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BackgroundDespite tremendous advancements in the field, our understanding of mild cognitive impairment (MCI) and Alzheimer's disease (AD) among Mexican Americans remains limited.ObjectiveThe aim of this study was to characterize MCI and dementia among Mexican Americans and non-Hispanic whites.MethodsBaseline data were analyzed from n = 1,705 (n = 890 Mexican American; n = 815 non-Hispanic white) participants enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD).ResultsAmong Mexican Americans, age (OR = 1.07), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.01) were associated with dementia, but none of these factors were associated with MCI. Among non-Hispanic whites, male gender (OR = 0.33), neighborhood deprivation (OR = 1.34), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.03) were associated with MCI, while depression (OR = 1.09) and APOEɛ4 genotype (OR = 4.38) were associated with dementia.ConclusionFindings from this study revealed that the demographic, clinical, sociocultural and biomarker characteristics of MCI and dementia are different among Mexican Americans as compared to non-Hispanic whites.

BackgroundHispanics are expected to experience the largest increase in Alzheimer's disease (AD) and AD related dementias over the next several decades. However, few studies have examined biomarkers of AD among Mexican Americans, the largest segment of the U.S. Hispanic population.ObjectiveWe sought to examine proteomic profiles of an MRI-based marker of neurodegeneration from the AT(N) framework among a multi-ethnic, community-dwelling cohort.MethodsCommunity-dwelling Mexican Americans and non-Hispanic white adults and elders were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T MRI of the brain. A neurodegeneration MRI meta-ROI biomarker for the AT(N) framework was calculated.ResultsData was examined from n = 1,291 participants. Proteomic profiles were highly accurate for detecting neurodegeneration (i.e., N+) among both Mexican Americans (AUC = 1.0) and non-Hispanic whites (AUC = 0.98). The proteomic profile of N + was different between ethnic groups. Further analyses revealed that the proteomic profiles of N + varied by diagnostic status (control, MCI, dementia) and ethnicity (Mexican American versus non-Hispanic whites) though diagnostic accuracy was high for all classifications.ConclusionA proteomic profile of neurodegeneration has tremendous value and point towards novel diagnostic and intervention opportunities. The current findings demonstrate that the underlying biological factors associated with neurodegeneration are different between Mexican Americans versus non-Hispanic whites as well as at different levels of disease progression.

BackgroundThe need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population.ObjectiveThis study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults.MethodsPlasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome.ResultsIn distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS.ConclusionAdvanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.

Background: Examination of Alzheimer's disease (AD) related biomarkers among diverse communities has remained limited. Objective: The aim of this study was to expand on prior work to provide a characterization of ptau181 among a diverse community sample. Consideration was taken regarding the impact of comorbidities on ptau181 levels including medical. Methods: 3,228 (n = 770 African American [AA], n = 1,231 Hispanic, and n = 1,227 non-Hispanic white [NHW]) Health and Aging Brain Study- Health Disparities (HABS-HD) participants were included in this study. ANCOVAs were conducted to examine differences in ptau181 levels across race and ethnic groups. Violin plots were also generated stratified by APOEɛ4 carrier status, Amyloid PET positivity status, medical comorbidity (hypertension, dyslipidemia, chronic kidney disease [CKD], and diabetes) and by cognitive diagnosis. Results: Ptau181 levels were found to differ between Hispanics and NHW after covarying for age, sex, and APOEɛ4 status. Amyloid PET positivity was associated with higher ptau181 levels across all groups. APOEɛ4 positivity status was only significantly associated with ptau181 levels among AAs. Across all race and ethnic groups, those with a diagnosis of CKD had higher levels of ptau181. When stratified by cognitive diagnosis, cognitively unimpaired Hispanics had higher ptau181 if they also had a diagnosis of CKD or diabetes. p-values ≤0.01. Conclusions: Differences in ptau181 levels were shown in a diverse community sample. Medical comorbidities had a differing effect on ptau181 levels particularly among Hispanics even without cognitive impairment. Findings support the need for future work to consider comorbid conditions when examining the utility of ptau181. [ABSTRACT FROM AUTHOR]

Background: Blood biomarkers have the potential to transform Alzheimer's disease (AD) diagnosis and monitoring, yet their integration with common medical comorbidities remains insufficiently explored. Objective: This study aims to enhance blood biomarkers' sensitivity, specificity, and predictive performance by incorporating comorbidities. We assess this integration's efficacy in diagnostic classification using machine learning, hypothesizing that it can identify a confident set of predictive features. Methods: We analyzed data from 1,705 participants in the Health and Aging Brain Study-Health Disparities, including 116 AD patients, 261 with mild cognitive impairment, and 1,328 cognitively normal controls. Blood samples were assayed using electrochemiluminescence and single molecule array technology, alongside comorbidity data gathered through clinical interviews and medical records. We visually explored blood biomarker and comorbidity characteristics, developed a Feature Importance and SVM-based Leave-One-Out Recursive Feature Elimination (FI-SVM-RFE-LOO) method to optimize feature selection, and compared four models: Biomarker Only, Comorbidity Only, Biomarker and Comorbidity, and Feature-Selected Biomarker and Comorbidity. Results: The combination model incorporating 17 blood biomarkers and 12 comorbidity variables outperformed single-modal models, with NPV12 at 92.78%, AUC at 67.59%, and Sensitivity at 65.70%. Feature selection led to 22 chosen features, resulting in the highest performance, with NPV12 at 93.76%, AUC at 69.22%, and Sensitivity at 70.69%. Additionally, interpretative machine learning highlighted factors contributing to improved prediction performance. Conclusions: In conclusion, combining feature-selected biomarkers and comorbidities enhances prediction performance, while feature selection optimizes their integration. These findings hold promise for understanding AD pathophysiology and advancing preventive treatments. [ABSTRACT FROM AUTHOR]

Background: The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) was the first-ever large-scale anti-inflammatory prevention trial targeting Alzheimer's disease. Objective: The overall goal of this study was to evaluate predictive blood biomarker profiles that identified individuals most likely to be responders on NSAID treatment or placebo at 12 and 24 months. Methods: Baseline (n = 193) and 12-month (n = 562) plasma samples were assayed. The predictive biomarker profile was generated using SVM analyses with response on treatment (yes/no) as the outcome variable. Results: Baseline (AUC = 0.99) and 12-month (AUC = 0.99) predictive biomarker profiles were highly accurate in predicting response on Celecoxib arm at 12 and 24 months. The baseline (AUC = 0.95) and 12-month (AUC = 0.9) predictive biomarker profile predicting response on Naproxen were also highly accurate at 12 and 24 months. The baseline (AUC = 0.93) and 12-month (AUC = 0.99) predictive biomarker profile was also highly accurate in predicting response on placebo. As with our prior work, the profiles varied by treatment arm. Conclusions: The current results provide additional support for a precision medicine model for treating and preventing Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Despite the tremendous amount of research on Alzheimer's disease (AD) biomarkers, very little data is available regarding the fundamental biomarkers of AD among Mexican Americans.Objective: Here we sought to examine the link between metabolic markers and brain amyloid among Mexican Americans as compared to non-Hispanic whites from the Health & Aging Brain Study -Health Disparities (HABS-HD) cohort.Methods: PET amyloid (florbetaben) data was analyzed from 34 Mexican American and 22 non-Hispanic white participants.Results: Glucagon (t = 3.84, p < 0.001) and insulin (t = -2.56, p = 0.02) were both significantly related to global SUVR levels among Mexican Americans. Glucagon and insulin were both related to most ROIs. No metabolic markers were significantly related to brain amyloid levels among non-Hispanic whites.Conclusion: Metabolic markers are related to brain amyloid burden among Mexican Americans. Given the increased risk for diabetes, additional research is needed to determine the impact of diabetes on core AD biomarkers among this underserved population. [ABSTRACT FROM AUTHOR]

Background: The REFLECT trials were conducted to examine the treatment of mild-to-moderate Alzheimer's disease utilizing a peroxisome proliferator-activated receptor gamma agonist.Objective: To generate a predictive biomarker indicative of positive treatment response using samples from the previously conducted REFLECT trials.Methods: Data were analyzed on 360 participants spanning multiple negative REFLECT trials, which included treatment with rosiglitazone and rosiglitazone XR. Support vector machine analyses were conducted to generate a predictive biomarker profile.Results: A pre-defined 6-protein predictive biomarker (IL6, IL10, CRP, TNFα, FABP-3, and PPY) correctly classified treatment response with 100%accuracy across study arms for REFLECT Phase II trial (AVA100193) and multiple Phase III trials (AVA105640, AV102672, and AVA102670). When the data was combined across all rosiglitazone trial arms, a global RSG-predictive biomarker with the same 6-protein predictive biomarker was able to accurately classify 98%of treatment responders.Conclusion: A predictive biomarker comprising of metabolic and inflammatory markers was highly accurate in identifying those patients most likely to experience positive treatment response across the REFLECT trials. This study provides additional proof-of-concept that a predictive biomarker can be utilized to help with screening and predicting treatment response, which holds tremendous benefit for clinical trials. [ABSTRACT FROM AUTHOR]

Background: To date, the therapeutic paradigm for Alzheimer's disease (AD) has focused on a single intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy. Here we test a precision-medicine approach to AD therapy.Objective: To determine if a baseline, blood-based proteomic companion diagnostic predicts response to NSAID therapy.Methods: Proteomic assays of plasma from a multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to rofecoxib (25 mg once daily), naproxen (220 mg twice-daily) or placebo.Results: 474 participants with mild-to-moderate AD were screened with 351 enrolled into the trial. Using support vector machine (SVM) analyses, 89% of the subjects randomized to either NSAID treatment arms were correctly classified using a general NSAID companion diagnostic. Drug-specific companion diagnostics yielded 98% theragnostic accuracy in the rofecoxib arm and 97% accuracy in the naproxen arm.Conclusion: Inflammatory-based companion diagnostics have significant potential to identify select patients with AD who have a high likelihood of responding to NSAID therapy. This work provides empirical support for a precision medicine model approach to treating AD. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive complaints in cognitively normal adults have been linked to later cognitive decline and dementia. Research on the characteristics of this group has been conducted on a variety of clinical and community-based populations. The current study focuses on the rapidly expanding population of Mexican-American elders.Objective: The objective of the study is the determination of characteristics of cognitively normal Mexican-Americans with cognitive complaints.Methods: Data on 319 cognitively normal participants in a large-scale community-based study of elderly Mexican-Americans (HABLE) were analyzed comparing those with cognitive complaints with those without on clinical characteristics, affective status, neuropsychological functioning, and proteomic markers.Results: Those expressing concern about cognitive decline scored lower on the MMSE, were more likely to have significantly more affective symptoms, higher levels of diabetic markers, poorer performance on attention and executive functioning, and a different pattern of inflammatory markers.Conclusion: Although longitudinal research is needed to determine the impact of these differences on later cognition, possible targets for early intervention with Mexican-Americans were identified. [ABSTRACT FROM AUTHOR]

Background: Mexican Americans face a significant health disparity when it comes to Alzheimer's disease (AD) as they present with higher rates of the disease and develop AD at an earlier age compared to other ethnic groups. Recent work identified a proteomic profile of AD among this population; however, no work to date has sought to examine the biological profile of pre-AD among Mexican Americans.Objective: This study aims to identify an amnestic mild cognitive impairment (aMCI) proteomic profile among Mexican Americans.Methods: Data were analyzed from 284 Mexican American participants (aMCI, n = 73; normal controls, n = 211) from the Health & Aging Brain among Latino Elders study. Fasting serum samples were analyzed using a multi-plex biomarker assay platform. A biomarker profile was generated using random forest analyses.Results: Among aMCI cases, the biomarker profile was found to be largely inflammatory with the top three markers shown to include TNFα, IL10, and TARC. The overall diagnostic accuracy of the biomarkers in detecting aMCI was 96% (sensitivity = 0.82; specificity = 0.97). Inclusion of clinical variables with the selected biomarkers did not impact the overall detection accuracy (area under the curve = 0.96) but led to a slight improvement in specificity (specificity = 0.99) and decrease in sensitivity (sensitivity = 0.74).Conclusion: The biomarker profile of aMCI was shown to be different from our previously generated AD profile among Mexican Americans, which was largely metabolic in nature. The findings implicate a possible interplay between inflammatory and metabolic processes and additional work is needed to further examine this. [ABSTRACT FROM AUTHOR]

Research on the link between APOEε4 and neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) has been inconsistent. Previous work has shown a relationship between serum biomarkers of vascular risk and inflammation and NPS in AD. The current study investigated the impact of APOEε4 status on the relationship between biomarkers of cardiovascular risk, systemic inflammation, and NPS. The sample was drawn from the TARCC Longitudinal Research Cohort; the final sample of 190 consisted of 124 females and 66 males meeting the diagnostic criteria for mild to moderate AD. 115 individuals were APOEε4 carriers and 75 were non-carriers. Serum-based clinical biomarkers of vascular risk and biomarkers of inflammation related to AD were analyzed. NPS data was gathered from caretakers/family members using the Neuropsychiatric Inventory. The significant biomarkers differed for carriers and non-carriers with IL15 being a negative biomarker of total NPS accounting for 12% of the variance for carriers and IL18 and TNFα negative predictors for non-carriers (18% of variance). Patterns related to specific symptoms were similar. Stratification by gender revealed significant biomarkers of total NPS for female carriers were negative IL15 and IL1ra (18% of variance) and for female non-carriers were negative IL18 and positive homocysteine. Total cholesterol was a positive biomarker of total NPS for both male carriers (36% of variance) and non-carriers (negative TNFα and total cholesterol, 32% of variance). These findings suggest that dysregulation of inflammatory activity is related to NPS, that cholesterol is a significant factor in the occurrence of NPS, and that gender and APOE status need to be considered. [ABSTRACT FROM AUTHOR]

Numerous serum and plasma based biomarkers of systemic inflammation have been linked to both neuropsychiatric disorders and Alzheimer's disease (AD). The present study investigated the relationship of clinical biomarkers of cardiovascular risk (cholesterol, triglycerides, and homocysteine) and a panel of markers of systemic inflammation (CRP, TNF-α, IL1-ra, IL-7, IL-10, IL-15, IL-18) and microvascular pathology (ICAM-1, VCAM-1) to neuropsychiatric symptoms in a sample with mild AD. Biomarker data was analyzed on a sample of 194 diagnosed with mild to moderate probable AD. The sample was composed of 127 females and 67 males. The presence of neuropsychiatric symptoms was gathered from interview with caretakers/family members using the Neuropsychiatric Inventory. For the total sample, IL-15, VCAM (vascular adhesion molecule), and triglycerides were significantly and negatively related to number of neuropsychiatric symptoms, and total cholesterol and homocysteine were positively related and as a group accounted for 16.1% of the variance. When stratified by gender, different patterns of significant biomarkers were found with relationships more robust for males for both total symptoms and symptom clusters. A combination of biomarkers of systemic inflammation, microvascular pathology, and clinical biomarkers of cardiovascular risk can account for a significant portion of the variance in the occurrence of neuropsychiatric symptoms in AD supporting a vascular and inflammatory component of psychiatric disorders found in AD. Gender differences suggest distinct impact of specific risks with total cholesterol, a measure of cardiovascular risk, being the strongest marker for males and IL-15, a marker of inflammation, being the strongest for females. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the link between C-reactive protein (CRP) and Alzheimer's disease (AD) and mild cognitive impairment (MCI) among Mexican Americans. Methods: Non-fasting serum CRP levels, Mini-Mental State Examination scores, and Clinical Dementia Rating scale (CDR) scores were analyzed from 1,066 participants (Mexican American n = 471; non-Hispanic n = 595) of the Texas Alzheimer's Research & Care Consortium. Results: Among the total cohort, CRP levels among AD cases were significantly decreased as compared to normal controls (p < 0.001) and MCI cases (p = 0.002). CRP levels among MCI cases were decreased relative to controls (p = 0.03). Among Mexican American and non-Hispanic AD cases, CRP levels were significantly decreased among AD cases as compared to controls. CRP levels were only associated with disease severity (CDR scores) among non-Hispanics (p = 0.03) AD cases. Conclusions: These results show that while CRP levels are decreased among Mexican American AD cases, CRP does not appear to be related to clinical variables as it is among non-Hispanic whites. [ABSTRACT FROM AUTHOR]

The purpose of the study was to provide characterization of Mexican Americans who meet criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI). For the study, 1,069 participants ages 40 and above who self-identified as either non-Hispanic white (n = 633) or Mexican American (n = 436) were recruited using a community-based participatory research approach. Global cognition was assessed via the Mini-Mental State Examination (MMSE), dementia severity by the Clinical Dementia Rating Scale, and depression via the Geriatric Depression Scale 30-item version. Age, gender, education, ApoE ℇ4 allele frequency, and diabetic diagnoses were also analyzed. The findings showed that Mexican Americans (normal controls, MCI, and AD) were younger, less highly educated, performed more poorly on the MMSE, endorsed more symptoms of depression, were more likely to be diagnosed with diabetes, and possessed the ApoE ℇ4 allele less frequently. Age was the only significant risk factor for cognitive dysfunction (AD/MCI) among Mexican Americans (OR = 1.06, 95% CI = 1.03-1.09). Age (B = 0.07, std = 0.02, p < 0.001) and ApoE ℇ4 presence (B = 0.9, std = 0.4, p = 0.02) were significantly related to increased disease severity. Given the rapidly growing and aging Mexican American population, there is a substantial need for research into cognitive aging, MCI, and AD among this ethnic group. The current findings hold important implications for both clinic and research settings and point to additional research needs. [ABSTRACT FROM AUTHOR]

Functional impairment is common in Alzheimer's disease (AD) and related to increased caregiver burden and institutionalization. There is a dearth of research investigating the relationship between specific biomarkers and basic activities of daily living (BADLs) such as toileting, feeding, dressing, grooming, bathing, and ambulating. The present study examined the relationship between serum based biomarkers and specific ADLs in a sample of AD patients. Data were collected from 196 participants enrolled in the Texas Alzheimer's Research and Care Consortium Project and diagnosed with AD. BADLs were measured using the Lawton-Brody Physical Self-Maintenance Scale. A panel of 22 biomarkers previously found to be related to AD pathology was used for the analysis. Stepwise regression modeling was used to assess the link between the biomarkers and BADLs. Results were also examined by gender. Nine of the 22 biomarkers were significantly related to BADLs. When stratified by gender, the biomarkers accounted for 32% of the variance in the males and 27% in females. The pattern of significant biomarkers differed by gender with IL 7 and Tenascin C significantly related to BADLs for females and IL 15 significantly related to BADLs for males. The results of this study indicated that a small number of serum based biomarkers are related to BADLs, and these biomarkers differed by gender. [ABSTRACT FROM AUTHOR]