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BACKGROUND: We investigated the association of peak expiratory flow (PEF) with dementia; cognitive impairment, no dementia (CIND); and transition from CIND to dementia, and possible underlying neuropathological mechanisms. METHODS: A population‐based cohort of adults aged 60+ was followed over 15 years to detect dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria), CIND (assessed through a cognitive battery), and progression from CIND to dementia, in relation to baseline PEF observations. A subsample (n = 462) had 6‐year follow‐up data on brain magnetic resonance imaging markers of neurodegeneration and small vessel disease. RESULTS: In fully adjusted models, poor PEF performance (< 10th vs. ≥ 80th percentile) was associated with increased hazards for dementia (hazard ratio [HR] = 1.89; 95% confidence interval [CI] = 1.23–2.92) and CIND (HR = 1.55; 95% CI = 1.01–2.38) and CIND progression to dementia, although not statistically significantly (HR = 2.44; 95% CI = 0.78–6.88). People with poor PEF also experienced the fastest ventricular enlargement (β coefficient = 0.67 mL/year; 95% CI = 0.13–1.21) and had the highest likelihood of developing lacunes (odds ratio = 5.05; 95% CI = 1.01–25.23). DISCUSSION: Poor lung function contributes to cognitive deterioration possibly through accelerated brain atrophy and microvascular damage. Highlights: Poor lung function increased the risk of dementia and mild cognitive impairment (MCI).Poor lung function accelerated the progression from MCI to dementia.Poor lung function was linked to brain microvascular damage and global brain atrophy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We investigated the association of cognitive reserve (CR) with transitions across cognitive states and death. METHODS: This population‐based cohort study included 2631 participants (age ≥60 years) who were dementia‐free at baseline and regularly examined up to 15 years. Data were analyzed using the Markov multistate models. RESULTS: Each 1‐point increase in the composite CR score (range: ‐4.25 to 3.46) was significantly associated with lower risks of transition from normal cognition to cognitive impairment, no dementia (CIND) (multivariable‐adjusted hazards ratio = 0.78; 95% confidence interval = 0.72–0.85) and death (0.85; 0.79–0.93), and from CIND to death (0.82; 0.73–0.91), but not from CIND to normal cognition or dementia. A greater composite CR score was associated with a lower risk of transition from CIND to death in people aged 60‐72 but not in those aged ≥ 78 years. DISCUSSION: CR contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. Highlights: We use Markov multistate model to examine the association between cognitive reserve and transitions across cognitive states and death.A great cognitive reserve contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia.A great cognitive reserve is associated with a lower risk of transition from cognitive impairment, no dementia to death in people at the early stage of old age, but not in those at the late stage of old age. [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: 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]

Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. Methods: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. Results: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14–0.55) for dementia and 0.18 (0.07–0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60–74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38–0.69) for MCI and 0.46 (0.33–0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education. [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: Cognitive reserve (CR) partly explains cognitive variability in the presence of pathological brain aging. Objective: We investigated the interplay of lifelong CR with age, sex, and brain aging markers in cognitive phenotypes among older adults with very limited education. Methods: This population-based cross-sectional study included 179 dementia-free participants (age ≥65 years; 39.7% women; 67.0% had no or elementary education) examined in 2014–2016. We assessed lacunes and volumes of hippocampus, ventricles, grey matter, white matter (WM), and white matter hyperintensities. Lifelong CR score was generated from six lifespan intellectual factors (e.g., education and social support). We used Mini-Mental State Examination (MMSE) score to assess cognition and Petersen's criteria to define mild cognitive impairment (MCI). Data were analyzed using general linear and logistic models. Results: The association of higher lifelong CR score (range: –4.0–5.0) with higher MMSE score was stronger in women (multivariable-adjusted β-coefficient and 95% CI: 1.75;0.99–2.51) than in men (0.68;0.33–1.03) (pinteraction = 0.006). The association of higher CR with MCI (multivariable-adjusted odds ratio and 95% CI: 0.77;0.60–0.99) did not vary by age or sex. Among participants with low CR (<1.4[median]), greater hippocampal and WM volumes were related to higher MMSE scores with multivariable-adjusted β-coefficients being 1.77(0.41–3.13) and 0.44(0.15–0.74); the corresponding figures in those with high CR were 0.15(–0.76–1.07) and –0.17(–0.41–0.07) (pinteraction <0.01). There was no statistical interaction of CR with MRI markers on MCI. Conclusion: Greater lifelong CR capacity is associated with better late-life cognition among people with limited education, possibly by compensating for impact of neurodegeneration. [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 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]