aging, respectively. CONCLUSION: This study demonstrated how indoor air quality in areas using clean fuels differentially affected the associations of long-term exposure to low-level air pollutants with cognition. Tightening air quality standards may help prevent dementia.

Association of subclinical depressive symptoms and sleep with cognition in the community-dwelling older adults.

BACKGROUND: /Purpose: This study aimed to explore the association of subclinical depressive symptoms and sleep with cognition in community-dwelling Taiwanese older adults. METHODS: This four-year prospective cohort study (2015-2019) included 379 participants aged 65 years or older from the annual senior health checkup program at National Taiwan University Hospital who were followed up two years later. Global and domain cognitive functions were assessed using validated neuropsychological tests. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression (CES-D) Scale. Sleep quality was evaluated using the Pittsburg Sleep Quality Index (PSQI). Excessive daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Generalized linear mixed models were used to explore the associations of subclinical depressive symptoms and sleep variables with cognition, adjusting for important covariates. Stratification analyses were performed using the sleep variables. RESULTS: Over time, depressive symptoms were associated with poor performance of memory (߈ = 0.24, P = 0.04) and executive function (߈ = -0.24, P = 0.03). Poor sleep quality (elevated PSQI score) was associated with poor memory performance (߈ = -0.04 to -0.03, P < 0.05). Excessive daytime sleepiness (elevated ESS score) was associated with poor performance of memory (߈ = -0.02, P < 0.05) and executive function (߈ = -0.02, P = 0.001). At baseline, better sleep quality and no excessive daytime sleepiness were associated with better memory performance over time. CONCLUSION: Subclinical depressive symptoms, worse sleep quality, and excessive daytime sleepiness were differentially associated with impairment of cognitive domains (mainly memory and executive function).

The association between retinal vascular fractal dimension and cognitive function in the community-dwelling older adults cohort TIGER.

BACKGROUND/PURPOSE: The small retinal vessels reflect cerebral microcirculation and its fractal dimension (Df), representing the complexity of the retinal microcirculation. However, the connection between retinal circulation and cognitive function lacked consistent and longitudinal evidence. This study aimed to explore the association between retinal vascular complexity and cognitive impairment over time in non-demented community-dwelling older adults. METHODS: This four-year prospective cohort study (2015-2019) is part of the ongoing Taiwan Initiative for Geriatric Epidemiological Research (TIGER, 2011 to present). Of the 434 older adults (age >65) recruited, 207 participants were included for analysis. The retinal vascular Df was assessed by baseline images from fundus photography (2015-2017). Global (Montreal Cognitive Assessment-Taiwanese version, MoCA-T) and domain-specific cognition were assessed at the baseline and 2-year follow-up (2017-2019). The multivariable linear regression models and generalized linear mixed models were used to evaluate the association of Df with cognitive decline/impairment over time. RESULTS: Decreased left retinal vascular complexity was associated with poor attention performance (ß = -0.40). As follow-up time increased, decreased vascular complexity was associated with poor memory performance (right: ß = -0.25; left: ß = -0.19), and decreased right vascular complexity was associated with poor attention performance (ß = -0.18). CONCLUSION: Low retinal vascular complexity of the right or left eye may be differentially associated with cognitive domains in community-dwelling older adults over two years. The retinal vascular Df of either eye may be served as a screening tool for detecting cognitive impairment in the preclinical phase of dementia.

Association between Helicobacter pylori infection and cognitive impairment in the elderly.

BACKGROUND/PURPOSE: Helicobacter pylori (H. pylori) infection has been positively associated with cognitive impairment. However, previous studies have shown inconsistent findings. METHODS: This cross-sectional study included 587 elderly participants (age ≧ 65) from the annual elderly health checkup program at the National Taiwan University Hospital from 2011 to 2013. Both global and domain-specific cognition were assessed using various neuropsychiatric tests. Multivariable linear regression and logistic regression models were utilized to assess the association between the serum H. pylori IgG level and cognitive impairment. RESULTS: Compared with the lowest quartile of H. pylori IgG (Q1), the highest quartile (Q4) was associated with lower scores on verbal fluency-vegetables (ß = -0.24), domain-specific attention [digit span-forward: ß = -0.19; odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.03-3.24], and attention factors (ß = -0.20; OR= 2.67, 95% CI = 1.51-4.73). No significant association was observed for global cognition. Stratified analyses revealed that, among men, the highest quartile of serum H. pylori IgG (Q4) was associated with impaired scores on verbal fluency-vegetables (ß = -0.38; OR = 3.01, 95% CI = 1.42-6.38). CONCLUSION: Our findings disclosed a positive association between serum H. pylori level and cognitive impairment, which provides important information for the primary prevention of cognitive impairment through the eradication of H. pylori.

Predicting the risk of osteopenia for women aged 40-55 years.

BACKGROUND/PURPOSE: Osteoporosis has been linked to an increased fracture risk and subsequent mortality in the later life. Previous prediction models have focused on osteoporosis in postmenopausal women; however, a prediction tool for osteopenia is needed. Our objective was to establish a prediction model for osteopenia risk in women aged 40-55 years. METHODS: This was a cross-sectional study. A total of 1350 Taiwanese women aged 40-55 years were recruited from a health checkup center from 2009 to 2010. The main outcome measure was osteopenia (-1≥bone mineral density T-score > -2.5). RESULTS: The Osteoporosis Preclinical Assessment Tool (OPAT) developed in this study was based on variables with biological importance to osteopenia and variables that remained significant (p<0.05) in the multivariable analysis, which include age, menopausal status, weight, and alkaline phosphatase level. The OPAT has a total score that ranges from 0 to 7, and categorizes women into high-, moderate-, and low-risk groups. The predictive ability of the OPAT (area under the receiver operating characteristic curve=0.77) was significantly better than that of the Osteoporosis Self-assessment Tool for Asians (area under the receiver operating characteristic curve=0.69). The inclusion of serum total alkaline phosphatase level in the model, which is easy to obtain from routine health checkups, significantly enhanced the sensitivity (McNemar test, p=0.004) for detecting osteopenia in women aged 40-55 years. CONCLUSION: Our findings provide an important tool for identifying women at risk of osteoporosis at the preclinical phase.

Leisure activities, apolipoprotein E e4 status, and the risk of dementia.

BACKGROUND/PURPOSE: Leisure activities have been associated with a decreased risk of dementia. However, to date, no study has explored how apolipoprotein E (ApoE) e4 status or vascular risk factors modified the association between leisure activities and dementia risks. METHODS: This case-control study recruited patients (age ≥ 60 years) with Alzheimer's disease (AD; n = 292) and vascular dementia (VaD; n = 144) and healthy controls (n = 506) from three teaching hospitals in Taiwan between 2007 and 2010. Information on patient's leisure activities were obtained through a questionnaire. Conditional logistic regression models were used to assess the association of leisure activities and ApoE e4 status with the risk of dementia. RESULTS: High-frequency physical activity was associated with a decreased risk of AD [adjusted odds ratio (AOR) = 0.45], and the results become more evident among ApoE e4 carriers with AD (AOR = 0.30) and VaD (AOR = 0.26). Similar findings were observed for cognitive (AOR = 0.42) and social activities (AOR = 0.55) for AD. High-frequency physical, cognitive, and social activities were associated with a decreased risk of VaD (AOR = 0.29-0.60). Physical and social activities significantly interacted with each other on the risk of VaD (pinteraction = 0.04). CONCLUSION: Physical activity consistently protects against AD and VaD. Significant interactions were identified across different types of leisure activities in lowering dementia risk.

Handgrip strength asymmetry and cognitive impairment risk: Insights from a seven-year prospective cohort study.

OBJECTIVES: This study aimed to explore the links of handgrip strength and asymmetry with cognitive impairment. DESIGN: This was a seven-year prospective cohort study. SETTING AND PARTICIPANTS: We used data from wave 3 (2015-2017) to wave 5 (2019-2022) from the ongoing Taiwan Initiative of Geriatric Epidemiological Research (TIGER), with wave 3 as the baseline (n = 446). The study included community-dwelling participants aged 65 years or older. MEASUREMENTS: Handgrip strength was measured, and abnormalities were determined based on handgrip strength weakness and asymmetry. Handgrip strength asymmetry was categorized into three groups at baseline based on the handgrip strength ratio (left handgrip strength/right handgrip strength). Cognitive tests evaluating global and specific cognitive domains were conducted at baseline and two biennial follow-ups. Generalized linear mixed models were utilized to assess the associations of abnormal handgrip strength with global cognition and multiple cognitive domain progression over time. RESULTS: This study included 392 dementia-free participants, with an average age of 75.8 years and 179 (45.7%) males. Mild handgrip strength asymmetry was present in 88 participants (22.4%), while 53 (13.5%) exhibited moderate asymmetry. In men, the coexistence of low handgrip strength and handgrip strength asymmetry was linked to cognitive impairment over time. These associations were observed in global cognition (ß^ = -1.76, 95% CI: -2.79 to -0.74), memory (immediate free recall: ß^ = -0.67, 95% CI: -1.17 to -0.17), executive function (Trail Making Test-A: ß^ = -0.54, 95% CI: -0.94 to -0.13), and attention (Digit span-forward: ß^ = -1.00, 95% CI: -1.46 to -0.54). CONCLUSIONS: This study found that individuals with reduced handgrip strength and handgrip strength asymmetry had an increased risk of cognitive impairment across various domains. Moreover, this association appears to be more pronounced among men than women. Incorporating these simple assessments into regular clinical practice improves the allocation of limited screening resources and timely clinical interventions in older adults.

Cohort profile: the Taiwan Initiative for Geriatric Epidemiological Research - a prospective cohort study on cognition.

Objectives: The Taiwan Initiative for Geriatric Epidemiological Research (TIGER) was founded in 2011 to elucidate the interrelationships among various predictors of global and domain-specific cognitive impairment, with the aim of identifying older adults with an increased risk of dementia in the preclinical phase. Methods: TIGER, a population-based prospective cohort, recruited 605 older adults (aged 65 and above) at baseline (2011-2013). Participants have undergone structured questionnaires, global and domain-specific cognitive assessments, physical exams, and biological specimen collections at baseline and biennial follow-ups to date. Results: By 2022, TIGER has included 4 biennial follow-ups, with the participants comprising 53.9% women and having a mean age of 73.2 years at baseline. After an 8-year follow-up, the annual attrition rate was, reflecting a combination of 9.9% of participants who passed away and 36.2% who dropped out. TIGER has published novel and multidisciplinary research on cognitive-related outcomes in older adults, including environmental exposures (indoor and ambient air pollution), multimorbidity, sarcopenia, frailty, biomarkers (brain and retinal images, renal and inflammatory markers), and diet. Conclusion: TIGER's meticulous design, multidisciplinary data, and novel findings elucidate the complex etiology of cognitive impairment and frailty, offering valuable insights into factors that can be used to predict and prevent dementia in the preclinical phase.

Association between oral health and cognitive impairment in older adults: Insights from a Six-year prospective cohort study.

OBJECTIVE: This study aims to investigate the relationships between four baseline oral conditions (periodontal status, dental caries, tooth wear, and dentition) and repeated global cognition or domain-specific cognition (memory, executive function, attention, and verbal fluency) in non-demented older adults over time. METHODS: This prospective cohort study (2011-2019) enrolled 516 non-demented community-dwelling older adults (age ≥ 65) to explore the association between oral health and cognitive function. Global and domain-specific cognition were assessed biennially (four repeats) using a battery of neuropsychological tests. The baseline oral health conditions were examined, including periodontal status, dental caries, tooth wear, and dentition. The association of these oral conditions with cognition was evaluated by generalized linear mixed models. Stratified analyses were performed by important covariates. RESULTS: Over time, dental caries was associated with poor memory in two different logical memory tests (ß^= -0.06 and ß^= -0.04). Incomplete dentition with less than 28 teeth was associated with poor performance in attention (ß^= -0.05) and verbal fluency (ß^= -0.03). These associations became more evident in those with an elevated inflammatory marker (IL-6, ß^= -0.11 to -0.08). In contrast, tooth wear was associated with better memory in two different logical memory tests (ß^= 0.33 and ß^= 0.36) and better executive function (ß^= 0.06) over time, and this association became more evident in those with the lowest inflammatory marker (IL-6, ß^= 0.10). CONCLUSIONS: Dental caries and incomplete dentition were associated with poor memory, attention, and verbal fluency performance. Conversely, tooth wear was associated with better memory performance and executive function. CLINICAL SIGNIFICANCE: For early prevention of dementia, an evaluation of multiple dental and periodontal status in older adults helps predict the risk of dementia in the preclinical phase. Maintaining intact tooth structure without caries progression and eventually tooth loss may help prevent the worsening of memory, attention, and verbal fluency over time.

Association Between Olfactory Dysfunction and Cognitive Impairment in Dementia-Free Older Adults: A Prospective Cohort Study in Taiwan.

BACKGROUND: Previous studies assessing olfactory function and cognition have mostly been cross-sectional, and few have investigated the Asian geriatric population. OBJECTIVE: To examine the relationships of olfaction with global or domain-specific cognitive function in Taiwanese community-dwelling older adults. METHODS: This cohort study (2015-2019) is part of the Taiwan Initiative for Geriatric Epidemiological Research. The Taiwanese version of the Montreal Cognitive Assessment (MoCA-T) and a battery of neuropsychological tests were assessed at baseline and at a two-year follow-up. The cross-culture modified Sniffin' Sticks Identification Test (SSIT) was utilized to measure olfactory function. Generalized linear mixed models were used to examine the association of olfaction with cognitive performance over two years. RESULTS: Data were collected from 376 participants (55.1% women), with a mean age of 75.6 years. A one-point decrease in the SSIT score (worsening of olfaction) was associated with worse global cognition (MoCA-T: ߈= -0.13), memory (߈= -0.08 to -0.06), and verbal fluency (߈= -0.07). Compared with an SSIT score ≥ 11 (normosmia), an SSIT score < 8 (anosmia) was associated with worse global cognition (MoCA-T: ߈= -0.99), memory (߈= -0.48 to -0.42), executive function (Trail Making Test A: ߈= -0.36), attention (digit span backward: ߈= -0.34), and verbal fluency (߈= -0.45). After stratified analyses, the associations remained in older adults ≥ 75 years, males, and non-carriers of apolipoprotein E ɛ4 in terms of global cognition, memory, and verbal fluency. CONCLUSIONS: Odor identification deficits were associated with poor global or domain-specific cognitive function in a four-year cohort of community-dwelling older adults. Cognitive assessments should be conducted in dementia-free elderly individuals with impaired odor identification.

Grip Strength and Sarcopenia Predict 2-Year Cognitive Impairment in Community-Dwelling Older Adults.

OBJECTIVES: Using the Asian Working Group for Sarcopenia (AWGS2019) and the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, this study examined associations of sarcopenia and its components with specific domains of cognitive impairment over time. DESIGN: A prospective cohort study with a 2-year follow-up. SETTING AND PARTICIPANTS: This study is part of the Taiwan Initiatives for Geriatric Epidemiological Research (TIGER), which recruited participants aged 65 years old who attended the senior health checkup program at National Taiwan University Hospital (NTUH). METHODS: Grip strength was measured using a handgrip dynamometer. Walking speed (m/s) was measured as the time required to walk 8 feet. Muscle mass was measured by performing a bioelectrical impedance analysis. Global cognition (assessed using the Taiwanese version of the Montreal Cognitive Assessment) and 4 cognitive domains (memory, executive function, verbal fluency, and attention) were assessed over time. Associations of sarcopenia and its components with cognitive impairment were evaluated after stratification by sex using generalized linear mixed models adjusted for essential covariates for cognitive impairment. RESULTS: Compared with robust women, those with severe sarcopenia were more likely to have a global cognitive impairment over time (ß = -0.87, P = .03 based on AWGS2019 criteria and ß = -1.07, P = .02 based on the EWGSOP2 criteria). Among men, low grip strength was associated with poor scores on measures of global cognition (ß = -0.80, P = .03), executive function (ß = -0.35, P = .001), verbal fluency (ß = -0.31, P = .02), and attention (ß = -0.34, P = .008) over time. CONCLUSIONS AND IMPLICATIONS: Severe sarcopenia predicted global and specific domains of cognitive impairment in older adults. Poor grip strength predicted cognitive impairment in men but not in women. A screen for sarcopenia severity and low muscle strength may be used to identify the risk of cognitive impairment.

Multimorbid Patterns and Cognitive Performance in the Presence of Informative Dropout Among Community-Dwelling Taiwanese Older Adults.

Background and Objectives: Longitudinal studies among older adults often feature elevated dropout rates and multiple chronic conditions. How Taiwanese multimorbid patterns relate to different cognitive domains remains unclear. This study aims to identify sex-specific multimorbid patterns and associate them with cognitive performance while modeling the risk for dropout. Research Design and Methods: A prospective cohort study (2011-19) in Taiwan recruited 449 Taiwanese older adults without dementia. Global and domain-specific cognition were assessed biennially. We used exploratory factor analysis to identify baseline sex-specific multimorbid patterns of 19 self-reported chronic conditions. We utilized a joint model incorporating longitudinal and time-to-dropout data to examine the association between multimorbid patterns and cognitive performance accounting for the informative dropout via the shared random effect. Results: At the end of the study, 324 participants (72.1%) remained in the cohort, with an average annual attrition rate of 5.5%. We found that advanced age, low levels of physical activities, and poor cognition at baseline were associated with increased dropout risks. Besides, 6 multimorbid patterns were identified, labeled Mental, Renal-vascular, and Cancer-urinary patterns in men, and Mental, Cardiometabolic, and Cancer-endocrine patterns in women. For men, as the follow-up time increased, the Mental pattern was associated with poor global cognition and attention; the Renal-vascular pattern was associated with poor executive function. For women, the Mental pattern was associated with poor memory; as follow-up time increased, and Cardiometabolic patterns were related to poor memory. Discussion and Implications: Sex-specific multimorbid patterns identified in the Taiwanese older population showed differences (notably Renal-vascular pattern in men) from patterns found in Western countries and were differentially associated with cognitive impairment over time. When informative dropout is suspected, appropriate statistical methods should be applied.

Longitudinal trajectories of dietary quality and cognitive performance in older adults: Results from a 6-year cohort study.

BACKGROUND: Diet affects cognitive performance, but most previous studies only assessed diet once. Trajectory analysis of diet measured at multiple timepoints can identify subpopulations requiring more interventional efforts. We thus assessed associations between dietary trajectories and cognitive performance in older adults. METHODS: This was a 6-year prospective cohort study involving 356 ethnically Chinese, non-demented, community-dwelling older adults recruited between 2011 and 2013. At baseline and at 4th- and 6th-year follow-ups, dietary intakes of the participants were assessed using food frequency questionnaires. Dietary quality was graded using the modified Alternative Healthy Eating Index (mAHEI) with seven components; longitudinal trajectories of dietary quality were derived using latent growth mixture modelling. Outcomes were global- and domain-specific cognitive performance (attention, memory, executive functions, and verbal fluency). Multivariable regressions adjusting for important covariates (sex, age, energy intake, APOE risk alleles, depressive symptoms, and body mass index (BMI)) assessed associations between the dietary trajectories and cognitive outcomes. RESULTS: Included participants had a mean age of 71.6 years and a mean BMI of 23.8 kg/m2. Three mutually exclusive dietary quality trajectories, namely "deteriorating", "improving", and "stable-high", were derived. Compared with the stable-high trajectory, the improving trajectory was associated with a lower z-score for the memory domain (ß: -0.403; 95% CI: -0.656, -0.151; P = 0.002), which was consistently observed for the four individual tests of the domain (ß range: -0.324 to -0.448; all P < 0.05). In unadjusted analysis, the deteriorating trajectory was associated with a 0.369 lower z-score for the verbal fluency domain (95% CI: -0.700, -0.039 P = 0.028), though attenuated to borderline significance with adjustment for covariates. Sex and BMI modified some of these associations. No other associations were observed for global cognition or other cognitive domains. CONCLUSIONS: In Taiwanese older adults, consistently high dietary quality is associated with better cognitive performance. Interventions to promote and sustain better dietary quality over time can have substantial impacts on cognitive function.

Arabidopsis SUMO E3 ligase SIZ1 is involved in excess copper tolerance.

The reversible conjugation of the small ubiquitin-like modifier (SUMO) to protein substrates occurs as a posttranslational regulatory process in eukaryotic organisms. In Arabidopsis (Arabidopsis thaliana), several stress-responsive SUMO conjugations are mediated mainly by the SUMO E3 ligase SIZ1. In this study, we observed a phenotype of hypersensitivity to excess copper in the siz1-2 and siz1-3 mutants. Excess copper can stimulate the accumulation of SUMO1 conjugates in wild-type plants but not in the siz1 mutant. Copper accumulated to a higher level in the aerial parts of soil-grown plants in the siz1 mutant than in the wild type. A dramatic difference in copper distribution was also observed between siz1 and wild-type Arabidopsis treated with excess copper. As a result, the shoot-to-root ratio of copper concentration in siz1 is nearly twice as high as that in the wild type. We have found that copper-induced Sumoylation is involved in the gene regulation of metal transporters YELLOW STRIPE-LIKE 1 (YSL1) and YSL3, as the siz1 mutant is unable to down-regulate the expression of YSL1 and YSL3 under excess copper stress. The hypersensitivity to excess copper and anomalous distribution of copper observed in the siz1 mutant are greatly diminished in the siz1ysl3 double mutant and slightly in the siz1ysl1 double mutant. These data suggest that SIZ1-mediated sumoylation is involved specifically in copper homeostasis and tolerance in planta.

The association between metabolic syndrome and successful aging- using an extended definition of successful aging.

OBJECTIVES: To examine the association between metabolic syndrome (MetS) and successful aging among community-dwelling older adults. METHODS: Adults aged ≥ 65 years who participated in the senior health checkup program at National Taiwan University Hospital during 2011-2013 were recruited (N = 467 at baseline). The participants were followed after 4 years and 6 years. MetS was assessed at baseline. Successful aging was evaluated at baseline, 4-year follow-up, and 6-year follow-up. We adopted an extended definition of successful aging, which was defined as three major domains: physiological, psychological, and sociological and economic domains. Generalized linear mixed models were used to assess the association between MetS and successful aging adjusting for time (follow-up years), age, sex, years of education, alcohol consumption and MetS×time interaction term. RESULTS: The mean age of the study population was 72.9 (SD 5.5) years. The absence of baseline MetS had a positive effect on the probability of successful aging over six years. The absences of abdominal obesity, hyperglycemia, reduced high-density lipoprotein cholesterol, and hypertension were associated with the physiological successful aging. The absence of hypertension was the most significant predictor of physiological successful aging [aOR (95% CI) = 2.76 (1.67-4.58), p<0.001]. Significant increased trend was found in the overall and physiological successful aging across MetS status (No MetS, pre MetS, MetS; Ptrend <0.001). CONCLUSIONS: We found that MetS is a risk factor of successful aging among community-dwelling older adults. Public health policy should aim at avoidance of MetS in order to facilitate successful aging in older population.

A Longitudinal Study on the Association of Interrelated Factors Among Frailty Dimensions, Cognitive Domains, Cognitive Frailty, and All-Cause Mortality.

BACKGROUND: Cognitive frailty integrating impaired cognitive domains and frailty dimensions has not been explored. OBJECTIVE: This study aimed to explore 1) associations among frailty dimensions and cognitive domains over time and 2) the extended definitions of cognitive frailty for predicting all-cause mortality. METHODS: This four-year cohort study recruited 521 older adults at baseline (2011-2013). We utilized 1) generalized linear mixed models exploring associations of frailty dimensions (physical dimension: modified from Fried et al.; psychosocial dimension: integrating self-rated health, mood, and social relationship and support; global frailty: combining physical and psychosocial frailty) with cognition (global and domain-specific) over time and 2) time-dependent Cox proportional hazard models assessing associations between extended definitions of cognitive frailty (cognitive domains-frailty dimensions) and all-cause mortality. RESULTS: At baseline, the prevalence was 3.0% for physical frailty and 37.6% for psychosocial frailty. Greater physical frailty was associated with poor global cognition (adjusted odds ratio = 1.43-3.29, ß: -1.07), logical memory (ß: -0.14 to -0.10), and executive function (ß: -0.51 to -0.12). Greater psychosocial frailty was associated with poor global cognition (ß: -0.44) and attention (ß: -0.15 to -0.13). Three newly proposed definitions of cognitive frailty, "mild cognitive impairment (MCI)-psychosocial frailty," "MCI-global frailty," and "impaired verbal fluency-global frailty," outperformed traditional cognitive frailty for predicting all-cause mortality (adjusted hazard ratio = 3.49, 6.83, 3.29 versus 4.87; AIC = 224.3, 221.8, 226.1 versus 228.1). CONCLUSION: Notably, extended definitions of cognitive frailty proposed by this study better predict all-cause mortality in older adults than the traditional definition of cognitive frailty, highlighting the importance of psychosocial frailty to reduce mortality in older adults.

Incorporation of covariates in simultaneous localization of two linked loci using affected relative pairs.

BACKGROUND: Many dichotomous traits for complex diseases are often involved more than one locus and/or associated with quantitative biomarkers or environmental factors. Incorporating these quantitative variables into linkage analysis as well as localizing two linked disease loci simultaneously could therefore improve the efficiency in mapping genes. We extended the robust multipoint Identity-by-Descent (IBD) approach with incorporation of covariates developed previously to simultaneously estimate two linked loci using different types of affected relative pairs (ARPs). RESULTS: We showed that the efficiency was enhanced by incorporating a quantitative covariate parametrically or non-parametrically while localizing two disease loci using ARPs. In addition to its help in identifying factors associated with the disease and in improving the efficiency in estimating disease loci, this extension also allows investigators to account for heterogeneity in risk-ratios for different ARPs. Data released from the collaborative study on the genetics of alcoholism (COGA) for Genetic Analysis Workshop 14 (GAW 14) were used to illustrate the application of this extended method. CONCLUSIONS: The simulation studies and example illustrated that the efficiency in estimating disease loci was demonstratively enhanced by incorporating a quantitative covariate and by using all relative pairs while mapping two linked loci simultaneously.

Long-Term Exposure to Air Pollutants and Cognitive Function in Taiwanese Community-Dwelling Older Adults: A Four-Year Cohort Study.

BACKGROUND: Previous studies have assessed limited cognitive domains with relatively short exposure to air pollutants, and studies in Asia are limited. OBJECTIVE: This study aims to explore the association between long-term exposure to air pollutants and cognition in community-dwelling older adults. METHODS: This four-year prospective cohort study recruited 605 older adults at baseline (2011-2013) and 360 participants remained at four-year follow-up. Global and domain-specific cognition were assessed biennially. Data on PM2.5 (particulate matter≤2.5µm diameter, 2005-2015), PM10 (1993-2015), and nitrogen dioxide (NO2, 1993-2015) were obtained from Taiwan Environmental Protection Administration (TEPA). Bayesian Maximum Entropy was utilized to estimate the spatiotemporal distribution of levels of these pollutants. RESULTS: Exposure to high-level PM2.5 (>29.98µg/m3) was associated with an increased risk of global cognitive impairment (adjusted odds ratio = 4.56; ß= -0.60). High-level PMcoarse exposure (>26.50µg/m3) was associated with poor verbal fluency (ß= -0.19). High-level PM10 exposure (>51.20µg/m3) was associated with poor executive function (ß= -0.24). Medium-level NO2 exposure (>28.62 ppb) was associated with better verbal fluency (ß= 0.12). Co-exposure to high concentrations of PM2.5, PMcoarse or PM10 and high concentration of NO2 were associated with poor verbal fluency (PM2.5 and NO2: ß= -0.17; PMcoarse and NO2: ß= -0.23; PM10 and NO2: ß= -0.21) and poor executive function (PM10 and NO2: ß= -0.16). These associations became more evident in women, apolipoprotein ɛ4 non-carriers, and those with education > 12 years. CONCLUSION: Long-term exposure to PM2.5 (higher than TEPA guidelines), PM10 (lower than TEPA guidelines) or co-exposure to PMx and NO2 were associated with poor global, verbal fluency, and executive function over 4 years.

Impacts of Kidney Dysfunction and Cerebral Cortical Thinning on Cognitive Change in Elderly Population.

BACKGROUND: Cerebral cortical thickness is a neuroimaging biomarker to predict cognitive decline, and kidney dysfunction (KD) is associated with cortical thinning. OBJECTIVE: This study aimed to investigate the effects of KD and cortical thinning on cognitive change in a prospective cohort study. METHODS: A total of 244 non-demented participants were recruited from elderly health checkup program and received cognitive exams including Montreal Cognitive Assessment (MoCA) and different cognitive domains at baseline and three biannual follow-ups afterwards. KD was defined as having either glomerular filtration rate <60 ml/min/1.73 m2 or proteinuria. Cortical thickness of global, lobar, and Alzheimer's disease (AD) signature area were derived from magnetic resonance imaging at baseline, and cortical thinning was defined as the lowest tertile of cortical thickness. Generalized linear mixed models were applied to evaluate the effects of KD and cortical thinning on cognitive changes. RESULTS: KD was significantly associated with the decline in attention function (ß= -0.29). Thinning of global (ß= -0.06), AD signature area (ß= -0.06), temporal (ß= -0.06), and parietal lobes (ß= -0.06) predicted poor verbal fluency over time, while temporal lobe thinning also predicted poor MoCA score (ß= -0.19). KD modified the relationship between thinning of global, frontal, and limbic, and change of logical memory function (pinteraction < 0.05). When considering jointly, participants with both KD and cortical thinning had greatest decline in attention function compared with those without KD or cortical thinning (ß= -0.51, ptrend = 0.008). CONCLUSIONS: KD and cortical thinning have joint effect on cognitive decline, especially the attention function. Reverse associations may exist between cortical thinning and memory function in participants with KD, though the results should be interpreted cautiously as an exploratory analysis.