Increased risk of cognitive impairment and hyperglycemia-related mortality in late middle-aged African Americans with low serum adropin levels

Recent data implicate the secreted peptide adropin in the physiology of aging. In humans, adropin is highly expressed in brain tissues, and correlates positively with transcriptomic signatures of mitochondrial and synaptic functions. Adropin treatment improves performance of old mice in cognitive tests requiring learning and memory. While detected in the circulation of humans, no studies have investigated relationships between adropin, cognitive decline and aging. Here we compared serum adropin concentrations with Mini-Mental State Exam (MMSE) and animal naming test results from a cohort study of African Americans in late-middle age (baseline ages 49-65y, n=357). Using the lowest quintile of the MMSE to identify participants at risk for mild cognitive impairment (MCI) indicated lower serum concentrations (2.95±1.32 ng/ml vs. 3.31±1.56, P<0.05). Grouping into bins using 1-ng/ml increments in serum adropin concentrations further indicated an association between very low serum adropin concentrations and MCI. Using fructosamine as an indicator of moderate-term glucose levels suggested low serum adropin concentration correlate with increased risk of 10-year all-cause mortality in situations of poor glucose control. In summary, these data suggest low circulating adropin concentrations identify late-middle aged people at risk for cognitive impairment, and for all-cause mortality in situations of poor glucose control.

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Association Between the APOE ɛ2/ɛ4 Genotype and Alzheimer’s Disease and Mild Cognitive Impairment Among African Americans

Journal of Alzheimer s Disease ◽

10.3233/jad-201613 ◽

2021 ◽

pp. 1-6

Author(s):

Dianxu Ren ◽

Oscar L. Lopez ◽

Jennifer H. Lingler ◽

Yvette Conley

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

African Americans ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Increased Risk ◽

Similar Risk

We examined the association between APOE ɛ2/ɛ4 with incident Alzheimer’s disease (AD) and mild cognitive impairment (MCI) among African Americans using the national dataset from the National Alzheimer’s Coordinating Center (NACC) from 2005 to September 2019. Compared to ɛ3/ɛ3 carriers, ɛ2/ɛ4 carriers exhibited a similar risk of incident AD (adjusted hazard ratio [aHR] = 0.85, 95% CI [0.39, 1.84]) among the AD cohort and similar risk of incident MCI (aHR = 0.88, 95% CI [0.51, 1.50]) among the MCI cohort. Our findings suggest that, unlike the increased risk of AD and MCI in non-Latino whites, APOE ɛ2/ɛ4 genotype is not associated with the incidence of AD and MCI among African Americans.

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P4151Changes in incidence and risk factors for heart failure over a 21-year follow-up period in two cohorts of middle aged men born 30 years apart

European Heart Journal ◽

10.1093/eurheartj/ehz745.0723 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

C Ergatoudes ◽

P.-O Hansson ◽

K Svardsudd ◽

A Rosengren ◽

E Thunstrom ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Antihypertensive Medication ◽

Piecewise Linear ◽

Risk Profile ◽

Middle Aged ◽

Glucose Levels ◽

Increased Risk ◽

Baseline Characteristics

Abstract Background Several characteristics or conditions are associated with increased risk for heart failure (HF). In recent years we have witnessed gradually improved cardiovascular prevention and treatment. However, how the risk profile of HF has changed during the last decades remains inadequately studied. Purpose To compare risk factors for heart failure in two generations of middle-aged men from the general population born 30 years apart. Methods Two cohorts of randomly selected men born in 1913 (n=855) and in 1943 (n=798) and resident in Gothenburg, Sweden were first examined at 50 years of age in 1963 and 1993, respectively, and followed longitudinally over 21 years until age 71. Data about medical history, concomitant diseases and general health were collected by questionnaires, repeated medical examinations and review of individual medical records. The outcome was defined as hospitalization with HF as a discharge diagnosis or HF reported on the death certificate. Cox-regression analysis was used to examine the impact of baseline characteristics and time-updated atrial fibrillation (AF), ischemic heart disease (IHD) and diabetes mellitus (DM) on the outcome. Furthermore the incidence of HF overall between the two cohorts was also compared. Significance was defined as p<0.05 for all two-sided tests, except for interaction terms where p<0.10 was applied. Results During a 21-year follow up, 80 men born in 1913 (9.4%) and 36 men born in 1943 (4.6%) developed HF. Men born in 1943 had a 52% lower risk for HF (adjusted HR 0.48 95% CI 0.29–0.77 p=0.003) compared to men born in 1913. Baseline characteristics associated with higher HF risk in both cohorts were higher body mass index (BMI) and the use of antihypertensive medication. Higher heart rate was associated with an increased risk only in men born 1913 whereas higher systolic blood pressure (SBP), smoking, higher glucose levels and higher total cholesterol levels were associated with higher risk in men born 1943. Onset of AF, IHD or DM was associated with higher HF risk in both cohorts. Multivariable models using stepwise regression showed that AF, IHD, higher BMI (continuous variable), use of antihypertensive medication and higher heart rate (piecewise linear) were independent predictors for HF in men born in 1913 whereas AF, higher glucose levels, IHD and higher SBP (piecewise linear) in men born in 1943. Finally, interaction analyses showed that in comparison with those born in 1913, the relative importance as risk factors for HF among those born in 1943 has decreased for AF whereas it has increased for systolic blood pressure and cholesterol. Of note, impact of IHD as risk factor decreased numerically, and that of physical activity increased, but for both without reaching statistical significance. Cox proportional hazard analysis Conclusions The incidence of HF in middle aged men living in Gothenburg has decreased during the last decades, and in the meantime risk profile for incident HF has also changed.

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Alcohol-related dementia: a 21st-century silent epidemic?

The British Journal of Psychiatry ◽

10.1192/bjp.bp.108.051425 ◽

2008 ◽

Vol 193 (5) ◽

pp. 351-353 ◽

Cited By ~ 88

Author(s):

Susham Gupta ◽

James Warner

Keyword(s):

Cognitive Impairment ◽

Alcohol Consumption ◽

21St Century ◽

Heavy Drinking ◽

Health Indicators ◽

Protective Effects ◽

Middle Aged ◽

Aged People ◽

Low Levels

SummaryEvidence suggests a J-shaped relationship between alcohol consumption and cognitive impairment and other health indicators, with low levels of consumption having better outcomes than abstention or moderate to heavy drinking. Most research to date has focused on the protective effects of drinking small amounts of alcohol. As alcohol consumption is escalating rapidly in many countries, the current cohort of young and middle-aged people may face an upsurge of alcohol-related dementia. The dangers of heavy drinking and its effect on cognition require further attention.

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Health Variables Are Informative in Screening for Mild Cognitive Impairment Among Elderly African Americans

Journal of Applied Gerontology ◽

10.1177/0733464817711961 ◽

2017 ◽

Vol 38 (10) ◽

pp. 1421-1444 ◽

Cited By ~ 3

Author(s):

Siny Tsang ◽

Scott A. Sperling ◽

Moon-Ho Park ◽

Ira M. Helenius ◽

Ishan C. Williams ◽

...

Keyword(s):

Primary Care ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

African Americans ◽

Primary Care Physicians ◽

Primary Care Providers ◽

Care Providers ◽

Cognitive Difficulties ◽

Increased Risk ◽

State Examination

To aid primary care providers in identifying people at increased risk for cognitive decline, we explored the relative importance of health and demographic variables in detecting potential cognitive impairment using the Mini-Mental State Examination (MMSE). Participants were 94 older African Americans coming to see their primary care physicians for reasons other than cognitive complaints. Education was strongly associated with cognitive functioning. Among those with at least 9 years of education, patients with more vascular risk factors were at greater risk for mild cognitive impairment. For patients with fewer than 9 years of education, those with fewer prescribed medications were at increased risk for dementia. These results suggest that in addition to the MMSE, primary care physicians can make use of patients’ health information to improve identification of patients at increased risk for cognitive impairment. With improved identification, physicians can implement strategies to mitigate the progression and impact of cognitive difficulties.

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Effectiveness of technology-based interventions in detection, prevention, monitoring and treatment of patients at risk or diagnosed with mild cognitive impairment: protocol for a systematic review

BMJ Open ◽

10.1136/bmjopen-2020-045978 ◽

2021 ◽

Vol 11 (8) ◽

pp. e045978

Author(s):

Jordi Martínez-Soldevila ◽

Roland Pastells-Peiró ◽

Carolina Climent-Sanz ◽

Gerard Piñol-Ripoll ◽

Mariona Rocaspana-García ◽

...

Keyword(s):

Systematic Review ◽

At Risk ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Meta Analysis ◽

Cognitive Disorders ◽

Increased Risk ◽

Patients At Risk ◽

Review Protocol

IntroductionThe gradual changes over the decades in the longevity and ageing of European society as a whole can be directly related to the prolonged decline in the birth rate and increase in the life expectancy. According to the WHO, there is an increased risk of dementia or other cognitive disorders as the population ages, which have a major impact on public health. Mild cognitive impairment (MCI) is described as a greater than expected cognitive decline for an individual’s age and level of education, but that does not significantly interfere with activities of daily living. Patients with MCI exhibit a higher risk of dementia compared with others in the same age group, but without a cognitive decline, have impaired walking and a 50% greater risk of falling.The urban lifestyle and advent of smartphones, mobility and immediate access to all information via the internet, including health information, has led to a totally disruptive change in most general aspects.This systematic review protocol is aimed at evaluating the effectiveness of technology-based interventions in the detection, prevention, monitoring and treatment of patients at risk or diagnosed with MCI.Methods and analysisThis review protocol follows the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols reporting guidelines. The search will be performed on MEDLINE (PubMed), CENTRAL, CINAHL Plus, ISI Web of Science and Scopus databases from 2010 to 2020. Studies of interventions either randomised clinical trials or pre–post non-randomised quasi-experimental designs, published in English and Spanish will be included. Articles that provide relevant information on the use of technology and its effectiveness in interventions that assess improvements in early detection, prevention, follow-up and treatment of the patients at risk or diagnosed with MCI will be included.Ethics and disseminationEthics committee approval not required. The results will be disseminated in publications and congresses.

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Associations Between Anemia, Cognitive Impairment, and All-Cause Mortality in Oldest-Old Adults: A Prospective Population-Based Cohort Study

Frontiers in Medicine ◽

10.3389/fmed.2021.613426 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jia Wangping ◽

Han Ke ◽

Wang Shengshu ◽

Song Yang ◽

Yang Shanshan ◽

...

Keyword(s):

Cohort Study ◽

Cognitive Impairment ◽

Mortality Risk ◽

Proportional Hazards ◽

Oldest Old ◽

Population Based ◽

Cox Proportional Hazards ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality

Objective: To evaluate the combined effects of anemia and cognitive function on the risk of all-cause mortality in oldest-old individuals.Design: Prospective population-based cohort study.Setting and Participants: We included 1,212 oldest-old individuals (men, 416; mean age, 93.3 years).Methods: Blood tests, physical examinations, and health questionnaire surveys were conducted in 2012 were used for baseline data. Mortality was assessed in the subsequent 2014 and 2018 survey waves. Cox proportional hazards models were used to evaluate anemia, cognitive impairment, and mortality risk. We used restricted cubic splines to analyze and visualize the association between hemoglobin (Hb) levels and mortality risk.Results: A total of 801 (66.1%) deaths were identified during the 6-year follow-up. We noted a significant association between anemia and mortality (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14–1.54) after adjusting for confounding variables. We also observed a dose-response relationship between the severity of anemia and mortality (P < 0.001). In the restricted cubic spline models, Hb levels had a reverse J-shaped association with mortality risk (HR 0.88, 95% CI 0.84–0.93 per 10 g/L-increase in Hb levels below 130 g/L). The reverse J-shaped association persisted in individuals without cognitive impairment (HR 0.88, 95% CI 0.79–0.98 per 10 g/L-increase in Hb levels below 110 g/L). For people with cognitive impairment, Hb levels were inversely associated with mortality risk (HR 0.83, 95% CI 0.78–0.89 per 10 g/L-increase in Hb levels below 150 g/L). People with anemia and cognitive impairment had the highest risk of mortality (HR 2.60, 95% CI 2.06–3.27).Conclusion: Our results indicate that anemia is associated with an increased risk of mortality in oldest-old people. Cognitive impairment modifies the association between Hb levels and mortality.

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Abstract MP94: Short Sleep Duration Modifies the Relationship Between Cognitive Impairment Associated with Cardiovascular Disease and All-cause Mortality

Circulation ◽

10.1161/circ.133.suppl_1.mp94 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Julio Fernandez-Mendoza ◽

Fan He ◽

Alexandros N Vgontzas ◽

Duanping Liao ◽

Edward O Bixler

Keyword(s):

Cognitive Impairment ◽

Sleep Duration ◽

Population Sample ◽

Vascular Cognitive Impairment ◽

Short Sleep Duration ◽

Short Sleep ◽

Increased Risk ◽

All Cause Mortality ◽

Penn State ◽

The Relationship

Introduction: Short sleep duration has been associated with increased risk of cardiovascular and cerebrovascular disease (CVD), cognitive impairment (CI) and mortality. However, the role of sleep duration in predicting mortality in the context of CVD and CI is still not well-understood. Hypothesis: Short sleep duration is a key effect modifier of the relationship between CI associated with CVD and all-cause mortality. Methods: We addressed this hypothesis in the Penn State Adult Cohort, a random, general population sample of 1,741 middle-aged adults who were studied in the sleep lab and followed-up for 15y. An in-lab, 8-hour polysomnography was performed to ascertain sleep duration. CI associated with CVD was defined by the presence of hypertension, diabetes, heart disease and/or stroke with impaired higher-order, executive cognitive functioning, including slow processing speed. We tested the interaction between sleep duration and CI associated with CVD on all-cause mortality with multiple logistic regression while adjusting for sex, age, race, obesity, smoking, cholesterol, depression, insomnia, dementia, and sleep apnea. Results: The odds of mortality associated with CI-alone, CVD-alone, and CI associated with CVD were 1.3 (95% CI: 0.7-2.4), 1.7 (95% CI: 1.1-2.8), and 4.6 (95% CI: 2.8-7.7), respectively. As shown in Figure 1, the interaction between CI associated with CVD and sleep duration was significant (p < .01), indicating that the probability of mortality increased significantly as a function of shorter sleep duration in individuals with CI associated with CVD. Conclusion: We found that objective sleep duration modifies the relationship between CI associated with CVD and all-cause mortality in a dose-response manner. Short sleep duration in individuals with probable vascular cognitive impairment (VCI) may serve as a biomarker of the severity of central autonomic dysfunction. Future studies should examine whether improving sleep reduces the odds of mortality in individuals with VCI.

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Abstract P146: Serum Magnesium and Mortality in the General US Population: Results From the NHANES I Epidemiologic Follow-up Study

Circulation ◽

10.1161/circ.133.suppl_1.p146 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Xi Zhang ◽

Jin Xia ◽

Liana C. Del Gobbo ◽

Adela Hruby ◽

Ka He ◽

...

Keyword(s):

Proportional Hazards ◽

Reference Group ◽

Serum Magnesium ◽

Cox Proportional Hazards ◽

Follow Up Study ◽

Normal Reference ◽

Increased Risk ◽

All Cause Mortality ◽

Low Serum

Introduction: Low magnesium (Mg) intake and/or status has been associated with increased risk of chronic disease, including cardiovascular disease (CVD) and cancer. However, whether and to what extent low serum Mg levels are associated with all-cause or cause-specific mortality in the general population is uncertain. Hypothesis: We aimed to quantify the dose-response associations between low concentrations of serum Mg and mortality from all causes, cancer, CVD, and stroke in the general US population. Methods: We analyzed prospective data on 14,353 participants aged 25-74 years with baseline measures of serum Mg concentrations from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study 1971-2006. We estimated the mortality hazard ratios (HRs) for participants within predefined and clinically meaningful categories of serum Mg levels, including <0.7, 0.7-0.74, 0.75-0.79, 0.8-0.9 (normal reference), 0.9-0.94, 0.95-0.99, and ≥1.0 mmol/L, using Cox proportional hazards models. Restricted cubic spline models were applied to examine potentially nonlinear relationships between serum Mg and mortality. Results: During a mean follow-up of 27.6 years, 7,072 deaths occurred, 3,310 (47%) CVD deaths, 1,533 (22%) cancer deaths, and 281 (4%) stroke deaths. Twenty-one percent of all participants had low levels of serum Mg (<0.8 mmol/L) and 1.5% had extremely low serum Mg (<0.7 mmol/L). Age-adjusted all-cause mortality rates were 3845, 3491, 3471, 3400 (normal reference), 3531, 3525, and 3836 per 100,000 person-years for increasing categories of serum Mg; the HRs and 95% confidence intervals for increasing serum Mg were 1.32 (1.02-1.72), 0.93 (0.74-1.16), and 1.06 (0.96-1.18), 1.07 (0.97-1.18), 0.94 (0.77-1.13), and 0.93 (0.72-1.21), compared to the reference group (0.8-0.9 mmol/L). An L-shaped association between serum Mg concentrations and all-cause mortality was observed after adjusting for potential confounders (Figure). No statistically significant associations were observed between serum Mg and cancer, CVD, or stroke mortality. Conclusions: Very low serum Mg levels were significantly associated with all-cause mortality in the general US population. Our findings support the hypothesis that Mg deficiency as defined by very low serum Mg may have an important influence on mortality.

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Day-To-Day Home Blood Pressure Variability and All-Cause Mortality in a Memory Clinic Population

Journal of Alzheimer s Disease ◽

10.3233/jad-215002 ◽

2021 ◽

pp. 1-13

Author(s):

Rinske A. Haverkamp ◽

René J.F. Melis ◽

Jurgen A.H.R. Claassen ◽

Rianne A.A. de Heus

Keyword(s):

Blood Pressure ◽

Cognitive Impairment ◽

Blood Pressure Variability ◽

Home Blood Pressure ◽

Future Research ◽

Memory Clinic ◽

Time To Death ◽

Increased Risk ◽

All Cause Mortality ◽

Cox Proportional Hazard Regression

Background: High day-to-day blood pressure variability (BPV) has been associated with an increased risk for cognitive decline and mortality in the general population. Whether BPV is associated with increased all-cause mortality in older people with cognitive impairment is unknown. Objective: To investigate the association between day-to-day home BPV and all-cause mortality in older patients attending a memory clinic. Methods: We included 279 patients attending a memory clinic, who measured home blood pressure (BP) for 7 consecutive days in the morning and evening. Within-subject BPV was defined as the variation independent of the mean (VIM). Time-to-death was verified through the Dutch population registry. Cox proportional hazard regression was used. Separate analyses were performed for morning-to-morning and evening-to-evening BPV. Results: Mean age was 73±9 years, dementia and mild cognitive impairment were diagnosed in 35% and 34% respectively, and mean home BP was 139/79 mmHg. After a mean follow-up of 3.2 years, 52 patients had died. Neither day-to-day systolic nor diastolic VIM were associated with mortality (adjusted hazard ratio [HR] systolic VIM: 0.99, 95% -CI 0.92–1.06, p = 0.770, HR diastolic VIM: 1.04, 95% -CI 0.93–1.17, p = 0.517). When morning and evening measurements were analyzed separately, systolic morning-to-morning VIM was associated with mortality (adjusted HR: 1.09, 95% -CI 1.01–1.18, p = 0.033). Conclusion: In this study, day-to-day BPV was not associated with all-cause mortality in patients attending a memory clinic. However, morning-to-morning BPV was. Due to the short assessment window, there is still a lack of clarity; hence future research is warranted to clarify the role of all BPV components in aging.

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Low fasting glucose and future risks of major adverse outcomes in people without baseline diabetes or cardiovascular disease: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-026010 ◽

2019 ◽

Vol 9 (7) ◽

pp. e026010 ◽

Cited By ~ 2

Author(s):

Hung-Wei Liao ◽

Jeffrey Saver ◽

Hsin-Chieh Yeh ◽

Chi-Hsin Sally Chen ◽

Yi-Ling Wu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Events ◽

Fasting Glucose ◽

Meta Analysis ◽

Fasting Blood Glucose ◽

Glucose Levels ◽

Major Cardiovascular Events ◽

Increased Risk ◽

All Cause Mortality ◽

Normal Fasting Glucose

ObjectiveTo investigate the link between low fasting blood glucose levels and all-cause mortality and cardiovascular outcomes among people without baseline diabetes or cardiovascular disease.DesignSystematic review and meta-analysis.Data sourcesPubMed and Embase (1966–February 2019).Selection criteriaProspective cohort studies were included for meta-analysis if they reported adjusted HRs with 95% CIs for associations between risk of all-cause mortality, stroke, major cardiovascular events, coronary heart disease and low fasting glucose levels (<4.6 mmol/L and/or 4.0 mmol/L, respectively) versus normal fasting glucose levels.Data extraction and statistical analysisTwo independent reviewers extracted data from eligible studies. Heterogeneity was assessed by p value of χ2tests and I2. We assessed four characteristics for each included study based on items developed by the US Preventive Task Force, as well as the modified checklist used in previous studies.ResultsEleven articles (consisting of 129 prospective cohort studies) with 2 674 882 participants without diabetes and cardiovascular disease at baseline were included in this meta-analysis. Pooled results from the random effects model showed increased risks of all-cause mortality (HR: 1.56; 95% CI 1.09 to 2.23), total stroke (HR: 1.08, 95% CI 1.03 to 1.13) and ischaemic stroke (HR: 1.06, 95% CI 1.01 to 1.10), and major cardiovascular events (HR: 1.05, 95% CI 1.03 to 1.07) among people with a fasting glucose <4.0 mmol/L, as compared with people with normal fasting glucose. The less stringent low fasting glucose level, <4.6 mmol/L, was not associated with increased risk of any endpoints.Discussion and conclusionsAmong people without baseline diabetes or cardiovascular disease, a fasting blood glucose level of <4.0 mmol/L is associated with increased risk of all-cause mortality, major cardiovascular events and stroke.

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