The Association of Neighborhood Socioeconomic Status with Executive Function and Processing Speed in Cognitively Normal Mexican American Elders from the Health and Aging Brains Study: Health Disparities Cohort.

INTRODUCTION: Neighborhood socioeconomic status (NSES) has been linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic whites (NHWs) and Mexican Americans (MAs) from the Health and Aging Brain: Health Disparities Study (HABS-HD). METHODS: The HABS-HD is a longitudinal study conducted at the University of North Texas Health Science Center. The final sample analyzed (n = 1,312) were 50 years or older, with unimpaired cognition, and underwent an interview, neuropsychological examination, imaging, and blood draw. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered socioeconomic variables. Executive function and processing speed were assessed by the trail making tests (A and B) and the digit-symbol substitution test, respectively. Linear regression was used to assess the association of ADI and cognitive measures. RESULTS: MAs were younger, more likely to be female, less educated, had higher ADI scores, performed worse on trails B (all p < 0.05), and had lower prevalence of APOE4 + when compared to NHWs (p < 0.0001). A higher percentage of MAs lived in the most deprived neighborhoods than NHWs. For NHWs, ADI did not predict trails B or DSS scores, after adjusting for demographic variables and APOE4. For MAs, ADI predicted trails A, trails B, and DSS after adjusting for demographic covariates and APOE4 status. CONCLUSION: Our study revealed that living in an area of higher deprivation was associated with lower cognitive function in MAs but not in NHWs, which is important to consider in future interventions to slow cognitive decline.

Empirically derived psychosocial-behavioral phenotypes in Black/African American and Hispanic/Latino older adults enrolled in HABS-HD: Associations with AD biomarkers and cognitive outcomes.

INTRODUCTION: Identification of psychosocial-behavioral phenotypes to understand within-group heterogeneity in risk and resiliency to Alzheimer's disease (AD) within Black/African American and Hispanic/Latino older adults is essential for the implementation of precision health approaches. METHODS: A cluster analysis was performed on baseline measures of socioeconomic resources (annual income, social support, occupational complexity) and psychiatric distress (chronic stress, depression, anxiety) for 1220 racially/ethnically minoritized adults enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD). Analyses of covariance adjusting for sociodemographic factors examined phenotype differences in cognition and plasma AD biomarkers. RESULTS: The cluster analysis identified (1) Low Resource/High Distress (n = 256); (2) High Resource/Low Distress (n = 485); and (3) Low Resource/Low Distress (n = 479) phenotypes. The Low Resource/High Distress phenotype displayed poorer cognition and higher plasma neurofilament light chain; differences between the High Resource/Low Distress and Low Resource/Low Distress phenotypes were minimal. DISCUSSION: The identification of psychosocial-behavioral phenotypes within racially/ethnically minoritized older adults is crucial to the development of targeted AD prevention and intervention efforts.

Medical comorbidities and ethnicity impact plasma Alzheimer's disease biomarkers: Important considerations for clinical trials and practice.

INTRODUCTION: Despite the clinical implementation, there remain significant gaps in our knowledge regarding the impact of race/ethnicity or common medical comorbidity on plasma Alzheimer's disease (AD) biomarkers. METHODS: Plasma biomarkers of amyloid beta (Aß)40, Aß42 , total tau, and neurofilament light chain (NfL) were measured across cognitively normal Mexican Americans (n = 445) and non-Hispanic Whites (n = 520). RESULTS: Dyslipidemia was associated with elevated Aß40 (P = .01) and Aß42 (P = .001) while hypertension was associated with elevated Aß40 (P = .003), Aß42 (P < .001), and total tau (P = .002) levels. Diabetes was associated with higher Aß40 (P < .001), Aß42 (P < .001), total tau (P < .001), and NfL (P < .001) levels. Chronic kidney disease (CKD) was associated with elevations in Aß40 (P < .001), Aß42 (P < .001), total tau (P < .001), and NfL (P < .001) levels. Mexican Americans had significantly lower Aß40 (P < .001) and higher total tau (P = .005) levels. DISCUSSION: Plasma AD biomarkers vary significantly in association with common medical comorbidities as well as ethnicity. These findings are important for those using these biomarkers in clinical practice and clinical trials.

Comparison of genetic and health risk factors for mild cognitive impairment and Alzheimer's disease between Hispanic and non-Hispanic white participants.

INTRODUCTION: The influence of apolipoprotein E (APOE) genotype on mild cognitive impairment (MCI) and Alzheimer's disease (AD) is well studied in the non-Hispanic white (NHW) population but not in the Hispanic population. Additionally, health risk factors such as hypertension, stroke, and depression may also differ between the two populations. METHODS: We combined three data sets (National Alzheimer's Coordinating Center [NACC], Alzheimer's Disease Neuroimaging Initiative [ADNI], Health and Aging Brain Study: Health Disparities [HABS-HD]) and compared risk factors for MCI and AD between Hispanic and NHW participants, with a total of 24,268 participants (11.1% Hispanic). RESULTS: APOEε4 was associated with fewer all-cause MCI cases in Hispanic participants (Hispanic odds ratio [OR]: 1.114; NHW OR: 1.453), and APOEε2 (Hispanic OR: 1.224; NHW OR: 0.592) and depression (Hispanic OR: 2.817; NHW OR: 1.847) were associated with more AD cases in Hispanic participants. DISCUSSION: APOEε2 may not be protective for AD in Hispanic participants and Hispanic participants with depression may face a higher risk for AD. HIGHLIGHTS: GAAIN allows for discovery of data sets to use in secondary analyses. APOEε2 was not protective for AD in Hispanic participants. APOEε4 was associated with fewer MCI cases in Hispanic participants. Depression was associated with more AD cases in Hispanic participants.

Plasma NT1-tau and Aß42 correlate with age and cognitive function in two large Down syndrome cohorts.

INTRODUCTION: People with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and Aß isoforms predict cognitive impairment. METHODS: Plasma NT1-tau, Aß37 , Aß40 , and Aß42 levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort. RESULTS: Discovery cohort linear mixed models for NT1-tau, Aß42 , and Aß37:42 were significant for age; there was no main effect of time. In cross-sectional models, NT1-tau increased and Aß42 decreased with age. NT1-tau predicted cognitive and functional scores. The discovery cohort linear model for NT1-tau predicted levels in the validation cohort. DISCUSSION: NT1-tau correlates with age and worse cognition in DS. Further validation of NT1-tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.

The Link between APOE4 Presence and Neuropsychological Test Performance among Mexican Americans and Non-Hispanic Whites of the Multiethnic Health & Aging Brain Study - Health Disparities Cohort.

INTRODUCTION: The APOEε4 allele is the single strongest genetic risk for late-onset Alzheimer's disease (AD). Prior work demonstrates that not only the APOEε4 allele varies by race/ethnicity but also the risk for AD and cognitive impairment conveyed by the APOEε4 allele varies by the racial/ethnic group as well as genetic ancestry. Here, we sought to examine the link between the APOEε4 and neuropsychological functioning among Mexican Americans (MAs). METHODS: Data were examined from 1,633 (852 MAs and 781 non-Hispanic Whites [NHWs]) participants of the Health & Aging Brain Study - Health Disparities (HABS-HD) and were enrolled with all requisite data to be included into the current analyses. RESULTS: The frequency of both ε4 and ε2 alleles was significantly lower among MAs as compared to NHWs. Among MAs, APOEε4 allele presence was associated specifically with poorer immediate and delayed memory (Wechsler Memory Scale - Third Edition [WMS-III] Logical Memory and Spanish-English Verbal Learning Test [SEVLT]). Among NHWs, APOEε4 allele presence was associated with poorer immediate and delayed memory as well as worse executive functioning (Trials B) and verbal fluency (Animal naming). DISCUSSION/CONCLUSION: The APOEε4 allele was associated with poorer cognition across multiple domains among NHWs; however, allele presence was specifically associated with poorer memory performance among MAs. When combined with prior work, the current findings demonstrate that the risk factors associated with cognitive dysfunction differ among MAs as compared to NHWs and require additional investigation.

Characterizing plasma NfL in a community-dwelling multi-ethnic cohort: Results from the HABLE study.

INTRODUCTION: No large-scale characterizations of neurofilament light chain (NfL) have been conducted in diverse populations. METHODS: Baseline data were analyzed among n = 890 Mexican Americans and n = 813 non-Hispanic Whites from the multi-ethnic Health & Aging Brain among Latino Elders (HABLE) study. Plasma NfL was measured on the Simoa platform. RESULTS: In unadjusted models, NfL was significantly associated with age (P < .001), hypertension (P  < .001), dyslipidemia (P = .02), and diabetes (P  < .001). Covarying for age and sex, NfL was associated with neurodegeneration (P  < .001) and global amyloid burden levels (P = .02) in a subset with available data. NfL levels were significantly associated with diagnostic groups (Normal Cognition [NC], mild cognitive impairment [MCI], Dementia; P  < .001); however, there was no cut-score that yielded acceptable diagnostic accuracy. NfL levels produced a sensitivity of 0.60 and specificity of 0.78 with negative predictive value of 89% for detecting amyloid positivity. DISCUSSION: Plasma NfL levels are significantly impacted by age and medical co-morbidities that are common among older adults, which complicate its utility as a diagnostic biomarker.

A blood screening tool for detecting mild cognitive impairment and Alzheimer's disease among community-dwelling Mexican Americans and non-Hispanic Whites: A method for increasing representation of diverse populations in clinical research.

INTRODUCTION: Representation of Mexican Americans in Alzheimer's disease (AD) clinical research has been extremely poor. METHODS: Data were examined from the ongoing community-based, multi-ethnic Health & Aging Brain among Latino Elders (HABLE) study. Participants underwent functional exams, clinical labs, neuropsychological testing, and 3T magnetic resonance imaging of the brain. Fasting proteomic markers were examined for predicting mild cognitive impairment (MCI) and AD using support vector machine models. RESULTS: Data were examined from n = 1649 participants (Mexican American n = 866; non-Hispanic White n = 783). Proteomic profiles were highly accurate in detecting MCI (area under the curve [AUC] = 0.91) and dementia (AUC = 0.95). The proteomic profiles varied significantly between ethnic groups and disease state. Negative predictive value was excellent for ruling out MCI and dementia across ethnic groups. DISCUSSION: A blood-based screening tool can serve as a method for increasing access to state-of-the-art AD clinical research by bridging between community-based and clinic-based settings.

Probing the proteome to explore potential correlates of increased Alzheimer's-related cerebrovascular disease in adults with Down syndrome.

Cerebrovascular disease is associated with symptoms and pathogenesis of Alzheimer's disease (AD) among adults with Down syndrome (DS). The cause of increased dementia-related cerebrovascular disease in DS is unknown. We explored whether protein markers of neuroinflammation are associated with markers of cerebrovascular disease among adults with DS. Participants from the Alzheimer's disease in Down syndrome (ADDS) study with magnetic resonance imaging (MRI) scans and blood biomarker data were included. Support vector machine (SVM) analyses examined the relationship of blood-based proteomic biomarkers with MRI-defined cerebrovascular disease among participants characterized as having cognitive decline (n = 36, mean age ± SD = 53 ± 6.2) and as being cognitively stable (n = 78, mean age = 49 ± 6.4). Inflammatory and AD markers were associated with cerebrovascular disease, particularly among symptomatic individuals. The pattern suggested relatively greater inflammatory involvement among cognitively stable individuals and greater AD involvement among those with cognitively decline. The findings help to generate hypotheses that both inflammatory and AD markers are implicated in cerebrovascular disease among those with DS and point to potential mechanistic pathways for further examination.

Addressing the disparities in dementia risk, early detection and care in Latino populations: Highlights from the second Latinos & Alzheimer's Symposium.

The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances in AD biomarkers, and novel cognitive assessments for Spanish-speaking populations, as well as the need to effectively recruit and retain Latinos in clinical research, and how best to deliver health-care services and to aid caregivers of Latinos living with AD.

Using Fractional Anisotropy Imaging to Detect Mild Cognitive Impairment and Alzheimer's Disease among Mexican Americans and Non-Hispanic Whites: A HABLE Study.

INTRODUCTION: Alzheimer's disease (AD) is the most frequently occurring neurodegenerative disease; however, little work has been conducted examining biomarkers of AD among Mexican Americans. Here, we examined diffusion tensor MRI marker profiles for detecting mild cognitive impairment (MCI) and dementia in a multi-ethnic cohort. METHODS: 3T MRI measures of fractional anisotropy (FA) were examined among 1,636 participants of the ongoing community-based Health & Aging Brain among Latino Elders (HABLE) community-based study (Mexican American n = 851; non-Hispanic white n = 785). RESULTS: The FA profile was highly accurate in detecting both MCI (area under the receiver operating characteristic curve [AUC] = 0.99) and dementia (AUC = 0.98). However, the FA profile varied significantly not only between diagnostic groups but also between Mexican Americans and non-Hispanic whites. CONCLUSION: Findings suggest that diffusion tensor imaging markers may have a role in the neurodiagnostic process for detecting MCI and dementia among diverse populations.

Human plasma biomarker responses to inhalational general anaesthesia without surgery.

BACKGROUND: Postoperative neurocognitive disorders may arise in part from adverse effects of general anaesthetics on the CNS, especially in older patients or individuals otherwise vulnerable to neurotoxicity because of systemic disease or the presence of pre-existing neuropathology. Previous studies have documented cytokine and injury biomarker responses to surgical procedures that included general anaesthesia, but it is not clear to what degree anaesthetics contribute to these responses. METHODS: We performed a prospective cohort study of 59 healthy volunteers aged 40-80 yr who did not undergo surgery. Plasma markers of neurological injury and inflammation were measured immediately before and 5 h after induction of general anaesthesia with 1 minimum alveolar concentration of sevoflurane. Biomarkers included interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), C-reactive protein (CRP), and neural injury (tau, neurofilament light [NF-L], and glial fibrillary acidic protein [GFAP]). RESULTS: Baseline biomarkers were in the normal range, although NF-L and GFAP were elevated as a function of age. At 5 h after induction of anaesthesia, plasma tau, NF-L, and GFAP were significantly decreased relative to baseline. Plasma IL-6 was significantly increased after anaesthesia, but by a biologically insignificant degree (<1 pg ml-1); plasma TNF-α and CRP were unchanged. CONCLUSIONS: Sevoflurane general anaesthesia without surgery, even in older adults, did not provoke an inflammatory state or neuronal injury at a concentration that is detectable by an acute elevation of measured plasma biomarkers in the early hours after exposure. CLINICAL TRIAL REGISTRATION: NCT02275026.

Cardiovascular risk factors in Mexico and the United States: a comparative cross-sectional study between the HABLE and MHAS participants.

INTRODUCTION: In the United States, information on the Mexican-American population is available through the Health and Aging Brain among Latino Elders (HABLE) study; in Mexico, the results of the Mexican Health and Aging Study (MHAS) are available. OBJECTIVE: To compare the prevalence of cardiovascular risk factors between men and women of the HABLE and MHAS studies. METHOD: The prevalence of hypertension, diabetes, hypercholesterolemia and abdominal obesity was transversely analyzed in 559 HABLE participants and compared with data from 13,663 MHAS participants. The comparison was made using Student's t-test and the chi-square test, according to the type of variable. RESULTS: The analysis showed that the prevalence of hypertension (50 %, 95 % CI = 41.8-51.8), diabetes (35.5 %, 95 % CI = 27.6-43.8) and abdominal obesity (59.3 %, 95 % CI = 50.5-68.1) were significantly higher in HABLE males, whereas females had a higher prevalence of diabetes (36.8 %, 95 % CI = 32.2-41.5) and abdominal obesity (89.6 %, 95 % CI = 86.6-92.5). Hypercholesterolemia had a higher prevalence in MHAS females (53.3%, 95% CI = 50.3-56.2). CONCLUSION: The prevalence of cardiovascular risk factors was higher in Mexican American HABLE participants, than in Mexican MHAS participants.

INTRODUCCIÓN: En Estados Unidos se dispone de información acerca de la población mexicoamericana por el Estudio de Salud y Envejecimiento del Cerebro en Latinos Mayores (HABLE); en México se dispone de los resultados del Estudio Nacional de Salud y Envejecimiento en México (ENASEM). OBJETIVO: Comparar la prevalencia de factores de riesgo cardiovascular entre hombres y mujeres de HABLE y ENASEM. MÉTODO: Se analizó transversalmente la prevalencia de hipertensión, diabetes, hipercolesterolemia y obesidad abdominal en 559 participantes de HABLE y se comparó con datos de 13 663 participantes del ENASEM. La comparación se realizó mediante t de Student y chi cuadrada, según el tipo de variable. RESULTADOS: El análisis demostró que la prevalencia de hipertensión (50 %, IC 95 % = 41.8-51.8), diabetes (35.5 %, IC 95 % = 27.6-43.8) y obesidad abdominal (59.3 %, IC 95 % = 50.5-68.1) fueron significativamente mayores en hombres del HABLE, mientras que las mujeres presentaron una prevalencia más elevada de diabetes (36.8 %, IC 95 % = 32.2-41.5) y obesidad abdominal (89.6 %, IC 95 % = 86.6-92.5). La hipercolesterolemia tuvo una prevalencia más elevada en mujeres del ENASEM (53.3 %, IC 95 % = 50.3-56.2). CONCLUSIÓN: La prevalencia de factores de riesgo cardiovascular fue mayor en mexicoamericanos participantes del HABLE, que en mexicanos participantes del ENASEM.

Vascular Depression and Cognition in Mexican Americans.

BACKGROUND: Mexican Americans are at increased risk of developing mild cognitive impairment (MCI) and Alzheimer's disease compared to non-Hispanic whites. This study sought to examine the relationship between vascular risk, depression, and cognition in Mexican American elders. METHODS: Data from 470 (390 normal controls, 80 MCI patients) Mexican Americans enrolled in the Health and Aging Brain among Latino Elders (HABLE) study were used. The cardiovascular risk was assessed by the Framingham Risk Score. Cognition was assessed with a neuropsychological battery, and depression was assessed based on scores from the Geriatric Depression Scale (GDS). ANOVAs were utilized to determine the differences in neuropsychological scores of normal controls with and without depression and CVD risk (low vs. high). Follow-up logistic regression was conducted to determine MCI risk. RESULTS: The results of this study indicated that comorbid depression and a high CVD risk were associated with poorer cognitive performance in Mexican Americans. Depressed women with high CVD risk were more likely to have executive dysfunction, language deficits, and poorer global cognition than nondepressed women with a high CVD risk. In Mexican American men, those with a high vascular risk and depression were more likely to have executive dysfunction and poorer immediate memory than the nondepressed high-risk group. Higher GDS scores (OR = 1.10; 95% CI 1.02-1.10, p = 0.001) and higher vascular risk scores (OR = 1.05; 95% CI 1.02-1.10, p = 0.001) significantly predicted MCI status in Mexican Americans. CONCLUSION: The results of this study indicated that comorbid depression and a high CVD risk were associated with poorer cognitive performance and increased risk of MCI in Mexican Americans.

Current state of Alzheimer's fluid biomarkers.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aß42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic ß-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement. METHODS: Water T2, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. RESULTS: Plasma and serum water T2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma. CONCLUSIONS: Water T2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual's metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.

Depression, inflammation, and memory loss among Mexican Americans: analysis of the HABLE cohort.

BACKGROUND: This study explored the combined impact of depression and inflammation on memory functioning among Mexican-American adults and elders. METHODS: Data were analyzed from 381 participants of the Health and Aging Brain study among Latino Elders (HABLE). Fasting serum samples were collected and assayed in duplicate using electrochemiluminesce on the SECTOR Imager 2400A from Meso Scale Discovery. Positive DepE (depression endophenotype) was codified as any score >1 on a five-point scale based on the GDS-30. Inflammation was determined by TNFα levels and categorized by tertiles (1st, 2nd, 3rd). WMS-III LMI and LMII as well as CERAD were utilized as measures of memory. ANOVAs examined group differences between positive DepE and inflammation tertiles with neuropsychological scale scores as outcome variables. Logistic regressions were used to examine level of inflammation and DepE positive status on the risk for MCI. RESULTS: Positive DepE as well as higher inflammation were both independently found to be associated with lower memory scores. Among DepE positive, those who were high in inflammation (3rd tertile) were found to perform significantly worse on WMS-III LM I (F = 4.75, p = 0.003), WMS-III LM II (F = 8.18, p < 0.001), and CERAD List Learning (F = 17.37, p < 0.001) when compared to those low on inflammation (1st tertile). The combination of DepE positive and highest tertile of inflammation was associated with increased risk for MCI diagnosis (OR = 6.06; 95% CI = 3.9-11.2, p < 0.001). CONCLUSION: Presence of elevated inflammation and positive DepE scores increased risk for worse memory among Mexican-American older adults. Additionally, the combination of DepE and high inflammation was associated with increased risk for MCI diagnosis. This work suggests that depression and inflammation are independently associated with worse memory among Mexican-American adults and elders; however, the combination of both increases risk for poorer memory beyond either alone.

Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic.

The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

A depressive endophenotype of poorer cognition among cognitively healthy community-dwelling adults: results from the Western Australia memory study.

OBJECTIVE: The objective was to evaluate in a cognitively normal population the utility of an endophenotype of the depression-cognition link previously shown to be related to cognitive functioning in mild cognitive impairment and Alzheimer's disease. METHODS: The data of 460 cognitively normal adults aged 32-92 years (M = 63.5, standard deviation = 9.24) from the Western Australian Memory Study with the Cross-national comparisons of the Cambridge Cognitive Examination-revised (CAMCOG-R) scores and 30-item Geriatric Depression Scale (GDS) scores were analyzed to determine the relationship between the five-item depressive endophenotype (DepE) scale drawn from the GDS and level of performance on a measure of cognitive functioning. RESULTS: For the entire sample, there was a nonsignificant trend toward a negative relationship between DepE and CAMCOG-R scores. When analyzed for those 65 years and older, there was a significant negative relationship between the two measures (p = 0.001) with DepE scores significantly increasing the risk for performing more poorly on the CAMCOG-R (odds ratio = 1.53). Analysis of data for those 70 years and older showed that DepE was the only predictor significantly related to poorer CAMCOG-R performance (p = 0.001). For the 70 years and older group, DepE scores significantly increased the risk of poorer CAMCOG-R scores (odds ratio = 2.23). Analysis of the entire sample on the basis of ApoEε4 carrier status revealed that DepE scores were significantly negatively related only to ApoEε4 noncarrier regardless of age. CONCLUSIONS: Elevated DepE scores are associated with poor neuropsychological performance among cognitively normal older adults. Use of the DepE may allow for the identification of a subset of older adults where depression is a primary factor in cognitive decline and who may benefit from antidepressant therapies.