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Background: People experiencing homelessness suffer from deficient access to health care and disproportionately poor health outcomes. The American Association of Colleges of Nursing (AACN) maintains learning competencies for prelicensure nursing students. Shelters are rich environments for students to garner experiences with the inequities plaguing our health care system and to fulfill AACN competencies., Method: We established a psychiatric and mental health nursing practicum at a homeless shelter. Following a retrospective pretest methodology, we evaluated student learning with the Health Care Professional's Attitudes Toward the Homeless Inventory (HPATHI). Students, faculty, and shelter staff provided qualitative feedback postpracticum., Results: Students' median HPATHI scores increased on 16 of 19 survey items. Qualitative feedback was largely positive and reinforced HPATHI data., Conclusion: The practicum provided rich learning experiences for students. Educators establishing shelter-based practica should prioritize continuity, develop referral pathways for residents with illness, maintain a flexible mindset, administer prospective student surveys, and solicit feedback from shelter residents. [ J Nurs Educ . 2025;64(1):56-59.] ., Competing Interests: Disclosure: The authors have disclosed no potential conflicts of interest, financial or otherwise.

Importance: Older adults with lower intake and tissue levels of long-chain ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) have more brain white matter lesions (WMLs), an association suggesting that small-vessel ischemic disease, a major contributor to the development of dementia, including Alzheimer disease, may be preventable through ω-3 treatment., Objective: To determine whether ω-3 treatment reduces WML accumulation in older adults without dementia harboring WMLs and with suboptimal ω-3 status., Design, Setting, and Participants: This quadruple-blinded, placebo-controlled, randomized clinical trial with treatment stratification by apolipoprotein E ε4 allele (APOE*E4) carrier status used linear mixed-effects models to estimate mean annual change between groups. The study was conducted at Oregon Health & Science University, a major academic medical center in the Pacific Northwest, from May 2014 to final participant visit in September 2019. Data analysis concluded in July 2022. Participants were adults without dementia aged 75 years and older with WMLs greater than or equal to 5 cm3 and plasma ω-3 PUFA less than 5.5 weight percentage of total., Intervention: Three-year treatment with 1.65 g of ω-3 PUFA (975 mg of EPA and 650 mg of DHA) vs a soybean oil placebo matched for taste, smell, and appearance., Main Outcomes and Measures: The primary outcome was annual WML progression measured using magnetic resonance imaging. Secondary outcomes included diffusion tensor imaging of fractional anisotropy (DTI-FA), representing neuronal integrity breakdown., Results: A total of 102 participants (62 women [60.8%]; mean age, 81 years [range, 75-96 years]) were equally randomized, 51 per treatment group. Although the ω-3 group had less annual WML accumulation than the placebo group, the difference was not statistically significant (1.19 cm3 [95% CI, 0.64-1.74 cm3] vs 1.34 cm3 [95% CI, 0.80-1.88 cm3]; P = .30). Similarly, the ω-3 group had less annual DTI-FA decline than the placebo group, but the difference was not statistically significant (-0.0014 mm2/s [95% CI, -0.0027 to 0.0002 mm2/s] vs -0.0027 mm2/s [95% CI, -0.0041 to -0.0014 mm2/s]; P = .07). Among APOE*E4 carriers, the annual DTI-FA decline was significantly lower in the group treated with ω-3 than the placebo group (-0.0016 mm2/s [95% CI, -0.0032 to 0.0020 mm2/s] vs -0.0047 mm2/s [95% CI, -0.0067 to -0.0025 mm2/s]; P = .04). Adverse events were similar between treatment groups., Conclusions and Relevance: In this 3-year randomized clinical trial, ω-3 treatment was safe and well-tolerated but failed to reach significant reductions in WML accumulation or neuronal integrity breakdown among all participants, which may be attributable to sample size limitations. However, neuronal integrity breakdown was reduced by ω-3 treatment in APOE*E4 carriers, suggesting that this treatment may be beneficial for this specific group., Trial Registration: ClinicalTrials.gov Identifier: NCT01953705.

Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Neuropsychiatric symptoms (NPS) severely affect patients and their caregivers, and are associated with worse long-term outcomes. This study tested the hypothesis that altered protein levels in blood plasma could serve as biomarkers of NPS; and that altered protein levels are associated with persisting NPS and cognitive decline over time. We performed a cross-sectional and longitudinal study in older subjects with cognitive impairment and cognitively unimpaired in a memory clinic setting. NPS were recorded through the Neuropsychiatric Inventory Questionnaire (NPI-Q) while cognitive and functional impairment was assessed using the clinical dementia rating sum of boxes (CDR-SoB) score at baseline and follow-up visits. Shotgun proteomic analysis based on liquid chromatography-mass spectrometry was conducted in blood plasma samples, identifying 420 proteins. The presence of Alzheimer's Disease (AD) pathology was determined by cerebrospinal fluid biomarkers. Eighty-five subjects with a mean age of 70 (±7.4) years, 62% female and 54% with mild cognitive impairment or mild dementia were included. We found 15 plasma proteins with altered baseline levels in participants with NPS (NPI-Q score > 0). Adding those 15 proteins to a reference model based on clinical data (age, CDR-SoB) significantly improved the prediction of NPS (from receiver operating characteristic area under the curve [AUC] 0.75 to AUC 0.91, p = 0.004) with a specificity of 89% and a sensitivity of 74%. The identified proteins additionally predicted both persisting NPS and cognitive decline at follow-up visits. The observed associations were independent of the presence of AD pathology. Using proteomics, we identified a panel of specific blood proteins associated with current and future NPS, and related cognitive decline in older people. These findings show the potential of untargeted proteomics to identify blood-based biomarkers of pathological alterations relevant for NPS and related clinical disease progression., (© 2022 International Society for Neurochemistry.)

The role of nutrition has been investigated for decades under the assumption of one-size-fits-all. Yet there is heterogeneity in metabolic and neurobiological responses to diet. Thus a more personalized approach may better fit biological reality and have increased efficacy to prevent dementia. Personalized nutrition builds on the food exposome, defined as the history of diet-related exposures over the lifetime, and on its interactions with the genome and other biological characteristics (eg, metabolism, the microbiome) to shape health. We review current advances of personalized nutrition in dementia research. We discuss key questions, success milestones, and future roadmap from observational epidemiology to clinical studies through basic science. A personalized nutrition approach based on the best prescription for the most appropriate target population in the most relevant time-window has the potential to strengthen dementia-prevention efforts., (© 2021 the Alzheimer's Association.)

Observational studies suggest that nutritional factors have a potential cognitive benefit. However, systematic reviews of randomised trials of dietary and nutritional supplements have reported largely null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal View, the Nutrition for Dementia Prevention Working Group presents what we consider to be limitations in the existing nutrition clinical trials for dementia prevention. On the basis of this evidence, we propose recommendations for incorporating dietary patterns and the use of genetic, and nutrition assessment tools, biomarkers, and novel clinical trial designs to guide future trial developments. Nutrition-based research has unique challenges that could require testing both more personalised interventions in targeted risk subgroups, identified by nutritional and other biomarkers, and large-scale and pragmatic study designs for more generalisable public health interventions across diverse populations.

Background: Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer's disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical disease progression., Methods: We quantified a panel of 38 neuroinflammation and vascular injury markers in paired serum and cerebrospinal fluid (CSF) samples in a cohort of cognitively normal and impaired older subjects. We performed neuropsychiatric and cognitive evaluations and measured CSF biomarkers of AD pathology. Multivariate analysis determined serum and CSF neuroinflammatory alterations associated with NPS, considering cognitive status, AD pathology, and cognitive decline at follow-up visits., Results: NPS were associated with distinct inflammatory profiles in serum, involving eotaxin-3, interleukin (IL)-6 and C-reactive protein (CRP); and in CSF, including soluble intracellular cell adhesion molecule-1 (sICAM-1), IL-8, 10-kDa interferon-γ-induced protein, and CRP. AD pathology interacted with CSF sICAM-1 in association with NPS. Presenting NPS was associated with subsequent cognitive decline which was mediated by CSF sICAM-1., Conclusions: Distinct systemic and CNS inflammatory processes are involved in the pathophysiology of NPS in older people. Neuroinflammation may explain the link between NPS and more rapid clinical disease progression., (© 2022. The Author(s).)

Although neuropsychiatric symptoms (NPS) are common and severely affect older people with cognitive decline, little is known about their underlying molecular mechanisms and relationships with Alzheimer’s disease (AD). The aim of this study was to identify and characterize cerebrospinal fluid (CSF) proteome alterations related to NPS. In a longitudinally followed-up cohort of subjects with normal cognition and patients with cognitive impairment (MCI and mild dementia) from a memory clinic setting, we quantified a panel of 790 proteins in CSF using an untargeted shotgun proteomic workflow. Regression models and pathway enrichment analysis were used to investigate protein alterations related to NPS, and to explore relationships with AD pathology and cognitive decline at follow-up visits. Regression analysis selected 27 CSF proteins associated with NPS. These associations were independent of the presence of cerebral AD pathology (defined as CSF p-tau181/Aβ1−42 > 0.0779, center cutoff). Gene ontology enrichment showed abundance alterations of proteins related to cell adhesion, immune response, and lipid metabolism, among others, in relation to NPS. Out of the selected proteins, three were associated with accelerated cognitive decline at follow-up visits after controlling for possible confounders. Specific CSF proteome alterations underlying NPS may both represent pathophysiological processes independent from AD and accelerate clinical disease progression.

Background: Recent evidence point towards an interaction between omega-3 (n-3) polyunsaturated fatty acids (PUFA) and plasma homocysteine (Hcy)., Objectives: This study tested the hypothesis that effects of red blood cell n-3 PUFA are modified according to baseline plasma Hcy in the large Mulit-domain Alzheimer Prevention Trial (MAPT) throughout the 3-years of treatment with an additional 2 years of observational follow-up., Design: Experimental study., Participants: From the 1680 participants that were randomized in the four groups of the MAPT study (two of which received n-3 PUFA, the other two without n-3 PUFA), 782 were selected because they had baseline data on both Hcy and n-3 PUFA., Measurements: Cognitive performance was measured with a broad set of cognitive tests including free and total recall of the cued selective reminding test, digit symbol substitution test, category naming test and Trail-making tests (TMT-A and B) and Clinical dementia rating scale., Results: We found a significant association between TMT-A and red blood cell n-3 PUFA levels in participants with Hcy values ≤16.8 µMol/L after adjustments at baseline (Estimate: -1.3, 95% CI: -2.3; -0.3, p=0.01). Additionally, participants with high Hcy values had a significant worsening after adjustments in TMT-B after a 5-year n-3 PUFA supplementation, compared to low levels of Hcy (Mean difference: 34.8, 95% CI: 7.8;61.7)., Conclusion: This study shows that Hcy levels could modify the association between red blood cell n-3 PUFA and executive function. People with high Hcy may benefit less from a n-3 PUFA supplementation to prevent cognitive decline., Competing Interests: none to report

Introduction: Human neurodevelopment is complete by the 4th decade of life at which point brain atrophy ensues with variable rate and regionality into old age. Literally all regions of the brain experience atrophy with older age, however the pattern and rate of atrophy can dictate the behavioral consequences (i.e., cognitive impairment, Alzheimer's disease). Substantial research has aimed to discover the reasons why some people experience greater morphologic changes that produce undesirable consequences with aging and how it may be prevented. One possible explanation is diet, particularly fish consumption and the intake of omega-3 polyunsaturated fatty acids (omega 3) concentrated in fish oil. This narrative review examines the available evidence on the association between omega-3 and brain volume in non-demented older adults., Methods: A PubMed search of the literature was conducted in search of studies that investigated the associations of omega-3 on brain morphology and volume in cognitively intact older adults. Inclusion criteria were: populations of adults aged 45 years or over, who were cognitively intact, free of any central nervous system disease, and free of advanced structural brain atrophy. Study participants had to have DHA and EPA levels measured either by blood testing or scoring of dietary intake. There were no restrictions to dates of publication. Studies including demented participants, or participants with substantial white or grey matter atrophy visible on magnetic resonance imaging were excluded., Results and Conclusion: The search identified only 12 studies, 8 of which were cross-sectional observational studies, 3 longitudinal observational studies, and 1 randomized controlled trial published between 2007 and 2019. The largest amount of evidence indicated that the hippocampus was most frequently involved in this association, with a higher volume associated with higher omega-3 levels. Larger total grey matter, total brain volume, and lower white matter lesion volume were also associated with higher omega-3 among four of the reviewed studies. However, most studies reviewed provided mixed findings regarding the presence or absence of the association of interest, and the findings were observed to be brain region-dependent. Current evidence is still insufficient to formulate recommendations for omega-3 intake to support brain health specifically., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Multiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypothesize that specific molecular patterns indicating both known and yet unidentified pathway alterations are associated with distinct aspects of AD pathology., Methods: We performed multi-level cerebrospinal fluid (CSF) omics in a well-characterized cohort of older adults with normal cognition, mild cognitive impairment, and mild dementia. Proteomics, metabolomics, lipidomics, one-carbon metabolism, and neuroinflammation related molecules were analyzed at single-omic level with correlation and regression approaches. Multi-omics factor analysis was used to integrate all biological levels. Identified analytes were used to construct best predictive models of the presence of AD pathology and of cognitive decline with multifactorial regression analysis. Pathway enrichment analysis identified pathway alterations in AD., Results: Multi-omics integration identified five major dimensions of heterogeneity explaining the variance within the cohort and differentially associated with AD. Further analysis exposed multiple interactions between single 'omics modalities and distinct multi-omics molecular signatures differentially related to amyloid pathology, neuronal injury, and tau hyperphosphorylation. Enrichment pathway analysis revealed overrepresentation of the hemostasis, immune response, and extracellular matrix signaling pathways in association with AD. Finally, combinations of four molecules improved prediction of both AD (protein 14-3-3 zeta/delta, clusterin, interleukin-15, and transgelin-2) and cognitive decline (protein 14-3-3 zeta/delta, clusterin, cholesteryl ester 27:1 16:0 and monocyte chemoattractant protein-1)., Conclusions: Applying an integrative multi-omics approach we report novel molecular and pathways alterations associated with AD pathology. These findings are relevant for the development of personalized diagnosis and treatment approaches in AD.

Introduction: Multinutrient approaches may produce more robust effects on brain health through interactive qualities. We hypothesized that a blood-based nutritional risk index (NRI) including three biomarkers of diet quality can explain cognitive trajectories in the multidomain Alzheimer prevention trial (MAPT) over 3-years., Methods: The NRI included erythrocyte n-3 polyunsaturated fatty acids (n-3 PUFA 22:6n-3 and 20:5n-3), serum 25-hydroxyvitamin D, and plasma homocysteine. The NRI scores reflect the number of nutritional risk factors (0-3). The primary outcome in MAPT was a cognitive composite Z score within each participant that was fit with linear mixed-effects models., Results: Eighty percent had at lease one nutritional risk factor for cognitive decline (NRI ≥1: 573 of 712). Participants presenting without nutritional risk factors (NRI=0) exhibited cognitive enhancement ( β  = 0.03 standard units [SU]/y), whereas each NRI point increase corresponded to an incremental acceleration in rates of cognitive decline (NRI-1: β  = -0.04 SU/y, P  = .03; NRI-2: β  = -0.08 SU/y, P  < .0001; and NRI-3: β  = -0.11 SU/y, P  = .0008)., Discussion: Identifying and addressing these well-established nutritional risk factors may reduce age-related cognitive decline in older adults; an observation that warrants further study., (© 2019 The Authors.)

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.

Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm³, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61% were female, 28% were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm.

The systems-level relationship between the proteomes of cerebrospinal fluid (CSF) and plasma has not been comprehensively described so far. Recently developed shotgun proteomic workflows allow for deeper characterization of the proteomes from body fluids in much larger sample size. We deployed state-of-the-art mass spectrometry-based proteomics in paired CSF and plasma samples volunteered by 120 elders with and without cognitive impairment to comprehensively characterize and examine compartmental proteome differences and relationships between both body fluids. We further assessed the influence of blood-brain barrier (BBB) integrity and tested the hypothesis that BBB breakdown can be identified from CSF and plasma proteome alterations in nondemented elders. We quantified 790 proteins in CSF and 422 proteins in plasma, and 255 of the proteins were identified in both compartments. Pearson's statistics determined 28 proteins with associated levels between CSF and plasma. BBB integrity as defined with the CSF/serum albumin index influenced 76 CSF/plasma protein ratios. In least absolute shrinkage and selection operator models, CSF and plasma proteins improved identification of BBB impairment. In conclusion, we provide here a first comprehensive draft map of interacting human CSF and plasma proteomes, in view of their complex and dynamic compositions, and influence of the BBB.

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., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Blood-brain barrier (BBB) breakdown is observed in older versus younger adults and in late-onset Alzheimer's disease versus age-matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders., Methods: Cerebrospinal fluid and serum inflammatory markers were measured using sandwich immunoassays in 120 subjects. Least Absolute Shrinkage and Selection Operator-logistic regression selected cerebrospinal fluid and serum signatures that best classified BBB impairment defined by the cerebrospinal fluid albumin index ≥9. Linear regression examined changes in Clinical Dementia Rating sum of boxes as a function of BBB integrity at baseline., Results: Mean age was 70 years, mean Mini–Mental State Examination was 27, and BBB impairment was recorded in 13.5%. BBB breakdown was associated with cognitive decline (P = .015). Cerebrospinal fluid intercellular adhesion molecule-1, vascular endothelial growth factor, interleukin-8, serum amyloid A, macrophage derived chemokine, and gender generated an area under the curve of 0.95 for BBB impairment, and serum IL-16, VEGF-D, IL-15, and other variables generated an AUC of 0.92 for BBB impairment., Discussion: BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated., (Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: Altered proteome profiles have been reported in both postmortem brain tissues and body fluids of subjects with Alzheimer disease (AD), but their broad relationships with AD pathology, amyloid pathology, and tau-related neurodegeneration have not yet been fully explored. Using a robust automated MS-based proteomic biomarker discovery workflow, we measured cerebrospinal fluid (CSF) proteomes to explore their association with well-established markers of core AD pathology., Methods: Cross-sectional analysis was performed on CSF collected from 120 older community-dwelling adults with normal (n = 48) or impaired cognition (n = 72). LC-MS quantified hundreds of proteins in the CSF. CSF concentrations of β-amyloid 1-42 (Aβ 1-42 ), tau, and tau phosphorylated at threonine 181 (P-tau181) were determined with immunoassays. First, we explored proteins relevant to biomarker-defined AD. Then, correlation analysis of CSF proteins with CSF markers of amyloid pathology, neuronal injury, and tau hyperphosphorylation (i.e., Aβ 1-42 , tau, P-tau181) was performed using Pearson's correlation coefficient and Bonferroni correction for multiple comparisons., Results: We quantified 790 proteins in CSF samples with MS. Four CSF proteins showed an association with CSF Aβ 1-42 levels (p value ≤ 0.05 with correlation coefficient (R) ≥ 0.38). We identified 50 additional CSF proteins associated with CSF tau and 46 proteins associated with CSF P-tau181 (p value ≤ 0.05 with R ≥ 0.37). The majority of those proteins that showed such associations were brain-enriched proteins. Gene Ontology annotation revealed an enrichment for synaptic proteins and proteins originating from reelin-producing cells and the myelin sheath., Conclusions: We used an MS-based proteomic workflow to profile the CSF proteome in relation to cerebral AD pathology. We report strong evidence of previously reported CSF proteins and several novel CSF proteins specifically associated with amyloid pathology or neuronal injury and tau hyperphosphorylation.

Background: Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults., Methods: Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1-42 peptide chain [Aβ 1-42 ] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status., Results: The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, Aβ 1-42 , tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers., Conclusions: We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers.

Background: In vitro and animal studies have linked neuroinflammation to Alzheimer's disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarkers of amyloid and tau pathology in older adults without cognitive impairment or with beginning cognitive decline., Objective: To identify blood-based and CSF neuroinflammation marker signatures associated with AD pathology (i.e. an AD CSF biomarker profile) and to investigate associations of inflammation markers with CSF biomarkers of amyloid, tau pathology, and neuronal injury., Design/methods: Cross-sectional analysis was performed on data from 120 older community-dwelling adults with normal cognition (n=48) or with cognitive impairment (n=72). CSF Aβ1-42, tau and p-tau181, and a panel of 37 neuroinflammatory markers in both CSF and serum were quantified. Least absolute shrinkage and selection operator (LASSO) regression was applied to determine a reference model that best predicts an AD CSF biomarker profile defined a priori as p-tau181/Aβ1-42 ratio >0.0779. It was then compared to a second model that included the inflammatory markers from either serum or CSF. In addition, the correlations between inflammatory markers and CSF Aβ1-42, tau and p-tau181 levels were assessed., Results: Forty-two subjects met criteria for having an AD CSF biomarker profile. The best predictive models included 8 serum or 3 CSF neuroinflammatory markers related to cytokine mediated inflammation, vascular injury, and angiogenesis. Both models improved the accuracy to predict an AD biomarker profile when compared to the reference model. In analyses separately performed in the subgroup of participants with cognitive impairment, adding the serum or the CSF neuroinflammation markers also improved the accuracy of the diagnosis of AD pathology. None of the inflammatory markers correlated with the CSF Aβ1-42 levels. Six CSF markers (IL-15, MCP-1, VEGFR-1, sICAM1, sVCAM-1, and VEGF-D) correlated with the CSF tau and p-tau181 levels, and these associations remained significant after controlling for age, sex, cognitive impairment, and APOEε4 status., Conclusions: The identified serum and CSF neuroinflammation biomarker signatures improve the accuracy of classification for AD pathology in older adults. Our results suggest that inflammation, vascular injury, and angiogenesis as reflected by CSF markers are closely related to cerebral tau pathology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Elevated total plasma homocysteine is a risk factor for Alzheimer's disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical β-amyloid (Aβ) in older adults at risk of dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this relationship was also explored., Design: This is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial., Setting: French community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia., Participants: Individuals were from the MAPT trial (n = 177) with data on total plasma homocysteine at baseline and cortical Aβ load., Measurements: Cortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Total baseline plasma homocysteine was measured using an enzymatic cycling assay. Baseline omega 3 index was measured using gas chromatography. Cross-sectional associations were explored using adjusted multiple linear regression models., Results: We found that total baseline plasma homocysteine was not significantly associated with cortical Aβ as demonstrated using multiple linear regression models adjusted for age, sex, education, cognitive status, time interval between baseline and PET-scan, omega-3 index, MAPT group allocation and Apolipoprotein E ε4 status (B-coefficient -0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that homocysteine was however significantly associated with cortical Aβ in subjects with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E ε4 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10), but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95 % CI: -0.023,0.003, p = 0.132, n = 66)., Conclusions: The role of n-3 PUFAs on the relationship between homocysteine and cerebral Aβ warrants further investigation., Competing Interests: The authors declare that they have no conflict of interest.

Background: Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer's disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve classification of older adults developing an AD dementia., Objective: Identify and describe plasma protein expressions that best classify subjects with CSF-defined presence of AD pathology and cerebral amyloidosis., Methods: We performed a cross-sectional analysis of samples collected from community-dwelling elderly with (n = 72) or without (n = 48) cognitive impairment. CSF Aβ1-42, tau, and phosphorylated tau (P-tau181) were measured using ELISA, and mass spectrometry quantified the plasma proteomes. Presence of AD pathology was defined as CSF P-tau181/Aβ1-42 > 0.0779, and presence of amyloidosis was defined as CSF Aβ1-42 < 724 pg/mL., Results: Two hundred and forty-eight plasma proteins were quantified. Plasma proteins did not improve classification of the AD CSF biomarker profile in the whole sample. When the analysis was separately performed in the cognitively impaired individuals, the diagnosis accuracy of AD CSF profile was 88.9% with 19 plasma proteins included. Within the full cohort, there were 16 plasma proteins that improved diagnostic accuracy of cerebral amyloidosis to 92.4%., Conclusion: Plasma proteins improved classification accuracy of AD pathology in cognitively-impaired older adults and appeared representative of amyloid pathology. If confirmed, those candidates could serve as valuable blood biomarkers of the preclinical stages of AD or risk of developing AD.

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer's disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration.

Introduction: Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time and that total white matter hyperintensity volume (WMH) mediates this association., Methods: Eighty-six non-demented older adults were followed over 4 years after measurement of plasma O3PUFA with annual evaluations of cognitive function. A subset of these participants also had brain MRI of total WMH available to conduct a formal mediation analysis of a putative relationship between O3PUFA and cognitive function., Results: Mean age at baseline was 86, 62% were female and 11% carried the APOE4 allele. Each 100 μg/ml increase in plasma O3PUFA associated with 4 s less change in executive decline per year of aging (p = 0.02, fully adjusted model). O3PUFA was not associated with verbal memory or global cognitive changes. The significance of the association between O3PUFA and better executive function was lost once WMH was added to the regression model., Conclusion: Executive decline with age appears to be a cognitive domain particularly sensitive to plasma O3PUFA in longitudinal examination. O3PUFA may modulate executive functioning by mechanisms underlying the development of WMH, a biologically plausible hypothesis that warrants further investigation.

Background: Research in recent years has suggested a role of vitamin D in the central nervous system. The final converting enzyme and the vitamin D receptor are found throughout the human brain. From animal studies vitamin D appears important in neurodevelopment, up-regulation of neurotrophic factors, stabilization of mitochondrial function, and antioxidation., Objective: To examine the relationship between serum vitamin D and neuropsychiatric function in persons with Parkinson's disease (PD)., Methods: This is an add-on study to a longitudinal study following neuropsychiatric function in persons with PD. Baseline neuropsychiatric performance and serum 25-hydroxyvitamin D were examined for 286 participants with PD. Measures of global cognitive function (MMSE, MOCA, Mattis Dementia Scale), verbal memory (Hopkins Verbal Learning Test), fluency (animals, vegetables, and FAS words), visuospatial function (Benton Line Orientation), executive function (Trails Making Test and Digit-Symbol Substitution), PD severity (Hoehn & Yahr and Unified Parkinson's Disease Rating Scale) and depression (Geriatric Depression Scale (GDS)) were administered. Multivariate linear regression assessed the association between vitamin D concentration and neuropsychiatric function, in the entire cohort as well as the non-demented and demented subsets., Results: Using a multivariate model, higher vitamin D concentrations were associated with better performance on numerous neuropsychiatric tests in the non-demented subset of the cohort. Significant associations were specifically found between vitamin D concentration and verbal fluency and verbal memory (t = 4.31, p < 0.001 and t = 3.04, p = 0.0083). Vitamin D concentrations also correlated with depression scores (t = -3.08, p = 0.0083) in the non-demented subset., Conclusions: Higher plasma vitamin D is associated with better cognition and better mood in this sample of PD patients without dementia. Determination of causation will require a vitamin D intervention study.

Objectives: To elucidate the mechanism through which vitamin D is associated with decreased falls., Design: This was a convenience sample from a larger observational study examining correlations between vitamin D and 1) falls, 2) motor function, and 3) cognition (n=159)., Setting: Falls data were collected via weekly on-line surveys completed in the participants' homes. Yearly evaluations of motor and cognitive function were conducted in an out-patient setting of a large tertiary medical center., Participants: Participants from the Intelligent Systems for Assessment of Aging Changes Study (ISAAC), a community-based cohort study of independently living older adults over age 70, who had vitamin D concentration within 6 months of clinical evaluations were included in the analysis., Results: Participants mean age was 85 years and 74% were women. Fallers (n=37) had significantly lower vitamin D concentration (32.9ng/ml) compared to non-fallers (39.2ng/ml) (p<0.01). The relationship between vitamin D and falls remained significant after adjusting for age, health status (via CIRS), and supplement use (p=0.004). Vitamin D concentration were significantly associated with cognitive impairment (Clinical Dementia Rating = 0.5) (p=0.02) and MMSE (p<0.01) after adjusting for age, gender, and education. Vitamin D concentrations did not correlate with any motor measures., Conclusion: Vitamin D concentrations correlated with cognition and falls, but not with motor measures. Further research is needed to demonstrate a causal relationship between vitamin D and cognitive function and determine if cognition plays a role in falls reduction.

This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer's disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging., (Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.)

Background. Blood-brain barrier (BBB) dysfunction may have a significant role in the pathogenesis of Alzheimer's disease (AD). Modifiable factors associated with BBB function may have therapeutic implication. This study tested the hypothesis that dyslipidemia is associated with BBB impairment in mild-to-moderate AD. Methods. Thirty-six subjects with AD were followed for 1 year. Fasting CSF and plasma were collected with clinical assessments at baseline and 12 months. BBB impairment was defined as CSF albumin index ≥9. Independent t-tests and linear regression assessed the relationship between plasma lipoproteins and BBB integrity. Results. Dyslipidemia was prevalent in 47% of the population, and in 75% of those with BBB impairment. Subjects with BBB impairment had significantly higher mean plasma triglyceride and lower HDL cholesterol (TG, P = 0.007; HDL, P = 0.043). Plasma triglycerides explained 22% of the variance in BBB integrity and remained significant after controlling for age, gender, ApoE-4 genotype, blood pressure, and statin use. Conclusion. Dyslipidemia is more prevalent in AD subjects with BBB impairment. Plasma triglyceride and HDL cholesterol may have a role in maintaining BBB integrity in mild-to-moderate Alzheimer's disease.

Introduction: There is great interest in the nutritional strategies for the prevention of age-related cognitive decline, yet the best methods for nutritional assessment in the populations at risk for dementia are still evolving. Our study objective was to examine the reliability and validity of the 2 common nutritional assessments (plasma nutrient biomarkers and Food Frequency Questionnaire) in the people at risk for dementia., Methods: Thirty-eight elders, half with amnestic-mild cognitive impairment were recruited. Nutritional assessments were collected together at the baseline and again at 1 month. Intraclass and Pearson correlation coefficients quantified reliability and validity., Results: Twenty-six nutrients were examined. The reliability was very good or better for 77% (20/26, intraclass correlation coefficients or ICC ≥0.75) of the plasma nutrient biomarkers and for 88% of the food frequency questionnaires (FFQ) estimates. Twelve of the nutrient biomarkers were as reliable as the commonly measured plasma cholesterol (ICC≥0.92). FFQ and plasma long-chain fatty acids (docosahexaenoic acid, r=0.39, eicosapentaenoic acid, r=0.39) and carotenoids (α-carotene, r=0.49; lutein + zeaxanthin, r=0.48; β-carotene, r=0.43; β-cryptoxanthin, r=0.41) were correlated, but these significant correlations were present only in non-impaired elders., Conclusion: The reliability and validity of the FFQ and nutrient biomarkers vary according to the nutrient of interest. Memory deficit attenuates validity and inflates reliability of FFQ reports. Many plasma nutrient biomarkers have very good reliability over 1-month, regardless of memory state. This objective method can circumvent sources of error seen in other less direct and subjective methods of nutritional assessment., (Copyright © 2011 by Lippincott Williams & Wilkins)

Certain micronutrients are protective against cognitive decline. We examined whether there is any uniform pattern of circulating micronutrients cross-culturally that are associated with successful cognitive aging. For the U.S. sample, we used the stored serum/plasma of 115 participants, collected in Oregon, USA. The Okinawa sample consisted of 49 participants selected using similar inclusion criteria as the Oregon sample, from the Keys to Optimal Cognitive Aging Project. All participants were aged 85 years and older without cognitive impairment. We found that the Okinawan elders used fewer vitamin supplements but had similar levels of vitamin B(12) and α-tocopherol, lower folate and γ-tocopherol, compared with Oregonian elders. That is, we did not find a uniform pattern of circulating micronutrients, suggesting that micronutrients other than those examined here or other lifestyle factors than nutrition could play an important role in achieving successful cognitive aging.

Oxidative damage is a consistent finding in a number of central nervous system (CNS) disorders. Uric acid (UA) is a potent hydrophilic antioxidant that is modified by diet and drug. Several lines of evidence suggest that plasma UA may modulate outcomes in neurologic disease, but little attention has been paid to CNS levels of UA. Our objective was to test the hypothesis that cerebrospinal fluid (CSF) UA is determined by plasma UA, modified by blood-brain barrier (BBB) integrity and associated with rate of cognitive decline in Alzheimer's disease (AD). Also, since UA and ascorbic acid may act as antioxidants for one another, we also explored a potential interaction between them in the brain. Thirty-two patients with mild to moderate AD (Mini-Mental Status Exam 19 +/- 5) participated in a longitudinal biomarker study for one year involving standardized clinical assessments. CSF and blood were collected at baseline for UA, ascorbic acid, and albumin. Cognitive measures were collected at baseline and again one year later. CSF UA was independent of age, gender, and AD severity. CSF and plasma UA were positively correlated (r=0.669, p=0.001) and BBB impairment was associated with higher CSF levels of UA (p=0.028). Neither plasma nor CSF UA reached significant association with rates of cognitive decline over 1 year. CSF UA and CSF ascorbic acid were positively correlated (r=0.388, p=0.001). The hypothesis that CSF UA is determined by plasma UA and BBB integrity is supported, as is the hypothesis that UA and ascorbic acid are associated in CSF but not plasma. Adequately powered prospective studies would help assess any role for UA in primary and secondary prevention of AD.

The brain maintains high levels of ascorbic acid (AA) despite a concentration gradient favoring diffusion from brain to peripheral tissues. Dietary antioxidants, including AA, appear to modify the risk of Alzheimer's disease (AD). The objective of this study was to test the hypothesis that neurodegeneration in AD is modified by brain levels of AA. Thirty-two patients with mild to moderate AD participated in a biomarker study involving standardized clinical assessments over one year. Cerebrospinal fluid (CSF) and serum were collected at baseline for AA and albumin content. Cognitive measures were collected at baseline and one year. CSF and plasma AA failed to predict cognitive decline independently, however, CSF: plasma AA ratio did. After adding CSF Albumin Index (an established marker of blood-brain barrier integrity) to the regression models the effect of CSF: plasma AA ratio as a predictor of cognitive decline was weakened. CSF: plasma AA ratio predicts rate of decline in AD. This relationship may indicate that the CSF: plasma AA ratio is an index of AA availability to the brain or may be an artifact of a relationship between blood-brain barrier impairment and neurodegeneration.

The prevalence of Cryptosporidium and Giardia infections in pigs was investigated by the use of a direct immunofluorescence assay on two Ohio farms with different management systems. Cryptosporidium and Giardia infections were detected only in weanlings on the farm with slotted and wire floors, but in both weanlings and nursing piglets on the farm with porous concrete floors. Giardia infection was also detected in sows on the latter farm. The farm with porous concrete floors had a significantly higher Cryptosporidium infection rate in nursing piglets and Giardia infection rates in weanlings than the farm with slotted and wire floors. Sows were implicated as the source of both Cryptosporidium and Giardia infections for nursing piglets.

The effect of pseudorabies in a commercial farrow-to-finish operation on selected production and economic values was estimated. Pseudorabies was first diagnosed in this herd by circle testing done in March 1988, as a required part of follow up from another herd that had been diagnosed with pseudorabies in the area. A pseudorabies virus vaccination program was initiated in the herd at that time. The mean litter size of pigs born alive varied from 9.26 to 10.02 pigs/litter throughout the study period; however, there was a twofold increase in suckling pig mortality and a 2.6-fold increase in nursery pig mortality when the months of the epizootic were compared with pre-epizootic months. In the 6-month period following the epizootic, suckling pig mortality was three-fold higher than that reported in the preepizootic months. Total net loss for this operation was estimated at $99,700 from when the epizootic started until eradication, when calculating losses directly. The major economic losses (76.5% of total loss) were related to suckling pig mortality, which was $16,240 during the epizootic or $24/inventoried sow/week; $19,395 in the 6 months following the epizootic or $3.8/inventoried sow/week; and $40,628 thereafter until eradication 26 months later or $0.37/inventoried sow/week. Nursery pig mortality losses were 12.6% of total net losses; $754 during the epizootic, $357 in the 6 months after the enzootic, and $11,444 thereafter until eradication 26 months later. Sow culling and deaths accounted for 9.4% of net losses that took place from 6 months after the epizootic until eradication.(ABSTRACT TRUNCATED AT 250 WORDS)

Nine dairy herds (mean size, 149 cows) with bulk-tank milk somatic cell counts of less than 300,000 cells/ml and greater than 80% of cows with Dairy Herd Improvement Association linear somatic cell counts less than or equal to 4 were selected for study. Each herd was monitored for 12 consecutive months. Duplicate quarter-milk specimens were collected from each cow for bacteriologic culturing at beginning of lactation, cessation of lactation, and at the time of each clinical episode of mastitis. Streptococcus agalactiae was never isolated and Staphylococcus aureus was isolated from less than 1% of all quarters. There were 554 episodes of clinical mastitis. During the year of study, the incidence rate of clinical mastitis varied from 15.6 to 63.7% of cows among the 9 herds. Mean costs per cow per year in herd for mastitis prevention were: $10 for paper towels, $3 for nonlactating cow treatment, and $10 for teat disinfectants. Mean cost associated with clinical mastitis was $107/episode. Approximately 84% ($90) of the costs attributed to a clinical episode were associated with decreased milk production and nonsalable milk. Costs of medication and professional veterinary fees per clinical episode varied significantly among the 9 herds. Three of the herds did not have a veterinarian treat a clinical episode of mastitis during the year of study even though 2 of these herds had the first and third highest incidence rates of clinical mastitis. When calculated on a per cow in herd basis, mean costs of $40/cow/year were attributed to clinical mastitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Serratia liquefaciens mastitis was detected and investigated in a 41-cow Holstein herd. Twenty cows were treated for mastitis over a 3-month period. Serratia liquefaciens was isolated from milk samples obtained from 8 of 12 cows tested during the epizootic. Results of an epidemiologic investigation suggested that extensive frostbite of the teats decreased the udder defense. Poor milking technique and hygiene were responsible for increased exposure of the damaged teats to potential udder pathogens. Treatment of each cow resulted in initial clinical improvement, but exacerbations occurred in 75% of the cows with documented S liquefaciens infections.

Bacterial counts were monitored for 1 yr in bedding materials used on nine commercial dairies. Organic materials used to bed lactating cows had significantly higher moisture content and gram-negative bacterial, coliform, Klebsiella species, and streptococcal counts than did inorganic materials. Klebsiella species counts were higher in sawdust than in chopped straw. Streptococcal counts were higher in chopped straw than sawdust. Bacterial counts did not differ between sand and crushed limestone. Gram-negative bacterial and coliform counts were higher during summer and fall than in winter and spring months. Streptococcal counts did not differ among seasons of the year. Linear relationships were significant between total rates of clinical mastitis during lactation and both gram-negative bacterial and Klebsiella species counts in lactating cow bedding. These data indicate that bacterial populations differed between both types of bedding and among seasons of the year. Rates of clinical mastitis were related to bacterial counts in bedding.

Factors associated with bulk tank milk bacterial and somatic cell counts were investigated for one year on nine well managed dairies. Geometric mean total bacterial count among dairies was 4.4 × 10 3 colony cfu/ml. Geometric mean bulk tank milk somatic cell counts among herds was 265 × 10 3 ml. Bacterial counts in bulk tank milk were correlated with rates of coliform and environmental streptococcal clinical mastitis cases. Rates of total clinical cases were also correlated with bulk tank milk somatic cell counts. Correlations were measured among bulk tank milk bacterial counts and gram-negative bacterial, coliform, Klebsiella species, and streptococcal counts in materials used to bed lactating cows. Total bacterial and staphylococcal bulk tank milk counts increased when synthetic rubber liners were used greater than 800 quarter milkings. Correlations measured indicated that monitoring bulk tank milk may be an effective means of detecting management changes in herds with low bacterial and milk somatic cell counts.

Nine commercial dairy herds, each with low herd milk somatic cell counts, were monitored for 1 yr to determine prevalence of intramammary infections and rates of clinical mastitis. Staphylococcus species was the bacterial group most frequently isolated from quarters at calving and at drying off. Environmental streptococci and coliform intramammary infections totaled less than 6% of quarters at both calving and at drying off. Staphylococcus aureus were isolated from less than 1% of quarters and Streptococcus agalactiae from 0% of quarters at both calving and drying off. A total of 646 clinical cases of mastitis were diagnosed in 548 quarters of 406 cows. Mean rate of clinical mastitis among herds was .457 clinical cases/305 cow-days. Rates of clinical mastitis ranged among herds from .273 to .748 clinical cases/305 cow-days. Coliforms and bacteriologically negative and environmental streptococci accounted for 82.3% of clinical cases. Rates of clinical mastitis and severity of clinical signs differed among herds, seasons of the year, parity groups, and stages of lactation. Rates of clinical mastitis were highest during summer, in first lactation cows, and during the first 7 d of lactation.