A Systematic Review of Omega-3 Fatty Acid Consumption and Cognitive Outcomes in Neurodevelopment.

INTRODUCTION: This systematic review addresses the effects of n-3 long-chain polyunsaturated fatty acids consumption on human neurodevelopment. It evaluates articles published between 2000 and 2022 investigating the cognitive outcomes during the period of neurodevelopment: from fetal development to adolescence. For the purpose of this review the terms LC PUFA and omega-3 fatty acid will be used interchangeably. METHOD: Data were sourced from several major databases including PubMed (MEDLINE), Web of Science, and ProQuest Central. Randomized controlled trials (RCTs), nonrandomized controlled trials, prospective or retrospective cohort studies, and observational studies investigating the effects of omega-3 fatty acid consumption from dietary supplements, multiple-nutrient supplement, or food questionnaire on neurodevelopment were considered. Study population was separated in three developmental phases: (1) in-utero, (2) lactation/infancy, and (3) childhood/adolescence. Each article was evaluated for several key factors such as study type, type/dosage of PUFAs, number of subjects, length of intervention, participant age range, population characteristics, outcome measure (both primary/cognitive and secondary/other), results, conclusion, and confounding variables/limitations. RESULTS: A total of 88 articles were included in the review, 69 RCTs and 19 longitudinal or observational studies. The results indicate equivocal effect of intervention, with some short-term benefits observed in the areas of visual attention, working memory, executive function, and communication. Omega-3 supplement might have a short-term positive impact on neurodevelopment in all three phases. Supplementation is recommended throughout life, rather than only during the earliest developmental stage.

A Systematic Review of Omega-3 Consumption and Neuroprotective Cognitive Outcomes.

Context: While a great deal of interest has been accorded to the cognitive effects of n-3 long-chain polyunsaturated fatty acids (LC PUFAs), there is a need for systematic review data that assess this outcome across the lifespan, accounting for population differences and highlighting methodological limitations of extant studies. Objective: This systematic review addresses the effects of n-3s on human cognition and provides an overview on the current state of research and recommendations for future efforts. Data Sources: Based on a thorough review of highly powered articles from PubMed (MEDLINE), Web of Science, and ProQuest Central, the authors evaluated articles published between 2000 and 2020 assessing LC PUFA status on cognition as a primary outcome measure. Using the PRISMA guidelines, the researchers' primary aim was to provide a comprehensive overview of the articles. Conclusions: The results indicate inconsistent effects of intervention, with benefits for specific groups on specific outcomes. Although results were rarely definitive across cognitive domains, and the majority of studies indicated the presence of a possible threshold effect in which LC PUFA needs were already being met, and supplementation did not have an additional effect, there is evidence for trends towards benefit in cognitive functions, in those experiencing early cognitive decline.

Retinal Venular Tortuosity Jointly with Retinal Amyloid Burden Correlates with Verbal Memory Loss: A Pilot Study.

INTRODUCTION: Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration. In this exploratory retinal curcumin-fluorescence imaging (RFI) study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status. METHODS: We used quantitative RFI in a cohort of patients with cognitive impairment to automatically compute retinal amyloid burden. Retinal blood vessels were segmented, and the vessel tortuosity index (VTI), inflection index, and branching angle were quantified. We assessed the correlations between retinal vascular and amyloid parameters, and cognitive domain Z-scores using linear regression models. RESULTS: Thirty-four subjects were enrolled and twenty-nine (55% female, mean age 64 ± 6 years) were included in the combined retinal amyloid and vascular analysis. Eleven subjects had normal cognition and 18 had impaired cognition. Retinal VTI was discriminated among cognitive scores. The combined proximal mid-periphery amyloid count and venous VTI index exhibited significant differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs. 0.91 ± 1.4, p = 0.006), and correlated with both the Wechsler Memory Scale-IV and SF-36 mental component score Z-scores (p < 0.05). CONCLUSION: This pilot study showed that retinal venular VTI combined with the proximal mid-periphery amyloid count could predict verbal memory loss. Future research is needed to finesse the clinical application of this retinal imaging-based technology.

Gut dysbiosis, insulin resistance and Alzheimer's disease: review of a novel approach to neurodegeneration.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) share many common features including inflammation, oxidative stress and neuronal degeneration. Insulin resistance (IR) appears to be a common path in these pathological processes. IR is an early pathogenic event in AD, which leads to augmentation of hyperphosphorylated tau and Amyloid beta (Aß). The reviewed studies related to AD have revealed a positive association between T2DM and AD. This association was maintained in peripheral hyperinsulinemia cases without the presence of T2DM, which might be due to decreased insulin transport to the brain or the inadequate cerebral insulin production. Gut dysbiosis induces inflammation and consequently provokes both peripheral and cerebral IR and can amplify processes promoting AD. Additionally, the risk of increased progression of AD was revealed due to pre-diabetes, T2DM and gut dysbiosis. The pro-inflammatory changes might affect progression of AD pathology by inhibition of the autophago-lysosomal pathway and cerebral insulin signaling pathway. This review elaborates the role that cerebral IR might play in the underlying pathological events in AD.

Sectoral segmentation of retinal amyloid imaging in subjects with cognitive decline.

INTRODUCTION: Despite advances in imaging retinal amyloidosis, a quantitative and topographical investigation of retinal amyloid beta burden in patients with cognitive decline has never been reported. METHODS: We used the specific amyloid-binding fluorophore curcumin and laser ophthalmoscopy to assess retinal amyloid imaging (RAI) in 34 patients with cognitive decline. We automatically quantified retinal amyloid count (RAC) and area in the superotemporal retinal sub-regions and performed correlation analyses with cognitive and brain volumetric parameters. RESULTS: RAC significantly and inversely correlated with hippocampal volume (HV; r = -0.39, P = .04). The proximal mid-periphery (PMP) RAC and RA areas were significantly greater in patients with Montreal Cognitive Assessment (MOCA) score < 26 (P = .01; Cohen d = 0.83 and 0.81, respectively). PMP showed significantly more RAC and area in subjects with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to cognitively normal (P = .04; Cohen d = 0.83). CONCLUSION: Quantitative RAI is a feasible technique and PMP RAC may predict HV. Future larger studies should determine RAI's potential as a biomarker of early AD.

Alzheimer Disease and Cancer: A National Inpatient Sample Analysis.

INTRODUCTION: Studies have demonstrated an inverse relationship between Alzheimer dementia (AD) and cancer. This inverse relationship was further explored. In addition, Pin1 expression has been implicated in the cell cycle regulation of both disease processes. The relationship of Pin1 expression in 10 cancer types and secondary diagnosis of AD was examined. MATERIALS AND METHODS: A cross-sectional analysis was performed using discharge data from the National Inpatient Sample from 1999 to 2008. Cancer was defined as the primary discharge diagnosis and AD was defined as the secondary discharge diagnosis. Cancer types were grouped according to their Pin1 expression to examine its relationship with AD. Analysis was performed by logistic regression. RESULTS: Of ∼3 million cancer discharge diagnoses, 1.0% had a secondary diagnosis of AD. Discharge data of all 10 cancer types revealed a lower likelihood of secondary AD diagnosis. Prostate [crude odds ratios (OR): 0.26 (0.24 to 0.29), multivariate OR: 0.39 (0.35 to 0.43)], ovarian [crude OR: 0.38 (0.32 to 0.44), multivariate OR: 0.35 (0.30 to 0.41)], and lung cancer [crude OR: 0.39 (0.36 to 0.41), multivariate OR: 0.41 (0.39 to 0.44)] demonstrated the lowest odds of secondary AD diagnosis. When cancer types were grouped per Pin1 expression, cancer types with Pin1 underexpression were more likely to be associated with secondary diagnosis of AD than cancer types with Pin1 overexpression [crude OR: 1.4 (1.3 to 1.4), multivariate OR: 1.08 (1.02 to 1.14)]. DISCUSSION: This secondary data analysis further demonstrated an inverse relationship between AD and 10 cancer types, with prostate, ovarian, and lung cancers displaying the greatest inverse relationship. Pin1 underexpressing cancer types had a significantly higher likelihood of secondary diagnosis of AD than Pin1 overexpressing cancer types.

Preventing Alzheimer's: Our Most Urgent Health Care Priority.

Dementia is the fastest growing epidemic in the developed nations, and if not curtailed, it will single handedly collapse our health care system. The prevalence of dementia is 1 in 10 individuals older than 65 years and increases to 50% of all individuals older than 85 years. The prevalence of Alzheimer's dementia (AD), the most common form of dementia, has been increasing rapidly and is projected to reach 16 million individuals by the year 2050. Several prevailing myths about the science of dementia are discussed, such as that AD is inevitable and that it is exclusively a genetic disease. The fact is that AD is dependent on a multitude of genetic, epigenetic, and environmental factors that interact with one another. In fact, 4 core drivers represent 90% of what determines disease progression in AD. These are (1) glucose or energy dysregulation, (2) lipid dysregulation, (3) inflammation, and (4) oxidation. Lifestyle change can significantly alter the course of AD. The authors have created an acronym-NEURO-to help lifestyle practitioners and the public remember the most important lifestyle elements in the treatment and prevention of AD based on the evidence. "N" is for Nutrition, "E" for Exercise, "U" for Unwind (stress management), "R" for Restorative Sleep, and "O" for Optimizing mental and social activity. The evidence base for each of the components is reviewed.

Strong Association Between Migraine and Transient Global Amnesia: A National Inpatient Sample Analysis.

The purpose of this article was to explore sex- and race-specific variables and comorbidities associated with transient global amnesia (TGA) using a nationally representative database. Data were obtained from the Nationwide Inpatient Sample using ICD-9 and procedure codes. Descriptive and survey logistic regression analyses were conducted and adjusted for influence of comorbidities, demographic characteristics, and hospitalization-related factors. Patients with migraines were 5.98 times more likely to also have a diagnosis of TGA compared with patients without migraines. Similarly, patients with TGA were more likely to have hypertension, precerebral disease, and hyperlipidemia. The odds of being diagnosed with TGA was lower among African Americans and Hispanics as well as among patients classified as Asian/Other, compared with Caucasians. TGA was associated with lower hospital charges ($14,242 versus $21,319), shorter hospital stays (mean days: 2.49 [SE=0.036] versus 4.72 [SE=0.025]), and routine hospital discharges (91.4% versus 74.5%). Patients with migraines and patients classified as Caucasian had higher odds of being diagnosed with TGA. All minority populations showed a lower rate of diagnosis that fell short of statistical significance.

Insulin resistance and cognitive test performance in elderly adults: National health and nutrition examination survey (NHANES).

OBJECTIVES: To examine the relationship between homeostatic model of insulin resistance (HOMA-IR) and cognitive test performance among population≥60years in a national database. HYPOTHESIS: Higher insulin resistance is associated with lower cognitive test performance score in the population≥60years. PARTICIPANTS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2001-2002. MEASUREMENTS: Cognitive test performance was measured by the Digit Symbol Substitution (DSS) exercise score. The main independent variable was the homeostasis model assessment of insulin resistance (HOMA-IR). We used bivariate analysis and generalized linear model adjusting for age, gender, race, education, body mass index, and systolic and diastolic blood pressures; total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride levels; and physical activity, diabetes mellitus, stroke, and congestive heart failure. STATA 14 was used to analyze the data taking into consideration the design, strata and weight. RESULTS: Of the 1028 participants, 44% were male and 85% were white. The mean age was 70.0±0.28 (SE) years. Their average HOMA-IR was 3.6±0.14 and they had a mean of 49.2±0.8 correct DSS score in the cognitive test. Adjusting for the confounding variables, HOMA-IR was associated with decline in DSS score (B=-0.30, 95% confidence interval=-0.54 and -0.05, p=0.01). The model explained 44% of the variability of the DSS score (R2=0.44). Significant predictors of decline in DSS score were age, gender, race, and education (p=0.01). CONCLUSION: Insulin resistance as measured by HOMA-IR was independently associated with lower cognitive test performance score among elderly participants aged ≥60years. Longitudinal studies are needed to test the mechanism and the causal relationship.

Time Trends and Characteristics of Prevalent Dementia among Patients Hospitalized for Stroke in the United States.

BACKGROUND: Little is known about how prevalent dementia rates among patients with stroke have evolved over the last decade or how this relationship varies by gender, race ethnicity, stroke type, or dementia type. We assessed time trends and demographic predictors of coexisting dementia in a large cohort of patients hospitalized for stroke. MATERIALS AND METHODS: Patient admission data between 1999 and 2012 were sourced from the National Inpatient Sample. Patient admission records were included in the retrospective analysis if they were diagnosed with ischemic or hemorrhagic stroke during admission. Predictors of dementia subtype were analyzed using unadjusted and adjusted multinomial logistic regression. RESULTS: Of 1,170,051 patients hospitalized for stroke between 1999 and 2012, 66,703 (5.7%) had a coexisting diagnosis of dementia. Female gender was associated with increased odds of Alzheimer's dementia (AD) (adjusted odds ratio [aOR] 1.15, 95% confidence interval [CI] 1.11-1.19) but decreased odds of both vascular dementia (VaD) (aOR .50, 95% CI .44-.58) and non-Alzheimer's-nonvascular dementia (aOR .79, 95% CI .79, 95% CI .74-.83). Relative to whites, African-Americans had higher odds of AD (aOR 1.25, 95% CI 1.18-1.32) and VaD (aOR 1.51, 95% CI 1.40-1.64). Similarly, Hispanics had increased odds of AD (aOR 1.40, 95% CI 1.30-1.50). CONCLUSIONS: Rates of coexisting dementia among patients hospitalized for stroke in the United States have risen over the last decade. Prevalence of dementia among these patients varies by gender and race-ethnicity. Key demographic groups may need to be targeted to reduce disparities in dementia occurrence.

Trajectories in Leisure-Time Physical Activity and Risk of Stroke in Women in the California Teachers Study.

BACKGROUND AND PURPOSE: Whether changes in leisure-time physical activity (LTPA) over time are associated with lower risk of stroke is not well established. We examined the association between changes in self-reported LTPA 10 years apart, with risk of incident stroke in the CTS (California Teachers Study). We hypothesized that the risk of stroke would be lowest among those who remained active. METHODS: Sixty-one thousand two hundred and fifty-six CTS participants reported LTPA at 2 intensity levels (moderate and strenuous activity) at 2 time points (baseline 1995-96; 10-year follow-up 2005-2006). LTPA at each intensity level was categorized based on American Heart Association (AHA) recommendations (moderate, >150 minutes/week; strenuous, >75 minutes/week). Changes in LTPA were summarized as follows: (1) not meeting recommendations at both time points; (2) meeting recommendations only at follow-up; (3) meeting recommendations only at baseline; and (4) meeting recommendations at both time points. Incident strokes were identified through California state hospitalization records. Using multivariable Cox models, we examined the associations between changes in LTPA with incident stroke. RESULTS: Nine hundred and eighty-seven women were diagnosed with stroke who completed both questionnaires. Meeting AHA recommendations at both the time points was associated with a lower risk of all stroke (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72-0.98). The protective effects for stroke were driven by meeting AHA recommendations for moderate activity and largely observed for ischemic strokes (adjusted hazard ratio, 0.70; 95% confidence interval, 0.55-0.88). CONCLUSIONS: Meeting AHA recommendations for moderate activity had a protective effect for reducing ischemic stroke risk. Participants who met AHA recommendations at baseline but not at follow-up, however, were not afforded reduced stroke risk.

Ischemic Stroke Risk After Acute Coronary Syndrome.

BACKGROUND: Prior studies show an increased risk of ischemic stroke (IS) after myocardial infarction; however, there is limited evidence on long-term risk and whether it is directly related to cardiac injury. We hypothesized that the risk of IS after acute coronary syndrome is significantly higher if there is evidence of cardiac injury, such as ST-segment elevation myocardial infarction (STEMI) or non-STEMI, than when there is no evidence of cardiac injury, such as in unstable angina. METHODS AND RESULTS: Administrative claims data were obtained from all emergency department encounters and hospitalizations at California's nonfederal acute care hospitals between 2008 and 2011. Patients with STEMI, non-STEMI, and unstable angina were identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. The primary outcome was IS during 2 years of follow-up. Unadjusted and adjusted Cox proportional hazards models were used to determine the association between acute coronary syndrome subtype and IS risk. We identified 73 059 patients with a diagnosis of STEMI (n=26 427), non-STEMI (n=39 833), or unstable angina (n=6819) during the study period. In the fully adjusted models that included potential confounders such as atrial fibrillation and congestive heart failure, the risk of IS was higher with STEMI (hazard ratio 4.17, 95% CI 3.00-5.83; P<0.001) and non-STEMI (hazard ratio 3.73, 95% CI 2.68-5.19, P<0.001) compared with unstable angina. CONCLUSIONS: Non-STEMI and STEMI confer an equally increased risk of IS. Studies exploring IS mechanisms in cardiac patients are needed to improve and tailor stroke prevention strategies.

The Association Between Diabetes and Dementia Among Elderly Individuals: A Nationwide Inpatient Sample Analysis.

BACKGROUND/AIM: To date, few studies have cross-examined the relationship between diabetes mellitus (DM) and dementia nationally. There is also a lack of evidence regarding dementia subtypes and how this relationship changes among older individuals. The objective was to better delineate this relationship and influence of multiple comorbidities using a nationwide sample. METHODS: Data were obtained from the Nationwide Inpatient Sample 1998 to 2011 using appropriate International Classification of Diseases, Ninth Version codes. Descriptive and bivariate analysis was performed. Multivariate nominal logistic regression models adjusted for age, sex, race, and comorbidities explored the independent relationship between Alzheimer dementia (AD), non-Alzheimer dementia (VaD), and diabetes. RESULTS: 21% of the participants were diabetic patients, 3.7% had AD, and 2.2% had VaD. Diabetes prevalence in AD, VaD, and no dementia groups were 20.6%, 24.3%, and 26.2%, respectively. In the unadjusted model, those with DM had lower odds of AD (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.72-0.74) and VaD (OR 0.91, 95% CI 0.89-0.92). Adjusting for age, sex, race, and comorbidities, diabetic patients had significantly higher odds of VaD (OR = 1.10, 95% CI 1.08-1.11) and lower odds of AD (OR 0.87, 95% CI 0.86-0.88). Inclusion of interaction terms (age, race/ethnicity, depression, stroke, and hypertension) made the relationship between diabetes and VaD not significant (OR 1.002, 95% CI 0.97-1.03), but the relationship of DM with AD remained significant (OR 0.57, 95% CI 0.56-0.58; P < .05). CONCLUSION: Patients with a diagnosis of diabetes mellitus had lower odds of having AD. Age, race/ethnicity, depression, stroke, and hypertension modified the relationship between DM and both VaD and AD. Further exploration of the relationship between DM and AD is warranted.

Micronutrients and Risk of Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Although the precise pathogenetic mechanisms of PD remain undetermined, there appears to be both genetic and environmental factors that contribute to the risk of developing PD. With regard to environmental risk factors, there has been significant interest related to the role of diet, nutrition, and nutrients on the onset and progression of PD. As the current treatments are predominantly focused on symptomatic management, efforts must be directed toward prevention of the PD and identification of potentially modifiable risk and preventive factors. This comprehensive review gives an overview of studies examining the role of micronutrients in PD, and provides guidance on the value of the reported outcomes.

Dementia in the Oldest-Old: A Nationwide Inpatient Sample Database Analysis.

OBJECTIVE: The aim of this study was to explore gender and race-specific mortality and comorbidities associated with dementia hospitalizations among the oldest-old. METHOD: Using the 1999-2008 Nationwide Inpatient Sample, we identified the association between dementia mortality and hospital characteristics in the oldest-old population. RESULTS: The oldest-old population was mostly comprised of Whites (81.1%) and women (76.0%), had shorter length of hospital stay (6.12 days), and lower hospital charges (US$18,770.32) than the young-old, despite the higher in-hospital mortality. Crude in-hospital mortality was higher for White males in the young-old population, followed by Hispanics and African Americans. However, Hispanic males had the highest mortality, followed by Whites then African Americans in the oldest-old group. After adjusting for different variables, these relationships did not change. DISCUSSION: There should be a greater focus on potential pre-existing biases regarding hospital care in the elderly, especially the oldest-old and elderly minority groups.

The Women's Health Care Empowerment Model as a Catalyst for Change in Developing Countries.

Women's empowerment has been attempted through a number of different fields including the realms of politics, finance, and education, yet none of these domains are as promising as health care. Here we review preliminary work in this domain and introduce a model for women's empowerment through involvement in health care, titled the "women's health care empowerment model." Principles upon which our model is built include: acknowledging the appropriate definition of empowerment within the cultural context, creating a women's network for communication, integrating local culture and tradition into training women, and increasing the capability of women to care for their children and other women.

The CHADS2 Components Are Associated with Stroke-Related In-hospital Mortality in Patients with Atrial Fibrillation.

BACKGROUND: The CHADS2 score predicts stroke risk in patients with atrial fibrillation. Although strokes caused by atrial fibrillation carry the highest mortality when compared with other etiologies, it is not known whether the CHADS2 score predicts stroke-related mortality in patients with atrial fibrillation. We hypothesized that higher CHADS2 scores would be associated with higher stroke-related in-hospital mortality. METHODS: Data were obtained from administrative claims data from all emergency department encounters and hospitalizations at California's nonfederal acute care hospitals between 2008 and 2011. Patients with atrial fibrillation and an admission for acute stroke were identified using appropriate International Classification of Diseases, Ninth Revision (ICD-9), Clinical Modification codes. Age and ICD-9 codes for hypertension, diabetes, congestive heart failure, and prior stroke were used to calculate the CHADS2 score of patients with atrial fibrillation. The primary outcome was in-hospital stroke mortality and the primary predictor was CHADS2 score. A multivariate logistic regression model adjusted for sex and race was used to determine the odds ratio (OR) and 95% confidence interval (CI) for the association between CHADS2 and mortality. RESULTS: Between January 1, 2008, and December 31, 2011, 25,599 patients with atrial fibrillation were hospitalized with a stroke. The odds of in-hospital mortality was significantly higher with a CHADS2 score of 2 more versus less than 2 (OR, 1.15; 95% CI, 1.08-1.23); however, there was no dose-response association between the CHADS2 score and in-hospital mortality. Among the individual CHADS2 score items, factors associated with increased in-hospital mortality were congestive heart failure (OR, 1.61; 95% CI, 1.53-1.70), age 75 years or older (OR, 1.27; 95% CI, 1.19-1.35), and diabetes (OR, 1.24; 95% CI, 1.14-1.35). CONCLUSIONS: Unlike prior studies, our studies show that the prestroke CHADS2 score is of limited use in predicting in-hospital mortality in ischemic stroke hospitalizations in patients with atrial fibrillation.

Use of Recombinant Factor VIIa in Symptomatic Intracerebral Hemorrhage Following Intravenous Thrombolysis.

Symptomatic intracerebral hemorrhage (sICH) occurs in up to 7% of stroke patients treated with thrombolytic therapy. There are limited data on the effectiveness of the reversal agents used for intravenous tissue plasminogen activator related intracranial bleeds. We report a patient with sICH following intravenous thrombolysis whose intracerebral hemorrhage continued to expand despite treatment with platelets and cryoprecipitate, needing recombinant factor VIIa use for stabilization before surgical evacuation. Factor VIIa along with routine reversal agents following intravenous thrombolysis related sICH may further enhance clot stability and reduce the risk of hematoma expansion. It could be a bridge to definitive surgical management in those patients.