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.

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.

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.

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.

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.

Unraveling patterns and processes of diversification in the South Andean-Patagonian Nassauvia subgenus Strongyloma (Asteraceae, Nassauvieae).

Congruence among different sources of data is highly desirable in phylogenetic analyses. However, plastid and nuclear DNA may record different evolutionary processes such that incongruence among results from these sources can help unravel complex evolutionary histories. That is the case of Nassauvia subgenus Strongyloma (Asteraceae), a taxon with five putative species distributed in the southern Andes and Patagonian steppe. Morphometric and phylogeographic information cast doubt on the integrity of its species, and previous molecular data even questioned the monophyly of the subgenus. We tested those questions using plastid and nuclear DNA sequences by the application of different methods such as phylogenetic trees, networks, a test of genealogical sorting, an analysis of population structure, calibration of the trees, and hybridization test, assembling non-synchronous incongruent results at subgenus and species levels in a single reconstruction. The integration of our molecular analyses and previous taxonomic, morphological, and molecular studies support subgenus Strongyloma as a monophyletic group. However, the topology of the nuclear trees and the evidence of polyploids within subgenus Nassauvia, suggest a hypothetical origin and initial radiation of Nassauvia related to an ancient hybridization event that occurred around 17-6.3 Myr ago near the Andes in west-central Patagonia. Plastid data suggest a recent diversification within subgenus Strongyloma, at most 9.8 Myr ago, towards the Patagonian steppe east of the Andes. These processes cause phylogenies to deviate from the species tree since each putative species lack exclusive ancestry. The non-monophyly of its species using both plastid and nuclear data is caused mainly by incomplete lineage sorting occurred since the Miocene. The final uplift of the Andes and Pliocene-Pleistocene glacial-interglacial and its consequences on the landscape and climate structured the genetic composition of this group of plants in the Patagonian steppe. The molecular data presented here agree with previous morphological studies, in that the five putative species typically accepted in this subgenus are not independent taxa. This study emphasizes that adding more than one sequence per species, not combining data with dissimilar inheritance patterns without first performed incongruence tests, exploring data through different methodologies, considering the timing of events, and searching for the causes of poorly resolved and/or incongruent phylogenies help to reveal complex biological underlying processes, which might otherwise remain hidden.

Using integrative taxonomy and multispecies coalescent models for phylogeny reconstruction and species delimitation within the "Nastanthus-Gamocarpha" clade (Calyceraceae).

The Calyceraceae (47 spp.) is a small family of plants that is sister to the Asteraceae (∼ 25,000 spp.), one of the largest families of angiosperms. Most members of Calyceraceae are endemic to the Andes and Patagonia, representing an excellent model within which to study diversification patterns in these regions. The single phylogenetic study of Calyceraceae conducted to date revealed that the boundaries of most genera and several species of this family require further analyses, especially the "Nastanthus-Gamocarpha" clade. In this study, we reconstructed the phylogeny of the "Nastanthus-Gamocarpha" clade using multispecies coalescent models under BPP and StarBeast2 programs, sampling 63 individuals from 13 of the 14 species recognized to date. We then used this phylogenetic framework to delimit species using BFD and the A11 method implemented in BPP. Species limits suggested through a coalescent approach were then re-evaluated in the light of morphology, geography, and phenology. Coalescent-based methods indicated that most putative lineages could be recognized as distinct species. Morphological, geographical, ecological, and phenological data further supported species delimitation. Necessary taxonomic changes are proposed. Namely, the paraphyletic Nastanthus is synonymized under Gamocarpha, while five species of Boopis are transferred into Gamocarpha. We used an integrative taxonomic approach to recognize 13 species and one subspecies within the newly circumscribed genus Gamocarpha.

Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

Fates of angiosperm species following long-distance dispersal: Examples from American amphitropical Polemoniaceae.

PREMISE OF THE STUDY: Following establishment after long-distance dispersal, species may experience stasis, accumulate changes leading to new species identity, diversify into multiple species, interact with related species to form novel species, and even become extirpated. We examined each species of temperate Polemoniaceae in South America via the literature and new analyses to better understand the fates of species in this family after their dispersal from North America. METHODS: We reviewed literature for the 15 species of Polemoniaceae in South America amphitropically disjunct from their relatives in North America. We conducted DNA sequence analyses to infer relationships, timing of dispersal, and processes involved since dispersal in Microsteris gracilis, three Gilia, two Giliastrum, and three Collomia. Analyses included construction of haplotype networks and phylogenetic trees using maximum likelihood and Bayesian inference. KEY RESULTS: For all species examined in detail, origins in South America are compatible with dispersal via epizoochory from ca. 0.092-19.46 million years ago. Most species in South America are unique relative to their North American congeners, yet few have radiated into two or more species. Relative stasis, divergence, and hybridization with, and without, allopolyploid formation have occurred postdispersal in Polemoniaceae, as well as extirpation following at least brief establishment. CONCLUSIONS: Polemoniaceae that have established in South America share many features likely inherited from their North American progenitors, but some traits may have arisen in situ in specific taxa, such as cleistogamy, self-incompatibility, and the annual habit, evidencing the rich nature of diversification processes.

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.

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.

Total cholesterol and neuropsychiatric symptoms in Alzheimer's disease: the impact of total cholesterol level and gender.

BACKGROUND: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD. METHODS: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed. RESULTS: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC. CONCLUSION: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC.

The Hachinski ischemic scale and cognition: the influence of ethnicity.

OBJECTIVE: cardiovascular burden is considered a risk factor for the development of cognitive dysfunction and dementia. While this link is well established in the literature, implementing this work in primary care settings remains a challenge. The goal of this study is to examine the utility of the Hachinski Ischemic Scale (HIS) in identifying cognitive dysfunction and diagnosis of mild cognitive impairment (MCI) in an ethnically diverse sample. METHODS: data were analysed on 517 participants (211 Mexican Americans and 306 non-Hispanic Whites) recruited from Project FRONTIER, a study of rural health. Neuropsychological measures were utilised to assess for cognitive functioning. RESULTS: among non-Hispanic Whites, HIS scores were significantly related to poorer performance on tasks of global cognition [B (SE) = -0.13 (0.06), P = 0.02], immediate memory [B (SE) = -0.85 (0.26), P < 0.001], attention [B (SE) = -1.6 (0.36), P < 0.001] and executive functioning [B (SE) = 0.46 (0.12), P < 0.001], and significantly predicted diagnosis of MCI [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.2-1.6]. For Mexican Americans, HIS scores were significantly related to immediate memory [B (SE) = -0.78 (0.28), P = 0.01], attention [B (SE) = -0.74 (0.36), P = 0.04] and executive functioning [B (SE) = 0.37 (0.14), P = 0.01]; however, HIS scores were not significantly related to diagnosis of MCI in Mexican Americans (OR = 1.2, 95% CI = 0.96-1.4, P = 0.116). CONCLUSION: HIS scores were related to cognitive functioning; however, these results differed by ethnicity. It is possible that these findings indicate that vascular factors may increase risk for MCI among non-Hispanic Whites but not for Mexican Americans. These findings are consistent with past research that suggests risk factors for MCI may differ by ethnicity.

Developing molecular tools and insights into the Penstemon genome using genomic reduction and next-generation sequencing.

BACKGROUND: Penstemon's unique phenotypic diversity, hardiness, and drought-tolerance give it great potential for the xeric landscaping industry. Molecular markers will accelerate the breeding and domestication of drought tolerant Penstemon cultivars by, creating genetic maps, and clarifying of phylogenetic relationships. Our objectives were to identify and validate interspecific molecular markers from four diverse Penstemon species in order to gain specific insights into the Penstemon genome. RESULTS: We used a 454 pyrosequencing and GR-RSC (genome reduction using restriction site conservation) to identify homologous loci across four Penstemon species (P. cyananthus, P. davidsonii, P. dissectus, and P. fruticosus) representing three diverse subgenera with considerable genome size variation. From these genomic data, we identified 133 unique interspecific markers containing SSRs and INDELs of which 51 produced viable PCR-based markers. These markers produced simple banding patterns in 90% of the species × marker interactions (~84% were polymorphic). Twelve of the markers were tested across 93, mostly xeric, Penstemon taxa (72 species), of which ~98% produced reproducible marker data. Additionally, we identified an average of one SNP per 2,890 bp per species and one per 97 bp between any two apparent homologous sequences from the four source species. We selected 192 homologous sequences, meeting stringent parameters, to create SNP markers. Of these, 75 demonstrated repeatable polymorphic marker functionality across the four sequence source species. Finally, sequence analysis indicated that repetitive elements were approximately 70% more prevalent in the P. cyananthus genome, the largest genome in the study, than in the smallest genome surveyed (P. dissectus). CONCLUSIONS: We demonstrated the utility of GR-RSC to identify homologous loci across related Penstemon taxa. Though PCR primer regions were conserved across a broadly sampled survey of Penstemon species (93 taxa), DNA sequence within these amplicons (12 SSR/INDEL markers) was highly diverse. With the continued decline in next-generation sequencing costs, it will soon be feasible to use genomic reduction techniques to simultaneously sequence thousands of homologous loci across dozens of Penstemon species. Such efforts will greatly facilitate our understanding of the phylogenetic structure within this important drought tolerant genus. In the interim, this study identified thousands of SNPs and over 50 SSRs/INDELs which should provide a foundation for future Penstemon phylogenetic studies and breeding efforts.

Cognitive differences among depressed and non-depressed MCI participants: a project FRONTIER study.

OBJECTIVE: Depression is the most commonly reported psychiatric symptom in patients with mild cognitive impairment (MCI). However, more research is needed examining the impact of depression on cognitive functioning in MCI patients. The purpose of this study was to examine differences in cognitive functioning in a sample of community- based, depressed, and non-depressed MCI patients. METHODS: One hundred and five participants with MCI were included in this study. Participants were recruited from Project FRONTIER, a study of rural health. Depression was assessed via the Geriatric Depression Scale (GDS-30), and cognition was measured using the Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS: The results indicated that depressed MCI participants performed significantly worse than their non-depressed counterparts on several cognitive measures. MCI participants with depression scored significantly lower on immediate memory (t = 3.4, p < 0.01) and delayed memory (t = 2.8, p < 0.01) indices than their non-depressed counterparts. CONCLUSIONS: The results of this study indicated that MCI participants with depression experienced greater deficits in cognitive functioning than their non-depressed counterparts. Depressed MCI participants exhibited greater deficits in both immediate and delayed memory. Thus, identifying and treating depression in individuals with MCI may improve memory and cognitive functioning.

The impact of GPX1 on the association of groundwater selenium and depression: a Project FRONTIER study.

BACKGROUND: Prior animal model and human-based studies have linked selenium concentrations to decreased risk for depression; however, this work has not focused on household groundwater levels or specific depressive symptoms. The current study evaluated the link between groundwater selenium levels and depression. We also sought to determine if a functional polymorphism in the glutathione peroxidase 1 (GPX1) gene impacted this link. METHODS: We used a cross-sectional design to analyze data from 585 participants (183 men and 402 women) from Project FRONTIER, a study of rural health in West Texas. Residential selenium concentrations were estimated using Geospatial Information System (GIS) analyses. Linear regression models were created using Geriatric Depression Scale (GDS-30) total and subfactor scores as outcome variables and selenium concentrations as predictor variables. Analyses were re-run after stratification of the sample on GPX1 Pro198Leu genotype (rs1050454). RESULTS: Selenium levels were significantly and negatively related to all GDS and subfactor scores accounting for up to 17% of the variance beyond covariates. Selenium was most strongly protective against depression among homozygous carriers of the C allele at the Pro198Leu polymorphism of the GPX1 gene. Analyses also point towards a gene-environmental interaction between selenium exposure and GPX1 polymorphism. CONCLUSION: Our results support the link between groundwater selenium levels and decreased depression symptoms. These findings also highlight the need to consider the genetics of the glutathione peroxidase system when examining this relationship, as variation in the GPX1 gene is related to depression risk and significantly influences the protective impact of selenium, which is indicative of a gene-environment interaction.

Plasma Biomarkers of Alzheimer's Disease Are Associated with Physical Functioning Outcomes Among Cognitively Normal Adults in the Multiethnic HABS-HD Cohort.

In this study, we examined the link between plasma Alzheimer's disease (AD) biomarkers and physical functioning outcomes within a community-dwelling, multiethnic cohort. Data from 1 328 cognitively unimpaired participants (n = 659 Mexican American and n = 669 non-Hispanic White) from the ongoing Health & Aging Brain Study-Health Disparities (HABS-HD) cohort were examined. Plasma AD biomarkers (amyloid beta [Aß]40, Aß42, total tau [t-tau], and neurofilament light chain [NfL]) were assayed using the ultra-sensitive Simoa platform. Physical functioning measures were the Timed Up and Go (TUG) and the Short Physical Performance Battery (SPPB). Cross-sectional linear regression analyses revealed that plasma Aß 40 (p < .001), Aß 42 (p = .003), and NfL (p < .001) were each significantly associated with TUG time in seconds. Plasma Aß 40 (p < .001), Aß 42 (p < .001), t-tau (p = .002), and NfL (p < .001) were each significantly associated with SPPB Total Score. Additional analyses demonstrate that the link between plasma AD biomarkers and physical functioning outcomes were strongest among Mexican Americans. Plasma AD biomarkers are receiving a great deal of attention in the literature and are now available clinically including use in clinical trials. The examination of AD biomarkers and physical functioning may allow for the development of risk profiles, which could stratify a person's risk for neurodegenerative diseases, such as AD, based on plasma AD biomarkers, physical functioning, ethnicity, or a combination of these measures prior to the onset of cognitive impairment.

Association of cardiovascular risk factors and blood biomarkers with cognition: The HABS-HD study.

Introduction: To determine if cardiovascular risk factor (CVRF) burden is associated with Alzheimer's disease (AD) biomarkers and whether they synergistically associate with cognition. Methods: We cross-sectionally studied 1521 non-demented Mexican American (52%) and non-Hispanic White individuals aged ≥50 years. A composite score was calculated by averaging the z-scores of five cognitive tests. Plasma ß-amyloid (Aß) 42/40, total tau (t-tau), and neurofilament light (NfL) were assayed using Simoa. CVRF burden was assessed using the Framingham Risk Score (FRS). Results: Compared to low FRS (< 10% risk), high FRS (≥ 20% risk) was independently associated with increased t-tau and NfL. High FRS was significantly associated with higher NfL only among Mexican American individuals. Intermediate or high FRS (vs. low FRS) were independently associated with lower cognition, and the association remained significant after adjusting for plasma biomarkers. Hypertension synergistically interacted with t-tau and NfL (p < 0.05). Discussion: CVRFs play critical roles, both through independent and neurodegenerative pathways, on cognition.

Precision Medicine for Preventing Alzheimer's Disease: Analysis of the ADAPT Study.

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.

Evolutionary origin of the Asteraceae capitulum: Insights from Calyceraceae.

PREMISE OF THE STUDY: Phylogenies based on molecular data are revealing that generalizations about complex morphological structures often obscure variation and developmental patterns important for understanding the evolution of forms, as is the case for inflorescence morphology within the well-supported MGCA clade (Menyanthaceae + Goodeniaceae + Calyceraceae + Asteraceae). While the basal families share a basic thyrsic/thyrsoid structure of their inflorescences, Asteraceae possesses a capitulum that is widely interpreted as a racemose, condensed inflorescence. Elucidating the poorly known inflorescence structure of Calyceraceae, sister to Asteraceae, should help clarify how the Asteraceae capitulum evolved from thyrsic/thyrsoid inflorescences. METHODS: The early development and structure of the inflorescence of eight species (five genera) of Calyceraceae were studied by SEM, and patterns of evolutionary change were interpreted via phylogenetic character mapping. KEY RESULTS: The basic inflorescence structure of Calyceraceae is a cephalioid (a very condensed botryoid/thyrsoid). Optimization of inflorescence characters on a DNA sequence-derived tree suggests that the Asteraceae capitulum derives from a simple cephalioid through two morphological changes: loss of the terminal flower and suppression of the cymose branching pattern in the peripheral branches. CONCLUSIONS: Widely understood as a condensed raceme, the Asteraceae capitulum is the evolutionary result of a very reduced, condensed thyrsoid. Starting from that point, evolution worked separately only on the racemose developmental control/pattern within Asteraceae and mainly on the cymose developmental control/pattern within Calyceraceae, producing head-like inflorescences in both groups but with very different diversification potential. We also discuss possible remnants of the ancestral cephalioid structure in some Asteraceae.