Methods used in 'ALDH2*2 association with longevity and reduced risk of cognitive decline in Japanese-American men'

Abstract ALDH2*2 is a loss of function mutation common in East Asian populations associated with facial flushing on exposure to alcohol and increased risk of certain cancers. Conversely, absence of the ALDH2*2 mutation is associated with increased risk of hypertension and cerebral microbleeds, and two recent studies report a higher frequency of ALDH2*2 alleles in nonagenarians compared to population control samples. We used survival analysis to investigate the association between ALDH2*2 and risk of cognitive impairment and death after controlling for midlife alcohol consumption and other covariates. Participants are 621 Japanese-American men (72 to 92) enrolled in the Honolulu Asia Aging Study (HAAS) and assessed for cognitive impairment for up to 20 years. Impairment was defined as crossing below a threshold score of 74 on the Cognitive Assessment Screening Instrument (CASI). Age at death was determined by Hawaii state death certificate. Ounces of ethyl alcohol consumed per month was assessed by structured interview (number, frequency, and type of beverage) conducted 25 years prior to baseline cognitive assessment. Persons heterozygous for the ALDH2*2 variant have reduced risk of cognitive impairment and reduced risk of death, compared to homozygote non-carriers. Covarying by alcohol exposure had no effect on observed associations. This study replicates previous findings associating ALDH2*2 with longevity, and provides evidence the protective effect extends to cognition. This poster details the statistical analysis carried out to obtain these results.

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Racial and Ethnic Health Inequalities in Accelerated Transitions in Mild Cognitive Impairment and Dementia

Innovation in Aging ◽

10.1093/geroni/igaa057.945 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 295-295

Author(s):

Ginny Natale ◽

Yun Zhang ◽

Sean Clouston

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

The United States ◽

Survival Models ◽

Racial Inequalities ◽

Suppression Effect ◽

Risk Of Death ◽

Obesity And Diabetes ◽

Increased Risk ◽

Reduced Risk

Abstract Background: It is unclear how the expected risk of Mild Cognitive Impairment (MCI) and conversion to dementia in the United States differs by Race/ethnicity and gender in older adults. It is unclear whether expectations about racial disparities have changed in light of changing trends in obesity and diabetes. Method: We analyzed six waves of the National Health and Aging Trends Study (NHATS), a nationally representative prospective cohort study of U.S. residents aged 65 and older. Participants were classified into four clinically meaningful mutually-exclusive groups: unimpaired, MCI, probable dementia and death. We used multistate survival models to examine individuals’ cognitive transitions and reported predictors using hazards ratios. Results: Participants (n=6,078) were 77 years old, on average, and the majority were white, females and high school graduates. Increased age was associated with risk of MCI and death. Adjusted for obesity status and diabetes, Hispanics were had a net reduced risk of death from dementia (HR=0.60; 95% CI [0.38-0.96]) but lived longer with MCI and dementia before death. Cognitively normal Blacks faced significantly increased risk of developing MCI (HR=2.54 95% CI [1.81-3.53]) and dementia (HR=1.77 95% CI [1.34-2.35]). Obese and overweight elderly had reduced risk across transitions to MCI then to dementia, but similar risks of death compared to lower body mass indices (BMI). BMI and diabetes reveal a suppression effect and racial inequalities became more apparent. Discussion: Results showed persistent racial inequalities in MCI, probable dementia, and death, supporting the theory that racial/ethnic factors are important to expectations of aging Americans.

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Cognitive Impairment after Lacunar Stroke and the Risk of Recurrent Stroke and Death

Cerebrovascular Diseases ◽

10.1159/000514261 ◽

2021 ◽

pp. 1-7

Author(s):

Abraham Kwan ◽

Jingkai Wei ◽

N. Maritza Dowling ◽

Melinda C. Power ◽

Zurab Nadareshvili ◽

...

Keyword(s):

Cognitive Impairment ◽

Memory Impairment ◽

Recurrent Stroke ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Cognitive Screening ◽

Lacunar Stroke ◽

Domain Specific ◽

Risk Of Death ◽

Increased Risk

Introduction: Patients with poststroke cognitive impairment appear to be at higher risk of recurrent stroke and death. However, whether cognitive impairment after lacunar stroke is associated with recurrent stroke and death remains unclear. We assessed whether global or domain-specific cognitive impairment after lacunar stroke is associated with recurrent stroke and death. Methods: We considered patients from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial with a baseline cognitive exam administered in English by certified SPS3 personnel, 14–180 days after qualifying lacunar stroke. We considered a baseline score of ≤86 on the Cognitive Assessment Screening Instrument to indicate global cognitive impairment, <10 on the Clock Drawing on Command test to indicate executive function impairment, and domain-specific summary scores in the lowest quartile to indicate memory and nonmemory impairment. We used Cox proportional hazards models to estimate the association between poststroke cognitive impairment and subsequent risk of recurrent stroke and death. Results: The study included 1,528 participants with a median enrollment time of 62 days after qualifying stroke. During a mean follow-up of 3.9 years, 11.4% of participants had recurrent stroke and 8.2% died. In the fully adjusted models, memory impairment was independently associated with an increased risk of recurrent stroke (hazard ratio, 1.48; 95% confidence interval [95% CI]: 1.04–2.09) and death (hazard ratio, 1.87; 95% CI: 1.25–2.79). Global impairment (hazard ratio, 1.66; 95% CI: 1.06–2.59) and nonmemory impairment (hazard ratio, 1.74; 95% CI: 1.14–2.67) were associated with an increased risk of death. Discussion/Conclusion: After lacunar stroke, memory impairment was an independent predictor of recurrent stroke and death, while global and nonmemory impairment were associated with death. Cognitive screening in lacunar stroke may help identify populations at higher risk of recurrent stroke and death.

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Erythropoietin in perinatal hypoxic-ischemic encephalopathy: a systematic review and meta-analysis

Journal of Perinatal Medicine ◽

10.1515/jpm-2018-0360 ◽

2019 ◽

Vol 47 (4) ◽

pp. 478-489 ◽

Cited By ~ 8

Author(s):

Abdul Razak ◽

Asif Hussain

Keyword(s):

Systematic Review ◽

Cerebral Palsy ◽

Cognitive Impairment ◽

Brain Injury ◽

Meta Analysis ◽

Hypoxic Ischemic Encephalopathy ◽

Cochrane Central Register ◽

Risk Of Death ◽

Ischemic Encephalopathy ◽

Reduced Risk

Abstract Background Erythropoietin (EPO) appears to confer neuroprotection to the injured brain. Randomized clinical trials (RCTs) have demonstrated its safety in neonates with hypoxic-ischemic encephalopathy (HIE); however, the evidence is unclear. The objective of this study was to examine the role of EPO in perinatal HIE by a systematic review and meta-analysis. Methods Database search included Embase, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). RCTs reporting a death, neurodevelopmental outcomes or brain injury were included. Two authors extracted the data independently from included studies and assessed the level of evidence (LOE). Results Six RCTs (EPO=5 and darbepoetin α=1) involving 454 neonates were included. A trend toward a lower risk of death was identified in infants treated with EPO [EPO with or without hypothermia: five RCTs, 368 participants, relative risk (RR) 0.74, 95% confidence interval (CI) 0.47–1.19, LOE−low; EPO without hypothermia: four RCTs, 318 participants, RR 0.89, 95% CI 0.49–1.32, LOE−low]. EPO treatment without hypothermia compared to placebo resulted in a reduced risk of cerebral palsy (two RCTs, 230 participants, RR 0.47, 95% CI 0.27–0.80, LOE−moderate) and moderate to severe cognitive impairment (two RCTs, 226 participants, RR 0.49, 95% CI 0.28–0.85, LOE−moderate). A reduced risk of brain injury was identified in EPO treated infants (EPO with or without hypothermia, two RCTs, 148 participants, RR 0.70, 95% CI 0.53–0.92, LOE−moderate). Conclusion EPO administration in neonates with perinatal HIE reduces the risk of brain injury, cerebral palsy and cognitive impairment. The evidence is limited to suggest its role as an adjuvant to hypothermia. Larger powered trials are underway to overcome this limitation.

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Only Large Reductions in Concentrations of Natriuretic Peptides (BNP and NT-proBNP) Are Associated with Improved Outcome in Ambulatory Patients with Chronic Heart Failure

Clinical Chemistry ◽

10.1373/clinchem.2008.108928 ◽

2009 ◽

Vol 55 (1) ◽

pp. 78-84 ◽

Cited By ~ 27

Author(s):

Wayne L Miller ◽

Karen A Hartman ◽

Diane E Grill ◽

John C Burnett ◽

Allan S Jaffe

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Natriuretic Peptide ◽

Natriuretic Peptides ◽

Heart Association ◽

Class Iii ◽

Heart Failure Hospitalization ◽

Risk Of Death ◽

Increased Risk ◽

Reduced Risk

Abstract Background: Concentrations of B-type natriuretic peptides (BNPs), including N-terminal pro-B-type natriuretic peptide (NT-proBNP), can be used to estimate prognosis in chronic heart failure. Large biologic variability, however, limits the usefulness of serial measurements in individual patients. As a result, the magnitude of change in peptide concentrations that is clinically meaningful remains to be established. Methods: We studied 172 New York Heart Association class III–IV outpatients. Primary endpoints were death/transplantation or heart failure hospitalization. The magnitude of peptide changes was categorized as no change (<20% increase or decrease from enrollment), ≥20% to ≤80% increase or decrease; and >80% increase or decrease. Changes were also assessed using cutpoints (500 ng/L for BNP and 1000 ng/L for NT-proBNP). Results: Fifty-two patients died or received transplants during the course of the study. Risk reduction for heart failure hospitalization was demonstrated only for BNP decreases of >80% from enrollment [hazard ratio (HR) 0.318, P = 0.0315]. BNP increases from less than to more than the prespecified cutpoint of 500 ng/L were associated with increased mortality risk (HR 2.101, P = 0.0069), whereas decreases from more than to less than the cutpoint did not reduce risk. NT-proBNP decreases from more than to less than the cutpoint of 1000 ng/L were associated with reduced risk of death/transplantation (HR 0.119, P = 0.0354). Conclusions: BNP increases from less than to more than the cutpoint were associated with increased risk of events, whereas further increases did not add to risk. In contrast, only substantial natriuretic peptide decreases (>80%) reduced risk. These data suggest that only robust decreases in natriuretic peptide concentrations should be targeted to reduce mortality and heart failure-related hospitalizations.

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Influenza Vaccination is Associated with Reduced Cardiovascular Mortality in Adults with Diabetes. A Nationwide Cohort Study

10.2337/figshare.12436376.v1 ◽

2020 ◽

Author(s):

Daniel Modin ◽

Brian Claggett ◽

Lars Køber ◽

Morten Schou ◽

Jens Ulrik Stæhr Jensen ◽

...

Keyword(s):

Influenza Vaccination ◽

Vaccine Coverage ◽

Influenza Infection ◽

Chronic Obstructive Lung Disease ◽

Cardiovascular Death ◽

Chronic Obstructive ◽

Risk Of Death ◽

Increased Risk ◽

Reduced Risk

Background: Recent influenza infection is associated with an increased risk of atherothrombotic events, including acute myocardial infarction (AMI) and stroke. Little is known about the association between influenza vaccination and cardiovascular outcomes in patients with diabetes mellitus (DM). Methods: We used nationwide register data to identify DM patients in Denmark during 9 consecutive influenza seasons in the period 2007-2016. DM was defined as use of glucose-lowering medication. Patients who were not 18-100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer or cerebrovascular disease were excluded. Patient exposure to influenza vaccination was assessed prior to each influenza season. We considered outcomes death from all causes, from cardiovascular causes and death from AMI or stroke. For each season, patients were followed from December 1 until April 1 the next year. Results: A total of 241,551 Patients were followed for a median of 4 seasons (interquartile range: 2-8 seasons) for a total follow-up of 425,318 person-years. The vaccine coverage during study seasons ranged from 24% to 36%. During follow-up, 8,207 patients died of all-causes (3.4%), 4,127 patients died of cardiovascular causes (1.7%) and 1,439 patients died of AMI/stroke (0.6%). After adjustment for confounders, vaccination was significantly associated with reduced risks of all-cause death (HR 0.83, p<0.001), cardiovascular death (HR 0.84, p<0.001), death from AMI or stroke (HR 0.85, p=0.028) and a reduced risk of being admitted to hospital with acute complications associated with DM (diabetic ketoacidosis, hypoglycemia or coma) (HR 0.89, p=0.006). Conclusion: In patients with DM, influenza vaccination was associated with a reduced risk of death, cardiovascular death and death from AMI or stroke. Influenza vaccination may improve outcome in patients with DM.

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Retinal Vascular Measures from Diabetes Retinal Screening Photographs and Risk of Incident Dementia in Type 2 Diabetes: A GoDARTS Study

10.1101/2020.11.15.20230490 ◽

2020 ◽

Author(s):

Alexander SF Doney ◽

Aditya Nar ◽

Yu Huang ◽

Emanuele Trucco ◽

Tom MacGillivray ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fractal Dimension ◽

Competing Risk ◽

Imaging Biomarkers ◽

Prevention Strategies ◽

Risk Of Death ◽

Increased Risk ◽

Patients With Diabetes ◽

Reduced Risk

AbstractObjectivePatients with diabetes have an increased risk of dementia. Improved prediction of dementia is an important goal in developing future prevention strategies. Diabetic retinopathy screening (DRS) photographs may be a convenient source of imaging biomarkers of brain health. We therefore investigated the association of retinal vascular measures (RVMs) from DRS photographs in patients with type 2 diabetes with dementia risk.Research Design and MethodsRVMs were obtained from 6,111 patients in the GoDARTS bioresource using VAMPIRE software. Their association, independent of Apo E4 genotype and clinical parameters, was determined for incident all cause dementia (ACD) and separately Alzheimer’s dementia (AD) and vascular dementia (VD). We used Cox’s proportional hazards with competing risk of death without dementia. The potential value of RVMs to increase the accuracy of risk prediction was evaluated.ResultsIncreased retinal arteriolar fractal dimension associated with increased risk of ACD (csHR 1.17; 1.08-1.26) and AD (HR 1.33; 1.16-1.52), whereas increased venular fractal dimension (FDV) was associated with reduced risk of AD (csHR 0.85; 0.74-0.96). Conversely, FDV was associated with increased risk of VD (csHR 1.22; 1.07-1.40). Wider arteriolar calibre was associated with a reduced risk of ACD (csHR 0.9; 0.83-0.98) and wider venular calibre was associated with a reduced risk of AD (csHR 0.87; 0.78-0.97). Accounting for competing risk did not substantially alter these findings. RVMs significantly increased the accuracy of prediction.ConclusionsConventional DRS photographs could enhance stratifying patients with diabetes at increased risk of dementia facilitating the development of future prevention strategies.

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Influenza Vaccination is Associated with Reduced Cardiovascular Mortality in Adults with Diabetes. A Nationwide Cohort Study

10.2337/figshare.12436376 ◽

2020 ◽

Author(s):

Daniel Modin ◽

Brian Claggett ◽

Lars Køber ◽

Morten Schou ◽

Jens Ulrik Stæhr Jensen ◽

...

Keyword(s):

Influenza Vaccination ◽

Vaccine Coverage ◽

Influenza Infection ◽

Chronic Obstructive Lung Disease ◽

Cardiovascular Death ◽

Chronic Obstructive ◽

Risk Of Death ◽

Increased Risk ◽

Reduced Risk

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Abstract WP427: Cognitive Function of Ten-year Stroke Survivors Compared to Non-stroke Individuals: the Lund Stroke Register

Stroke ◽

10.1161/str.47.suppl_1.wp427 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Hossein Delavaran ◽

Ann-Cathrin Jönsson ◽

Håkan Lövkvist ◽

Susanne Iwarsson ◽

Sölve Elmståhl ◽

...

Keyword(s):

Cognitive Impairment ◽

Cognitive Assessment ◽

Executive Dysfunction ◽

Screening Methods ◽

Stroke Survivors ◽

Cognitive Screening ◽

Severe Cognitive Impairment ◽

Post Stroke ◽

Increased Risk

Introduction: Post-stroke cognitive impairment (PSCI) has a considerable impact on patients and society. However, the characteristics and prevalence of long-term PSCI may be influenced by assessment methods and selection bias. We therefore used two cognitive screening methods to assess PSCI in ten-year stroke survivors, made comparisons with non-stroke individuals, and compared these screening methods. Methods: The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were administered and compared in a population-based consecutive sample of ten-year stroke survivors. In addition, age- and sex-matched non-stroke controls were assessed with the MMSE. Regression analyses adjusting for education compared the stroke survivors’ MMSE performance with the controls. Moderate/severe cognitive impairment, approximating to dementia, was defined using MMSE<24 and MoCA<20 as cut-offs. To detect those with mild cognitive impairment, alternative cut-offs of MMSE<27 and MoCA<25 were also used. Results: In total, 127 of 145 stroke survivors participated. The total MMSE-scores were similar for stroke survivors (median 27) and 354 controls (median 27; p =0.922); as well as proportions with MMSE<24 (23% vs. 17%; p =0.175) or MMSE<27 (47% vs. 49%; p =0.671). After adjustment for education, stroke survivors showed an increased risk for moderate/severe cognitive impairment defined by MMSE<24 (OR=1.82; p =0.036). Executive dysfunction was seen in 42% of the stroke survivors vs. 16% of the controls as evaluated by MMSE ( p <0.001). According to MoCA, moderate/severe cognitive impairment (MoCA<20) was observed in 28% of the stroke survivors; any degree of cognitive impairment (MoCA<25) was seen in 61%; and 45-61% displayed executive function deficits. Conclusions: PSCI including executive dysfunction is common among ten-year stroke survivors, who have an increased risk of moderate/severe cognitive impairment compared to non-stroke controls. The prevalence of long-term PSCI may have been previously underestimated, and MoCA may be more suitable for post-stroke cognitive assessment.

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A 2-min cognitive screener for predicting 1-year functional recovery and survival in older adults after hip fracture repair

The Journals of Gerontology Series A ◽

10.1093/gerona/glab156 ◽

2021 ◽

Author(s):

Sileno de Queiroz Fortes-Filho ◽

Márlon Juliano Romero Aliberti ◽

Juliana de Araújo Melo ◽

Daniel Apolinario ◽

Maria do Carmo Sitta ◽

...

Keyword(s):

Cognitive Impairment ◽

Hip Fracture ◽

Functional Recovery ◽

Cognitive Assessment ◽

Older Patients ◽

Fracture Repair ◽

Screening Tools ◽

Hip Surgery ◽

Word Recall ◽

Risk Of Death

Abstract Background Implementing cognitive assessment in older people admitted to hospital with hip fracture – lying in bed, experiencing pain – is challenging. We investigated the value of a quick and easy-to-administer 10-point cognitive screener (10-CS) in predicting 1-year functional recovery and survival after hip surgery. Methods Prospective cohort study comprising 304 older patients (mean age=80.3±9.1 years; women=72%) with hip fracture consecutively admitted to a specialized academic medical center that supports secondary hospitals in Sao Paulo Metropolitan Area, Brazil. The 10-CS, a 2-minute bedside tool including temporal orientation, verbal fluency, and three-word recall, classified patients as having normal cognition, possible cognitive impairment, or probable cognitive impairment on admission. Outcomes were time-to-recovery activities of daily living (ADLs; Katz index) and mobility (New Mobility Score), and survival during 1-year after hip surgery. Hazard models, considering death as a competing risk, were used to associate the 10-CS categories with outcomes after adjusting for sociodemographic and clinical measures. Results On admission, 144 (47%) patients had probable cognitive impairment. Compared to those cognitively normal, patients with probable cognitive impairment presented less postsurgical recovery of ADLs (77% vs. 40%; adjusted sub-hazard ratio [HR]=0.44; 95%CI=0.32-0.62) and mobility (50% vs. 30%; adjusted sub-HR=0.52; 95%CI=0.34-0.79), and higher risk of death (15% vs. 40%; adjusted HR=2.08; 95%CI=1.03-4.20) over 1-year follow-up. Conclusions The 10-CS is a strong predictor of functional recovery and survival after hip fracture repair. Cognitive assessment using quick and easy-to-administer screening tools like 10-CS can help clinicians make better decisions and offer tailored care for older patients admitted with hip fracture.

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An Interview-Based Assessment of the Experience of Cognitive Impairment in Multiple Sclerosis: The Cognitive Assessment Interview (CAI)

Frontiers in Neurology ◽

10.3389/fneur.2021.637895 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tehila Eilam-Stock ◽

Pamela Best ◽

Kathleen Sherman ◽

Michael T. Shaw ◽

Joseph Ventura ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Cognitive Assessment ◽

Cognitive Impairments ◽

Cognitive Remediation ◽

Structured Interview ◽

Self Report ◽

Neuropsychological Screening ◽

Assessment Interview ◽

Remédiation Cognitive

Background: Cognitive impairment is a common feature of multiple sclerosis (MS). A semi-structured interview, including informant input, can characterize the experience of individuals living with MS and cognitive involvement.Objective: We administered the Cognitive Assessment Interview (CAI), a patient- and informant-based semi-structured interview, to characterize the experience of cognitive impairments in those living with MS.Methods: Trained raters administered the CAI to a sample of MS participants and their informants enrolled for a trial of cognitive remediation. Cognitive impairments on the CAI were characterized and compared to those captured by neuropsychological and self-report measures.Results: A total of n = 109 MS participants (mean age = 50.3 ± 12.2) and their available informants (n = 71) were interviewed. Participants reported experiencing processing speed (90/106, 85%), working memory (87/109, 80%), and learning and memory (79/109, 72%) problems most commonly. CAI-based ratings were moderately correlated with a self-report measure (Multiple Sclerosis Neuropsychological Screening Questionnaire, rs = 0.52, p < 0.001) and only mildly correlated with objective neuropsychological measures specific to executive functions (rs = 0.21, p = 0.029). For those with informant interviews, ratings were overall consistent, suggesting that the CAI is valid even in cases in which an informant is unavailable and the interview is conducted with the patient alone (as is often the case in clinical and research settings).Conclusions: The CAI provides a semi-structured interview to characterize the experience of cognitive impairment in MS, with findings representing real-world functioning, adding valuable information to both self-report measures and neuropsychological assessment.

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