Cued memory decline in biomarker-defined preclinical Alzheimer disease

Objective:To determine whether a decline in cued recall is observable in the preclinical stage of Alzheimer disease (AD) in clinically normal older adults with elevated β-amyloid (Aβ) burden on PET imaging.Methods:Clinically normal older adults underwent baseline neuroimaging (PET to assess Aβ+/− status and MRI) and annual neuropsychological testing. Cox proportional hazards models were used to assess the relative risk of cued memory decline (drop of 1, 2, 3, or 4 points on the total score of the Free and Cued Selective Reminding Test) in relation to neuroimaging measures, functional status, age, sex, and education.Results:A total of 276 older adults (Clinical Dementia Rating = 0, mean Mini-Mental State Examination score = 29 ± 1.06) were followed up for a mean of 3.6 ± 1.2 years. Despite the infrequency of cued memory decline (only 19% of participants scored ≤46/48 in total recall by year 3), Aβ+ participants were 3.55 times (95% confidence interval = 1.77–7.12) more likely to exhibit decline in total recall (≤46/48) compared with their Aβ− peers. Furthermore, Aβ+ participants who scored ≤46/48 had smaller hippocampal volumes (t = 3.37, p = 0.001) and evidence of early functional decline, i.e., greater risk of progression to global Clinical Dementia Rating of 0.5 (χ2 = 14.30, p < 0.001), compared with their Aβ+ peers with intact total recall.Conclusions:Cued memory decline in healthy older adults may be particularly indicative of Aβ-related decline during the preclinical stage of AD and useful for identifying Aβ+ clinically normal individuals at greatest risk of short-term clinical progression.

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Long-term Cognitive Decline in Older Subjects Was Not Attributable to Noncardiac Surgery or Major Illness

Anesthesiology ◽

10.1097/aln.0b013e3181bc9719 ◽

2009 ◽

Vol 111 (5) ◽

pp. 964-970 ◽

Cited By ~ 107

Author(s):

Michael S. Avidan ◽

Adam C. Searleman ◽

Martha Storandt ◽

Kara Barnett ◽

Andrea Vannucci ◽

...

Keyword(s):

Alzheimer Disease ◽

Cognitive Decline ◽

Proportional Hazards ◽

Public Health Problem ◽

Noncardiac Surgery ◽

Cox Proportional Hazards ◽

Clinical Dementia Rating ◽

Postoperative Cognitive Decline ◽

Major Illness

Background Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer disease to overcome some limitations. Methods In this retrospective cohort study, three groups were identified from participants tested annually at the Washington University Alzheimer's Disease Research Center in St. Louis, Missouri: those with noncardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression. Results Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented participants. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common after surgery or illness. Conclusions The study did not detect long-term cognitive decline independently attributable to surgery or illness, nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer disease, may be made without factoring in the specter of persistent cognitive deterioration.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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Association of Brain Natriuretic Peptide With Mortality in Exceptionally Long-Lived Families

Innovation in Aging ◽

10.1093/geroni/igaa057.681 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 211-211

Author(s):

Allison Kuipers ◽

Robert Boudreau ◽

Mary Feitosa ◽

Angeline Galvin ◽

Bharat Thygarajan ◽

...

Keyword(s):

Older Adults ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Sex Education ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Time To Event ◽

Healthy Older Adults ◽

Secondary Analyses

Abstract Natriuretic peptides are produced within the heart and released in response to increased chamber wall tension and heart failure (HF). N-Terminal prohormone Brain Natriuretic Peptide (NT-proBNP) is a specific natriuretic peptide commonly assayed in persons at risk for HF. In these individuals, NT-proBNP is associated with future disease prognosis and mortality. However, its association with mortality among healthy older adults remains unknown. Therefore, we determined the association of NT-proBNP with all-cause mortality over a median follow-up of 10 years in 3253 individuals free from HF at baseline in the Long Life Family Study, a study of families recruited for exceptional longevity. We performed cox proportional hazards analysis (coxme in R) for time-to event (mortality), adjusted for field center, familial relatedness, age, sex, education, smoking, alcohol, physical activity, BMI, diabetes, hypertension, and cancer. In addition, we performed secondary analyses among individuals (N=2457) within the normal NT-proBNP limits at baseline (<125pg/ml aged <75 years; <450pg/ml aged ≥75 years). Overall, individuals were aged 32-110 years (median 67 years; 44% male), had mean NT-proBNP of 318.5 pg/ml (median 91.0 pg/ml) and 1066 individuals (33%) died over the follow-up period. After adjustment, each 1 SD greater baseline NT-proBNP was associated with a 1.30-times increased hazard of mortality (95% CI: 1.24-1.36; P<0.0001). Results were similar in individuals with normal baseline NT-proBNP (HR: 1.21; 95% CI: 1.11-1.32; P<0.0001). These results suggest that NT-proBNP is a strong and specific biomarker for mortality in older adults independent of current health status, even in those with clinically-defined normal NT-proBNP.

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Association Between Informant-Reported Sleep Disturbance and Incident Dementia: An Analysis of the National Alzheimer’s Coordinating Center Uniform Data Set

Journal of Applied Gerontology ◽

10.1177/0733464820967202 ◽

2020 ◽

pp. 073346482096720

Author(s):

Woojung Lee ◽

Shelly L. Gray ◽

Douglas Barthold ◽

Donovan T. Maust ◽

Zachary A. Marcum

Keyword(s):

Older Adults ◽

Sleep Disturbance ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cognitive Screening ◽

Cognitive Level ◽

Data Set ◽

Cox Proportional Hazards Models ◽

Incident Dementia ◽

Normal Cognition

Informants’ reports can be useful in screening patients for future risk of dementia. We aimed to determine whether informant-reported sleep disturbance is associated with incident dementia, whether this association varies by baseline cognitive level and whether the severity of informant-reported sleep disturbance is associated with incident dementia among those with sleep disturbance. A longitudinal retrospective cohort study was conducted using the uniform data set collected by the National Alzheimer’s Coordinating Center. Older adults without dementia at baseline living with informants were included in analysis. Cox proportional hazards models showed that participants with an informant-reported sleep disturbance were more likely to develop dementia, although this association may be specific for older adults with normal cognition. In addition, older adults with more severe sleep disturbance had a higher risk of incident dementia than those with mild sleep disturbance. Informant-reported information on sleep quality may be useful for prompting cognitive screening.

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Air Pollution Is Associated with Cognitive Deterioration of Alzheimer’s Disease

Gerontology ◽

10.1159/000515162 ◽

2021 ◽

pp. 1-9

Author(s):

Feng Cheng Lin ◽

Chih Yin Chen ◽

Chung Wei Lin ◽

Ming Tsang Wu ◽

Hsuan Yu Chen ◽

...

Keyword(s):

Risk Factors ◽

Air Pollution ◽

Social Engagement ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Rank Test ◽

Cognitive Deterioration ◽

Clinical Dementia Rating ◽

Severe Stage ◽

Increased Risk

Introduction: Dementia is one of the major causes of disability and dependency among older people worldwide. Alzheimer’s disease (AD), the most common cause of dementia among the elderly, has great impact on the health-care system of developed nations. Several risk factors are suggestive of an increased risk of AD, including APOE-ε4, male, age, diabetes mellitus, hypertension, and low social engagement. However, data on risk factors of AD progression are limited. Air pollution is revealed to be associated with increasing dementia incidence, but the relationship between air pollution and clinical AD cognitive deterioration is unclear. Methods: We conducted a case-control and city-to-city study to compare the progression of AD patients in different level of air-polluted cities. Clinical data of a total of 704 AD patients were retrospectively collected, 584 residences in Kaohsiung and 120 residences in Pingtung between 2002 and 2018. An annual interview was performed with each patient, and the Clinical Dementia Rating score (0 [normal] to 3 [severe stage]) was used to evaluate their cognitive deterioration. Air pollution data of Kaohsiung and Pingtung city for 2002–2018 were retrieved from Taiwan Environmental Protection Administration. Annual Pollutant Standards Index (PSI) and concentrations of particulate matter (PM10), sulfur dioxide (SO2), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO) were obtained. Results: The PSI was higher in Kaohsiung and compared with Pingtung patients, Kaohsiung patients were exposed to higher average annual concentrations of CO, NO2, PM10, and SO2. AD patients living in Kaohsiung suffered from faster cognitive deterioration in comparison with Pingtung patients (log-rank test: p = 0.016). When using multivariate Cox proportional hazards regression analysis, higher levels of CO, NO2, PM10, and SO2 exposure were associated with increased risk of AD cognitive deterioration. Among all these air pollutants, high SO2 exposure has the greatest impact while O3 has a neutral effect on AD cognitive deterioration. Conclusions: Air pollution is an environment-related risk factor that can be controlled and is associated with cognitive deterioration of AD. This finding could contribute to the implementation of public intervention strategies of AD.

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Suicide risk within one year of cognitive impairment diagnosis in older adults: a nationwide retrospective cohort study

10.21203/rs.2.19129/v1 ◽

2019 ◽

Author(s):

Jae Woo Choi ◽

Kang Soo Lee ◽

Euna Han

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mental Disorders ◽

Suicide Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

One Year

Abstract Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.

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Pre-Existing Disability and Its Risk of Fragility Hip Fracture in Older Adults

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16071237 ◽

2019 ◽

Vol 16 (7) ◽

pp. 1237

Author(s):

Jayeun Kim ◽

Soong-Nang Jang ◽

Jae-Young Lim

Keyword(s):

Older Adults ◽

Hip Fracture ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Cox Proportional Hazards Model ◽

Mental Disabilities ◽

Term Care ◽

Fragility Hip Fracture

Background: Hip fracture is one of the significant public concerns in terms of long-term care in aging society. We aimed to investigate the risk for the incidence of hip fracture focusing on disability among older adults. Methods: This was a population-based retrospective cohort study, focusing on adults aged 65 years or over who were included in the Korean National Health Insurance Service–National Sample from 2004 to 2013 (N = 90,802). Hazard ratios with 95% confidence interval (CIs) were calculated using the Cox proportional hazards model according to disability adjusted for age, household income, underlying chronic diseases, and comorbidity index. Results: The incidence of hip fracture was higher among older adults with brain disability (6.3%) and mental disability (7.5%) than among those with other types of disability, as observed during the follow-up period. Risk of hip fracture was higher among those who were mildly to severely disabled (hazard ratio for severe disability = 1.59; 95% CI, 1.33–1.89; mild = 1.68; 95% CI, 1.49–1.88) compared to those who were not disabled. Older men with mental disabilities experienced an incidence of hip fracture that was almost five times higher (hazard ratio, 4.98; 95% CI, 1.86–13.31) versus those that were not disabled. Conclusions: Older adults with mental disabilities and brain disability should be closely monitored and assessed for risk of hip fracture.

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Nonfatal Stroke and All-Cause Mortality among Community-Dwelling Older Adults Living in Rural Ecuador: A Population-Based, Prospective Study

Journal of Neurosciences in Rural Practice ◽

10.4103/jnrp.jnrp_79_18 ◽

2018 ◽

Vol 09 (04) ◽

pp. 551-555

Author(s):

Oscar H. Del Brutto ◽

Robertino M. Mera ◽

Victor J. Del Brutto

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Rural Setting ◽

Nonfatal Stroke ◽

All Cause Mortality ◽

History Of ◽

Univariate Analyses

ABSTRACT Background: Stroke is a leading cause of disability in developing countries. However, there are no studies assessing the impact of nonfatal strokes on mortality in rural areas of Latin America. Using a population-based, prospective cohort study, we aimed to assess the influence of nonfatal strokes on all-cause mortality in older adults living in an underserved rural setting. Methods: Deaths occurring during a 5-year period in Atahualpa residents aged ≥60 years were identified from overlapping sources. Tests for equality of survivor functions were used to estimate differences between observed and expected deaths for each covariate investigated. Cox proportional hazards models were used to estimate Kaplan–Meier survival curves of variables reaching significance in univariate analyses. Results: Of 437 individuals enrolled over 5 years, follow-up was achieved in 417 (95%), contributing 1776 years of follow-up (average 4.3 ± 1.3 years). Fifty-one deaths were detected, for an overall cumulative 5-year mortality rate of 12.2% (8.9%–15.6%). Being older than 70 years of age, having poor physical activity, edentulism, and history of a nonfatal stroke were related to mortality in univariate analyses. A fully adjusted Cox proportional hazards model showed that having history of a nonfatal stroke (P = 0.024) and being older than 70 years of age (P = 0.031) independently predicted mortality. In contrast, obesity was inversely correlated with mortality (P = 0.047). Conclusions: A nonfatal stroke and increasing age increase the risk of all-cause mortality in inhabitants of a remote rural village. The body mass index is inversely related to death (obesity paradox).

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Illiteracy, dementia risk, and cognitive trajectories among older adults with low education

Neurology ◽

10.1212/wnl.0000000000008587 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2247-e2256 ◽

Cited By ~ 3

Author(s):

Miguel Arce Rentería ◽

Jet M.J. Vonk ◽

Gloria Felix ◽

Justina F. Avila ◽

Laura B. Zahodne ◽

...

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Independent Effect ◽

Growth Curve Models ◽

Cox Proportional Hazards Models ◽

Dementia Risk ◽

Incident Dementia ◽

Low Education

ObjectiveTo investigate whether illiteracy was associated with greater risk of prevalent and incident dementia and more rapid cognitive decline among older adults with low education.MethodsAnalyses included 983 adults (≥65 years old, ≤4 years of schooling) who participated in a longitudinal community aging study. Literacy was self-reported (“Did you ever learn to read or write?”). Neuropsychological measures of memory, language, and visuospatial abilities were administered at baseline and at follow-ups (median [range] 3.49 years [0–23]). At each visit, functional, cognitive, and medical data were reviewed and a dementia diagnosis was made using standard criteria. Logistic regression and Cox proportional hazards models evaluated the association of literacy with prevalent and incident dementia, respectively, while latent growth curve models evaluated the effect of literacy on cognitive trajectories, adjusting for relevant demographic and medical covariates.ResultsIlliterate participants were almost 3 times as likely to have dementia at baseline compared to literate participants. Among those who did not have dementia at baseline, illiterate participants were twice as likely to develop dementia. While illiterate participants showed worse memory, language, and visuospatial functioning at baseline than literate participants, literacy was not associated with rate of cognitive decline.ConclusionWe found that illiteracy was independently associated with higher risk of prevalent and incident dementia, but not with a more rapid rate of cognitive decline. The independent effect of illiteracy on dementia risk may be through a lower range of cognitive function, which is closer to diagnostic thresholds for dementia than the range of literate participants.

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Estimated GFR and Mortality in Older Men: Are All eGFR Formulae Equal?

American Journal of Nephrology ◽

10.1159/000445757 ◽

2016 ◽

Vol 43 (5) ◽

pp. 325-333 ◽

Cited By ~ 13

Author(s):

Muna T. Canales ◽

Terri Blackwell ◽

Areef Ishani ◽

Brent C. Taylor ◽

Allyson Hart ◽

...

Keyword(s):

Older Adults ◽

Cystatin C ◽

Proportional Hazards ◽

Older Men ◽

Cardiovascular Death ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Sleep Study ◽

Disease Epidemiology ◽

Net Reclassification Improvement

Background: Recently, the first estimated glomerular filtration rate (eGFR) formula specifically developed for community-dwelling older adults, the Berlin Initiative Study Equation 2 (BIS2), was reported. To date, however, no study has examined the performance of the BIS2 to predict death in older adults as compared to equations used clinically and in research. Methods: We prospectively followed 2,994 community-dwelling men (age 76.4 ± 5.6) enrolled in the MrOS Sleep Study. We calculated baseline eGFR from serum creatinine and cystatin-C using the BIS2, Chronic Kidney Disease Epidemiology (CKD-EPIcr,cysc), CKD-EPIcysc and CKD-EPIcr equations. Analyses included Cox-proportional hazards regression and net reclassification improvement (NRI) for the outcomes of all-cause and cardiovascular death. Results: Follow-up time was 7.3 ± 1.9 years. By BIS2, 42 and 11% had eGFR <60 and <45, respectively, compared to CKD-EPIcr (23 and 6%), CKD-EPIcysc (36 and 13%) and CKD-EPIcr,cysc (28 and 8%). BIS2 eGFR <45 was associated with twofold higher rate of all-cause mortality when compared to eGFR ≥75 after multivariate adjustment (HR 2.1, 95% CI 1.5-2.8). Results were similar for CKD-EPIcr,cysc <45 (HR 2.1, 95% CI 1.6-2.7) and CKD-EPIcysc <45 (HR 2.1, 95% CI 1.7-2.7) and weaker for CKD-EPIcr <45 (HR 1.5, 95% CI 1.2-2.0). In NRI analyses, when compared to CKD-EPIcr,cysc, both BIS2 and CKD-EPIcr equations more often misclassified participants with respect to mortality. We found similar results for cardiovascular death. Conclusion: The BIS2 did not outperform and the CKD-EPIcr was inferior to the cystatin C-based CKD-EPI equations to predict death in this cohort of older men. Thus, the cystatin C-based CKD-EPI equations are the formulae of choice to predict death in community-dwelling older men.

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