Gender difference in the association between TyG index and subclinical atherosclerosis: results from the I-Lan Longitudinal Aging Study.

BACKGROUND: Insulin resistance (IR) is a known risk factor for cardiovascular disease (CVD) in non-diabetic patients through the association of hyperglycemia or associated metabolic factors. The triglyceride glucose (TyG) index, which was defined by incorporating serum glucose and insulin concentrations, was developed as a surrogate marker of insulin resistance. We aimed to investigate the association between the TyG index and the early phase of subclinical atherosclerosis (SA) between the sexes. METHODS: The I-Lan Longitudinal Aging Study (ILAS) enrolled 1457 subjects aged 50-80 years. For each subject, demographic data and the TyG index {ln[fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)]/2} were obtained. Patients were further stratified according to sex and the 50th percentile of the TyG index (≥ 8.55 or < 8.55). SA was defined as the mean carotid intima-media thickness (cIMT) at the 75th percentile of the entire cohort. Demographic characteristics and the presence of SA were compared between the groups. Logistic regression analysis was performed to assess the relationship between TyG index and SA. RESULTS: Patients with a higher TyG index (≥ 8.55) had a higher body mass index (BMI), hypertension (HTN) and diabetes mellitus (DM). They had higher lipid profiles, including total cholesterol (T-Chol) and low-density lipoprotein (LDL), compared to those with a lower TyG index (< 8.55). Gender disparity was observed in non-diabetic women who had a significantly higher prevalence of SA in the high TyG index group than in the low TyG index group. In multivariate logistic regression analysis, a high TyG index was independently associated with SA in non-diabetic women after adjusting for traditional risk factors [adjusted odds ratio (OR): 1.510, 95% CI 1.010-2.257, p = 0.045] but not in non-diabetic men. The TyG index was not associated with the presence of SA in diabetic patients, irrespective of sex. CONCLUSION: A high TyG index was significantly associated with SA and gender disparity in non-diabetic patients. This result may highlight the need for a sex-specific risk management strategy to prevent atherosclerosis.

Large-Scale Structural Covariance Networks Predict Age in Middle-to-Late Adulthood: A Novel Brain Aging Biomarker.

The aging process is accompanied by changes in the brain's cortex at many levels. There is growing interest in summarizing these complex brain-aging profiles into a single, quantitative index that could serve as a biomarker both for characterizing individual brain health and for identifying neurodegenerative and neuropsychiatric diseases. Using a large-scale structural covariance network (SCN)-based framework with machine learning algorithms, we demonstrate this framework's ability to predict individual brain age in a large sample of middle-to-late age adults, and highlight its clinical specificity for several disease populations from a network perspective. A proposed estimator with 40 SCNs could predict individual brain age, balancing between model complexity and prediction accuracy. Notably, we found that the most significant SCN for predicting brain age included the caudate nucleus, putamen, hippocampus, amygdala, and cerebellar regions. Furthermore, our data indicate a larger brain age disparity in patients with schizophrenia and Alzheimer's disease than in healthy controls, while this metric did not differ significantly in patients with major depressive disorder. These findings provide empirical evidence supporting the estimation of brain age from a brain network perspective, and demonstrate the clinical feasibility of evaluating neurological diseases hypothesized to be associated with accelerated brain aging.

Associations between low circulatory low-density lipoprotein cholesterol level and brain health in non-stroke non-demented subjects.

Low-density lipoprotein cholesterol (LDL-C) and hypertension have independent and synergistic effects on atherosclerotic cardiovascular disease. However, the role of circulatory LDL-C and its possible interactions with hypertension in brain health have been poorly investigated. The study aimed to investigate the relationship between the circulatory LDL-C level and (1) brain structures, grey-matter volume (GMV) and white matter hyperintensity (WMH) and (2) cognitive functions, and whether hypertension plays a role in these relationships. Subjects who were non-stroke and non-demented were prospectively recruited from the community-based I-Lan Longitudinal Aging Study. High-resolution 3T MRI was performed with GM and WMH segmentation. GMVs, total and regional including Alzheimer's disease-susceptible area, and WMH volumes were measured. Neurological tests including verbal memory, visuospatial, and verbal executive functions were assessed. Eight-hundred-and-two participants (59.2 ±â€¯5.7 years; 44% men) were included. Multivariate linear regression analyses showed that low circulatory LDL-C levels (<98 mg/dL) were significantly associated with reduced GMVs in frontal (standardized ß = -0.130; p = 0.003) and posterior cingulate (ß = -0.113; p = 0.032) regions in hypertensive but not normotensive subjects. In addition, low circulatory LDL-C levels, combined with hypertension, had the lowest posterior cingulate GMV (ß = -0.073; p = 0.021), highest periventricular WMH (ß = 0.089; p = 0.011) and lowest verbal memory test scores (ß = -0.088; p = 0.035) compared with neither low circulatory LDL-C level nor hypertension, and either hypertension or low circulatory LDL-C level. Age, sex, total intracranial volume, vascular risk factors, level of other circulatory lipids, and the taking of anti-hypertensive and lipid-lowering medications were adjusted. In conclusion, the role of circulatory LDL-C level and its interactive effect with hypertension on brain health are firstly demonstrated. A low circulatory LDL-C level was associated with reduced regional brain GMVs in hypertensive but not normotensive subjects. In addition, there seems a combined detrimental-effect of low circulatory LDL-C levels with hypertension on posterior cingulate GMV, WMH, and verbal memory.

Strictly Lobar Cerebral Microbleeds Are Associated With Cognitive Impairment.

BACKGROUND AND PURPOSE: Different distributions of cerebral microbleeds (CMBs) are associated with distinct pathological mechanisms. Lobar CMBs are thought to be related to cerebral amyloid angiopathy, whereas deep or infratentorial CMBs are related to hypertensive vasculopathy. The present study aimed to evaluate the effects of CMBs and their locations on a variety of cognitive domains. METHODS: Study subjects were selected from the community-based I-Lan Longitudinal Aging Study. We assessed cognitive domains, including verbal memory, language, visuospatial executive function, and verbal executive function. CMBs were evaluated using 3T susceptibility-weighted magnetic resonance imaging. RESULTS: We studied 959 subjects (mean±SD, 62.5±8.6 years; 425 [44.3%] men). CMBs were found in 14.2% of the population. We classified subjects with CMBs into 2 different groups based on the locations of their CMBs: (1) deep or infratentorial (85 subjects, 8.8% of population) and (2) strictly lobar (49, 5.1%). Multivariate linear analysis showed that strictly lobar CMBs were significantly associated with deficits in global cognitive function (Mini-Mental State Examination) and visuospatial executive function, as determined by the copy test of the Taylor complex figure test and the clock drawing test. We adjusted our results for age, sex, years of education, cardiovascular risk factors, and other markers of cerebral small vessel disease, lacunes, and white matter hyperintensity. Deep or infratentorial CMBs were not associated with changes in cognitive function in our population. CONCLUSIONS: Strictly lobar, but not deep or infratentorial, CMBs are associated with changes in cognitive function, especially in visuospatial executive functions. Cerebral amyloid angiopathy may be the underlying pathology associated with CMB-related cognitive impairment.

Reduced cerebellar gray matter is a neural signature of physical frailty.

Physical frailty has been recognized as a clinical syndrome resulting from declines in various physiological systems; however, the role of the central nervous system in the pathophysiology of frailty remains unclear. The I-Lan Longitudinal Aging Study randomly sampled community-dwelling people aged 50 or older for a brain magnetic resonance imaging study. All participants were assessed for frailty status (robust, prefrail, and frail) based on the presence of five frailty components: slow walking speed, muscle weakness, low physical activity, exhaustion and weight loss (Fried criteria). Gray matter volume (GMV) changes associated with frailty status and individual frailty components were examined. Overall, 456 participants (64.0 ± 8.5 years, 47.6% women) were included in this study. The prefrail (n = 178, 39.0%) and frail (n = 19, 4.2%) subjects were grouped for analysis. The prefrail-frail group showed reduced GMV, compared to the robust group (n = 259, 56.8%), in the cerebellum, hippocampi, middle frontal gyri, and several other cerebral regions (corrected P < 0.05). Each frailty component was associated with GMV changes in functionally related brain areas. Hierarchical cluster analysis categorized these components into three subsets. Motor-related components, including weakness, low activity, and slowness, comprised one subset with a common cerebellar involvement. Exhaustion and weight loss were the other two subsets without cerebellar changes. To conclude, physical frailty is associated with a decreased reserve in specific brain regions, especially cerebellum. Further longitudinal studies are needed to explore if the cerebellum- and noncerebellum-based frailty components reflect a distinctive future risk for developing frailty.

Association between masseter muscle volume, nutritional status, and cognitive status in older people.

OBJECTIVES: Clinical evidence has suggested that oral function is associated with cognitive, physical, and nutritional status of older people. A smaller volume of masseter, a crucial muscle for mastication, was associated with frailty. It has remained unknown if smaller masseter is associated with cognitive impairment. The current study investigated the association between masseter muscle volume, nutritional status, and cognitive status in older people. MATERIALS AND METHODS: We recruited 19 patients with mild cognitive impairment (MCI), 15 patients with Alzheimer's disease (AD), and 28 sex and age-matched non-cognitive impairment (non-CI) older subjects. The number of missing teeth (NMT), masticatory performance (MP), maximal hand-grip force (MGF), and calf circumference (CC) were assessed. The masseter volume index (MVI) was calculated based on the masseter volume measured using magnetic resonance imaging. RESULTS: The MVI was significantly lower in the AD group, compared to the MCI as well as the non-CI group. Multiple regression analyses revealed that the MVI was significantly associated with nutritional status (as indexed by CC) in the analysis of combination of NMT, MP, and the MVI. Moreover, the MVI was a significant predictor of CC only in patients with cognitive impairment (i.e., MCI+AD) but not in the non-CI group. CONCLUSIONS: Our findings suggested that in addition to the NMT and MP, masseter volume is a critical oral factor associated with cognitive impairment. CLINICAL RELEVANCE: Reduction of MVI should be carefully monitored for patients with dementia and frailty, to whom a lower MVI may indicate worse nutrient intake.

Low masseter muscle mass is associated with frailty in community-dwelling older adults: I-Lan Longitudinal Aging Study.

BACKGROUND: Sarcopenia, defined as age-related diminution of muscle mass and strength, is a key determinant of frailty status and progression. We investigated the hypothesis that changing masseter muscle structure with advancing age may contribute to the development of frailty. METHODS: Study data were excerpted from the I-Lan Longitudinal Aging Study, a research cohort of community-dwelling residents aged ≥53 years from Yilan (I-Lan) County, Taiwan. The study sample comprised 56 subjects classified as frail, 41 pre-frail, and 41 robust, according to Cardiovascular Health Study criteria; all groups were matched by age and sex. Masseter muscle volume was quantified based on T1-weighted magnetic resonance imaging, and adjusted for height to derive the masseter volume index (MVI). Appendicular skeletal muscle mass index (SMI) was determined by dual-energy X-ray absorptiometry, and used to derive the height-adjusted skeletal mass index (SMI). Nutrition status was assessed with the Mini-Nutritional Assessment (MNA) form. RESULTS: The MVI was significantly smaller in frail versus pre-frail subjects. Among frail individuals, only the MVI was significantly correlated with MNA scores. MVI, but not SMI, was associated with increased risk of being frail versus pre-frail. An MVI cut-off score of 9.5 cm3/m2 in males discriminated frail from pre-frail status with acceptable sensitivity and specificity. Low MVI was associated with the frailty criteria of slowness. CONCLUSIONS: MVI is a potential clinical index for evaluating phenotypic frailty. Diminished masseter muscle volume may predispose pre-frail/frail elders to depletion of physical reserves, consequent to its detrimental effect on oral functioning and nutrient intake.

Sex difference in the association between pathological albuminuria and subclinical atherosclerosis: insights from the I-Lan longitudinal aging study.

BACKGROUND: Pathological albuminuria (PAU) (urinary albumin creatinine ratio [UACR] ≥30 mg/g) is an independent risk factor of cardiovascular disease. PAU is more prevalent in men than women. We aimed to compare the association of PAU and the early phase of subclinical atherosclerosis (SA) between sexes. METHODS: 1228 subjects aged 50-90 years were stratified by sex and UACR (normal or PAU). SA was defined as mean carotid intima-media thickness ≥75th percentile of the cohort. Demographics and SA prevalence were compared between groups. Multivariate logistic regression was performed to assess the relationship between PAU and SA. RESULTS: Both men and women with PAU had increased prevalence of hypertension, anti-hypertensive therapy, and metabolic syndrome than controls. Men with PAU were older and had greater waist circumference and total body fat percentage. Sex disparity was observed in associations between waist-to-height ratio, total body fat, and UACR. After adjusting for traditional risk factors, multivariate logistic regression disclosed that PAU was independently associated with SA in men (adjusted odds ratio 1.867, 95% CI 1.066-3.210) but not in women. CONCLUSION: The relationship of PAU and SA differed between sexes. This result may highlight the need for sex-specific risk management strategies to prevent atherosclerosis.

The association between serum activin A levels and albuminuria among community-dwelling middle-aged and older adults in Taiwan.

Activin A, a cytokine belonging to the transforming growth factor-ß family, has been shown to play pivotal roles in tissue remodeling after renal injury and is present in elevated levels in diabetic patients. However, the association between activin A and albuminuria remains unclear. We aimed to evaluate their association by using cross-sectional data from community-dwelling middle-aged and older adults in Taiwan. We assessed 466 participants (67% male; mean age 71 ± 13 years) from the I-Lan Longitudinal Aging study for whom data pertaining to serum activin A level and urine albumin-to-creatinine ratio (UACR) were available. Of these, 323 (69%) had normal albuminuria, 123 (26%) had microalbuminuria, and 20 (4%) had overt albuminuria. Patients with overt albuminuria and microalbuminuria had significantly higher activin A concentrations than those in the normal albuminuria group (p < 0.001). Circulating activin A was significantly correlated with multiple risk factors, including higher systolic blood pressure and higher UACR. Univariate and multivariate results indicated that activin A level was an independent variable for albuminuria. The cutoff value of 602 pg/mL of activin A demonstrated a sensitivity of 70.6% and specificity of 75.7% (AUC 0.774) in diagnosing overt albuminuria. In conclusion, middle-aged and older adults with elevated activin A levels were associated with a higher incidence of albuminuria.

Unfavorable body composition and quality of life among community-dwelling middle-aged and older adults: What really matters?

OBJECTIVE: To evaluate the impact of individual components of unfavorable body composition and their combinations on quality of life (QoL) among middle-aged and older adults. METHODS: Data from 1779 participants (53.1 % female; mean age 63.9 ± 9.2 years) from the I-Lan Longitudinal Aging Study were analyzed in this study. Demographic characteristics of all participants and data from anthropometric measurements, functional assessments, dual-energy X-ray absorptiometry scans, and surveys of QoL were obtained. Low skeletal muscle mass was defined by the Asian Working Group of Sarcopenia consensus, and obesity was defined by waist circumference (WC), body fat percentage, or body mass index (BMI). QoL was assessed by the 12-Item Short Form Health Survey version 2, which was divided into the physical component summary (PCS) and mental component summary (MCS). The composite score was determined based on the items of unfavorable body composition. Independent associations between unfavorable body composition components and QoL were evaluated by the multivariate linear regression model. Z transformation was performed to facilitate evaluation between different components of body composition and their relationship with QoL. RESULTS: All definitions of obesity were significantly associated with a lower PCS score (WC: ß=-1.2, SE = 0.3, p < 0.001; body fat percentage: ß=-1.0, SE = 0.3, p < 0.001; BMI: ß=-0.9, SE = 0.3, p = 0.002 in the fully adjusted model). The PCS score decreased linearly as the composite score of unfavorable body composition increased, especially when obesity was defined by WC (score = 1: ß=-0.7, SE = 0.4, p = 0.053, score = 2: ß=-1.1, SE = 0.4, p = 0.008; score = 3: ß=-2.4, SE = 1.0, p = 0.013). After Z transformation, obesity was significantly negatively associated with the PCS score (ß=-0.9∼-0.2, SE = 0.1∼0.2, p values all less than 0.01). In contrast, a one-standard-deviation increase in WC was associated with a significantly higher MCS score (ß = 0.3, SE = 0.1, p = 0.019). CONCLUSIONS: Community-dwelling middle-aged and older people with obesity had significantly lower PCS scores, and the effect was enhanced when low skeletal muscle mass or osteopenia/osteoporosis was present. Central obesity was the only unfavorable body composition parameter with negative effects on both the physical and the mental domains of QoL. Further longitudinal or intervention studies are needed to evaluate the impact on QoL of changes in body composition that occur with aging.

The relationship between circulating vitamin D3 and subclinical atherosclerosis in an elderly Asian population.

The current evidence regarding the association between vitamin D deficiency and cardiovascular diseases/metabolic disorders is contradictory and inconclusive. In this large-scale observational study, we investigated the relationship between the serum 25-hydroxy vitamin D3 [25(OH)D] concentration and subclinical atherosclerosis in an elderly Asian population. In the I-Lan longitudinal study (ILAS), 1798 elderly, aged 50 and older, were enrolled. For each subject, serum 25-hydroxy vitamin D3 [25(OH)D] concentration and demographic data were recorded. The participants were divided into two groups according to their serum 25(OH)D level (sufficient, > 20 ng/mL and deficient, ≤ 20 ng/mL). Carotid intima-media thickness (cIMT) was measured at bilateral common carotid arteries. Subclinical atherosclerosis was defined as a mean cIMT > 0.81 mm. The mean subject age was 64 ± 9 years old, and 604 (33.6%) were identified as having serum 25(OH)D level ≤ 20 ng/mL. Subjects with serum 25(OH)D level ≤ 20 ng/mL were younger, more likely to be female and smoker, and had a higher incidence of hypertension, dyslipidemia, and metabolic syndrome, compared to those with serum 25(OH)D level > 20 ng/mL. Additionally, patients with serum 25(OH)D level ≤ 20 ng/mL were associated with a lower risk of subclinical atherosclerosis (crude OR: 0.63, 95% CI 0.50-0.81, p < 0.001), according to univariate analysis. However, after adjusting for gender and age, serum 25(OH)D level ≤ 20 ng/mL was not a significant risk factor for subclinical atherosclerosis. Serum 25(OH)D level ≤ 20 ng/mL was not an independent risk factor for subclinical atherosclerosis in this large elderly Asian population. Association observed in the univariate analysis may be confounded by gender or comorbidities.

Cerebellar-limbic neurocircuit is the novel biosignature of physio-cognitive decline syndrome.

Both physical and cognitive deficits occur in the aging process. We operationally defined the phenomenon as physio-cognitive decline syndrome (PCDS) and aimed to decipher its corresponding neuroanatomy patterns and neurocircuit. High resolution 3T brain magnetic resonance imaging (MRI) images from a community-dwelling longitudinal aging cohort were analysed. PCDS was defined as weakness (handgrip strength) and/or slowness (gait speed) concomitant with impairment in any cognitive domain (defined by 1.5 standard deviation below age, sex-matched norms), but without dementia or disability. Among 1196 eligible ≥ 50-year-old (62±9 years, 47.6%men) subjects, 15.9% had PCDS. Compared to the other participants, individuals with PCDS had significantly lower gray-matter volume (GMV) in the bilateral amygdala and thalamus, right hippocampus, right temporo-occipital cortex, and left cerebellum VI and V regions. The regions of reduced GMV in people with PCDS were similar between the middle-aged and older adults; whereas larger clusters with more extensive GMV-depleted regions were observed in ≥65-year-olds with PCDS. Diffusion-weighted tractography showed disrupted hippocampus-amygdala-cerebellum connections in subjects with PCDS. The neuroanatomic characteristics revealed by this study provide evidence for pathophysiological processes associated with concomitant physio-cognitive decline in the elderly. This neurocircuit might constitute a target for future preventive interventions.

Strictly Lobar Cerebral Microbleeds Are Associated with Increased White Matter Volume.

Cerebral small vessel diseases (CSVD), such as white matter hyperintensities (WMH), have been acknowledged as a cause of brain atrophy. However, the relationship between brain volumes and cerebral microbleeds (CMBs) has not yet been determined. We aimed to evaluate whether the presence and topography of CMBs are associated with altered volumes of gray matter (GMV) and white matter (WMV). Non-stroke and non-demented subjects were prospectively recruited from the I-Lan Longitudinal Aging Study. High-resolution 3-T MRI was performed to quantify total and regional WMV and GMV, including Alzheimer's disease-susceptible areas. CMBs were assessed with susceptibility-weighted imaging. Six hundred and fifty-nine subjects (62.1 ± 8.3 years, 290 (44%) men) were included. Thirty-two (4.9%) subjects had strictly lobar CMBs (SL-CMBs) and 51 (7.7%) had deep or infratentorial CMBs (DI-CMBs). We observed an association between CMBs and WMV, independent of age, sex, and vascular risk factors; the direction of association depended on the location of the CMBs. The SL-CMB group had an increased total, frontal, and occipital WMV compared with the no-CMB group, which remained significant after adjusting for other CSVDs (WMH volumes and lacune numbers). In contrast, the DI-CMB group had a decreased occipital WMV compared to the no-CMB group. However, this significance disappeared after taking other CSVDs into consideration. Our results showed no relationship between CMBs and GMV. In conclusion, the increased WMV in non-stroke, non-demented subjects with SL-CMBs observed here provides insight into the early pathogenesis of SL-CMBs. This may be a result of increased water content or amyloid accumulation.

Epidemiology of Sarcopenia and Factors Associated With It Among Community-Dwelling Older Adults in Taiwan.

BACKGROUND: Sarcopenia is a well-recognized geriatric syndrome. We sought to determine the prevalence of sarcopenia and factors associated with it among community-dwelling older adults in Taiwan. METHODS: A cross-sectional study was conducted in Yuanshan Township, Yilan County, Taiwan. Data of 731 community-dwelling adults aged 65 and older were evaluated. Demographic characteristics, anthropometry, medical history, biochemistry results, and dual-energy X-ray absorptiometry results were collected for analysis. RESULTS: Males had a higher rate of sarcopenia than did females and had lower values for body weight, body mass index, waist circumference, percentage of body fat, and lean body mass. Poor nutritional status as determined by the Mini Nutritional Assessment correlated positively with markers for sarcopenia. Levels of vitamin D and folic acid correlated positively with some sarcopenia markers. CONCLUSIONS: Gender differences and nutritional factors may influence the development of sarcopenia. Vitamin D is positively correlated with relative appendicular skeletal muscle mass in males with sarcopenia, and folic acid was positively correlated with gait speed in females with sarcopenia.

Location-Specific Association Between Cerebral Microbleeds and Arterial Pulsatility.

Objective: Increased arterial pulsatility index (API), usually representative of distal vascular resistance, have been linked to cerebral small vessel disease. However, their relationship with cerebral microbleeds (CMBs) is less well-studied. The present study aimed to evaluate the relationship between CMBs and API. Methods: We cross-sectionally evaluated participants from a non-clinical stroke, non-demented community-based population. APIs of cervical internal carotid and vertebral arteries were measured by ultrasonography. CMBs were assessed by susceptibility-weighted-imaging on 3T magnetic resonance imaging (MRI). Subjects were classified according to CMB locations: deep/infratentorial (DI) or strictly lobar (SL) CMB groups. DI-CMB group also included subjects with simultaneous lobar CMBs. Results: Of the 681 subjects [62.2 (8.4) years, 43.5% men] included, CMBs were found in 92 (13.5%) subjects: 57 (8.4%) with DI-CMB and 35 (5.1%) with SL-CMB. The results showed that CMB location influenced their association with API. DI-CMB was significantly associated with elevated API of internal carotid arteries (ß = 0.031; 95% confidence interval = 0.002-0.059; P = 0.03), while SL-CMB was significantly associated with elevated API of vertebral arteries (ß = 0.050; 95% confidence interval = 0.006-0.094; P = 0.025) in multivariate analyses adjusting for age, sex, cardiovascular risk factors, white matter hyperintensities (WMH), and lacunes. Conclusion: Our study again emphasizes (1) the association between API and cerebral small vessel disease and (2) the pathogenic differences between DI- and SL-CMBs. Our results lead to the postulation that in the presence of CMBs without clinical dysfunction yet, insidious small vascular disorders might already occur with corresponding topography.

High Circulatory Phosphate Level Is Associated with Cerebral Small-Vessel Diseases.

High phosphate is linked to vascular calcification and endothelial dysfunction; however, its relationship with cerebral small-vessel diseases (CSVDs) is still unknown. Study subjects were prospectively recruited from the community-based I-Lan Longitudinal Aging Study. CSVDs including lacunes, white matter hyperintensities (WMHs), and cerebral microbleeds were evaluated using 3T magnetic resonance images. Multivariate analyses were performed to study the associations between circulatory phosphate level and the presence of CSVDs. In vitro experiments included human brain microvascular endothelial cell (HBMEC) studies and western blotting. The present study included 186 subjects (age [mean ± standard deviation, range] 64.7 ± 8.6, 50-86.8 years; 93 men). Multivariate analysis revealed that circulatory phosphate levels > 3.925 mg/dL were associated with severe WMH with an odds ratio of 3.7 (95% confidence interval = 1.3-10.6) independent of age, sex, traditional vascular risk factors, total cholesterol, renal function, or circulatory calcium level. The in vitro study revealed a downregulation of tight junction protein (zona occludens-1, occludin, and claudin-5) expression in HBMECs after 48 h of treatment with high phosphate (2.5/5 mM). We are the first to report a relationship between circulatory phosphate and CSVDs. Our results suggest that high circulatory phosphate level might be a novel risk factor for CSVD, possibly by impairing BBB structures.

Brain signatures associated with swallowing efficiency in older people.

Swallowing is a complex movement consisting of the sequential and orderly activation of the swallowing muscles. Neuroimaging evidence has revealed a complex cortical and subcortical representation of voluntary swallowing. The repetitive saliva swallowing test (RSST) is a convenient and simple method for assessing swallowing performance in older people. It remains unclear whether individual differences in swallowing performance are associated with variations in structural brain signatures. We aimed to investigate the association between swallowing efficiency (SWE, measured by the RSST) and gray matter volume (GMV) in healthy older adults. Forty healthy older adults (52-82 years old, 28 female) underwent T1-weighted magnetic resonance imaging (MRI) and clinical assessments of SWE, stimulated/unstimulated salivary flow rate, masticatory cycle, and walking speed. GMV was quantified using a voxel-based morphometry (VBM) approach based on the MRI data. SWE was significantly negatively correlated with age. The association between SWE and hand grip strength, but not the other clinical metrics, was statistically significant. The GMV of the left posterior cerebellum (from cerebellum crus to lobule VIII) was significantly positively correlated with SWE, as evidenced by the results of whole-brain and cerebellum-specific VBM analyses. SWE was significantly positively correlated with the cerebellar volume in the region-of-interest analyses based on automated segmentation. In healthy older adults, swallowing efficiency was positively correlated with cerebellar GMV. The findings suggested that in older people, structural variations of the brain may play a key role in individual differences in swallowing performance.

What factors mediate the inter-relationship between frailty and pain in cognitively and functionally sound older adults? A prospective longitudinal ageing cohort study in Taiwan.

OBJECTIVES: The main aim was to investigate the complex inter-relationship between frailty and pain, and the mediating roles of cognitive function, morbidity and mood in this nexus. DESIGN: A cross-sectional analysis. SETTING: A prospective community-dwelling population-based cohort. PARTICIPANTS: 1682 adults age ≥50 years without evident cognitive or functional impairment, or history of cancer. PRIMARY AND SECONDARY OUTCOME MEASURES: The mediating effect of depression, cognitive function and comorbidity on the nexus between pain and frailty among older and middle-aged adults. RESULTS: The pain score among older subjects (≥65 years), increased with the degree of frailty (robust=0.96±0.82; pre-frail=1.13±0.86; frail=1.63±1.02; P<0.001); multivariate analysis gave the same result, while moderate pain was associated with frailty in older subjects (OR=3.00, 95% CI 1.30 to 6.60). Conversely, pain and frailty among middle-aged subjects (aged 50-64 years) did not appear to be significantly related; in mediation analysis, pain exerted an indirect effect on frailty via depression (indirect effect=0.03, 95% CI 0.01 to 0.07), while neither cognitive function nor comorbidity had any significant effect in mediating the relationship between pain and frailty. CONCLUSION: In cognitively and functionally sound community-dwelling adults aged ≥50 years, moderate pain was related to frailty in those older than 65 years, but not younger ones. Besides the direct influence of pain on frailty, depression partially mediated the pain-frailty nexus. The mechanism by which depression influences pain and frailty requires further investigation.

The Association Between Serum Activin A Levels and Hypertension in the Elderly: A Cross-Sectional Analysis From I-Lan Longitudinal Aging Study.

BACKGROUND: Hypertension is an important risk factor for cardiovascular disease. Activin A, a member of the transforming growth factor-ß cytokine family, has been shown to regulate blood pressure through the renin-angiotensin system. However, the relationship between activin A and blood pressure remains uncertain. The objective of this study was to determine whether serum activin A levels are associated with blood pressure. METHOD: A total of 470 participants of I-Lan longitudinal Aging Study (ILAS) were eligible for this study. Serum levels of activin A were assessed by enzyme-linked immunosorbent assay. Cross-sectional analyses were performed, including comparisons of demographic characteristics, hypertensive status, and activin A levels. RESULTS: Among the study participants (50% men, mean age, 69 years), 236 (50.2%) were hypertensive and 234 (49.8%) were normotensive. Hypertensive patients had significantly higher serum activin A levels than normotensives (normotensive vs. hypertensive: 507 ± 169 vs. 554 ± 176 pg/ml, mean ± SD, P < 0.001). All subjects were divided into 3 tertiles on the basis of serum activin A levels. Increasing tertiles of activin A were associated with higher systolic blood pressure (SBP), diastolic blood pressure and pulse pressure (PP) (all P < 0.001). After adjusting for all the potential confounding factors, serum activin A concentration was still significantly associated with SBP (P = 0.02) and PP (P = 0.03). CONCLUSIONS: Serum activin A level was associated with SBP and PP. Further studies are required to assess their causal relationship and the clinical relevance.

Healthy community-living older men differ from women in associations between myostatin levels and skeletal muscle mass.

BACKGROUND: Myostatin is a negative regulator of muscle growth but the relationship between serum myostatin levels and muscle mass is unclear. This study investigated the association between serum myostatin levels and skeletal muscle mass among healthy older community residents in Taiwan, to evaluate the potential of serum myostatin as a biomarker for diagnosing sarcopenia and/or evaluating the effect of its treatment. METHODS: Study data were excerpted from a random subsample of the I-Lan Longitudinal Aging Study population. Serum myostatin levels were determined and categorized into tertiles (low, medium, high). Relative appendicular skeletal muscle mass (RASM) was calculated as appendicular lean body mass by dual-energy X-ray absorptiometry divided by height squared (kg/m2 ). Low muscle mass was defined as recommended by the Asian Working Group for Sarcopenia. RESULTS: The analytic study sample comprised 463 adults (mean age: 69.1 years; 49.5% men). Compared with subjects with normal RASM, those with lower RASM were older and frailer, with significantly higher prevalence of malnutrition, lower serum dehydroepiandrosterone (DHEA) levels, and were more likely to have low serum myostatin status. Multivariable logistic regression analysis showed that male sex (OR 3.60, 95% CI 1.30-9.92), malnutrition (OR 4.39, 95% CI 1.56-12.36), DHEA (OR 0.99, 95% CI 0.99-1.00), and low myostatin (OR 3.23, 95% CI 1.49-7.01) were all independent risk factors for low RASM (all P < 0.05). In men, DHEA (OR 0.99, 95% CI 0.98-1.00) and low myostatin (OR 4.89, 95% CI 1.79-13.37) were significantly associated with low RASM (both P < 0.05); however, only malnutrition was associated with low RASM in women (OR 13.59, 95% CI 2.22-83.25, P < 0.05). CONCLUSIONS: Among healthy community-living older adults, low serum myostatin levels were associated with low skeletal muscle mass in men, but not in women. Our results do not support using serum myostatin levels to diagnose sarcopenia, or to monitor how it responds to treatments. Further research is needed to understand why men apparently differ from women in the interrelationship between their myostatin levels and muscle mass.