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Background and Purpose: Emerging evidence has linked impaired kidney function with dementia in older adults, but the neuropathological pathways underlying their association remain poorly understood. We sought to examine the relationships of kidney function with dementia and plasma biomarkers in a Chinese rural population. Methods: This population‐based study used data from the baseline examination of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND‐China) cohort (March–September 2018; n = 5715). Kidney function was assessed using estimated glomerular filtration rate (eGFR) based on serum creatinine level. Dementia, Alzheimer's disease (AD) and vascular dementia (VaD) were diagnosed according to the international criteria. Plasma biomarkers were measured using the SIMOA platform in a subsample (n = 1446). Data were analyzed using logistic, general linear, and mediation models. Results: Of the 5715 participants, 306 were diagnosed with dementia, including 195 with AD and 100 with VaD. Impaired kidney function (eGFR <60 vs. ≥90 mL/min/1.73 m2) was associated with multivariable‐adjusted odds ratios of 2.24 (95% confidence interval [CI] 1.44–3.46) for all‐cause dementia, 1.85 (1.07–3.18) for AD, and 2.49 (1.16–5.22) for VaD. In the biomarker subsample, impaired kidney function was significantly associated with higher plasma amyloid‐β (Aβ)40 (β‐coefficient = 54.36, 95% CI 43.34–65.39), Aβ42 (β‐coefficient = 3.14, 95% CI 2.42–3.86), neurofilament light chain (β‐coefficient = 10.62, 95% CI 5.62–15.62), and total tau (β‐coefficient = 0.68, 95% CI 0.44–0.91), and a lower Aβ42/Aβ40 ratio (β‐coefficient = −4.11, 95% CI −8.08 to −0.14). The mediation analysis showed that plasma total tau significantly mediated 21.76% of the association between impaired kidney function and AD (p < 0.05). Conclusion: Impaired kidney function is associated with dementia and plasma biomarkers among rural‐dwelling older Chinese adults, and the association with AD is partly mediated by plasma biomarkers for neurodegeneration. [ABSTRACT FROM AUTHOR]

INTRODUCTION: CD33 rs3865444 and hypertension (HTN) are related to cognitive impairment, individually. However, little is known about their combined effects on cognitive function in older adults. METHODS: This population‐based study included 4368 dementia‐free participants (age ≥65 years) in the Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND‐China), with data available in 1044 persons for gray matter volume and 85 persons for cerebral blood flow (CBF). We used general linear regression and mediation models to examine the associations of rs3865444 and HTN with cognition, brain atrophy, and CBF. RESULTS: Among rs3865444 CC carriers, HTN and late‐life HTN were significantly associated with impaired cognition. Midlife and late‐life HTN were correlated with brain atrophy. CD33 rs3865444 CC moderated the mediation effect of gray matter volume on the association between HTN and global cognition. HTN was correlated with low CBF in rs3865444 CC carriers. DISCUSSION: There are synergistic associations of CD33 rs3865444 and HTN with brain and cognitive aging in dementia‐free older adults. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined the associations of polygenic risk score (PRS) with Alzheimer's disease (AD) and plasma biomarkers in the Chinese population. METHODS: This population‐based study used baseline data from MIND‐China (2018; n = 4873) and follow‐up data from dementia‐free individuals (2014–2018; n = 2117). We measured AD‐related plasma biomarkers in a subsample (n = 1256). Data were analyzed using logistic and Cox regression models. RESULTS: We developed PRS with (PRSAPOE) and without (PRSnon‐APOE) apolipoprotein E (APOE) gene. In the longitudinal analysis, PRSAPOE was associated with a multivariable‐adjusted hazards ratio of 1.91 (95% CI = 1.13–3.23) for AD. PRSAPOE in combination with demographics yielded discriminative (area under the curve [AUC]) and predictive(C‐statistic) accuracy of 0.80 (95% confidence interval [CI] = 0.77–0.84) and 0.80 (0.77–0.82), respectively. PRSnon‐APOE showed an association with AD risk similar to PRSAPOE. PRSAPOE, but not PRSnon‐APOE, was associated with reduced plasma Aβ42/Aβ40 ratio and increased Neurofilament light chain (NfL) (p < 0.05). DISCUSSION: The PRS with and without APOE gene, in combination with demographics, shows good discriminative and predictive ability for AD. The AD‐related pathologies underlie AD risk associated with PRSAPOE. Highlights: The PRSAPOE and PRSnon‐APOE were associated with AD risk in the Chinese population.The PRSAPOE and PRSnon‐APOE, in combination with demographics, showed good discriminative and predictive ability for AD.The AD‐related pathologies underlie the AD risk associated with PRSAPOE but not PRSnon‐APOE. [ABSTRACT FROM AUTHOR]

Introduction: We sought to characterize cognitive profiles associated with enlarged perivascular spaces (EPVS) among Chinese older adults. Methods: This population‐based study included 1191 dementia‐free participants (age ≥60 years) in the MIND‐China MRI Substudy (2018–2020). We visually evaluated EPVS in basal ganglia (BG) and centrum semiovale (CSO), white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and cortical superficial siderosis. We used a neuropsychological test battery to assess cognitive function. Data were analyzed using general linear models. Results: Greater BG‐EPVS load was associated with lower z‐scores in memory, verbal fluency, and global cognition (p < 0.05); these associations became non‐significant when controlling for other cerebral small vessel disease (CSVD) markers (e.g., WMHs, lacunes, and mixed CMBs). Overall, CSO‐EPVS load was not associated with cognitive z‐scores (p > 0.05); among apolipoprotein E (APOE) ‐ε4 carriers, greater CSO‐EPVS load was associated with lower verbal fluency z‐score, even when controlling for other CSVD markers (p < 0.05). Discussion: The associations of BG‐EPVS with poor cognitive function in older adults are largely attributable to other CSVD markers. HIGHLIGHTS: The association of enlarged perivascular spaces (EPVS) with cognitive function in older people is poorly defined.The association of basal ganglia (BG)‐EPVS with poor cognition is attributed to other cerebral small vessel disease (CSVD) markers.In apolipoprotein E (APOE) ε4 carriers, a higher centrum semiovale (CSO)‐EPVS load is associated with poorer verbal fluency. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)‐related plasma biomarkers among older adults. METHODS: This population‐based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS: The number of chronic diseases was associated with dementia (multivariable‐adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non‐amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non‐amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05). DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD‐related plasma biomarkers in older adults. Highlights: We used hierarchical clustering to generate five clusters of multimorbidity.The presence and load of multimorbidity were associated with dementia and mild cognitive impairment.Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers. [ABSTRACT FROM AUTHOR]

Background: To explore the associations of the metabolic syndrome (MetS) and individual components with macular thickness and volume among rural-dwelling Chinese older adults. Methods: This population-based cross-sectional study included 705 participants (age ≥60 years) derived from the MIND-China study. In 2018–2019, we collected data through face-to-face interview, clinical examination, optical coherence tomography (OCT) examination, and blood test. We measured macular thickness and volume using spectral-domain OCT. MetS was defined following the International Diabetes Federation (IDF) criteria, the IDF/American Heart Association (AHA) criteria, the National Cholesterol Education Program-Adult Treatment Panel III criteria, and the Chinese Diabetes Society (CDS) criteria. Data were analyzed with multivariable general linear models. Results: MetS was significantly associated with thinner macula in central (multivariable-adjusted β = −5.29; 95% confidence interval: −9.31 to −1.26), parafoveal (−2.85; −5.73 to 0.04) and perifoveal regions (−4.37; −6.79 to −1.95) when using the IDF criteria, in the perifoveal regions (−3.82; −6.18 to −1.47) when using the IDF/AHA criteria, and in the central region (−5.63; −10.25 to −1.02) when using the CDS criteria, and with reduced macular volume when using the IDF (−0.16; −0.26 to −0.07) and IDF/AHA (−0.13; −0.22 to −0.04) criteria. In the parafoveal region, the IDF-defined MetS was significantly associated with thinner retina in men (β = −6.25; −10.94 to −1.56) but not in women. Abdominal obesity (−2.83; −5.41 to −0.25) and elevated fasting blood glucose (−2.65; −5.08 to −0.21) were associated with thinner macular thickness in the perifoveal region. Conclusion: MetS is associated with macular thinning and reduced macular volume among rural-dwelling older adults, and the associations vary by the defining criteria of MetS. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Is the TyG index, a surrogate marker of insulin resistance, associated with the function of global cognition and multiple cognitive domains and brain structures among older adults? • What is the main finding of this study? This large-scale population-based study of rural-dwelling older adults revealed inverted J-shaped associations between TyG index with z-scores of cognitive function, with the median of TyG index being the inflection point. A higher TyG index was correlated with greater global brain atrophy. • What is the meaning of the finding? TyG index in older adults may be a clinical marker for cognitive function and brain aging. To investigate the associations of triglyceride-glucose (TyG) index, a reliable surrogate marker for insulin resistance, with the function of various cognitive domains and brain structures among older adults. A population-based cross-sectional study. Older adults living in the rural communities in China. About 4,541 rural-dwelling dementia-free participants (age ≥65 years; 56.37% women) undertook examinations in March–September 2018 for MIND-China. TyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. A neuropsychological test battery was used to assess memory, attention, verbal fluency, and executive function. Volumetric brain measures were assessed on magnetic resonance imaging (MRI) in a subsample (n = 1,019). Data were analyzed with restricted cubic spline and multivariable general linear models. An inverted J-shaped association was observed between TyG index and z-scores of multiple cognitive domains, such that among individuals with TyG index ≥8.57 (median), a higher TyG index was significantly associated with lower z - scores of memory, attention, verbal fluency, executive function, and global cognition (all p < 0.05); among people with TyG index <8.57, a higher TyG index was significantly associated with a higher executive function z-score (p < 0.05), but not with any of the other examined cognitive domains. In the MRI subsample, a higher TyG index was significantly associated with lower volumes of total brain tissue, gray matter, and white matter as well as greater cerebrospinal fluid volume (p < 0.05), but not with white matter hyperintensity volume. Insulin resistance, as indicated by a high TyG index, was associated with poor function in multiple cognitive domains and global brain atrophy. [ABSTRACT FROM AUTHOR]

Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood. Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms. Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018–2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models. Results: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores. Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association. [ABSTRACT FROM AUTHOR]

Background: Plasma biomarkers have emerged as a promising approach for characterizing pathophysiology in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Objective: We aimed to characterize plasma biomarkers for AD and neurodegeneration across the AD clinical continuum, and to assess their ability to differentiate between AD, MCI, and normal cognition. Methods: This population-based study engaged 1,446 rural-dwelling older adults (age ≥60 years, 61.0% women) derived from MIND-China; of these, 402 were defined with MCI and 142 with AD. Plasma amyloid-β (Aβ), total tau (t-tau), and neurofilament light chain (NfL) concentrations were analyzed using the Simoa platform. Data were analyzed using linear and logistic regression models, and receiver operating characteristic (ROC) analysis. Results: Across the AD clinical spectrum, plasma Aβ40 and NfL increased, whereas Aβ42/Aβ40 ratio decreased. Plasma t-tau was higher in people with AD dementia than those with MCI or normal cognition. Plasma NfL outperformed other biomarkers in differentiating AD from normal cognition (area under the ROC curve [AUC] = 0.75), but all plasma biomarkers performed poorly to distinguish MCI from normal cognition (AUC <0.60). Plasma NfL in combination with age, sex, education, and APOE genotype yielded the AUC of 0.87 for differentiating between AD and normal cognition, 0.79 between AD and MCI, and 0.64 between MCI and normal cognition. Conclusions: In this Chinese population, AD plasma biomarkers vary by age, sex, and APOE genotype. Plasma Aβ, t-tau, and NfL differ across the AD clinical spectrum, and plasma NfL appears to be superior to plasma Aβ and t-tau for defining the clinical spectrum. [ABSTRACT FROM AUTHOR]

Background: Evidence has emerged that altered ventricular electrocardiogram profiles are associated with dementia, but the neuropathological mechanisms underlying their associations are poorly understood. Objective: To investigate the interrelationships of ventricular electrocardiogram profiles with dementia and plasma Alzheimer's disease (AD) biomarkers among older adults. Methods: This population-based cross-sectional study included 5,153 participants (age ≥65 years; 57.3% women) living in rural communities in China; of these, 1,281 had data on plasma amyloid-β (Aβ)40, Aβ42, total-tau, and neurofilament light chain (NfL) protein. The QT, QTc, JT, JTc, QRS intervals, and QRS axis were derived from the 10-second electrocardiogram recording. The DSM-IV criteria were followed for clinical diagnosis of dementia, the NIA-AA criteria for AD, and the NINDS-AIREN criteria for vascular dementia (VaD). Data were analyzed using general linear models, multinomial logistic models, and restricted cubic splines. Results: Of the 5,153 participants, 299 (5.8%) were diagnosed with dementia, including 194 with AD and 94 with VaD. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with all-cause dementia, AD, and VaD (p < 0.05). Left QRS axis deviation was significantly associated with all-cause dementia and VaD (p < 0.01). In the subsample of plasma biomarkers (n = 1,281), prolonged QT, JT, and JTc intervals were significantly associated with a lower Aβ42/Aβ40 ratio and higher plasma NfL concentrations (p < 0.05). Conclusion: Alterations in ventricular repolarization and depolarization are independently associated with all-cause dementia, AD, VaD, and AD plasma biomarkers in older adults (age ≥65 years). Ventricular electrocardiogram parameters may be valuable clinical markers for dementia and the underlying AD pathologies and neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Few community-based studies have examined occurrence and progression of subjective cognitive decline (SCD). Objective: To investigate prevalence and progression of SCD among rural-dwelling Chinese elderly people. Methods: This cohort study included 2,488 cognitively unimpaired adults (age≥65 years) who were examined at baseline (2014-2015) and followed in 2018. Demographic, epidemiological, clinical, and neuropsychological data were collected via in-person interviews and clinical examinations following a structured questionnaire. At baseline, SCD was assessed using the self-rated Ascertain Dementia 8-item Questionnaire. At follow-up, Alzheimer's disease (AD) and vascular dementia (VaD) were clinically diagnosed following the international criteria. Data were analyzed using logistic regression models. Results: The prevalence of SCD was 40.07%. SCD at baseline was associated with the multivariable-adjusted odds ratio (OR) of 1.51 (95% confidence interval 1.10–2.07) for incident cognitive impairment, no dementia (CIND) and 3.11 (1.64–5.93) for incident AD. Among people with SCD at baseline, the multivariable-adjusted OR of incident CIND was 0.55(0.32–0.96) for hyperlipidemia; the multivariable-adjusted OR of incident AD was 1.21 (1.14–1.30) for older age, 0.32 (0.12–0.88) for high education, 2.60 (1.11–6.08) for carrying APOEɛ4 allele, and 0.34 (0.13–0.86) for high social support, whereas the multivariable-adjusted OR of incident VaD was 6.30 (1.71–23.18) for obesity. Conclusion: SCD affects over 40% of rural-dwelling cognitively unimpaired older adults in China. SCD is associated with accelerated progression to CIND and AD. Older age, lack of school education, APOEɛ4 allele, and low social support are associated with an increased risk of progression from SCD to AD, whereas obesity is related to accelerated progression to VaD. [ABSTRACT FROM AUTHOR]

Background: Microvascular dysfunction (MVD) may contribute to cognitive impairment and Alzheimer's disease, but evidence is limited. Objective: To investigate the association of composite and organ-specific MVD burden with mild cognitive impairment (MCI) and cognition among rural-dwelling Chinese older adults. Methods: In this population-based cross-sectional study, we assessed MVD makers using optical coherence tomographic angiography for retinal microvasculature features, brain magnetic resonance imaging scans for cerebral small vessel disease (CSVD), and serum biomarkers for MVD. A composite MVD score was generated from the aforementioned organ-specific parameters. We used a neuropsychological test battery to assess memory, verbal fluency, attention, executive function, and global cognitive function. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were diagnosed following the Petersen's criteria. Data was analyzed with the linear and logistic regression models. Results: Of the 274 dementia-free participants (age≥65 years), 56 were diagnosed with MCI, including 47 with aMCI and 9 with naMCI. A composite MVD score was statistically significantly associated with an odds ratio (OR) of 2.70 (95% confidence interval 1.12–6.53) for MCI and β-coefficient of –0.29 (–0.48, –0.10) for global cognitive score after adjustment for socio-demographics, lifestyle factors, APOE genotype, the Geriatric Depression Scale score, serum inflammatory biomarkers, and cardiovascular comorbidity. A composite score of retinal microvascular morphology was associated with a multivariable-adjusted OR of 1.72 (1.09–2.73) for MCI and multivariable-adjusted β-coefficient of –0.11 (–0.22, –0.01) for global cognitive score. A composite CSVD score was associated with a lower global cognitive score (β= –0.10; –0.17, –0.02). Conclusion: Microvascular dysfunction, especially in the brain and retina, is associated with MCI and poor cognitive function among rural-dwelling older adults. [ABSTRACT FROM AUTHOR]

Introduction: Population‐based studies have rarely explored the associations of the triglyceride–glucose (TyG) index, a surrogate marker of insulin resistance, with dementia and plasma biomarkers for amyloid beta (Aβ) and neurodegeneration. Methods: This population‐based study included 5199 participants (age ≥ 65 years); of these, plasma Aβ, total tau, and neurofilament light chain (NfL) were measured in 1287 persons. Dementia and subtypes were diagnosed following the international criteria. TyG index was calculated as ln(fasting triglyceride(mg/dL) × fasting glucose[mg/dL]/2). Data were analyzed using logistic and general linear regression models. Results: Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were diagnosed in 301, 195, and 95 individuals, respectively. A high TyG index was significantly associated with increased likelihoods of dementia and AD; the significant association with dementia remained among participants without cardiovascular disease or diabetes. In the biomarker subsample, a high TyG index was correlated with elevated plasma Aβ, but not with total tau or NfL. Discussion: High TyG index is associated with dementia, possibly via Aβ pathology. [ABSTRACT FROM AUTHOR]

Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population‐based study included 4214 dementia‐free participants (age ≥65 years). Olfaction was assessed using the 16‐item Sniffin' Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)‐signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non‐amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non‐amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD‐signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies of mild cognitive impairment (MCI) and subtypes of MCI have rarely focused on rural residents in China. Methods: This population‐based study included 5068 participants (age ≥60 years) who were living in rural communities. We defined MCI, amnestic MCI (aMCI), and non‐amnestic MCI (naMCI) following the Petersen's criteria that integrated neuropsychological assessments with in‐person clinical evaluations. Results: The overall prevalence of MCI, aMCI, and naMCI was 26.48%, 22.30%, and 4.18%, respectively. The prevalence of MCI increased with age. The adjusted odds ratio (OR) of MCI was 0.71 (95% confidence interval [CI] 0.61 to 0.82) for primary school (vs. illiteracy), 0.30 (0.24 to 0.39) for middle school or above, 1.35 (1.09 to 1.67) for being farmers, 0.65 (0.54 to 0.78) for alcohol consumption, 1.43 (1.20 to 1.70) for stroke history, and 1.14 (0.95 to 1.36) for any apolipoprotein E (APOE) ε4 allele (vs ε3/ε3). Conclusions: MCI affects over one‐fourth of rural older adults in China. Overall MCI was associated with demographic factors, non‐alcohol consumption, and stroke, but not with APOE genotype and cardiometabolic factors. [ABSTRACT FROM AUTHOR]

Background and purpose: Little is known about whether nonalcoholic fatty liver disease (NAFLD) is associated with dementia or the role of serum proinflammatory cytokines in the association. We aimed to investigate the interrelationships of NAFLD, serum cytokines, and dementia among rural‐dwelling older adults. Methods: This population‐based cross‐sectional study included 5129 participants (aged ≥60 years; 61.79% women) who were living in rural communities and examined in March 2018–September 2018. NAFLD was defined through transabdominal ultrasound examination in the absence of hepatitis B or excessive alcohol consumption. Serum cytokines were measured in a subsample (n = 1686). Dementia, Alzheimer disease (AD), and vascular dementia (VaD) were diagnosed following international criteria. Data were analyzed with logistic regression and mediation models. Results: Of the 5129 participants, 455 (8.87%) were detected with moderate‐to‐severe NAFLD, and 292 (5.69%) were diagnosed with dementia (188 with AD and 96 with VaD). The multivariable adjusted odds ratios associated with moderate‐to‐severe (vs. no‐to‐mild) NAFLD were 2.22 (95% confidence interval [CI] = 1.41–3.49) for all‐cause dementia, 1.88 (95% CI = 1.01–3.50) for AD, and 2.62 (95% CI = 1.33–5.17) for VaD. In the cytokine subsample, controlling for multiple potential confounders, moderate‐to‐severe NAFLD was significantly associated with higher levels of serum monocyte chemotactic protein‐1, interleukin‐17A, interleukin‐6 (IL‐6), interleukin‐8, and tumor necrosis factor‐α (P < 0.05). The mediation analysis showed that IL‐6 mediated 12.56% of the association between NAFLD and VaD. Conclusions: Moderate‐to‐severe nonalcoholic fatty liver disease is associated with dementia and AD, especially with VaD, among rural‐dwelling Chinese older adults, in which the association with VaD is partly mediated by serum inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Sedentary behaviour is associated with a range of adverse health conditions. Population-based studies have rarely examined the distribution and associated factors of accelerometer-measured sedentary behaviour patterns in rural-dwelling older adults. This population-based study included 2096 rural-dwelling older adults (age ≥60 years; 59.0% women) derived from baseline participants of the MIND-China Study. Total sedentary time and patterns (e.g., uninterrupted bouts and breaks) were derived from the hip-worn accelerometers for 7 days. Physical function was assessed using the Short Physical Performance Battery test. Data were analysed using general linear models. Overall, participants spent 58.8% of daily waking time in sedentary behaviour, with nearly half of sedentary time being accumulated through sedentary bouts of 30+ minutes. Men spent more total and accumulated sedentary time than women in each sedentary bout duration, while women had more daily 1+ minute sedentary bouts than men (all P < 0.001). Controlling for moderate-to-vigorous physical activity and other confounders, more prolonged sedentary time and fewer breaks were significantly associated with poor physical function, balance, lower limb strength, and walking speed (all P < 0.001). In older adults living in rural communities, prolonged sedentary behaviour and less frequent breaks are associated with poor physical function. [ABSTRACT FROM AUTHOR]

Purpose: We explore the associations of individual and composite cardiovascular health metrics with all-cause dementia, Alzheimer's disease, and vascular dementia among rural-dwelling older adults and the potential age variations in their associations. Patients and Methods: This community-based cross-sectional study included 4980 older adults (age ≥ 65 years; 57.23% women) from the baseline examination of MIND-China. In March–September 2018, data were collected via face-to-face interviews, clinical examinations, and laboratory test. We defined six cardiovascular health metrics according to the modified American Heart Association's recommendations. We diagnosed dementia and its subtypes following the international criteria. Data were analyzed using logistic regression models. Results: Of all the participants, 250 were diagnosed with dementia, including 165 with Alzheimer's disease and 75 with vascular dementia. Ideal composite global cardiovascular health metrics (vs poor composite metrics) were associated with a multi-adjusted odds ratio (95% confidence interval) of 0.62 (0.42– 0.93) for dementia, 0.88 (0.52– 1.48) for Alzheimer's disease, and 0.31 (0.16– 0.60) for vascular dementia. Moreover, ideal biological cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.52 (0.28– 0.95) for dementia and 0.21 (0.06– 0.77) for vascular dementia in young–old adults (65– 74 years), whereas ideal behavioral cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.48 (0.26– 0.89) for dementia and 0.16 (0.06– 0.43) for vascular dementia in old–old adults (≥ 75 years). Conclusion: Our results suggest that ideal cardiovascular health metrics are cross-sectionally associated with a low likelihood of dementia and vascular dementia among rural-dwelling older Chinese adults. The associations vary with age, components of cardiovascular health metrics, and dementia subtypes. [ABSTRACT FROM AUTHOR]

Background: Olfactory impairment is associated with dementia in clinical settings. We examined the relationship of olfactory identification function with all‐cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) and assessed the discriminative ability of the Sniffin' Sticks Identification Test (SSIT), the self‐rated Ascertain Dementia 8‐item Questionnaire (AD8), and their combination for dementia detection among rural‐dwelling older adults in China. Methods: This population‐based cross‐sectional study included 4481 participants (age ≥ 65 years; 56.8% women; 38.1% illiteracy) living in rural communities. The 16‐item SSIT was performed to assess olfactory identification function. The self‐rated AD8 was administered to participants for cognitive status. We diagnosed dementia, AD, and VaD following the international criteria. Data were analyzed with logistic regression models and receiver operating characteristic curve. Results: Of the 4481 participants, dementia was diagnosed in 139 persons (3.1%), including 92 with AD and 42 with VaD. The SSIT score (range, 0–16) was associated with multiadjusted odds ratios of 0.83 (95% CI: 0.79–0.88) for dementia, 0.84 (0.79–0.90) for AD, and 0.79 (0.71–0.87) for VaD. The area under the curve for the discrimination between participants with and without dementia was 0.73 (95% CI: 0.69–0.77) for SSIT score ≤ 8 alone, 0.86 (0.82–0.89) for self‐rated AD8 score ≥ 3 alone, and 0.89 (0.86–0.92) for their combination using a logistic model. Conclusions: Olfactory impairment is a clinical marker for all‐cause dementia, AD, and VaD. The smell identification test, in combination with the brief self‐rated cognitive screening tool, is accurate for screening dementia among rural‐dwelling Chinese older adults with no or limited education. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined occurrence and progression of cognitive impairment, no dementia (CIND) in rural China.Objective: To determine the prevalence and incidence of CIND in rural-dwelling Chinese older adults, and to examine risk and protective factors associated with progression to CIND and dementia.Methods: This population-based study included 2,781 dementia-free participants (age≥65 years) who were examined at baseline (2014) and followed in 2018. Demographic, epidemiological, clinical, and neuropsychological data were collected following a structured questionnaire. We defined CIND according to subjective cognitive complaints and the age- and education-specific Mini-Mental State Examination (MMSE) score. Data were analyzed with the multinomial logistic regression models.Results: The overall prevalence of CIND was 10.54% and the incidence was 28.26 per 1,000 person-years. CIND at baseline was associated with the multi-adjusted odds ratio (OR) of 2.06 (95% confidence interval = 1.23-3.47) for incident dementia. Multinomial logistic regression analysis suggested that compared with no CIND, the multi-adjusted OR of incident CIND was 2.21 (1.51-3.23) for women and 0.62 (0.38-0.99) for high social support, whereas the multi-adjusted OR of incident dementia was 1.14 (1.09-1.18) for older age, 0.29 (0.16-0.53) for high education, and 2.91 (1.47-5.74) for having a stroke history.Conclusion: CIND affects over one-tenth of older adults living in rural communities of western Shandong province. People with CIND are twice as likely to progress to dementia as people without CIND. Female sex, low education, stroke history, and low social support are associated with an increased risk of progression from normal cognition to CIND or dementia. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the associations of genotypes of NDUFAF6 rs6982393 and APOE and their combined genotypes with the risk of Alzheimer's disease (AD) and mild cognitive impairment (MCI) in Chinese rural elderly. Methods: This cross-sectional population-based study included 5096 older adults (age ≥ 60 years, 57.1% female). Genotypes of NDUFAF6 rs6982393 and APOE were detected using the multiple-polymerase chain reaction amplification. We diagnosed AD following the criteria of Diagnostic and Statistical Manual of Mental Disorders, the fourth edition and diagnosed MCI following the Petersen's criteria MCI. Data were analyzed using the logistic regression model. Results: The overall prevalence of AD and MCI was 3.57% (95% confidence interval [CI]: 0.040, 0.053) and 22.65% (95% CI: 0.223, 0.247), separately. The TT versus CC/CT genotype of NDUFAF6 rs6982393 was related to a higher risk of AD with the multi-adjusted odds ratio (95% CI) being 1.61 (1.02, 2.54) in the total sample, 3.36 (1.48, 7.60) in those aged 60– 69, and 1.24 (0.71, 2.17) in those aged 70 years and above. The interaction between genotype of NDUFAF6 rs6982393 with age groups (60– 69 versus ≥ 70 years) was significant on the risk of AD. The presence of APOE ε4 was not significantly associated with the risk of AD. Carrying both NDUFAF6 TT and APOE ε4 was related to a higher risk of AD with the multi-adjusted odds ratio (95% CI) being 2.69 (1.10, 2.56). In addition, there was no significant association between the above genotypes and MCI. Conclusion: In Chinese rural elderly, the TT versus CT/CC genotype of NDUFAF6 rs6982393 was associated with an increased likelihood of AD; such an association only existed among young-old adults. Carrying both NDUFAF6 rs6982393-TT and APOE ε4 was related to a higher risk of AD. This finding highlights the importance of considering age and combined genotype in studying the genetic profiles of AD. [ABSTRACT FROM AUTHOR]

Background: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse.Objective: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status.Methods: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer's disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models.Results: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87-2.44), 1.00 (reference), 1.77 (1.07-2.93), and 2.28 (1.40-3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and β-coefficients of MMSE score.Conclusion: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia. [ABSTRACT FROM AUTHOR]

Background and purpose: Current evidence supports the involvement of lipids in brain aging. A range of serum lipids is explored in association with brain structure and cognitive function amongst rural‐dwelling older adults. Methods: This population‐based cross‐sectional study included 184 rural‐dwelling adults (age ≥ 65 years, 39.1% women) in Shandong, China. In 2014–2016, data on demographics, lifestyle, health conditions and serum lipids were collected. Volumes of gray matter, white matter, ventricles, hippocampus and white matter hyperintensity were automatically estimated on brain magnetic resonance imaging. Global cognitive function was assessed with the Mini‐Mental State Examination (MMSE), and mild cognitive impairment (MCI) was defined according to Petersen's criteria. Data were analyzed using the general linear regression, logistic regression and mediation models. Results: Of the 184 participants, 47 were defined with MCI. Low high‐density lipoprotein cholesterol (HDL‐C; <1.55 vs. ≥1.55 mmol/l) was significantly associated with reduced volumes of total white matter (multi‐adjusted β = −9.77, 95% confidence interval −19.48–0.06) and hippocampus (−0.23, −0.46–0.01), a lower MMSE score (−1.49, −2.67–0.31) and a higher likelihood of MCI (multi‐adjusted odds ratio 3.21, 95% confidence interval 1.42–7.29). The mediation effects of structural brain measures on the associations between a low level of HDL‐C and MMSE score or MCI were not statistically significant (p > 0.05). Conclusions: This study suggests that low HDL‐C may be involved in structural brain aging and cognitive dysfunction amongst rural‐dwelling older adults in China, but the association of low HDL‐C with cognitive aging phenotypes appears not to be mediated by brain structure. [ABSTRACT FROM AUTHOR]

Background: Structural brain magnetic resonance imaging (MRI) scans may provide reliable neuroimaging markers for defining amnestic mild cognitive impairment (aMCI).Objective: We sought to characterize global and regional brain structures of aMCI among rural-dwelling older adults with limited education in China.Methods: This population-based study included 180 participants (aged≥65 years, 42 with aMCI and 138 normal controls) in the Shandong Yanggu Study of Aging and Dementia during 2014-2016. We defined aMCI following the Petersen's criteria. Global and regional brain volumes were automatically segmented on MRI scans and compared using a region-of-interest approach. Data were analyzed using general linear regression models.Results: Multi-adjusted β-coefficient (95% confidence interval) of brain volumes (cm3) associated with aMCI was -12.07 (-21.49, -2.64) for global grey matter (GM), -18.31 (-28.45, -8.17) for global white matter (WM), 28.17 (12.83, 44.07) for cerebrospinal fluid (CSF), and 2.20 (0.24, 4.16) for white matter hyperintensities (WMH). Furthermore, aMCI was significantly associated with lower GM volumes in bilateral superior temporal gyri, thalamus and right cuneus, and lower WM volumes in lateral areas extending from the frontal to the parietal, temporal, and occipital lobes, as well as right hippocampus (p < 0.05).Conclusion: Brain structure of older adults with aMCI is characterized by reduced global GM and WM volumes, enlarged CSF volume, increased WMH burden, reduced GM volumes in bilateral superior temporal gyri, thalamus, and right cuneus, and widespread reductions of lateral WM volumes. [ABSTRACT FROM AUTHOR]

• WWC1 rs17070145 was marginally associated with AD and VaD in older adults. • WWC1 exonic SNPs rs3822660 and rs3822659 are in strong LD with rs17070145. • The strong LD may explain the association of WWC1 rs17070145 C allele with AD. • Stroke may partly explain the association of rs17070145 CC genotype with VaD. We sought to examine the associations of common WWC1 variants with Alzheimer's disease (AD) and vascular dementia (VaD) among rural-dwelling older adults in China. This population-based study used data from the baseline assessments (March –September 2018) of MIND-China. AD and VaD were diagnosed following the international criteria. Of the 5455 participants (age≥60 years, 57.27% women), 182 were diagnosed with AD and 88 with VaD. Logistic regression analysis suggested that WWC1 rs17070145 C allele (vs. T) was associated with multivariable-adjusted odds ratio of 1.23 (95% confidence interval 0.96–1.58) for AD, and that CC genotype (vs. TT) was associated with multivariable-adjusted odds ratio of 2.19(1.10–4.39) for VaD, but the association with VaD became non-significant when further adjusting for stroke history. Furthermore, exonic SNPs rs3822660 and rs3822659 were in strong linkage disequilibrium (LD) with rs17070145 (D' = 0.88). These results suggest that the strong LD between rs17070145 and 2 exonic SNPs may explain the association of WWC1 rs17070145 C allele with AD and that stroke may partly explain the association of WWC1 rs17070145 CC genotype with VaD. [ABSTRACT FROM AUTHOR]

• The lifestyle for brain health (LIBRA) index has been associated with cognitive function. • Whether CD33 rs3865444 polymorphism can modulate the association between the LIBRA index and cognition in dementia-free older adults is unknown. • Our study suggested that a higher LIBRA index was associated with worse cognitive performance in rural Chinese older adults, especially among the CD33 CC carriers. • This study contributes to our further understanding of the complex relationships of modifiable lifestyles and the CD33 gene with cognitive function, which has potential implications for preventive interventions to maintain late-life brain and cognitive health. We sought to examine the associations of the Lifestyle for Brain Health (LIBRA) index with cognitive function among rural Chinese older adults and to explore the potential role of cluster of differentiation 33 gene (CD33) in the associations. This population-based cross-sectional study included 4914 dementia-free participants (age ≥60 years; 56.43 % women) in the 2018 baseline examination of MIND-China. The LIBRA index was generated from 11 factors. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, executive function, and global cognition. The CD33 (rs3865444) polymorphism was detected using multiple-polymerase chain reaction amplification. Data were analyzed using the general linear regression models. A higher LIBRA index was associated with multivariable-adjusted β-coefficient (95 %CI) of -0.011(-0.020- -0.001) for global cognitive z-score, -0.020(-0.033- -0.006) for episodic memory, and -0.016(-0.029- -0.004) for verbal fluency. The CD33 (rs3865444) was associated with a lower global cognitive z-score in the additive (CA vs. CC: β-coefficient=0.042; 95 %CI=0.008–0.077), the dominant (CA+AA vs. CC: 0.040; 0.007–0.073), and the over-dominant (CA vs. CC+AA: 0.043; 0.009–0.077) models. Similar results were obtained for verbal fluency and attention. The CD33 gene showed statistical interactions with LIBRA index on cognitive function (P interaction <0.05) such that a higher LIBRA index was significantly associated with lower z-scores of global cognition and attention only among CD33 CC carriers (P < 0.05). This population-based study reveals for the first time that a higher LIBRA index is associated with worse cognitive performance in rural Chinese older adults and that CD33 gene could modify the association. [ABSTRACT FROM AUTHOR]

• TOMM40 genotype but not PVRL2 gene was associated with Alzheimer's disease in Chinese older adults, depending on APOE genotype. • TOMM40 could interact with PVRL2 to substantially increase the likelihood of Alzheimer's disease. • The TOMM40 GG genotype was associated with low plasma Aβ42 concentration and the Aβ42-to-Aβ40 ratio. Genetic studies have identified Alzheimer's disease (AD)-associated SNPs in TOMM40 and PVRL2 genes, but the underlying mechanisms remain unknown. We examined their associations and interactions with AD risk and plasma biomarkers among Chinese older adults. This population-based study included 4876 participants. TOMM40 (rs2075650) and PVRL2 (rs6859) polymorphisms were detected using multiple-polymerase chain reaction amplification. Plasma Aβ40, Aβ42, and t-tau concentrations were measured using SIMOA in a subsample (n = 1257). AD was diagnosed following the international criteria. Data were analyzed using multiple logistic and general linear models. AD was diagnosed in 182 participants. The multiadjusted odds ratio of AD was 6.24 (95% CI 1.73–22.48) for TOMM40 GG, 1.47 (0.89–2.42) for PVRL2 AA, and 12.87 (3.97–41.73) for having both risk alleles (P interaction = 0.0003). Among APOE ε3/ε3 carriers, the multiadjusted odds ratio of AD associated with TOMM40 AG was 2.90(1.15–7.31). In biomarker subsample, TOMM40 GG was significantly associated with lower plasma Aβ42 and the Aβ42-to-Aβ40 ratio (p < 0.05). TOMM40 genotype is differentially associated with AD risk depending on APOE genotype. TOMM40 and PVRL2 genes could interact to substantially increase AD risk, possibly through influencing Aβ metabolism. [ABSTRACT FROM AUTHOR]

The cross-sectional association between late-life obesity and dementia is often explained by the obesity paradox. We assessed the potential differential associations of various adiposity indices with dementia and subtypes of dementia in rural Chinese older adults. A population-based cross-sectional study. A total of 5277 participants (age ≥60 years; 57.23% female) who were living in rural communities and were examined in March–September 2018 for MIND-China. We used weight, height, and waist circumference (WC) to calculate 6 adiposity indices: body mass index (BMI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), A Body Shape Index (ABSI), body roundness index (BRI), and Conicity Index (ConI). Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were clinically diagnosed following the international criteria. Data were analyzed with logistic regression models. Of the 5277 participants, 303 were diagnosed with dementia, including 193 with AD and 99 with VaD. The multivariable-adjusted odds ratio (95% CI) of dementia associated with the highest (vs lowest) quintile of adiposity index was 2.32 (1.40–3.85) for WWI, 1.56 (1.03–2.36) for ABSI, and 1.40 (0.92–2.11) for ConI. Similarly, higher levels of these 3 adiposity indices were significantly associated with an increased likelihood of AD, whereas a higher BMI was associated with a decreased likelihood of AD. None of the 6 examined adiposity indices was significantly associated with VaD when adjusting for multiple confounders. The adiposity index WWI is linearly associated with the likelihood of dementia and AD. An increased WWI may be a clinical marker for the dementia syndrome and Alzheimer's dementia. [ABSTRACT FROM AUTHOR]

• A favorable CVH profile was associated with better physical function among rural chinese older adults. • The association was partially mediated via low chronic systemic inflammation. • This has implications for understanding the mechanisms linking CVH profile with physical function. We examined the association of modifiable cardiovascular health (CVH) metrics with physical function among rural older adults in China and the potential role of inflammatory mechanisms in the association. This study included 3733 stroke- and dementia-free participants (age ≥65 years; 56.9% women) in the baseline survey of a multimodal intervention study in rural China. From March-September 2018, data were collected via face-to-face interviews, clinical assessments, and laboratory tests. The Short Performance Physical Battery (SPPB) test was performed to assess physical function. We defined six modifiable CVH metrics according to the modified American Heart Association's recommendations. Serum interleukin (IL)-6 was measured in a subsample (n = 1156). Data were analyzed with multiple general linear and logistic regression models and structural equation modeling. Poor physical function (SPPB score ≤9) was defined in 1443 participants. Ideal CVH (vs. poor CVH) was associated with multivariable-adjusted odds ratio of 0.60 (95%CI 0.48–0.75) for poor physical function. Ideal CVH was significantly associated with higher scores on balance, chair stand, and walking speed tests (all p < 0.05). Moreover, ideal CVH profile was associated with lower serum IL-6 (multivariable-adjusted β=-0.04; 95% CI -0.06, -0.01). Mediation analysis revealed that serum IL-6 accounted for 14% of the association of CVH with total SPPB score and 10% of the association with walking speed score (p < 0.05). This study suggests that an ideal CVH profile is associated with better physical function among stroke- and dementia-free older adults, partly via inflammatory mechanisms. The preventive implications of these findings warrant further investigation in cohort studies. [ABSTRACT FROM AUTHOR]