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Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent. Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty. Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database. Levels of cerebrospinal fluid amyloid-β, p-tau, and t-tau were identified for AD-related pathology based on the amyloid-β/tau/neurodegeneration (AT[N]) framework. Frailty was measured using a modified Frailty Index-11 (mFI-11). Regression and interaction models were utilized to assess the relationship among frailty, AT(N) profiles, and cognition. Moderation models analyzed the correlation between AT(N) profiles and cognition across three frailty levels. All analyses were corrected for age, sex, education, and APOEɛ4 status. Results: In this study, frailty (odds ratio [OR] = 1.71, p < 0.001) and AT(N) profiles (OR = 2.00, p < 0.001) were independently associated with cognitive status. The model fit was improved when frailty was added to the model examining the relationship between AT(N) profiles and cognition (p < 0.001). There was a significant interaction between frailty and AT(N) profiles in relation to cognitive status (OR = 1.12, pinteraction = 0.028). Comparable results were obtained when Mini-Mental State Examination scores were utilized as the measure of cognitive performance. The association between AT(N) profiles and cognition was stronger with the levels of frailty. Conclusions: Frailty may diminish patients' resilience to AD pathology and accelerate cognitive decline resulting from abnormal AD-related pathology. In summary, frailty contributes to elucidating the relationship between AD-related pathology and cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Patients with transient ischemic attack (TIA) or ischemic stroke demonstrate an increased risk of cognitive dysfunction. Accumulating evidence indicates that ischemic cerebrovascular disease (ICVD) may interact with the amyloid/tau/neurodegeneration (AT[N]) biomarkers to promote dementia. However, the precise pathological mechanisms remain to be fully characterized. Objective: To elucidate the interrelationships among ICVD, ATN biomarkers in cerebrospinal fluid (CSF), and cognition. Methods: A total of 2524 participants were recruited from the CABLE study. ICVD referred to TIA/ischemic stroke. Cognitive performance was assessed by China Modified Mini-Mental State Examination (CM-MMSE) and Montreal Cognitive Assessment-b (MoCA-b). Multivariate linear regression analyses were performed to evaluate the associations of ICVD with CSF ATN biomarkers and cognition. Causal mediation analyses were used to identify whether the association was mediated by ATN biomarkers. Results: ICVD was associated with higher total-tau (t-tau) (p = 2.828×10–2) and poorer cognition (CM-MMSE: p = 1.539×10–5, MoCA-b: p = 4.552×10–6). Additionally, no discernible correlation surfaced between ICVD and amyloid-β (Aβ) 42 (p = 6.910×10–1) or phosphorylated tau (p-tau) (p = 4.324×10–1). The influence of ICVD on cognitive function was partially mediated by CSF t-tau (CM-MMSE: proportion: 2.74%, MoCA-b: proportion: 2.51%). Subgroup analyses revealed the influences of t-tau were especially evident in male (CM-MMSE: proportion: 5.45%, MoCA-b: proportion: 5.38%) and mid-life group (CM-MMSE: proportion: 9.83%, MoCA-b: proportion: 5.31%). Conclusions: These results delineated t-tau as a potential mediator for the influence of ICVD on cognition. Targeting brain ischemia and alleviating neuronal injury induced by ischemia may be a promising approach for preventing cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Frailty is a vulnerability state increasing the risk of many adverse health outcomes, but little is known about the effects of frailty on neuropsychiatric health. Objective: To explore the associations between frailty and the risk of neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD), especially in its different clinical stages. Methods: We included 2,155 individuals assessed using modified frailty index-11 (mFI-11), Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The relationships between frailty and NPSs were explored with logistic regression models and Cox proportional hazard regression models. Causal mediation analyses were conducted to explore the mediation factors between frailty and NPSs. Results: Among mild cognitive impairment (MCI) participants, frailty was cross-sectionally associated with an increased risk of apathy, and longitudinally associated with increased risk of depression and apathy. Among AD participants, frailty was cross-sectionally associated with increased risk of depression and anxiety, and longitudinally associated with an increased risk of apathy. Among participants with cognitive progression, frailty was associated with increased risk of depression and apathy. In MCI participants, the influence of frailty on NPSs was partially mediated by hippocampus volume, whole brain volume, and monocytes, with mediating proportions ranging from 8.40% to 9.29%. Conclusions: Frailty was associated with NPSs such as depression, anxiety, and apathy among MCI, AD, and cognitive progression participants. Atrophy of the hippocampus and whole brain, as well as peripheral immunity may be involved in the potential mechanisms underlying the above associations. [ABSTRACT FROM AUTHOR]