Sleep movements and respiratory coupling as a biobehavioral metric for early Alzheimer's disease in independently dwelling adults.

INTRODUCTION: Sleep disorder is often the first symptom of age-related cognitive decline associated with Alzheimer's disease (AD) observed in primary care. The relationship between sleep and early AD was examined using a patented sleep mattress designed to record respiration and high frequency movement arousals. A machine learning algorithm was developed to classify sleep features associated with early AD. METHOD: Community-dwelling older adults (N = 95; 62-90 years) were recruited in a 3-h catchment area. Study participants were tested on the mattress device in the home bed for 2 days, wore a wrist actigraph for 7 days, and provided sleep diary and sleep disorder self-reports during the 1-week study period. Neurocognitive testing was completed in the home within 30-days of the sleep study. Participant performance on executive and memory tasks, health history and demographics were reviewed by a geriatric clinical team yielding Normal Cognition (n = 45) and amnestic MCI-Consensus (n = 33) groups. A diagnosed MCI group (n = 17) was recruited from a hospital memory clinic following diagnostic series of neuroimaging biomarker assessment and cognitive criteria for AD. RESULTS: In cohort analyses, sleep fragmentation and wake after sleep onset duration predicted poorer executive function, particularly memory performance. Group analyses showed increased sleep fragmentation and total sleep time in the diagnosed MCI group compared to the Normal Cognition group. Machine learning algorithm showed that the time latency between movement arousals and coupled respiratory upregulation could be used as a classifier of diagnosed MCI vs. Normal Cognition cases. ROC diagnostics identified MCI with 87% sensitivity; 89% specificity; and 88% positive predictive value. DISCUSSION: AD sleep phenotype was detected with a novel sleep biometric, time latency, associated with the tight gap between sleep movements and respiratory coupling, which is proposed as a corollary of sleep quality/loss that affects the autonomic regulation of respiration during sleep. Diagnosed MCI was associated with sleep fragmentation and arousal intrusion.

Adherence to a Mediterranean diet is associated with cognitive function in an older non-Mediterranean sample: findings from the Maine-Syracuse Longitudinal Study.

Background: Adherence to a Mediterranean diet is associated with higher cognitive function and reduced risk of dementia in Mediterranean populations. However, few studies have investigated the association between Mediterranean diet adherence and cognition in populations outside of the Mediterranean basin. Furthermore, it is currently unknown whether the association between Mediterranean diet adherence and cognitive function differs between middle-aged and older individuals.Methods: Cross-sectional (n = 894) and longitudinal (n = 530) multivariable analyses were undertaken using data from community-dwelling adults from the Maine-Syracuse Longitudinal Study (MSLS). Mediterranean diet adherence was measured by applying a literature-based Mediterranean diet score to food frequency questionnaire data. Cognitive function was assessed with a battery of tests and composites scores were computed for global cognitive function, Visual-Spatial Organisation and Memory, verbal memory, working memory, scanning and tracking and abstract reasoning.Results: No cross-sectional associations between Mediterranean diet adherence and cognitive function were detected. Over a period of five years, higher adherence to a Mediterranean diet was associated with improvements in Global Cognitive Function, Visual-Spatial Organisation and Memory and scanning and tracking in participants ≥70 years. No significant longitudinal associations were observed for participants <70 years.Conclusion: Our findings suggest that higher adherence to a Mediterranean diet is associated with better cognitive performance, and therefore less cognitive decline, in older but not middle-aged individuals.

Higher yogurt intake is associated with lower blood pressure in hypertensive individuals: Cross-sectional findings from the Maine-Syracuse Longitudinal study.

Associations between fermented dairy products and blood pressure are unclear. The current study therefore examined the association between yogurt and blood pressure in hypertensive and non-hypertensive individuals. Cross-sectional analyses were undertaken on 915 community-dwelling adults from the Maine-Syracuse Longitudinal Study. Habitual yogurt consumption was measured using a food frequency questionnaire. The primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure. Secondary outcomes included BMI (kg m-2), total cholesterol (mg dL-1), glucose (mg dL-1), HDL (mg dL-1), LDL (mg dL-1), triglycerides (mg dL-1), and plasma homocysteine (µmol L-1). Multivariable regression analyses revealed significant inverse associations between yogurt and both SBP (p < 0.05) and MAP (p < 0.05) in hypertensive (n = 564) but not non-hypertensive participants (n = 351). Future observational and intervention studies should continue to focus on at-risk individuals to examine the potential benefits of yogurt.

Dairy food intake, diet patterns, and health: Findings from the Maine-Syracuse Longitudinal Study.

This study compared the intake of yogurt and other dairy foods in relation to other dietary habits, and associations with cardiovascular health indicators. Comparative analyses of dietary intakes and cardiometabolic health indicators were conducted in participants from the Maine-Syracuse Longitudinal Study, conducted in 2001-2006 (n = 699). Participants (10.2% of sample) who consumed yogurt more frequently (≥ 5 serves per week) also consumed more fruit, vegetables, nuts, and fish, but fewer sweets, sugar-sweetened soft drinks, and alcohol. The yogurt-healthy food score was significantly inversely associated with fasting plasma glucose (p = 0.044), waist circumference (p = 0.004), and smoking (p = 0.004), and significantly positively associated with physical activity (p < 0.001). In addition, the yogurt-healthy food score was associated with protection against MetS abdominal obesity (OR: 0.80, 95% CI: 0.66-0.07, p = 0.02). The yogurt-healthy dietary pattern was significantly associated with a better cardiometabolic profile.

Poorer Visual Acuity Is Associated with Declines in Cognitive Performance Across Multiple Cognitive Domains: The Maine-Syracuse Longitudinal Study.

OBJECTIVES: Prior studies have found associations between visual acuity (VA) and cognitive function. However, these studies used a limited range of cognitive measures and did not control for cardiovascular disease risk factors (CVD-RFs) and baseline function. The primary objective of this study was to analyze the associations of VA and cognitive performance using a thorough neuropsychological test battery. METHODS: This study used community-dwelling sample data across the sixth (2001-2006) and seventh (2006-2010) waves of the Maine-Syracuse Longitudinal Study (n=655). Wave 6 VA as measured by the Snellen Eye Test was the primary predictor of wave 6 and wave 7 Global cognitive performance, Visual-Spatial Organization and Memory, Verbal Episodic Memory, Working Memory, Scanning and Tracking, and Executive Function. Additionally, VA was used to predict longitudinal changes in wave 7 cognitive performance (wave 6 performance adjusted). We analyzed these relationships with multiple linear and logistic regression models adjusted for age, sex, education, ethnicity, depressive symptoms, physical function deficits in addition to CVD-RFs, chronic kidney disease, homocysteine, continuous systolic blood pressure, and hypertension status. RESULTS: Adjusted for demographic covariates and CVD-RFs, poorer VA was associated with concurrent and approximate 5-year declines in Global cognitive function, Visual-Spatial Organization and Memory, and Verbal Episodic Memory. DISCUSSION: VA may be used in combination with other screening measures to determine risk for cognitive decline. (JINS, 2018, 24, 746-754).

Risk for cognitive impairment across 22 measures of cognitive ability in early-stage chronic kidney disease.

Background: Chronic kidney disease (CKD) is a significant risk factor for cognitive impairment. Previous studies have examined differences in cognitive impairment between persons with and without CKD using multiple cognitive outcomes, but few have done this for an extensive battery of cognitive tests. We relate early-stage CKD to two indices of impairment for 22 measures of cognitive ability. Methods: The study was community-based and cross-sectional with 898 individuals free from dementia and end-stage renal disease. Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration equation and classified as <60 or ≥60 mL/min/1.73 m2, based on consensus definitions of Stage 3 or greater CKD. The eGFR classifications were related to modest [≥1 standard deviation (SD) below the mean] and severe (≥1.5 SD below the mean) impairment on each measure using logistic regression analyses adjusting for potential risk factors. Results: A total of 146 individuals (16.3%) had eGFR <60 mL/min/1.73 m2 (mean 51.6 ± 10.1 mL/min/1.73 m2). These participants had significantly greater risk for modestly impaired abilities in the scanning and tracking and visual-spatial organization/memory (VSOM) domains after accounting for comorbidity-related risk factors [odds ratios (ORs) between 1.68 and 2.16], as well as greater risk for severely impaired functioning in the language domain (OR = 2.65). Conclusions: Participants with eGFR <60 mL/min/1.73 m2 were at higher risk for cognitive impairment than those with eGFR ≥60 mL/min/1.73 m2 on the majority of cognitive abilities, specifically those within the VSOM, Language, and scanning and tracking domains. Targeted screening for cognitive deficits in kidney disease patients early in their disease course may be warranted.

Habitual chocolate intake and type 2 diabetes mellitus in the Maine-Syracuse Longitudinal Study: (1975-2010): Prospective observations.

Compounds in cocoa and chocolate have established cardiovascular benefits, including beneficial effects on insulin resistance, a risk factor for type 2 diabetes mellitus. The aims of this study was to investigate relations between habitual chocolate intakes and diabetes mellitus. Cross-sectional and prospective analyses were undertaken on 953 community-dwelling participants (mean age 62 years, 59% women) from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intakes, measured using a food frequency questionnaire, were related to prevalence of diabetes mellitus (cross-sectionally) and with risk of diabetes measured approximately five years later (prospectively). We also examined the relation between diabetes (the predictor) and chocolate consumption (the outcome) up to 30 years later. Chocolate intake was inversely associated with type 2 diabetes. Compared to participants who consumed chocolate more than once per week, those who never or rarely ate chocolate exhibited a significantly higher odds of having type 2 diabetes 5 years later (OR: 1.91, 95% CI: 1.03, 3.55, p = 0.04), after adjustment for cardiovascular, lifestyle and dietary factors including other polyphenol-rich beverages. However, individuals diagnosed with diabetes prior to the nutritional assessment consumed lower amounts of chocolate at the time of the dietary assessment. Our findings suggest that relations between chocolate and type 2 diabetes may be bi-directional.

Sugar-sweetened soft drinks are associated with poorer cognitive function in individuals with type 2 diabetes: the Maine-Syracuse Longitudinal Study.

The importance of adequate nutrition on cognitive performance is well recognised. Greater intakes of soft drinks are associated with a higher risk for type 2 diabetes, as well as other cardiometabolic diseases. A few studies have specifically examined whether the intake of soft drinks may be related to cognitive function. The aim of this study was to investigate whether soft drink intakes, including both sugar-sweetened and diet beverages, are associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors, and stratified according to type 2 diabetes status. Cross-sectional analyses were undertaken using 803 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study. Cognitive function was measured using an extensive battery of neuropsychological tests. Usual dietary intake of soft drinks was assessed using a FFQ. Stratification by type 2 diabetes indicated that a greater intake of sugar-sweetened soft drinks was significantly associated with poorer performance in visual spatial memory, working memory, scanning and tracking, executive function, the global composite and the Mini-Mental State Examination in diabetic individuals. These relations were not attenuated with statistical control for BMI and other cardiovascular, lifestyle and dietary factors. Diet soft drink intake was unrelated to cognitive performance. Frequent sugar-sweetened soft drink intake was associated with poorer cognitive performance, particularly in individuals with type 2 diabetes, but the underlying causal mechanisms are yet to be determined. Longitudinal studies are needed to clarify these findings and the underlying causal mechanisms.

Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study.

This study examined the association of chocolate consumption with insulin resistance and serum liver enzymes in a national sample of adults in Luxembourg. A random sample of 1153 individuals, aged 18-69 years, was recruited to participate in the cross-sectional Observation of Cardiovascular Risk Factors in Luxembourg study. Chocolate consumption (g/d) was obtained from a semi-quantitative FFQ. Blood glucose and insulin levels were used for the homoeostasis model assessment of insulin resistance (HOMA-IR). Hepatic biomarkers such as serum γ-glutamyl-transpeptidase (γ-GT), serum aspartate transaminase and serum alanine transaminase (ALT) (mg/l) were assessed using standard laboratory assays. Chocolate consumers (81·8 %) were more likely to be younger, physically active, affluent people with higher education levels and fewer chronic co-morbidities. After excluding subjects taking antidiabetic medications, higher chocolate consumption was associated with lower HOMA-IR (ß=-0·16, P=0·004), serum insulin levels (ß=-0·16, P=0·003) and γ-GT (ß=-0·12, P=0·009) and ALT (ß=-0·09, P=0·004), after adjustment for age, sex, education, lifestyle and dietary confounding factors, including intakes of fruits and vegetables, alcohol, polyphenol-rich coffee and tea. This study reports an independent inverse relationship between daily chocolate consumption and levels of insulin, HOMA-IR and liver enzymes in adults, suggesting that chocolate consumption may improve liver enzymes and protect against insulin resistance, a well-established risk factor for cardiometabolic disorders. Further observational prospective research and well-designed randomised-controlled studies are needed to confirm this cross-sectional relationship and to comprehend the role and mechanisms that different types of chocolate may play in insulin resistance and cardiometabolic disorders.

Association between depressive symptoms, use of antidepressant medication and the metabolic syndrome: the Maine-Syracuse Study.

BACKGROUND: Both depression and the metabolic syndrome (MetS) are two major public health issues. The aim of this study was to examine associations between depressive symptoms, the use of antidepressant medications, and the prevalence of MetS. METHODS: Cross-sectional analyses were undertaken on 970 participants from the Maine-Syracuse Study. Depressive symptoms were measured using two self-reported depression scales, the Center for Epidemiological Studies Depression Scale (CES-D), and the Zung self-rating depression scale. Antidepressant medication use was also self-reported. MetS was defined according to the recent harmonized criteria. RESULTS: The risk of MetS were approximately 79 and 86 % higher for those in the highest quartile for the CESD and the Zung (CES-D: OR = 1.79, p = 0.003; Zung: OR = 1.71, p = 0.006), compared to those in the lowest quartile. With adjustment for socio-demographic variables, lifestyle factors and C-reactive protein (CRP), risk was attenuated, but remained statistically significant for the CES-D. In those who reported using antidepressant medication, the odds of having MetS were over 2-fold higher (OR = 2.22, p < 0.001, fully adjusted model), compared to those who did not use antidepressants. Both measures of depressed mood were also associated with low high density-lipoprotein (HDL) cholesterol levels. Antidepressant use was associated with elevated fasting plasma glucose concentrations, hypertension, and low HDL-cholesterol. CONCLUSION: Depressive symptoms and the use of antidepressant medications are associated with the prevalence of MetS, and with some of the individual components of the syndrome.

Chocolate intake is associated with better cognitive function: The Maine-Syracuse Longitudinal Study.

Chocolate and cocoa flavanols have been associated with improvements in a range of health complaints dating from ancient times, and has established cardiovascular benefits. Less is known about the effects of chocolate on neurocognition and behaviour. The aim of this study was to investigate whether chocolate intake was associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors. Cross-sectional analyses were undertaken on 968 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intake was related to cognitive performance, measured with an extensive battery of neuropsychological tests. More frequent chocolate consumption was significantly associated with better performance on the Global Composite score, Visual-Spatial Memory and Organization, Working Memory, Scanning and Tracking, Abstract Reasoning, and the Mini-Mental State Examination. With the exception of Working Memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors. Prospective analyses revealed no association between cognitive function and chocolate intake measured up to 18 years later. Further intervention trials and longitudinal studies are needed to explore relations between chocolate, cocoa flavanols and cognition, and the underlying causal mechanisms.

Demonstration of High Performance in Layered Deuterium-Tritium Capsule Implosions in Uranium Hohlraums at the National Ignition Facility.

We report on the first layered deuterium-tritium (DT) capsule implosions indirectly driven by a "high-foot" laser pulse that were fielded in depleted uranium hohlraums at the National Ignition Facility. Recently, high-foot implosions have demonstrated improved resistance to ablation-front Rayleigh-Taylor instability induced mixing of ablator material into the DT hot spot [Hurricane et al., Nature (London) 506, 343 (2014)]. Uranium hohlraums provide a higher albedo and thus an increased drive equivalent to an additional 25 TW laser power at the peak of the drive compared to standard gold hohlraums leading to higher implosion velocity. Additionally, we observe an improved hot-spot shape closer to round which indicates enhanced drive from the waist. In contrast to findings in the National Ignition Campaign, now all of our highest performing experiments have been done in uranium hohlraums and achieved total yields approaching 10^{16} neutrons where more than 50% of the yield was due to additional heating of alpha particles stopping in the DT fuel.

Improved Performance of High Areal Density Indirect Drive Implosions at the National Ignition Facility using a Four-Shock Adiabat Shaped Drive.

Hydrodynamic instabilities can cause capsule defects and other perturbations to grow and degrade implosion performance in ignition experiments at the National Ignition Facility (NIF). Here, we show the first experimental demonstration that a strong unsupported first shock in indirect drive implosions at the NIF reduces ablation front instability growth leading to a 3 to 10 times higher yield with fuel ρR>1 g/cm(2). This work shows the importance of ablation front instability growth during the National Ignition Campaign and may provide a path to improved performance at the high compression necessary for ignition.

First high-convergence cryogenic implosion in a near-vacuum hohlraum.

Recent experiments on the National Ignition Facility [M. J. Edwards et al., Phys. Plasmas 20, 070501 (2013)] demonstrate that utilizing a near-vacuum hohlraum (low pressure gas-filled) is a viable option for high convergence cryogenic deuterium-tritium (DT) layered capsule implosions. This is made possible by using a dense ablator (high-density carbon), which shortens the drive duration needed to achieve high convergence: a measured 40% higher hohlraum efficiency than typical gas-filled hohlraums, which requires less laser energy going into the hohlraum, and an observed better symmetry control than anticipated by standard hydrodynamics simulations. The first series of near-vacuum hohlraum experiments culminated in a 6.8 ns, 1.2 MJ laser pulse driving a 2-shock, high adiabat (α∼3.5) cryogenic DT layered high density carbon capsule. This resulted in one of the best performances so far on the NIF relative to laser energy, with a measured primary neutron yield of 1.8×10(15) neutrons, with 20% calculated alpha heating at convergence ∼27×.

Higher HDL cholesterol is associated with better cognitive function: the Maine-Syracuse study.

Few studies have examined associations between different subcategories of cholesterol and cognitive function. We examined relationships between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride levels and cognitive performance in the Maine-Syracuse Longitudinal Study, a community-based study of cardiovascular risk factors. Cross-sectional analyses were undertaken on data from 540 participants, aged 60 to 98 years, free of dementia and stroke. TC, HDL, LDL, and triglyceride levels were obtained. Cognitive function was assessed using a thorough neuropsychological test battery, including domains of cognitive function indexed by multiple cognitive tests. The cognitive outcomes studied were as follows: Visual-Spatial Memory and Organization, Verbal and Working Memory, Scanning and Tracking, Abstract Reasoning, a Global Composite score, and the Mini-Mental State Examination (MMSE). Significant positive associations were observed between HDL-cholesterol and the Global Composite score, Working Memory, and the MMSE after adjustment for demographic and cardiovascular risk factors. Participants with desirable levels of HDL (≥60 mg/dL) had the highest scores on all cognitive outcomes. There were no significant associations observed between TC, LDL, or triglyceride concentrations and cognition. In older individuals, HDL-cholesterol was related to a composite of Working Memory tests and for general measures of cognitive ability when adjusted for cardiovascular variables. We speculate that persons over 60 are survivors and thus less likely to show cognitive deficit in relation to TC, LDL-cholesterol, and triglycerides. Longitudinal studies are needed to examine relations between specific cognitive abilities and the different subcategories of cholesterol.

Cardiovascular health: a cross-national comparison between the Maine Syracuse Study (Central New York, USA) and ORISCAV-LUX (Luxembourg).

BACKGROUND: Cardiovascular disease is the number one cause of death in the United States and in most European countries. Cardiovascular health, as defined by the American Heart Association, is comprised of seven health metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting plasma glucose). No studies have compared US data with data collected elsewhere, using this index of cardiovascular health METHODS: We performed comparative analyses of cardiovascular health status in participants from 2 study sites in 2 different countries: the Maine-Syracuse Study, conducted in Central New York, USA in 2001-2006 (n=673), and the Observation of Cardiovascular Risk Factors in Luxembourg, conducted in 2007-2009 (n=1145). RESULTS: The Cardiovascular Health Score, the sum of the total number of metrics at ideal levels, was higher in the Luxembourg site than in the Central New York site. Ideal cardiovascular health levels for body mass index, smoking, physical activity, and diet were more prevalent in the Luxembourg site than the Central New York site. Ideal levels for blood pressure were more prevalent in Central New York. Differences between the two sites remained with control for age, gender and socioeconomic indicators. CONCLUSIONS: Cardiovascular health, as indexed by seven health metrics, was higher in the European study site than in the US study site. The largest differences were for the four lifestyle/behavior metrics, namely body mass index, smoking, physical activity, and diet. Preventative and intervention strategies will continue to be important for both countries in order to improve cardiovascular health.

Charged particle radiography.

New applications of charged particle radiography have been developed over the past two decades that extend the range of radiographic techniques providing high-speed sequences of radiographs of thicker objects with higher effective dose than can be obtained with conventional radiographic techniques. In this paper, we review the motivation and the development of flash radiography and in particular, charged particle radiography.

Bright laser-driven neutron source based on the relativistic transparency of solids.

Neutrons are unique particles to probe samples in many fields of research ranging from biology to material sciences to engineering and security applications. Access to bright, pulsed sources is currently limited to large accelerator facilities and there has been a growing need for compact sources over the recent years. Short pulse laser driven neutron sources could be a compact and relatively cheap way to produce neutrons with energies in excess of 10 MeV. For more than a decade experiments have tried to obtain neutron numbers sufficient for applications. Our recent experiments demonstrated an ion acceleration mechanism based on the concept of relativistic transparency. Using this new mechanism, we produced an intense beam of high energy (up to 170 MeV) deuterons directed into a Be converter to produce a forward peaked neutron flux with a record yield, on the order of 10(10) n/sr. We present results comparing the two acceleration mechanisms and the first short pulse laser generated neutron radiograph.

Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory.

BACKGROUND: Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function. METHODS: We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning). RESULTS: Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b=0.21SD decline per unit ln(eGFR), 95% CI: 0.04-0.38, P=.018], verbal episodic memory [b=0.28 SD decline per unit ln(eGFR), 95% CI: 0.02-0.54, P=0.038] and abstract reasoning [b=0.36 SD decline per unit ln(eGFR), 95% CI: 0.04-0.67, P=0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke. CONCLUSIONS: Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline.

Homocysteine Reduction for Stroke Prevention: Regarding the Recent AHA/ASA 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.

Reduction of secondary ischemic stroke risk following an initial stroke is an important goal. The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack assembles opportunities for up to 80% secondary stroke reduction. Homocysteine reduction was not included in the recommendations. The reduction of homocysteine with low doses of folic acid has been shown to reduce ischemic stroke and all stroke. This has been obscured by studies using high doses of folic acid and cyanocobalamin in patients with renal failure and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. The confounding impacts of high dose folic acid and cyanocobalamin toxicity in renal failure and MTHFR C677T subgroups are discussed. New studies show that their toxicity is due to non-bioequivalence to the natural dietary forms, L-methylfolate and methylcobalamin. Low doses of folic acid and cyanocobalamin are safer than high doses for these subpopulations. Even lower toxicity with greater effectiveness for reducing homocysteine is seen with L-methylfolate and methylcobalamin, which are safe at high doses. Retinal vascular imaging is a noninvasive method for evaluating central nervous system (CNS) microangiopathy. A formulation containing l-methylfolate and methylcobalamin has been shown to reduce homocysteine and increase perfusion in diabetic retinopathy. This supports homocysteine intervention for CNS ischemia. Future ischemic stroke intervention studies could benefit from monitoring retinal perfusion to estimate the impact of risk reduction strategies. The omission of a recommendation for homocysteine and secondary stroke reduction through the use of B vitamins should be reconsidered in light of re-analysis of major B vitamin intervention studies and new technologies for monitoring CNS perfusion. We recommend revision of the 2021 Guideline to include homocysteine reduction with low doses of folic acid and cyanocobalamin, or better yet, L-methylfolate and methylcobalamin, making a good clinical guideline better.